FAR EASTERN UNIVERSITY - DR. NICANOR REYES MEDICAL ... journals/JUNE 2016.pdf2 Far Eastern University - Dr. Nicanor Reyes Medical Foundation Medical Journal, Vol. 22, No. 1 - January

FAR EASTERN UNIVERSITY - DR. NICANOR REYES MEDICAL FOUNDATION

Medical JournalEditor-in-Chief

POLICARPIO B. JOVES JR., MD, MPH, MOH, FPAFP

Associate EditorMACARIO F. REANDELAR JR., MD, MSPH, FPAFP

FAR EASTERN UNIVERSITY - DR. NICANOR REYES MEDICAL FOUNDATION

BIOCHEMISTRY & NUTRITIONMari-Ann B. Bringas, MD, DPAAB

HUMAN STRUCTURAL BIOLOGYLeona Melodia T. Matheus, MD, FPCS,FPSGS

MICROBIOLOGY & PARASITOLOGYCerelyn E. Dacula, MD, DPPS, MSc

CLINICAL LAB./PATHOLOGYCheryl May C. Tan, MD, FPSP, MPM

CHILD HEALTHEva I. Bautista, MD, MSc, FPPS

COMMUNITY & FAMILY MEDICINEJenell O. Naldo, MD, MPH, FPAFP

OBSTETRICS & GYNECOLOGYLylah D. Reyes, MD, MSc, FPOGS

OPHTHALMOLOGYAngelico L. Alejo, MD, DPBO

RADIOLOGYMa. Theresa M. Bisquera, MD, FUSP, FPCR

SURGERYOmar O. Ocampo, MD, FPCS, FPSCRS, FPSGS, FPALES

ANESTHESIOLOGYKhristine I. Ramos, MD, FPSA

PHARMACOLOGYAbraham Daniel C. Cruz, MD, MSPH

PHYSIOLOGYRonald Allan G. Cruz, MD

OTORHINOLARYNGOLOGY-HEAD & NECKSURGERYCecile C. Cobangbang, MD, FPSOHNS

INTERNAL MEDICINEEleazar P. Daet, MD, FPCP, FPCC

SCHOOL OF RESPIRATORY THERAPYCesar Ayes M. Ong, MD, FPPS, FPAPP, MHPEd

SCHOOL OF NUTRITION & DIETETICSFelina P. Calimbo, RND, MPH

SCHOOL OF NURSINGBenilda V. Medallo, RN, MAN

GENERAL EDUCATIONRose Marie Mendoza, ChE, PhD

EDITORIAL CONSULTANTS

LINDA D. TAMESIS, MS, MD, MHADean, School of Medicine

REY H. DELOS REYES, MD, MHSA, FPOGSChief of Clinics

MAGDALENA F. NATIVIDAD, RMT, MSPH, PhDDean, School of Medical Technology

TITA Y. CRUZ, RN, MAN, EdDDean, School of Nursing

EDITHA C. DIZON, MD, FPARMDean, School of Physical Therapy

REY MELCHOR F. SANTOS, MD, MHA, FPCS, FACSChair, Research Development Office

PIO T. ESGUERRA, MD, FPCP, FPCCP, DIHDean, School of Respiratory Therapy

MARITES V. SINGH, RND, PhDDean, School of Nutrition & Dietetics

ROSALINDA C. SOLEVILLA, RPh, PhDDean, School of Pharmacy

MARCELINO E. MENDOZA, MD, FPCR, FUSPDean, School of Radiologic Technology

SCHOOL OF MEDICINE

SCHOOL OF RADIOLOGIC TECHNOLOGYNestor Q. Galvez, RRT, MPH

SCHOOL OF PHYSICAL THERAPYLeonilo F. Pallasigui, MRS, PT, PTRP, ACE-CPT

SCHOOL OF PHARMACYRobert Paul S. Lim, RPh

SCHOOL OF MEDICAL LABORATORY SCIENCESherwin N. Reyes, RMT, MSc, ISID

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FEU-NRMF Medical JournalVolume 22 Number 1 June, 2016

Contents

Case Reports

When Fever PersistsEpstein Barr Virus-associated Hemophagocytic Syndrome 1

Hannah M. Reandelar, MD

Primary Congenital Glaucoma 7Mervyn H. Fernandez, MD

Placenta Percreta-Induced Third Trimester Uterine Rupture In An Unscarred Uterus:A Diagnostic Dilemma 17

Samantha Quennie D. Wanasen, MD and Michelle Gamboa, MD, FPOGS, FPSRM

Multiple Rhinoplasty Procedures for Post-Medial MaxillectomyAssociated Deformities in a Patient with Fibrous Dysplasia 22

Nicole P. Ramos, MD and Cesar F. Villafuerte, MD, FPSO-HNS, FPCS

Intestinal Obstruction Secondary To Midgut Malrotation:A Diagnostic Dilemma In An Adult Patient 26

Jenine Joy C. Segismundo, MD; Joseph Carlo G. Kiat, MD;Omar O. Ocampo, MD FPCS and Wilfredo Y. Tayag, MD FPCS

Far Eastern University - Dr. Nicanor Reyes Medical Foundation Medical Journal, Vol. 22, No. 1 - January - June 2016 1

When Fever PersistsEpstein Barr Virus-associated Hemophagocytic Syndrome

Hannah M. Reandelar, MD*

Infectious mononucleosis, caused by the Epstein-Barr (EBV) virus, is characterized by systemic somaticcomplaints consisting primarily of fatigue, malaise, fever, generalized lymphadenopathy and sore throat.The virus most commonly triggers infection-associated hemophagocytic syndrome otherwise known asHemophagocytic Lymphohistiocytosis (HLH), or the aggressive proliferation of activated macrophagesand histiocytes, which phagocytose RBCs, WBCs, and platelets leading to the clinical symptoms.This is a case of a 5-year old female who presented with intermittent fever for one and a half month. Due tothe persistence of fever, pancytopenia, cough, palpable lymph nodes, joint pains, and hepatosplenomegaly,Systemic Inflammatory Response Syndrome, leukemia, and systemic lupus erythematosus were considered.On her second month of illness, she was finally diagnosed with Hemophagocytic Syndrome secondary toEpstein Barr virus infection. In the sad turn of events, the patient succumbed to the complications of theillness.This report, therefore, aims to discuss the clinical presentation and diagnosis of Acquired HemophagocyticSyndrome secondary to Epstein Barr Virus, and why secondary HLH should be considered as an importantdiagnostic consideration in patients who present with prolonged fever. Treatment and prognosis are alsodiscussed in this report.

Key words: Epstein barr virus-hemophagocytic syndrome

Hemophagocytic Lymphohistiocytosis (HLH) isthe aggressive proliferation of activated macrophagesand histiocytes, which phagocytose RBCs, WBCs, andplatelets leading to the clinical symptoms. Incidenceis reported to be 1.2 cases per million persons peryear.1 However, unpublished observations estimatethat the figures have slightly increased over timebecause of improved detection.

There are 2 types of HLH, first being the primaryor familial form, which is an autosomal recessivedisorder and is more prevalent with parentalconsanguinity, and the second, the secondary or

ABSTRACT

*First Year Resident, Department of Child Health

acquired form which occurs after strong immunologicactivation (systemic infection, immunodeficiency, orunderlying malignancy.2 In our case, the patient hasbeen infected with Epstein-Barr virus, which is thepathogen that most commonly triggers infection-associated hemophagocytic syndrome.3

THE CASE

This is a case of a 5-year old female with a chiefcomplaint of intermittent fever for 5 weeks.

The history of present illness started 7 weeks priorto admission, when the patient presented withintermittent, low to moderate-grade fever, cough,watery nasal discharge, vomiting of previouslyingested food, and epigastric pain for 4 days. She was

Far Eastern University - Dr. Nicanor Reyes Medical Foundation Medical Journal, Vol. 22, No. 1 - January - June 20162

admitted in our institution with a diagnosis of pediatriccommunity acquired pneumonia - moderate risk,dengue fever with warning signs. Pertinent PEfindings included non-tender, mobile bilateral cervicallymph nodes measuring 0.5cm x 0.5cm, and coarsecrackles on both lung fields. Chest x-ray revealedbilateral interstitial pneumonia. There were no palpableabdominal masses nor organomegaly, with no signs ofpallor. Dengue duo test was negative but series ofcomplete blood count results revealed a decreasingtrend in the WBC with lymphocytic predominance,hemoglobin, and platelet. There was nohemoconcentration and RBC Indices were normal.During the hospital stay, the patient was persistentlytachycardic (115-125bpm), and febrile. Patient wasgiven Cefuroxime for a week, which provided slightimprovement of the cough and watery nasaldischarge, and ferrous sulfate which was prescribedfor 3 months. Patient was discharged after 5 dayswith eventual increase in platelet count and lysis offever for 2 days.

A day after the discharge, the patient again hadintermittent low to moderate-grade fever, which lastedfor 4 days associated with the recurrence of coughand watery nasal discharge. Consultation was doneand she was diagnosed with atypical pneumonia. Shewas given Clarithromycin for 7 days, which providedtemporary relief of cough and colds.

The patient then remained apparently well for 2weeks.

Four weeks prior to admission, due to thepersistence of intermittent fever and the recurrenceof cough and colds, the patient was admitted for thesecond time at our institution with an admittingimpression of typhoid fever, rule out pulmonarytuberculosis. The patient also presented with unilateral,intermittent joint pains (shoulder, elbow, knee), andbody weakness. Pertinent PE findings includedbilateral, non-tender, mobile cervical lymph nodesmeasuring 0.5cm x 0.5cm, clear breath sounds,tachycardia (144-155 bpm), irregular rhythm, with S3gallop, with grade 3/6 systolic murmur at the leftparasternal border, a distended abdomen with palpableliver edge 4cm from the right costal margin, right upperquadrant tenderness, normoactive bowel sounds, andgeneralized pallor. The patient was transferred to thePICU due to episodes of widened pulse pressure. Thefollowing laboratory tests done revealed negativeresults: PPD, Typhi Dot, Dengue Duo and BloodCulture. Serum electrolytes, PT, Troponin I andUrinalysis revealed normal results. aPTT was

prolonged. Series of CBC showed persistentleukopenia (1.34-4.69), anemia, which improved aftertransfusion of pRBC, and thrombocytopenia (43-91)which eventually increased during the later course ofthe hospital stay. Peripheral blood smear showednormocytic, normochromic RBCs with fewhypochromic cells, WBCs were decreased withpredominance of neutrophils, with occasional atypicallymphocytes, platelets were decreased and therewere no blast cells seen. Total protein, albumin andglobulin were decreased. 20% albumin infusion wasthen started. CK-MB was slightly elevated. ECGrevealed sinus tachycardia and sinus arrhythmia. 2D-echo revealed left atrial and ventricular enlargement,ejection fraction was normal at 59%, with minimalpericardial effusion. Chest x-ray revealed bilateralinterstitial pneumonia with mild pulmonary congestion.With a working impression of clinical sepsis, patientwas started on ceftriaxone and oxacillin. The patientwas then discharged after 15 days with a final diagnosisof clinical sepsis, viral myocarditis, chronic anemia,etiology to be determined. Vitamins B and C werealso prescribed as myelostimulants.

Initially, pulmonary tuberculosis was considereddue to prolonged fever, palpable cervical lymph nodesand recurrent cough. However, it was ruled outbecause the radiographic findings did not show anysigns of tuberculosis and the patient had a negativePPD. Infective endocarditis was also consideredbecause of prolonged fever, chest pain, arthralgia,persistent episodes of tachycardia, systolic heartmurmurs and splenomegaly. Laboratories showedanemia and initial leukocytosis. It was immediatelyruled out because of lack of history that maypredispose to infective endocarditis, a negative bloodculture and negative echocardiographic findings.

The patient was apparently well for a week.Four days prior to admission, the patient presented

with continuous, high-grade fever associated cough,unilateral, intermittent joint pains on the shoulder, kneesand elbows, and vomiting of previously ingested meal.She was then brought to her private physician whereshe was given Clarithromycin, but did not provide reliefof symptoms. This prompted the relatives to bring thepatient to FEU-NRMF and was eventually admittedfor the third time with an admitting diagnosis ofsystemic viral illness.

Past medical history revealed that patient hadprimary Koch's infection in August 2014 andcompleted 6 months of triple anti-Koch's treatment.She had no history of allergies, malignancies nor


heredofamilial diseases such as blood-related diseases.Nutritional, immunization, personal and social historywere non-contributory.

Upon physical examination, she was conscious,coherent, in mild cardiorespiratory distress, pale,hydrated and febrile. No stunting or wasting was noted.She had pale palpebral conjunctivae, supple neck withnon-tender, mobile cervical lymph nodes approximately(1.5 x 1.5 cm) bilateral, with clear breath sounds, withadynamic precordium, tachycardic, with regularrhythm, with grade 3/6 systolic murmur over leftparasternal border; globular abdomen, normoactivebowel sounds, soft, non-tender, liver span of 7cm(palpable 4 cm from the right costal margin), withpalpable splenic edge (2 cm below the left costalmargin); with generalized pallor, and hyperpigmentedlesions on both lower extremities. Neurologicexamination was unremarkable.

C-reactive protein was 7.8x elevated, urinalysisrevealed hematuria, series of complete blood countshowed persistent pancytopenia. Blood culture andsensitivity was requested. LDH was 3.3x elevated andSGPT was normal. Creatinine and ANA titers werenormal. Whole abdominal ultrasound showed mildhepatomegaly and splenomegaly.

Throughout the course of hospital stay, the patienthad continuous high-grade fever despite administrationof paracetamol, ciprofloxacin, and azithromycin. Shewas transfused with packed red blood cells and plateletconcentrate. Blood culture and sensitivity revealed nogrowth. EBV IgM and IgG titers revealed positiveresults. Bone marrow aplasia secondary to infectionversus bone marrow abnormality and miscellaneousillnesses like lymphohistiocytic syndromes were nowconsidered. Bone marrow aspiration biopsy showedhypocellular marrow, few megakaryocytes, withatypical cells seen but not characteristics of blasts.There were occasional hemophagocytic cells.Considerations at this time were leukemia in preevolution phase versus bone marrow aplasiasecondary to sepsis versus primary bone abnormality.She was then subsequently transferred to agovernment institution due to financial constraints.

Systemic Inflammatory Response Syndrome(SIRS), and sepsis were ruled in because 2 out of 4criteria were met: Temperature of more than 38.5,tachycardia, and leukopenia. Sepsis was howeverruled out because of an undetermined focus ofinfection and a negative blood culture. SIRS however,was not totally ruled out. Systemic LupusErythematosus was also considered due to prolonged

fever, arthralgia, hepatosplenomegaly, anemia,leukopenia, and thrombocytopenia. It was ruled outbecause the patient had a negative ANA titer, andurinalysis did not show proteinuria/hematuria.

Malignancy such as leukemia was ruled in becauseof history of prolonged intermittent, low-grade fever,malaise and intermittent joint pains. Physical findingsalso revealed pallor, cervical lymphadenopathies, andhepatosplenomegaly. Laboratories revealedpancytopenia. However, it was ruled out becauseperipheral blood smear and bone marrow biopsy failedto demonstrate blast cells.

Upon arrival at the hospital of choice, the patientwas conscious, coherent, febrile (40.4ºC) with stablevital signs. Pertinent physical examination includedhyperpigmented lesions on lower extremities, palpablecervical lymphadenopathy bilateral (1-1.5cm), liverspan of 4cm below the right costal margin, and apalpable spleen 5cm from the left costal margin. Bloodtests still showed persistent pancytopenia, withelevated ferritin, SGPT levels, and triglycerides. A bonemarrow biopsy was performed presenting signs ofHLH. The diagnosis of hemophagocytic syndrome wasthen made.

Salient features of this patient included prolongedintermittent fever, palpable cervical lymph nodes,recurrent cough, hepatosplenomegaly, and large-jointarthritis.

Hemophagocytic syndrome is an aggressiveproliferation of activated macrophages and histiocytes,which phagocytose (RBCs, WBCs, and platelets)leading to the clinical symptoms. There are 2 types,first is the primary or familial form, which is anautosomal recessive disorder and is more prevalentwith parental consanguinity, and second, the secondaryor acquired form which occurs after strongimmunologic activation (systemic infection,immunodeficiency, or underlying malignancy. In ourcase, the patient has been infected with Epstein-Barrvirus, which is the pathogen that most commonlytriggers infection-associated hemophagocyticsyndrome.

Infectious mononucleosis, caused by Epstein Barrvirus, derived its name from mononuclearlymphocytosis with atypical-appearing lymphocytes(CD8 T lymphocytes). Infection is prevalent, affecting>95% of world population. 30-50% of cases inadolescents manifest with the classic triad of fatigue,pharyngitis, generalized lymphadenopathy. However,symptoms are rarely apparent in children younger than4 years of age, when most EBV infections are


asymptomatic.4 Our patient is a 5 year-old female whoonly presented with lymphadenopathy and did notpresent with pharyngitis, with fatigue presenting atthe later course of her illness.

Through transmission by kissing or close contactwith saliva of other infected children, the virus initiallyinfects the tonsillar crypts that cause pharyngitis andafter replicating intracellularly, the virus would spreadto nearby structures and would eventually causeviremia and consequential infection of B lymphocytesin the blood, liver and spleen. Once the B cells areaffected, atypical CD8 T lymphocytes will multiply,causing greater amounts of CD8 cytotoxiclymphocytes than CD4 cells, which is not normal. Thiswould then cause cytokine release causing themanifestations such as generalized lymphadenopathyand hepatosplenomegaly,4 which were present in ourpatient.

Leukocytosis (10,000-20,000 cells/ul) withpredominance of lymphocytes is the initial presentationin >90% of cases. Atypical lymphocytes on peripheralblood smear are also seen, which were observed inour patient. Elevation of hepatic transaminases is alsoseen in 50% of cases, without jaundice, which wasalso seen in our patient. A positive heterophile antibodytest from the 1st week of illness up to 2 years detects90% of infectious mononucleosis in adolescents butonly 50% in children less than 4 years. EBV IgM ispositive for 4 weeks up to 3 months, and EBV IgGpeaks late in the acute phase, declines slowly overthe next several weeks to months, and then persiststhroughout life. Both antibodies tested positive for ourpatient. Mild thrombocytopenia (50,000-200,000/ul) in50% of patients is also seen,4 which was also presentin our patient.

The mechanism of EBV-induced hemophagocyticsyndrome is the uncontrolled secretion of natural killercells and interleukins after T lymphocytes arechronically activated by EBV.5 This would causesustained macrophage activation, with phagocytosisof RBCs, WBCs, and platelets leading to the clinicalsymptoms.

The incidence of Hemophagocytic Syndrome waspreviously 1.2 / 1 million per year. However, due toimproved detection, incidence is now 1/50,000 at theFEU-NRMF Medical Center, only 2 cases werediagnosed with hemophagocytic syndrome. For thefamilial type, the most common age of onset is <1year old. For the acquired type, the most common ageof onset is >6 years old. There are no predilections inrace nor sex. Prognosis is fatal if not treated, and the

median survival time is 2-6 months after diagnosis.Remission is always temporary.

Normally, the cytotoxic function of natural killer(NK) cells and CD8 T cells is required for clearanceof viral infection as well as regulation and terminationof the inflammatory response.6 In the presence ofEBV infection, overwhelming T-cell and macrophageactivation results in the "cytokine storm," characterizedby marked elevation of cytokines, such as IFN-g, tumornecrosis factor a, interleukins, and macrophage colony-stimulating factor.7 IFN-g has been shown to play acritical role in macrophage activation andhemophagocytosis.8 Elevated tumor necrosis factorlevels lead to hypofibrinogenemia andhypertriglyceridemia.9 Gene expression studies onperipheral blood mononuclear cells in patients withactive HLH have revealed down-regulation of genesinvolved in innate and adaptive immune systems,including Toll-like receptor expression and B-cell andT-cell function. This finding suggests that patients withactive HLH experience an immunodeficient state thatmay lead to increased susceptibility to infections.10

HLH is a defect in immune regulation, and the alternatepathway of direct macrophage activation could play asignificant role in secondary HLH.

The diagnosis of HLH includes either a moleculardiagnosis consistent with HLH, or fulfilling 5 out ofthe 8 following criteria: 1) Fever of more than 7 days(38.5°C/101.3°F), 2) Splenomegaly - palpable spleengreater than 3cm below the costal margin,3) Cytopenia in two out of three cell lines: Hb <9 mg/dl(<10 mg/dl in infants <4weeks old), Platelets<100.000/uL, or Neutrophils <1000/uL,4) Hypertriglyceridemia (fasting triglycerides >265mg/dl), 5) Hemophagocytosis in bone marrow, spleen,lymph nodes, 6) Ferritin >500 ng/ml, 7) sCD25 >2.400U/ml, and/or, 8) Hypofibrinogenemia (fibrinogen <1.5g/l). In our case, the patient fulfilled 5 out of the 8criteria (fever, splenomegaly, pancytopenia, increasedserum ferritin, and hemophagocytic cells in the bonemarrow).7

The signs and symptoms include those due topancytopenia like recurrent infections which wereseen in our patient manifested by the recurrence ofcough, easy bruising and pallor; liver dysfunctionmanifested as coagulopathies, increased liver enzymeswhich was also seen in our patient; dermatologicfindings characterized as erythroderma to generalizedpurpuric macules and papules to morbilliform eruptions;neurologic findings such as seizures, ataxia,hemiplegia, mental status changes, or simply irritability;


lymphadenopathies, which were seen in our patient,constitutional signs and symptoms (malaise, anorexiawith or without weight loss, and failure to thrive),Colitis and hypogammaglobulinemia which are seenin the familial form.7

For familial HLH, the initial therapy for primaryHLH consists of immunosuppressive and/orchemotherapeutic agents and aimed at suppressingthe hyperinflammatory component of the disease aswell as eliminating activated cytotoxic lymphocytesand macrophages. Steroids inhibit inflammation byattenuating cytokine responses and inhibitingdifferentiation of dendritic cells. They also havecytotoxic effects on lymphocytes. Cyclosporin Adirectly affects cytotoxic T-cell activation as well asmacrophage function. Etoposide induces apoptosisin lymphocytes.

The HLH-2004 protocol7 consists of a two-weekinduction phase including etoposide, cyclosporin A,dexamethasone, intrathecal methotrexate, andintrathecal prednisone followed by a tapering phaseof 6 weeks. Remission could be achieved in 78% ofall patients treated with the HLH-94 protocol.11

However, there are no sufficient data to indicate ifand which patients with 'secondary' HLH need thefull treatment protocol. Although initial treatment withsteroids alone or in combination with cyclosporin Amay be justified in some patients, the timely use ofmore aggressive therapy is mandatory for a good-outcome. In patients with macrophage activatingsyndrome, immunosuppression with corticosteroidswith or without cyclosporin A in most cases leads to adramatic improvement of disease within days.12,13

Etoposide may be added if there is no response orhighly active disease.14

Control of the underlying disease is of keyimportance in the overall treatment concept. ForInfectious mononucleosis, there is no specifictreatment. The mainstays of management are rest,encouraging adequate fluid and nutrition intake, andsymptomatic treatment with acetaminophen or non-steroidal anti-inflammatory agents to manage fever,throat discomfort, and malaise.5

EBV-triggered HLH has been treated successfullywith rituximab (anti-CD20 antibody) in addition toconventional therapy.15,16,17 Immunoglobulins, whichmay act against pathological antigens or cytokines,have been used as an adjunct in infection-triggeredHLH.15

Our patient began treatment with IVIG,cyclosporine and etoposide, but there was clinical

deterioration with unremitting fever. Despite treatment,her clinical status worsened and rapidly evolved tomultiorgan failure. She died 10 days after admissionin a government hospital.

Although the prognosis varies between studies andwith different approaches to treatment, the disease isinvariably fatal if not treated. The median survival ratehas been reported to be 2-6 months without treatment,but survival time has dramatically improved with theadvent of the HLH-94 protocol. Despite advances intherapy, up to 40 to 60% of children initially do notrespond to treatment and die of HLH or die ofinfections or complications during therapy.15 The HLH-94 protocol-induced remission or allowed the patientto undergo hematopoietic stem cell transplant in 71%of cases.15 Patients with all forms of HLH who weretreated according to the HLH-94 protocol had a 5-year survival of 54%. Survival rates of 86% have beenreported in EBV-associated 'secondary' HLH afterHSCT in Japan.16 Unfortunately, many cases arediagnosed late in the course of the disease, afterirreversible damage has occurred.

CONCLUSION AND RECOMMENDATIONS

Initial symptoms of HLH may be non-specic andmisleading. Therefore, a high index of suspicion and athorough clinical, immunological, and genetic work-up is required. Prompt initiation of adequate treatmentis the key to survival. However, despite importantadvances in therapy, the overall survival rates remainunsatisfactory. Early recognition and treatment ofHLH is still highly associated with mortality in up to60%. Though rare, the disease is usually consideredwhen majority of the criteria are seen in the patient,which may be late in the course and after consideringother differential diagnoses. It is therefore crucial toeducate our fellow clinicians about the increasingprevalence of the disease and how it could start as ausual case of prolonged fever.

REFERENCES

1. Malloy, CA, Polinski C, Alkan S, et al. Hemophagocyticlymphohistiocytosis presentating with non-immune hydropsfetalis. J Perinatol 2004; 24(7): 458-60.

2. Feldmann J, Le Desit F, Ouachee-Chardin M et al. Functionalconsequences of perforin gene mutations in 22 patients withfamilial hemophagocytic lymphohistiocytosis Br J Hematol2002; 117(4): 965-72.


3. Koh KN, Im HJ. Chung NG, et al. Clinical features, genetics,and outcome of pediatric patients with hemophagocyticlymphohistiocytosis in Korea: report of a nationwide surveyfrom Korea Histiocytosis Working Party. Eur J Hematol2014 June 17.

4. Kliegman R. Epstein barr virus. Nelson's Textbook ofPediatrics 20th Edition. Philadelphia: Elsevier 2016; Chapter254.

5. Lay JD, Chuang SE, Rowe M, Su IJ. Epstein-barr viruslatent membrane protein-1 mediates upregulation of tumornecrosis factor-alpha in EBV-infected T cells: implicationsfor the pathogenesis of hemophagocytic syndrome. J BiomedSci 2003; 10(1): 146-55.

6. Lykens JE, Terrell CE, Zoller EE, Risma K, Jordan MB.Perforin is a crit- ical physiologic regulator of T-cellactivation. Blood 2011; 118: 618-26.

7. Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH,Imashuku S, et al. HLH-2004: Diagnostic and therapeuticguidelines for hemophagocytic lymphohistiocytosis.Pediatr Blood Cancer 2007; 48: 124-31.

8. Zoller EE, Lykens JE, Terrell CE, Aliberti J, Filipovich AH,Henson PM, et al. Hemophagocytosis causes a consumptiveanemia of inflammation. J Exp Med 2011; 208: 1203-14.

9. Henter JI, Carlson LA, Soder O, Nilsson-Ehle P, Elinder G.Lipoprotein alterations and plasma lipoprotein lipasereduction in familial hemophagocytic lymphohistiocytosis.Acta Paediatr Scand 1991; 80: 675-81.

10. Sumegi J, Barnes MG, Nestheide SV, Molleran-Lee S,Villanueva J, Zhang K, et al. Gene expression profiling ofperipheral blood mononuclear cells from children with activehemophagocytic lymphohistiocytosis. Blood 2011; 117:e151-60.

11. Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, ElinderG, Filipovich AH, Gadner H, Imashuku S, Komp D, LadischS, Webb D, Janka G; Histocyte Society: Treatment ofhemophagocytic lymphohistiocytosis with HLH-94immunochemotherapy and bone marrow transplantation.Blood 2002; 100: 2367-73.

12. Ravelli A, Viola S, De Benedetti F, Magni-Manzoni S, TziallaC, Martini A. Dramatic efficacy of cyclosporine A inmacrophage activation syndrome. Clin Exp Rheumatol 2001;19: 108.

13. Mouy R, Stephan JL, Pillet P, Haddad E, Hubert P, PrieurAM: Efficacy of cyclosporine A in the treatment ofmacrophage activation syndrome in juvenile arthritis: reportof five cases. J Pediatr 1996; 129: 750-4.

14. Ravelli A. Macrophage activation syndrome. Curr OpinRheumatol 2002; 14: 548-52.

15. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClainKL. How I treat hemophagocytic lymphohistiocytosis.Blood 2011; 118: 4041-52.

16. Trottestam H, Horne A, Aricò M, Egeler RM, FilipovichAH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G,Henter JI. Histiocyte Society: Chemoimmunotherapy forhemophagocytic lymphohistiocytosis: long-term results ofthe HLH-94 treatment protocol. Blood 118: 4577-84.


Primary Congenital Glaucoma

Mervyn H. Fernandez, MD*

This is a case of a 1-year 4-month old male who presented with bilateral enlargement of the eyes withcorneal opacity. Epiphora (tearing) and hard globes on digital palpation were noted. The initial impressionwas primary congenital glaucoma. Topical and oral anti-glaucoma medications were started and examinationunder anesthesia was done. Complete ophthalmologic examination revealed a bilateral enlargement of thecup disc ratio (cdr: 0.9), high intraocular pressure, enlarged corneal diameter and thinning of the sclerae.Hence, a superior approach 180º bilateral trabeculotomy was done with regular monitoring. Four monthspostoperatively, there was recurrence of high intraocular pressure, corneal opacity and epiphora. A secondexamination under anesthesia was done with the following findings bilateral decrease of the cup disc ratio(cdr: 0.7), high intraocular pressure and a myopic refraction. In consideration with the findings mentionedabove a secondary temporal approach 180º trabeculotomy with topical anti-glaucoma medications andregular monitoring was done. Congenital glaucoma signs improved favorably to the treatment. InOphthalmology service standpoint, there is a need for regular monitoring and family education regardingthe chronicity and visual rehabilitation of the patient. Currently the patient is being managed by thePediatric, Pediatric Ophthalmology and Glaucoma services.

Key words: glaucoma, epiphora

Childhood blindness refers to a group of diseasesand conditions occurring in childhood or earlyadolescence, which, if left untreated, result in loss ofvision or severe visual impairment that are likely tobe untreatable later in life. In low income countrieswith high under-5 mortality rates, the prevalence maybe as high as 1.5 per 1000 children or approximately1.4 million.1 Local data show that 2.4 million Filipinosare suffering from glaucoma and the disease is nowthe third leading cause of blindness in the country.Congenital glaucoma is among the top ten causes ofchildhood blindness in the Philippines.2 Loss of vision

ABSTRACT

*Department of Ophthalmology

is a condition that requires a holistic approach inmanagement which involves the whole family. For oneblind child there is also one member of the family whowill take care of the patient and that family memberis also not being able to work to aid in the financialneeds of the family. Hence, importance of earlyrecognition and treatment of preventable blindnessshould always be considered as a priority.

Eyes are also regarded as one of the most sensitiveand delicate parts of the human body and therefore,even slight irritation or decrease in clarity will promptthe patient to seek consult, much more an enlargementand opacification of the eye. These signs may be aresult of various ocular disease entities, ranging fromstructural defects (e.g. interferences in the ocularmedia). A definitive diagnosis usually can be made on


a thorough history, careful evaluation of signs andsymptoms combined with proper physical examinationof the eye. Hence, a physician equipped withknowledge of eye anatomy and physiology of vision,and instruments in examining the eye in complete detailshould assess and manage this condition. Earlyrecognition and management are vital in preventingcomplications such as pathologic myopia, cornealdecompensation and optic nerve compression leadingto blindness.

Childhood glaucomas are a heterogenous groupof disorders that result in elevated intraocular pressure(IOP) and subsequent damage to the optic nerve.Various presentations and etiologies characterize theserare glaucomas. Although pediatric glaucomas sharemany characteristics with adult-onset glaucoma, thereare numerous management issues unique to thepediatric population.3

Primary congenital glaucoma (PCG) ischaracterized by a congenital anomaly of the chamberangle at the level of the trabecular meshwork, whichobstructs the aqueous humor outflow pathways,leading to high intraocular pressure (IOP).3,4 Itaccounts for the majority of primary pediatricglaucomas. The prevalence in the population is8:100,000 children.4 Most cases are bilateral (70%)and are diagnosed within the first year of life (>75%).Primary congenital glaucoma occurs more frequentlyin males (65%) than females.3

The etiology is still not known until now but Barkanhypothesized the leading theory that a membranecovering the anterior chamber angle reduced outflowfacility. Although this membrane has not beenidentified, there appears to be a developmentalanomaly of the neural crest-derived tissue of theanterior chamber angle, with dysgenesis andcompression of the trabecular meshwork and ananterior insertion of the iris root.3,4

It presents with the classic triad of epiphora,photophobia, and blepharospasm. Careful investigationmust include a complete history, along with completephysical examination, laboratory and radiologic testingto help narrow the differential diagnosis. Since primarycongenital glaucoma is a relatively rare disease,primary care doctors and general ophthalmologistsmay never have seen a case that can lead tomisdiagnosis.3

Primary congenital glaucoma is difficult to managespecifically during the late stages of the disease andits chronicity even with primary surgical managementit tends to be persistent. Hence, early diagnoses and

intervention still poses a great modality of treatmentfor a better visual outcome of the patient.

THE CASE

This is a case of R.B., a 1-year 4-month old, male,Filipino, Roman Catholic, presently residing in SapangPalay, Bulacan, presented to the ophthalmology out-patient department with a chief complaint of opacityand enlargement of both eyes.

The present illness started 1 month prior to consultwhen the mother noticed increased lacrimation on botheyes. Associated with frequent eye manipulation andirritability. There were no signs of eye redness anddischarge. They did not seek consult or applied anymedications. The signs and symptoms mentionedabove persisted during the interim until the mothernoticed one day prior to consult that there is an opacityon the patient's eyes hence prompted consult the nextday to Ophthalmology out patient department. Uponexamination the initial impression was congenitalglaucoma. Topical and oral antiglaucoma medicationswere started. The family was then counseled regardingthe condition and explained the prompt need forintervention. The course of the disease needs earlyintervention to have a better prognosis. Examinationunder anesthesia was warranted to completelyevaluate the condition of the patient and to decidewhether surgical intervention (Bilateral Trabeculotomyunder general anesthesia) is needed. The family thenagreed to push through with the management. Referralto Pedia service for C-P clearance was requested andgranted.

Past Medical History

The patient was previously hospitalized due to SVI5 months ago. He was diagnosed with atopicdermatitis a year ago and given oral steriods. Therewere no history of ocular trauma, topical medicationuse, and operations. No known allergy to food anddrugs.

Family History

His father is a known hypertensive and her motherhas a history of asthma. His uncle (Paternal side)was diagnosed with glaucoma. Father has a 26 yearage gap with the mother. Siblings are apparentlywell.


Personal and Social Histories

The patient was born full term via normal spontaneousdelivery without the use of forceps at 3 kg. He is the5th born child. Immunizations are complete for age.Developmental milestones are at par with age.

Ophthalmologic Examination

The patient was awake, alert and not incardiorespiratory distress with normal vital signs.Ocular examination revealed a visual acuity of central,steady and maintained fixation (CSM) on both eyes.Extraocular movements were full and equal on botheyes. External examination revealed buphthalmos,tearing, matting of the eyelahes with slight cornealopacity on both eyes. Funduscopy noted bilateral faintred orange reflex. Digital palpation was hard on botheyeballs.

The examination findings are summarized in Table I.

Differential Diagnoses

1. Peters Anomaly

Peters anomaly is usually sporadic, although autosomaldominant and autosomal recessive forms have beenreported. The majority of cases are bilateral, and angleabnormalities cause glaucoma in approximately 50%of affected patients. It is a developmental conditionpresenting with an annular corneal opacity (leukoma)in the central visual axis. (Figure 1) Patients with

corneolenticular adhesions have a higher likelihood ofocular abnormalities, such as microcornea and angleabnormalities, and systemic abnormalities, includingthose of the heart, genitourinary tract, musculoskeletalsystem, ear, palate, and spine.3 This was considereddue to the resemblance in presentation of cornealopacity and glaucoma in this patient however by directexamination of the eye there was a distinct differencein the density of the corneal opacity, a decrease incorneal size which is the opposite in primary congenitalglaucoma and the systemic congenital anomalies thatmay come with it and which our patient did notmanifest.

2. Posterior Polymorphous Corneal Dystrophy

Posterior Polymorphous Dystrophy is a congenital,bilateral disorder of the cornea transmitted as an

Table 1. Ocular examination findings on admission.

Right Left

Visual Acuity Central steady and Central steady andmaintained fixation maintained fixation

External Examination (+) Buphthalmos (+) Buphthalmos(+) Tearing (+) Tearing(+) Eyelash matting (+) Eyelash matting(+) Corneal opacity (+) Corneal opacity

Fundoscopic Examination Faint red orange reflex, Faint red orange reflex,hazy media hazy media

Digital Tonometry Hard Hard

Ocular Movement Full and equal Full and equal

Note: Highlighted text indicates the characteristic findings in our case.

Figure 1. Corneal opacity in Peters anomaly.


autosomal dominant trait .5,6,7 Most casespredominantly present at 25-50 years of age.Gonioscopic findings reveal abnormal high insertionof iris, broad, anterior placed peripheral anteriorsynechiae (A) and presence of iridocornealadhesions. Abnormal tension exerted by high insertionof iris results in collapse of the trabecular meshworkand increased resistance to outflow. Other clinicalfeature of the disease includes posterior cornealopacities, viewed on specular microscopy as large,dark areas that cross endothelial cell boundaries (B).5,8

Clinically, PPD is characterized by bilateralendothelial bands, vesicles (C), and polymorphousopacities at the level of Descemet's membrane andendothelium (D) that can be accompanied byiridocorneal peripheral adhesions, iris atrophy, andcorectopia. (Figure 2) The differentiating factor ismade on the basis of the typical corneal endothelialabnormality and the later age of presentation ofclinical findings in this disease entity.

megalocornea may represent arrested buphthalmos(enlarged globe) and exaggerated growth of thecornea in relation to the rest of the eye. Congenitalglaucoma must be ruled out by intraocular pressuremeasurement and careful biomicroscopy.9,10 Hencewith the presentation of buphthalmos and the similarage of onset, this disease entity should be considered.However, this was ruled out because of other physicalfindings that were noted like hard on digitalpalpation and corneal opacity that is not seen in thiscondition.

4. Primary Congenital Glaucoma

Primary congenital galucoma is an infrequentdisease, an inherited developmental defect, occurringwithin the first year of life. The typical presentationis the tr iad of epiphora, photophobia andblepharospasm. In majority of patients, thepresentation is associated with corneal edema andopacity (Figure 3) due to the delay in consult to anophthalmologist. Past medical history could behelpful in the differentiation of the disease entity.Could it be due to trauma, infection and risk factorssuch as genetic predisposition.

Epiphora is usually present however it is a vaguesign for the parents to seek consult. Buphthalmoson the otherhand is not easily recognized by theparents hence it is not the main cause of concernfor their visit to the hospital. Hence, corneal opacityis the leading chief complaint for them to seekconsult which may imply chronicity of the diseaseand early intervention is heralded for a better visualprognosis for our patients. Examination of pediatricpatient also poses a challenge to physicians becauseof the different protocols and special techniques toevaluate them fully and to arrive at a correctdiagnosis to properly manage the patients. Hence,an examination under anesthesia is vital to arrive atthe proper diagnosis and to promptly decide rightafter the examination the next step in manging thepatient. Surgical intervention is the treatment ofchoice in primary congenital glaucoma because thedisease is most likely non responsive to medicaltherapy. The recurrence rate is still considerable aspreviously reported in other studies followingsurgery. Our patient presented with epiphora,corneal opacity and a hard digital palpation whichled to the impression of primary congenitalglaucoma.

Figure 2. Anterior segment findings of Posterior polymorphouscorneal dystrophyNote: Refer to the corresponding letter mentioned in the text forthe description of the pictures

3. Megalocornea

Megalocornea is a bilateral, non-progressive cornealenlargement with an X-linked recessive inheritancepattern. Rare cases of autosomal recessiveinheritance have been reported. Affected personshave histopathologically normal corneas measuring13.0 - 16.5 mm in diameter. Males are more typicallyaffected, but heterozygous women may demonstratea slight increase in corneal diameter. Alternatively,


Figure 3. Haab striae may lead to corneal edema. White arrowpoints to edge of Haab striae, and red arrow points to center ofHaab striae with corneal edema and opacification. (Part Acourtesy of Jody Pittz-Seymour, MD; part B courtesy of SharonFreedman, MD.)

Gonioscopy was done placing a Koeppe lens in frontof the cornea in order to visualize directly the anteriorchamber angles. Both eyes have deep chamber andopen angles. (Figure 5)

Examination under general anesthesia findings:

Intraocular pressure measurements were doneafter 5 minutes post induction of anesthesia usingSchiotz applanation tonometer with the readings onthe right eye of: 6, 6, 7 (29.4 mmHg) and on the lefteye: 7, 7, 8 (25.1 mmHg) noting that the normalintraocular pressure in this age group is 10 - 15 mmHg.General anesthetic agents also decrease theintraocular pressure.

Corneal assessment was done placing a lid retractorand then measuring the horizontal and verticaldiameter of both eyes using a calibrated caliper.(Figure 4)

Figure 4. Corneal measurement of right eye (A) Horizontaldiameter. (B) Vertical diameter.

Figure 5. (A) Direct gonioscopy of right eye. (B) Directgonioscopy of left eye. White arrows point to Haab striae.

Funduscopy using direct and indirect methodsrevealed (+) red orange reflex, 2:3 Arterio-venousratio, 0.9 cup to disc ratio, (-) hemorrhages andexudates with distinct disc borders on both eyes.

Retinoscopy findings on the right eye were - 0.50sphere with -3.00 cylinder at 90º axis and on the leftwere plano with -2.50 cylinder at 180º axis.

Horizontal Diameter Vertical Diameter

Right eye 13 mm 12.5 mm

Left eye 13 mm 13 mm

Figure 6. A trabeculotome being used to dissect the trabecularmeshwork during trabeculotomy. (A,B) Dissection of the righteye. (C,D) Dissection of the left eye. White arrows point to thedistal end of the trabeculotome inside the anterior chamberdissecting the trabecular meshwork.


Examination findings of increased intraocularpressure, increased corneal diameter, deep chamberon gonioscopy, haab striae, myopic refraction and 0.9cup to disc ratio combined with the clinical signs andsymptoms led us to the diagnosis of primary congenitalglaucoma. Hence, a prompt decision was made forthe patient to undergo a superior approach 180ºbilateral trabeculotomy under general anesthesia.

He was apparently well until 3 months postoperatively, there was recurrence of tearing, frequenteye manipulation, corneal edema and hard digitalpalpation on both eyes. Topical anti glaucomamedications were then given and slight improvementof signs and symptoms were noted. In considerationwith the findings mentioned earlier and for re-assessment of the outcome of the management thepatient was then scheduled for examination undergeneral anesthesia.

Secondary examination under anesthesiafindings:

Intraocular pressure measurements were doneafter 30 seconds post induction of anesthesia usingICare rebound tonometer with the readings on theright eye of: 42 mmHg and on the left eye: 37 mmHg.

Corneal measurement findings:

Gonioscopy was done using a Koeppe lens withanterior chamber findings of deep chamber and openangles on both eyes.

Table 1. Postoperative ocular examination findings on both eyes

Visual Acuity

External

Exam

Funduscopy

Digital Tonometry

OcularMovement

1 Week

CSM

(+)

tearing,cornealedema

FaintROR

Soft

Full andequal

3 Weeks

CSM

(-)


BrightROR

Firm

Full andequal

5 Weeks

CSM

(-)


BrightROR

Firm

Full andequal

2 Months

CSM

(-)


BrightROR

Firm

Full andequal

3 Months

CSM

(-)


BrightROR

Firm

Full andequal

3½ Months

CSM

(+)


FaintROR

Slightly

hardFull andequal

4 Months

CSM

(+)


FaintROR

Hard

Full andequal

*CSM: central, steady and maintained fixation; *ROR: red orange reflex

Figure 7. Horizontal diameter: (A) Right cornea. (B) Left cornea.Vertical diameter: (C) Right cornea. (D) Left cornea.

Horizontal Diameter Vertical Diameter

Right eye 13 mm 12.5 mm

Left eye 13 mm 13 mm


Funduscopy using direct and indirect methodsrevealed (+) red orange reflex, 2:3 Arterio-venousratio, 0.7 cup to disc ratio, (-) hemorrhages andexudates with distinct disc borders on both eyes.

Figure 8. Direct visualization of the anterior chamber angle.(A) Right chamber angle. (B) Left chamber angle. White arrowspoint to the pigmented trabecular meshwork.

Figure 9. Indirect funduscopic visualization of the optic nerve.(A) Right optic nerve. (B) Left optic nerve. White arrows pointto the optic nerve.

Retinoscopy findings on the right eye were - 2.50sphere and on the left were - 1.00 sphere.

Examination findings of increased intraocularpressure, increased myopic refraction and cornealedema correlated with subjective symptoms oftearing, frequent eye manipulation and irritabilityprompted us to do a secondary temporal approach180º bilateral trabeculotomy under generalanesthesia. Currently, the patient is being given topicalanti-glaucoma medications with no signs andsymptoms of tearing, eye manipulation and irritabily.Also, upon ocular examination corneal edema wassignificantly decreased, bright red orange reflex seenand a firm digital palpation on both eyes.

DISCUSSION

The patient's age, constitutional symptoms and grossocular examination findings help distinguish between

the various disorders of the anterior chamber of theeye. Initial findings of corneal opacity and glaucomain the pediatric population are quite rare. Manyanterior chamber congenital anomalies presents withglaucoma but often times assessment of other ocularfindings and systemic disorders would help us narrowdown our differential diagnoses. The signs orsymptoms present following birth are suggestive of aprimary condition. If other pathologies present beforethe onset of symptoms, they may suggest a secondaryevent.

Review of the patient's symptoms and systemiccomplaints, along with a good initial ocularexamination, is crucial for establishing an accurateclinical impression for lesions of the anterior chamberof the eye. Early consideration of such etiologieshelps us focus on the important parameters neededto arrive at the correct diagnosis. A completeophthalmologic examination is required to determinethe extent of the disease and this disorder may bemore potentially damaging with delayed treatment.Examination of pediatric patient's are often timesdifficult and usually with different protocols. Like inour case if the patient is an adult we could easily doa complete ophthalmologic evaluation at the officebut given a pediatric patient it is a different story. Weneed to be well versed and resourceful at our fieldgiven limited clues to arrive at an educated clinicalimpression. As for our case, weighing the risk andbenefits of undergoing general anesthesia just toevaluate the patient makes it a tough decision to call.And to make it even tougher we decide right thenand there whether to proceed to surgery aftercorrelating our findings. Surgical techniques inpediatric patients also are very different comparedto adults. Many surgical techniques are only appliedin pediatric patients hence only a few physicians areskilled enough to do the surgery. Diagnostic evaluationwould also be of help but there is still no gold standardof diagnostic or imaging to confirm the diagnosis itmay be due to the yet to be decided pathophysiologicaletiology of the disease.

Primary Congenital Glaucoma (PCG) ischaracterized by increased outflow resistance throughthe trabecular meshwork. In infancy it presents withthe classic triad of epiphora, photophobia andblepharospasm. Until age 3, elevated IOP causes thecornea to stretch, which leads to increased cornealdiameter and enlargement of the globe(buphthalmos). The corneal stretching produces Haab


striae, or breaks in the Descemet membrane, andleads to the development of corneal edema andopacification. After age 3, the cornea does notcontinue to enlarge, but persistently elevatedintraocular pressure may result in scleral stretchingand progressive myopia.3 Primary congenitalglaucoma is a clinical diagnosis that should be usedafter complete ophthalmologic examination. Mostcases occur sporadically and prevalence in thepopulation is 8:100,000 children.4 Most cases arebilateral (70%) and are diagnosed within the first yearof life (>75%). It occurs more frequently in males(65%) than females.3

One unique distinguishing factor of congenitalglaucoma compared to adult glaucoma is thereversibility of the optic nerve cupping which wasexhibited in our patient. During the first examinationthere was 0.9 cupping of the disc that was decreasedto 0.7 cup to disc ratio during the second examinationunder general anesthesia this may signify improvementand control of pressure. Optic disc cupping can bereversed at an early stage of primary congenitalglaucoma following successful reduction of IOP.Younger age at surgery was associated with reversalof cupping.11

Many theories have been highlighted for thepossible etiologic factors for PCG, but the etiologyremains unknown. It is likely associated with an arrestof development at 7 months gestation in which theiris root is still attached anteriorly which blocks thetrabecular meshwork (Figure 10) which is the outflowtract of aqueous fluid.12 There is also a popular theorywhich states that there is a transparent or semi-

transparent membrane (Barkan membrane) in avertical position from the Schwalbe's line to the irisangle that resists aqueous fluid outflow.13,14,15

The spectrum of medical treatment in primarycongenital glaucoma is supportive and adjuvant priorto surgery. Most of the topical anti-glaucomamedications could be used except for Alpha-2agonist, which could lead to CNS depression inpediatric patients, which warrants extreme cautionin use. Beta-blockers, carbonic anhydrase inhibitorsand prostaglandin analogues are still the bestweapon of choice in congenital glaucoma but asignificant number of patients seem to be resistantto medical therapy.17

Early surgical intervention is of prime importancein the management of patients with developmentalglaucoma. In some areas of the world, such as UnitedStates, patients may have only mild or moderatecorneal edema at referral for treatment. Thesepatients may be candidates for goniotomy, which hasa high success rate in the western population. In otherareas of the world, such as India or the Middle East,nearly all patients present with clouding andgoniotomy is technically impossible. In these areas,external trabeculotomy is the initial procedure ofchoice.18 As for our patient he presented withsignificant corneal edema hence a goniotomy is veryhard to accomplish because it is a prerequisite thatthe cornea is clear to proceed with goniotomy for thecornea is the window to view the anterior chamberto do the procedure.

Trabeculotomy has a number of advantages overthe alternative operation of goniotomy. It can be done

Figure 10. A histologic and schematic diagram of (A) a normal anterior chamber angle and (B) a congenital glaucomaanterior chamber angle. (A) Open anterior chamber angle (B) Anterior insertion of iris root with membrane of the anteriorchamber angle. White arrows point to the insertion of iris root. Black arrow point to the Barkan membrane. Gray arrowpoint tot the open trabecular meshwork.16


even if the cornea is hazy, can accomplish rupture ofthe inner wall of the Schlemm's canal and trabecularmeshwork with anatomical precision, does not requirethe introduction of sharp instruments across the ACand can be done with standard microsurgicaltechnique without the need of having to adapt withthe view of goniotomy lens. Considering congenitalglaucoma of all grades of severity, goniotomy controlsthe intraocular pressure (IOP) in about 64-77% ofeyes, while trabeculotomy controls IOP in over 90%of eyes. However, there are no prospective, controlledtrials to compare the success rate of these proceduresin the same study.18

CONCLUSION

Congenital glaucoma may present in many of theanterior chamber developmental anomalies and thepathophysiology of the disease is yet to be decided.There is a considerable clinical confusion among thisspectrum of disorders. To provide proper treatment,one of the crucial steps is differentiating it from othercongenital anterior chamber disorders. The keyapproach in dealing with such cases is thoroughhistory and examination for both ocular and systemicdisease. This usually leads to concise differentialdiagnosis and can guide further investigation. Thepresentations vary depending on the chronicity of thedisease and due to their young age, it poses a greatdeal of difficulty in order to have a completeophthalmologic evaluation which is needed to providethe proper management. Hence, examination undergeneral anesthesia is a reasonable method to enableus to have a thorough ophthalmologic evaluation andweighing the risks versus the benefits. It is also veryimportant for the physician to incorporate promptlyhis subjective and objective evaluation to decide whatsurgical management is appropriate right after theexamination. Ancillary tests could be a great deal ofhelp in the correlation of the clinical diagnosis.

Primary congenital glaucoma is one of the mostcommon causes of childhood glaucomas and is quiteresistant to medical therapy. The role of medicaltherapy is to temporarily lower the intraocularpressure and provide a clearer cornea in order to havea better view during examination and surgery. Surgeryshould always be considered in these cases. Surgicalprocedure should provide a stepladder approach andoptimal benefit in consideration with the perioperativemorbidity and postoperative maintenance of the

treatment. Trabeculotomy was the procedure ofchoice for it provides direct opening of the trabecularmeshwork and gives an opportunity for a secondaryintervention. Complications following this techniqueare infrequent.

As seen in our case, there was significantdecrease in disc cupping and corneal edema. A holisticapproach with good family education is important dueto the chronicity and difficulty in treatment. Havingknowledge of the different medical specialtiesprovides a multidiscipline approach needed to helpthe family accept the illness, cope with the conditionand seek the best possible treatment option thatpreserves their quality of life.

REFERENCES

1. World Health Organization, (2016). Prevention of Blindnessand Visual Impairment. Retrieved from http:// who.int/blindness/causes/priority/en/index3.html

2. Cataract Foundation Philippines, (September 2011).Prevalence of Blindess and Vision Impairment in thePhilippines. Retrieved from http:/ / http:/ /cataractfoundationphilippines.blogspot.com/2011/09/prevalence-of-blindness-and- vision.html

3. American Academy of Ophthalmology. 2015. Basic andClinical Science Course, Glaucoma Section 10, MN: TheEye M.D. Assocaiation; 2015;

4. Sampaolesi R., Zarate J. Sampaolesi J.R. The Glaucomas.Volume I. Pediatic Glaucomas. 2009 ed. Primary CongenitalGlaucoma. Chapter 1

5. Lam H, Wiggs J, Jurkunas U. Unusual presentation ofpresumed posterior polymorphous dystrophy associatedwith iris heterochromia, band keratopathy and keratoconus.Cornea 2010; 29(10): 1180-85.

6. Yellore V, et al. Analysis of the role of ZEB1 in thepathogenesis of posterior polymorphous cornealdystrophy. Invest Ophthalmol Vis Sci 201; 53: 273-8.

7. Todora M, et al. Anterior segment dysgenesis associatedwith Williams-Beuren syndrome: a case report and reviewof literature. BMC Ophthalmology 2014; 14: 70.

8. Shields MB. Axenfeld-Reiger Syndrome. In Ritch R, ShieldsMB, and Krupin T. The Glaucomas: Clinical Science. 2nded. St. Louis, Missouri: Mosby-Year Book, Inc; 1996.

9. Mackey DA, Buttery RG, Wise GM, Denton MJ.Description ofX-linked megalocornea with identificationof the gene locus. Arch Ophthalmol 1991; 109(6): 829-33.

10. Traboulsi EI, ed. Genetic Diseases ofthe Eye. 2nd ed. Cary,NC: Oxford University Press; 2011.

11. Canadian Journal of ophthalmology Volume 37, Issue 6,October 2002, pages 337-41.

12 Hansson HA, Jerndal T (1971) Scanning electron micro-scopic studies of the development of the iridocorneal anglein human eyes. Invest Ophthalmol Vis Sci 10: 252-65.

13. Barkan O. Technique of goniotomy. Arch Ophthalmol 1938;19: 217-21.


14. Barkan O. Operation for congenital glaucoma. Am JOphthalmol 1942; 25: 552-68.

15. Barkan O. Goniotomy for the relief of congenital glaucoma.Br J Ophthalmol 1948; 32: 701-28.

16. DeLouise VP, Anderson DR. Primary infantile glaucoma.Surv Ophthalmol 1983; 28: 1-19.

17. Medical and surgical aspects of congenital glaucoma. TuraçhME, Aktan G, Idil A. Acta Ophthalmol Scand 1995; 73(3):261-3.

18. Indian J Ophthalmol 2011; 59(Suppl1): S148-S157. doi:10.4103/0301- 4738.73683


Placenta Percreta-Induced Third Trimester Uterine Rupture InAn Unscarred Uterus: A Diagnostic Dilemma

Samantha Quennie D. Wanasen, MD* and Michelle Gamboa, MD, FPOGS, FPSRM

Cases of uterine rupture induced by placenta percreta in an unscarred uterus are rare. This is a case of 30-year-old, Gravida 2 Para 1 (1001) Pregnancy Uterine 31 weeks and 2 days age of gestation with persistentgeneralized abdominal pain found out to have uterine rupture secondary to placenta percreta. This paperaims to discuss the differential diagnoses for cases of third trimester abdominal pain, the appropriatediagnostic modalities and the best management for such case. Uterine rupture should be considered in thedifferential diagnosis in all pregnant women who present with acute abdomen even if there are no riskfactors. Exploratory laparotomy was done to investigate the cause of the patient's severe abdominal painon top of intrauterine fetal bradycardia. During the procedure, uterine rupture with massive bleeding wasdetected; therefore, subtotal abdominal hysterectomy was performed. The patient was discharged withoutany complications. Pathological analysis of the uterine specimen revealed placenta percreta to be thecause of the rupture.

Key words: Placenta accreta, increta, percreta, abruptio placentae, uterine rupture, total abdominalhysterectomy

Placenta accreta is any placental implantationcharacterized by an abnormally firm adherence to theuterine wall. Such abnormal adherence is secondaryto partial or total absence of decidua basalis andimperfect development of the fibrinoid layer. In thiscase, the placental villi are attached to the myometriumin placenta accreta, invade the myometrium in increta,or penetrate the myometrium in placenta percreta.Although an uncommon condition, abnormalplacentation assumes considerable clinical significancebecause of morbidity and, at times, mortality fromsevere haemorrhage, infection or in this case, uterineperforation and rupture.

ABSTRACT

*First Year Resident, Department of Obstetrics and Gynecology

This paper presents a case of a 30-year-old,Gravida 2 Para 1 (1001) Pregnancy Uterine 31 Weeksand 2 days age of gestation with persistent generalizedabdominal pain.

THE CASE

This is a case of a 30 year old Gravida 2 Para 1 (1001),Pregnancy Uterine 31 Weeks and 2 days age ofgestation who came in at the Emergency Room dueto severe abdominal pain. She had her previousprenatal check-ups with another private obstetrician.Prenatal check ups and ultrasound findings wereunremarkable. Her past medical, personal and socialhistories were all non-contributory. The conditionstarted few hours prior to consult when the patientexperienced a sudden onset of generalized, crampy,


non-radiating abdominal pain with a pain scale of 9/10. This was associated with one episode of vomitingof previously ingested food and a decreased perceptionof fetal movement. She was then immediately broughtat our institution for consult.

At the emergency room, the patient stil lcomplained of severe abdominal pain now 10/10 onthe pain scale. Her vital signs were stable with a bloodpressure of 110/70mmgHg, heart rate of 83bpm,respiratory rate of 17 cpm and afebrile at 36.9ºC. Onphysical examination, the abdomen was globular, soft,with tenderness on all four quadrants. The fundicheight was 31 cm, fundus was occupied by breech,fetal back was palpated on the left side and fetal smallparts were appreciated on the right. Fetal heart tonesof 150 beats per minute were best heard over the leftlower quadrant. Speculum examination revealed aclean looking cervix with whitish to yellowish foulsmelling discharge. Internal examination showed anormal looking external genitalia, parous introitus,vagina admits 2 fingers with ease, cervix was soft,closed. Initial assessment at this time was Gravida 2Para 1 (1001), Pregnancy Uterine 31 weeks and 2days AOG, Cephalic in Threatened Preterm Labor.Due to her severe abdominal pain, plan was to do admitthe patient to observe for progression of abdominalpain and to do laboratory work-ups such as CBC,urinalysis, wet smear and gram stain of the cervico-vaginal discharge as well as trans-abdominalultrasound. The patient was also referred to surgerydepartment for further evaluation of her abdominalpain and their initial consideration was acuteappendicitis hence they requested for a wholeabdominal ultrasound.

Upon admission, the patient was initiallyadmitted to the labor room for close monitoring. Shewas on NPO and was venoclyzed with D5LR 1 Lat KVO rate. She was hooked to continuouselec t ronic fe ta l moni tor ing and basel inecardiotocogram revealed category I tracing. Therewere mild uterine contractions noted occurringevery 3-4 minutes lasting only for 30 seconds. CBCrevealed mild anemia with a hemoglobin level of9.5 mg/dL. Urinalysis, wet smear and Gram stainof the cervico-vaginal discharge were requested.Wet smear revealed positive for fungal elementswhile gram stain result showed non-specificcervico-vaginitis. Trans-abdominal ultrasoundrevealed a single, live intrauterine pregnancycompatible to 33 weeks and 3 days age of gestationin cephalic presentation. Placenta was located in a

left anterior position. There seemed to be a part ofthe placenta that extends from anterior to posterioraspect of the uterus; Amniotic fluid volume wasadequate, the amniotic fluid index was 15.1 cm. Theest imated fe ta l weight was appropria te forgestational age at 2079 grams. The cervix was longand closed. Uterine contractions were noted duringthe scan. Whole abdominal ultrasound on the otherhand showed fatty changes of the liver, dilatedretroplacental vessels. No definitive evidence ofappendiceal or periappendiceal pathology; Normalsonogram of the bile ducts, gall bladder, pancreas,spleen, abdominal aorta and both kidneys. She wasstarted on Nifedipine 30 gitts/min as stat dose then20 mg/tab every 8 hours to control the uterinecontractions and Cefuroxime 500mg/tab every 12hours for the non-specific cervicovaginitis.

On the first hospital day, the patient was allowedto have light meal then NPO if with frequentcontractions. Still with uterine contraction occurringevery 5-10 minutes, Nifedipine was discontinued andwas shifted to Isoxsuprine at 10 gtts/min and wastitrated accordingly. However, the patient startedcomplaining of difficulty of breathing hence she wasreferred to Internal Medicine for evaluation andmanagement. Nebulization with Salbutamol every 8hours was given which afforded temporary relief. Thegeneralized abdominal pain was still persistent but nowdown to 5/10 on the pain scale. The uterinecontractions at this point started to decrease infrequency only occurring once in an hour and usuallylasting for less than 30 seconds. She also complainedof fronto-temporal headache hence Paracetamol 500mg/tab every 6 hours was given as needed for thepain. The patient's vital signs were monitored every 4hours and fetal heart tones were monitored every 2hours.

On the second hospital day, at around 6:30 in themorning, the patient suddenly complained of 10/10generalized abdominal pain with associated difficultyin breathing. Upon assessment of the patient, she hadgeneralized pallor, hypotensive at 80/50 mmHg andtachycardic at 112-124 bpm. The abdomen was tenderall over even on light palpation and fetal heart toneswere noted to be bradychardic at 80-90 beats perminute hence the decision to immediately operate onthe patient.

Intra-operatively, 2 liters of hemoperitoneum wereevacuated. There was a gravid dextro-rotated uterus.The fundal area was ruptured with the placenta notedto be invading the whole of the myometrium. The right


ovary was densely adherent to the anterior surface ofthe uterus. (Figures 1 - 3) Low transverse incisionwas done and the baby was delivered to a pretermbaby girl with an Apgar score of 3, 6 and 8, Birthweightof 1890 grams, Early Ballard's score of 32 weeks.There was difficulty in delivering the baby becausethe uterus was somehow contracted. Subtotalhysterectomy with right salpingo-oophorectomy wasdone. The estimated blood loss was 2800 mL. Thepatient tolerated the procedure well.

Figure 1. The massive hemoperitoneum and ruptured fundalarea of the uterus. The placenta is shown still attached to theuterus.

Figure 2. The site of rupture, specifically the fundal area of theuterus.

Figure 3. The whole uterus and its thick myometrium. The placentais seen attached almost invading the whole thickness of theuterine layers.

DISCUSSION

When presented with a case of a pregnant womancomplaining of severe abdominal pain in her thirdtrimester, several differential diagnoses can beentertained. In the case of our patient, we wereentertaining preterm labor, acute appendicitis, abruptioplacenta or possible beginning uterine rupture.

Acute appendicitis is the most common generalsurgical problem encountered during pregnancy andis actually the most common indication for surgery innon-obstetric conditions during pregnancy. Itsincidence is 1 in 500 to 1 in 635 pregnancies per year.Having this in mind, our patient was immediatelyreferred to surgery for further evaluation. Patient'smanifestation was not the classic presentation of acuteappendicitis since her pain was not localized to theright lower quadrant or even at the right upperquadrant. Whole abdominal ultrasound wasimmediately requested and the main purpose ofimaging was to reduce delays in surgical interventiondue to diagnostic uncertainty. However, the resultsshowed negative for appendiceal or peri-appendicealpathology.


Having ruled out acute appendicitis, we werethen left with just abruptio placenta, possiblebeginning uterine rupture or just preterm labor. Toarrive at a diagnosis, part of the plan was to do atransabdominal ultrasound in order to evaluate thegravid uterus as well as the surrounding pelvicstructures. The ultrasound findings were inconclusiveand mostly unremarkable. However, with findings ofa left anterior placenta with a part of it extendingfrom anterior to posterior aspect of the uterus, Ourworking diagnosis at this time was shifted more topreterm labor but could not totally rule out abruptioplacenta nor uterine rupture. The plan was to givetocolytics in the form of a beta-2 agonist and tofurther observe the patient.

All throughtout the patient's stay at the labor roomand even at the ward, her CTG revealed category Itracings and fetal distress was not noted. Not untilthe early morning of her 2nd hospital day, when thepatient started to complain of severe generalizedabdominal pain with associated pallor and drop in bloodpressure. At this point, our suspicion for a possibleabruptio placenta and/or uterine rupture becamestronger. Indeed, upon opening up, the uterus wasfound to have ruptured over the fundal area andplacenta was noted to be invading the entiremyometrial wall.

Both uterine rupture and placenta percreta wouldusually arise in a previously scarred uterus. Reviewof the literature suggested incidence of abnormalplacentation, including placenta percreta, to be varyingbetween 1 in 540 and 1 in 93,000 with an average of 1in 700. Spontaneous rupture of the uterus due toplacenta percreta is one of the most urgent obstetricalcomplications resulting in rapid exsanguination and highmortality which is more commonly seen in the thirdtrimester and is very rare in second trimester. It israrely recognized intrapartum and is very difficult todiagnose.

The precise etiology of all cases of placentaaccreta is unknown, however, there are known factorsthat increase the risk. Greatest among them arescarring of endometrial cavity with previous caesareansection, uterine curettage, myomectomy, Asherman'ssyndrome, iatrogenic uterine perforation and advancedmaternal age. However, in our patient, none of thesementioned risk factors were present. Even lesssignificant factors like advanced maternal age andhistory of curettage that may have been the cause ofplacenta percreta were also absent in this patient,making this case interesting.

Uterine rupture due to placenta percreta is veryrare, with an incidence of 1 in 5,000 pregnant women.As mentioned earlier, it often occurs in patients witha history of cesarean section. The dilemmas inmanaging this case include the delivery of a preterminfant and the possible hysterectomy in a 30 year oldpatient who is still desirous of future pregnancies. Wecan either do a conservative management or a moreradical approach such as hysterectomy. Conservativetreatments for placenta percreta-induced uterinerupture have been reported, such as uterine curettagealong with packing, adjuvant chemotherapy, andbilateral uterine vessel occlusion. But suchconservative management has a 4-fold increase inmortality rate compared with hysterectomy, hence, ourdecision to perform the latter.

The area of placenta percreta-induced uterinerupture exhibits more vascularization than the site ofprevious scar-induced rupture. This only proves thatuterine rupture caused by placenta percreta can bemore dangerous than that caused by a previous scar.We preferred total abdominal hysterectomy toconservative management because of the large, fragile,and thin uterine wall with abundant blood vessels onthe surface. The total estimated blood loss during theoperation was 1800 ml and the patient was transfused6 units of packed red blood cells. Her recovery wasuneventful, and she was discharged on postoperativeday 3.

Histopathology has been found to be the goldstandard for making the final diagnosis of placentapercreta. Ultrasonography and color Doppler studyfor the diagnosis of site of placentation along withmaternal serum alpha fetoprotein measurement indoubtful cases of placenta accreta seems to benecessary as early diagnosis renders conservativetreatment possible. In the case of our patient, the finalpathological examination revealed that the chorionicvilli had invaded the entire myometrium up to theserosa, confirming the diagnosis of placenta percreta.

CONCLUSION

In conclusion, uterine rupture should be considered inthe differential diagnosis in all pregnant women whopresent with acute abdomen even if there are no riskfactors. Several diagnostic modalities such asultrasonography and MRI can be helpful in thediagnosis but high index of suspicion and clinicaljudgment are still of higher value. Histopathology hasbeen found to be the gold standard for making the


final diagnosis of placenta percreta. Ultrasonographyand color Doppler study for the diagnosis of site ofplacentation along with maternal serum alphafetoprotein measurement in doubtful cases of placentaaccreta is necessary as early diagnosis rendersconservative treatment possible. The choice betweenhysterectomy or conservative therapy is dependenton the severity of the placenta percreta. Conservativemanagement has a 4-fold increase in mortality ratecompared with hysterectomy hence in emergencycases, hysterectomy is preferred.

REFERENCES

1. Jang DG, Lee GSR, Yoon JH, Lee SJ. Placenta percreta-induced uterine rupture diagnosed by laparoscopy in thefirst trimester. Int J Med Sci 2011; 8(5): 424-7. doi:10.7150/ijms.8.424.

2. O'Brien JM, Barton JR, Donaldson ES. The management ofplacenta percreta: conservative and operative strategies. AmJ Obstet Gynecol 1996; 175: 1632-8.

3. Dahiya P, Nayar KD, Gulati AJS, Dahiya K. Placenta accretacausing uterine rupture in second trimester of pregnancyafter in vitro fertilization: A case report. J Reprod Infertil2012; 13(1): 61-3.

4. Hudon L, Belfort MA, Broome DR. Diagnosis andmanagement of placenta percreta: a review. Obstet GynecolSurv 1998; 53: 509-17.

5. Legro RS, Price FV, Hill LM, Caritis SN. Nonsurgicalmanagement of placenta percreta: A case report. ObstetGynecol 1994; 83: 847-9.

6. Read JA, Cotton DB, Miller FC. Placenta accreta: changingclinical aspects and outcome. Obstet Gynecol 1980; 56: 31-4.


Multiple Rhinoplasty Procedures for Post-Medial MaxillectomyAssociated Deformities in a Patient with Fibrous Dysplasia

Nicole P. Ramos, MD and Cesar F. Villafuerte, MD, FPSO-HNS, FPCS

This is a case of a 41-year-old female with fibrous dysplasia who underwent medial maxillectomy whichresulted in a severe nasal deformity described as a crooked and flat nose with left paranasal depression.Multiple rhinoplasty procedures were done. The desire of the patient to improve aesthetically woulddetermine the chances of another surgery but she must be made aware of the risks and complications thatmay happen. The surgeon must also take note of the past surgeries done to the patient that may limit thesurgical options available. In the patient’s case, temporary fillers may be suggested with six months follow-up.

Key words: fibrous dysplasia, acquired nasal deformity, rhinoplasty

Hemophagocytic fibrous dysplasia is a benign bonedisorder characterized by abnormal proliferation offibrous tissue and disorganized bone.1 It is of unknownetiology, uncertain pathogenesis, and diversehistopathology.2 In the United States, it is estimatedthat between 9,000 to 18,000 people will be diagnosedwith fibrous dysplasia in their lifetime.3 The main aimof treatment in fibrous dysplasia is maximizingfunctionality and aesthetics wherein surgery isconsidered the best option.2,4

This paper discusses the case of a patient whounderwent medial maxillectomy for fibrous dysplasiawith a complication of facial deformity. Eight differentsurgical procedures were done to correct thedeformity, the most recent of which resulted inrejection of the implant.

ABSTRACT

*Department of Otorhinolaryngology - Head & Neck Surgery

THE CASE

A 41-year old, female, came in for consultation inJanuary 1994 with a chief complaint of a mass on theleft nostril associated with swelling of the left side ofthe face. Physical examination revealed asymmetricalae with a solid firm mass noted on the left side ofthe face. Biopsy revealed fibrous dysplasia. Medialmaxillectomy was performed. Post-operatively, thepatient noted asymmetry of the nose and depressionof the left paranasal area. The patient soughtconsultation again.

Following medial maxillectomy, the patient hadeight surgical procedures done for her nasaldeformity.

In July 1995, due to a crooked nose deformitysecondary to medial maxillectomy, septoplasty usingrib cartilage implant was done with medial and lateralosteotomies with a resulting outcome of straightenednose but still with a persistent depression on theparanasal area.

In 2005, because of the patient's desire for a betternasal dorsal profile, a triangular roof-shaped medporeimplant was placed over the nasal bones using a lateral


rhinotomy incision. Improvement of the nasal profileon the area of the nasal bones was noted.

In 2007 and 2008, due to the patient's desire foraugmentation of the left alar and paranasal area,hyaluronic acid based filler injection was used with aslight and temporary improvement of the nasal profile.

In 2008, for further augmentation of the nasaldorsum, dorsal augmentation rhinoplasty using conchalcartilage from the left ear was done.

In 2012, open rhinoplasty with tip plasty usingconchal cartilage graft from the right ear wasperformed. This included several techniques:collumelar strut graft and cap graft, transdomal andinterdomal suturing with rim alar cartilage graft.

In 2014, because of the medial maxillectomy, thepatient complained of asymmetry of the nostrils thusrhinoplasty for nasal vestibular stenosis using tragalcartilage graft was done. The patient was alreadycartilage-depleted.

One week prior to admission, she soughtconsultation at the OPD due to a depressed left lateralside wall. Physical examination revealed asymmetricalae with depression of the left lateral side wall. A3 cm incisional scar was noted from the left nasalbridge extending to the left paranasal border. Bothnostrils were patent. The patient underwentaugmentation of the left lateral side wall under generalanesthesia. A lateral rhinotomy-like incision was donefollowing the old scar. A Gore-tex implant was insertedthrough the undermined skin. No complication wasnoted. Antibiotics and analgesics were given. Thepatient was subsequently discharged.

At one week post-op, there was no active bleedingor pain but hematoma was noted at the postoperativesite extending to the left maxillary area. Removal ofsutures was done.

At two weeks post-op, minimal hematoma wasstill noted. There was no active bleeding, pain or pus.

At one month post-op, the postoperative area wasobserved to be erythematous with the Goretex implantadmixed with pus seen extruding inferiorly. Sheunderwent removal of the implant.

DISCUSSION

Fibrous dysplasia involves a defect in osteoblasticdifferentiation and maturation which causereplacement of normal bony tissue by fibrous tissueof varied cellularity and immaturely woven bone dueto a mutation of GNAS1 gene.1,5 Most of the time,

majority of patients are asymptomatic and arediscovered incidentally on radiographs with thecharacteristic ground glass appearance.6 The mostcommon presentation of patients seeking consultationis swelling; other manifestations include weakness,localized pain, fractures and compromised vision orhearing.5 It can also cause aesthetic deformities.2 Thepatient presented with a gradually enlarging mass onthe left nostril associated with swelling on the left sideof the face.

With the presentation of the patient, medialmaxillectomy was done aiming for complete resectionof the disease. Medial maxillectomy involves enblocresection of the medial maxillary sinus wall andipsilateral ethmoid sinus, including the laminapapyracea, lacrimal bone, and medial orbital floor.7

Complications following medial maxillectomy mayrange from mild to severe, temporary or permanent,acute or chronic. One of the chronic complicationsinclude unacceptable cosmesis.6 Due to unanticipatedcircumstances, the operation performed in our patientled to a severe nasal deformity described as a crookedand flat nose with left paranasal depression.

"Crooked nose" is a term commonly used for allclinical conditions involving deviation of the nasalpyramid for the median line. It may appear vaguelyC-shaped or S-shaped or wholly displaced to one sideor the other.8 Etiologic causes of crooked nose rangefrom congenital causes to postoperative complications.Other possible causes of crooked nose deformityinclude infection, trauma, primary or secondaryreduction rhinoplasties.9

In a nose with deviated dorsum, the septum isusually responsible for the crooked appearance.Septoplasty may be done by releasing the upper lateralcartilage from their attachment in the dorsal septum.This will release intrinsic cartilage forces andaccomplish dorsal straightening. This may be followedby medial and lateral osteotomies.1 Due to the crookednose deformity, septorhinoplasty or septoplasty withmedial and lateral osteotomies in the bony uppersection of the nose was performed.

Fillers, grafts and implants were also used toimprove the nasal profile of the patient. Soft tissuefillers have been used by aesthetic surgeons fordifferent facial contouring and correction procedure.They are less invasive, less expensive, with fewercomplications and shorter recovery period.10

Temporary fillers or non-permanent fillers stay in thetissue for less than twelve months.11 An example ofthis is the hyaluronic acid fillers, used in the patient. It


gave slight improvement of depression in the left alarand paranasal area. The effect however, was onlytemporary and the patient wanted a more permanentprocedure.

Grafts may be alloplastic or autologous. Autologoustissue remains the gold standard for nasal graftingmaterial. Autologous grafts include cartilage and bone.There is a reduced risk of infection or rejection due tobiocompatibility.12 The ear is the most frequent donorsite for cartilage graft. The auricular conchal cartilagegraft is well-shaped with a natural curve. Thisresembles the nasal tip to alar junction and may alsobe appropriately shaped and thinned to fit well on thepatient's nose.11 The patient had already undergonetwo augmentation procedures using both the right andleft conchal cartilage for tip plasty and dorsalaugmentation rhinoplasty so this surgical option cannotbe considered if the patient would undergo anotheraugmentation procedure. The other main source ofautologous cartilage is the costal cartilage.12 In thepatient, septorhinoplasty was done with rib cartilagegraft which helped in straightening the crooked nosedeformity of the patient. It did not however, addressthe depression on the post-medial maxillectomy area.

Alloplastic grafts constitute an alternative graftmaterial. These include non-porous materials (silicone)which may provide smooth, soft tissue augmentationbut lack stability due to their inability to host-tissueingrowth. Alternatively, porous materials are nowavailable such as Medpore which can promotefibrovascular in-growth with the surrounding hosttissue. They provide both mechanical stability andreduced risk of infection.12 Another type of alloplasticgraft is expanded Polytetrafluoroethylene (ePTFE) orGore-Tex. This is now being used frequently fordorsum and/or tip augmentation.14 Both Medpore andGore-Tex implant were used for augmentation in thepatient. A Medpore implant was used to improve thenasal dorsal profile by creating a triangular roof shapedimplant using a lateral rhinotomy incision. Gore-texwas also used to address the depression on the leftlateral side wall.

According to Nassab, et al., more alloplasticimplant-related complications such as displacement,extrusion or infection are more observed in Asianpopulations than in other ethnicities.15 Alloplastic graftsare also less physiologic and elicit an immunologicresponse that may cause damage to the tissues andmay eventually lead to extrusion of foreign body.16 Inthe patient, silicone implant was not used since it wasconsidered a reconstructive case rather than an

aesthetic one. The absence of the medial maxillacaused the thinning of the skin and nasal mucosa. Thepatient was warned that with or without perforationof the skin, there is a possibility of extrusion of implantand infection. Still she consented the procedure.Extrusion of Gore-Tex implant happened one monthpost-operatively.

Most people request surgical procedures forcosmesis to feel better psychologically, enhance theirquality of life, boost their self-esteem, and reducesocial anxiety. Rhinoplasty may be considered as apsychotherapeutic intervention which may providesatisfaction to patients. At times, the outcome doesnot coincide with the expectation. This creates aserious problem for both the patient and the surgeon.17

With the patient already at an age beyondaccelerated skeletal maturity, coupled with her desireof improving further aesthetically her nose, surgerycan still be performed. According to Lee, et al., if thepatient's psychosocial development is impaired due tofacial deformity, surgical contouring and/or resectionmay be warranted she and her family, however, mustbe made aware of this and the prospect of subsequentfailure of surgeries must be emphasized.17

Elimination of surgical options available for thepatient can be done. Alloplastic implants must beavoided because of history of extrusion. Autologousgrafts cannot be done due to depletion of availablecartilage graft. Temporary fillers maybe advised withsix months follow-up.

SUMMARY

This is a case of 41-year-old female with fibrousdysplasia who underwent medial maxillectomy whichresulted in a severe nasal deformity described as acrooked and flat nose with left paranasal depression.Multiple rhinoplasty procedures were done. The desireof the patient to improve aesthetically determines thechances of another surgery but she must be madeaware of the risks and complications that may happen.Previous surgeries done to the patient must be notedas they may limit the surgical options available. In thepatient’s case, temporary fillers may be suggested with6 months a follow-up.

REFERENCES

1. Cummings C, Flint P, Haughey B, Lund V, Niparko J, RobbinsK, et al. Radiology of the Nasal Cavity and Paranasal Sinuses.Cummings Otolaryngology Head and Neck Surgery 6th ed.Volume 1. Canada: Elsevier Saunders; 2015. p. 675


2. Cholakova R, Kanasirska P, Kanasirski N, Chenchev Iv,Dinkova A. Fibrous dysplasia in the maxillomandibularregion- A case report. Journal of IMAB - Annual Proceeding(Scientific Papers) vol. 16, book 4, 2010

3. "Fibrous Dysplasia Foundation - Helping PeopleWorldwide". Fibrousdysplasia.org. N.p., 2016. Web. 24 Mar.2016.

4. Subramaniam V, Herle ATV. Fibrous dysplasia of themaxillary sinus: case report. Rev Sul-Bras Odontol. 2010Jul-Sep;7(3):366-8.

5. Bailey, B, Calhuon, K. Atlas of Head & Neck Surgery-Otolaryngology. Volume 2. Lipincott Williams & Wilkins.

6. Adetayo O, Salcedo S, Borad V, Sara S, Richards BS, WorkmanA, et al. Fibrous dysplasia: An overview of disease process,indications for surgical management and a case report, Eplasty2015; 15:e6. eCollection.

7. Carrau R. Maxillectomy. retrieved August 16, 2016, fromhttp://emedicine.medscape.com/article/1890955-overview

8. Bocierri A. A crooked nose. Acta Otorhinolaryngol Ital 2013;33(3): 163-8.

9. Villafuerte C, Dy A, Lapena J. An initial survey ofseptorhinoplasty in crooked nose deformities. Phil JOtolaryngol Head Neck Surg 2016; 31 (1).

10. Pigott JR, Yazdani A. Hyaluronic acid used for the correctionof nasal deviation in an 18-year-old Middle Eastern man.Can J Plast Surg. 2011; 19(4): 156-8.

11. Vedamurthy M, Vedamurthy A. Dermal Fillers: Tips toachieve successful outcomes. J Cutan Aesthet Surg 2008;1(2): 64-7.

12. Choudhury N, Marais J. The use of porous polyethyleneimplants in nasal reconstruction. Clin Rhinol Int J 2011;4(2): 63-70.

13. Thornton J, Griffin J, Constantine F. Nasal reconstruction:An overview and nuances.

14. Bergeron L, Kuo-Ting Chen P. Asian rhinoplasty techniques.Sem Plast Surg 2009; 22 (1)

15. Nassab R, Matti B. Presenting concerns and surgicalmanagement of secondary rhinoplasty. Aesth Surg J 2015;35 (2): 137-44.

16. Bussi M, Palonta S, Toma S. Grafting in revision rhinoplasty.Acta Otorhinolaryngologica Italica 2013; 33: 183-9.

17. Belli H, Belli S, Ural C. Psychopathological evaluation ofpatients requesting cosmetic rhinoplasty A review WestIndian Med J 2012; 61 (2): 149.

18. Lee J, FitzGibbon E, Chen Y, Kim H, Lustig LR, AkintoyeSO. Clinical guidelines for the management of craniofacialfibrous dysplasia. Orphanet J Rare Dis 2012, 7(Suppl 1):S2


Intestinal Obstruction Secondary To Midgut Malrotation:A Diagnostic Dilemma In An Adult Patient

Jenine Joy C. Segismundo, MD; Joseph Carlo G. Kiat, MD;Omar O. Ocampo, MD FPCS and Wilfredo Y. Tayag, MD FPCS

A case of a 33-year-old-female, who manifested with a 22-year duration of recurrent partial intestinalobstruction which resolved spontaneously is presented. Diagnostic difficulties were encountered inestablishing the exact cause of the intestinal obstruction pre-operatively. The patient presented withcomplete gut obstruction requiring immediate surgery, thus, the unexpected finding of midgut malrotationas the primary cause of intestinal obstruction was noted incidentally. Intraoperatively, the cecum locatedat left upper quadrant area of the abdomen and the presence of Ladd's band were noted. A Ladd's procedurewas successfully performed. The postoperative course was uneventful.

Key words: Adult midgut malrotation, Ladd's procedure

Midgut malrotation is a congenital anomalyreferring to either lack of or incomplete rotation ofthe fetal intestines around the axis of the superiormesenteric artery during fetal development. The vastmajority of complications associated with midgutmalrotation usually present in the first month of life.1

In contrast, complications associated with midgutmalrotation presenting in the adult is very rare and itsincidence has been reported to be 0.2 per cent.2 Mostpatients with adult intestinal malrotation areasymptomatic and diagnosis is frequently madeincidentally during laparotomy for other unrelatedproblems. The clinical diagnosis in adults is difficultbecause it is seldom considered on clinical grounds.

Presented is a patient with recurrent episodes ofpartial intestinal obstruction, which frequently resolvedspontaneously for the past twenty two years.Unfortunately, she presented with complete gutobstruction during the admission requiring surgery.

ABSTRACT

*Department of Surgery

Diagnostic difficulties were encountered in establishingthe exact cause of the intestinal obstruction pre-operatively. And like in most studies, the unexpectedfinding of midgut malrotation as the primary cause ofintestinal obstruction was noted incidentally intra-operatively.

The objectives of this paper are to present thefirst documented local case of intestinal obstructionsecondary to midgut malrotation in adult patient,review its clinical manifestations, and discuss itsdiagnosis and management.

THE CASE

This is a case of a 33-year-old female who presentedwith progressive abdominal pain in the periumbilicalregion of the abdomen. The condition started twoweeks prior to admission when the patient experiencedgradual onset of intermittent but tolerable, colickyabdominal pain. This was accompanied by loss ofappetite, several episodes of bilous vomiting, andabdominal distention but there were no other


associated symptoms and signs such as fever norchanges in bowel movement. Progression of abdominalpain and distention prompted admission with a pre-operative diagnosis of intestinal obstruction.

Interval history noted recurrent episodes ofintestinal obstruction that resolved spontaneously forthe past twenty two years. However, despite repeatedhospital re-admissions, her attending physicians neverrecommended any surgical intervention. The pastmedical, family, personal, social, nutritional (BMI =22 kg/m2); and obstetrical and gynecological historieswere all unremarkable.

Physical examination on admission revealed thatthe patient was conscious, coherent, ambulatory,afebrile, and with stable vital signs. Further examinationshowed a distended abdomen with hypoactive bowelsounds, direct tenderness on the epigastric,periumbilical and hypochondriac regions on deeppalpation; and with no palpable mass. The rectalexamination and the rest of the physical examinationfindings were unremarkable.

Hypokalemia was noted on admission. Initial wholeabdominal ultrasound was unremarkable. Uppergastrointestinal series revealed an apparent shortsegment luminal narrowing at the pyloric region withconsequent delayed emptying of contrast media intothe duodenum, with the opacified small bowelsappearing normal in caliber and position; and withnormal mucosal pattern and intestinal transitsuggestive of hypertrophic pyloric stenosis (Figure 1).Contrast-enhanced computed tomography of thewhole abdomen demonstrated mucosal thickening ofthe midjejunal segment with consideration of ileitisversus lymphoma (Figure 2).

Figure 1. Upper GI series showing the stenotic area at thepylorus.

Figure 2. Transverse view of the whole abdominal CT scanwith contrast showing the jejunal thickening at the midsegment.

Esophagogastroduodenoscopy revealed bileamounting to 2.3 liters in the stomach. No gross massnor any lesion was reported in the duodenum,however, copious amount of fecaloid content wasnoted.

The patient was scheduled for exploratorylaparotomy under general anesthesia after five daysof having diagnostic dilemma, with the patient beingplaced on NPO, given total parenteral nutrition,inserted nasogastric tube for bowel decompression,given empiric antibiotics to prevent bacterialtranslocation as well as antacids to decreasegastrointestinal secretions, and inserted indwellingFoley catheter to monitor hydration. Cardiopulmonaryassessment was low risk for any adversecardiopulmonary events.

Intra-operatively, complete intestinal obstructionsecondary to midgut malrotation was noted. Theappendix was located at the left upper quadrant withmalrotation of the cecum. The small bowel was dilatedand edematous proximal to the obstruction caused bythe Ladd's band (Figure 3). Ladd's procedure wassuccessfully performed. The operation consisted ofdivision of Ladd's band overlying the duodenum torelease the intestinal obstruction, counterclockwisedetorsioning of the midgut volvulus, widening of thenarrowed root of the small bowel mesentery bymobilizing the duodenum and division of the adhesionsaround the superior mesenteric artery to preventfurther volvulus, and appendectomy to preventmisdiagnosis of acute appendicitis because of itsatypical location. The postoperative course wasuneventful.


DISCUSSION

At the beginning of the normal fetal development, theprimitive gut lies in a median sagittal plane. A 270ºcounterclockwise rotation of the intestines occursalong the superior mesenteric artery, and then it willtemporarily herniate into the umbilical cord outsidethe peritoneal cavity for it to be accommodated further.This is followed by independent rotation of stomachand duodenum, growth of the intestines and fixationof the mesentery of ascending and descending colon.Failure of any of these during embryologicdevelopment will lead to malrotation.3

Torres et, al. reported that about 60 to 85 percentof complications associated with midgut malrotationusually present in the first month of life.1 Von Fluenoted that more than 90 percent of patients will presentby the time of their first year of life.2 Majority of initialpresentation in pediatric population is bilous vomitingbecause of duodenal obstruction or volvulus which mayeventually lead to development of intestinal ischemiaand peritonitis. Acute intestinal obstruction due tomidgut malrotation is usually caused by Ladd's bandsthat run from cecum to the right lateral abdominal wall.

True incidence of malrotation in the adult isdifficult to estimate because most patients remainasymptomatic and often are left undiagnosed. Inadults, it presents in numerous ways and symptomsare non-specific. Diagnosing malrotation in this agegroup is concluded with difficulty because of its non-specific presentation and surgeons usually have lowindex of suspicion in the initial evaluation of adultpatients with bilous vomiting and abdominal pain.

Bastian, et al. presented case of an 85-year-old-man with non-specific abdominal complaints for twentyyears, who presented with sudden onset of centrally

Figure 3. Intraop finding: The appendix was located at the leftupper quadrant with malrotation of the cecum.

located abdominal pain. Emergency surgery withmedian laparotomy was done which showed a 360ºclockwise rotation of the small bowel around themesenteric pedicle of the superior mesenteric arteryand vein. Prior to surgery, he had been under thesurveillance of a gastroenterologist, undergoing seriesof diagnostic investigations including upper GI contraststudies and CT scan of upper abdomen, however, noactual cause for the repeated episodes of abdominalpain was found. Patient stayed in the ICU and slowlydeteriorated and died on the 48th post operative day.

Dietz, et al. studied a series of ten adults withbowel obstruction caused by intestinal malrotation andthe study showed that five adults presented withchronic symptoms of bowel obstruction with theduration of symptoms extending to thirty years.Moldrem et al reported that 48.5 per cent of their thirtythree patients presented with an acute abdomen. Theacute presentation of this disease entity is caused byvolvulus of the midgut or ileocecum, and it wasreported that this is the most common cause of bowelobstruction in adult malrotation.2

Diagnostic delays are common in this group ofpatients because of its non-specific nature. A studyby Moldrem, et al. stated that conventional plainradiography is neither sensitive nor specific in thediagnosis of gut malrotation. Although right-sidedjejunal marking and the absence of a stool-filled colonin the right colon are suggestive leading to furtherinvestigation.4

The reported gold standard diagnosis ofmalrotation is upper GI contrast study, and this is mostsignificant in the pediatric group. The study will showthe duodenum and duodenojejunal flexure located atthe right of spine. Computed tomography with orwithout upper GI series is increasingly usedpreferentially as it is now considered the investigationof choice, providing diagnostic accuracy of 80 percent.4 CT scan will show the superior mesenteric veinto be posterior and to the left of the superiormesenteric artery. What is diagnostic of malrotationis the appearance of midgut volvulus and thedistinctive "whirlpool" sign created by the twisting andwrapping around of the mesentery to the superiormesenteric artery pedicle.2

Radiologic studies suggested the possibility ofhypertrophic pyloric stenosis but was ruled outbecause this condition is rarely seen in adults. Otherdifferential diagnoses were either malignant tumorssuch as carcinoma, lymphoma, carcinoid or GIST, oreven benign conditions such as gastrointestinal


tuberculosis but these were all ruled out due to thepresentation of recurrent obstruction for more thantwo decades.

The patient was asymptomatic until her 11th yearof life when she started having symptoms ofobstruction like bilous vomiting, early satiety andabdominal pain. It was also noted that the abdominalpain was frequently relieved by vomiting. During herchildhood, no work-up was done and she was notbrought to a hospital. During her adulthood, she wasadmitted to different hospitals repeatedly but she didnot improve entirely. She was usually given anti-emeticand stool softeners as she was just constantly beingmanaged as a case of gastroesophageal reflux diseaseand chronic constipation. Several imaging tests weredone like ultrasound and CT scan but did not showany finding suggestive of intestinal obstruction. Shealso noted that during her pregnancies, her symptomsworsened. This is explained by the physiologicdecrease of peristaltic power and bowel motility.Nevertheless, she delivered her babies withoutcomplications.

Two weeks prior to admission, she had persistentabdominal pain, with a pain scale of 8/10 in the visualanalog scale, localized in the epigastric area, radiatingto the periumbilical and hypochondriac areas, crampyin character, aggravated by heavy intake of food, andrelieved by vomiting. She consulted our institution andseveral work-ups were done.

Electrolytes abnormalities especially hypokalemiaare common in obstruction of small bowels. Ongoingemesis will lead to loss of fluid containing electrolytes.Transudative loss of fluid from the intestinal lumeninto the peritoneal cavity causes this. If the boweldilatation is excessive due to the obstruction, intramuralvessels of the small intestines become compromisedand perfusion to the wall of the intestine is reduced.Once the perfusion of a segment of the bowel isinadequate to meet the metabolic needs, ischemia willoccur and will eventually lead to necrosis andperforation. This is the catastrophic resolution of anydiagnostic delay of a small bowel obstruction.

Several imaging modalities were requested to thispatient for the diagnosis to be establishedpreoperatively. However, none of the imagingmodalities showed findings suggestive of midgutmalrotation.

The management of symptomatic intestinalmalrotation is undoubtedly surgical intervention. Choi,et al. conducted a 35-year study on 177 patients. Theyhave found out that patients with asymptomatic

presentation had a low risk of intestinal volvulus.These patients were advised to undergo routineinvestigations. However, it should be considered thatpatients with intestinal malrotation should undergosurgical correction regardless of age because it isimpossible to predict which patients will develop fatalcomplications.6 The mainstay surgical treatment isLadd's procedure. Fu, et al. reported a completeresolution of symptoms in nine and near completeresolution in two of eleven patients. Dietz, et al. alsoreported a complete symptomatic resolution in eightof their ten patients treated surgically.

Recent reports of the use of laparoscopic approachin the surgical treatment of intestinal malrotationshowed that this technique appears to be safe andeffective although this is challenging and conversionto open procedure is common.6,7,9,10 Conversion rateto open surgery is about 8 per cent. Like any otherlaparoscopic surgery, short term results were superiorwith the laparoscopic approach in terms of earlier timeto start diet, decreased amount of time to attain fullfeeding, having lesser hospital stay, better pain control,and earlier return to premorbid condition.11

SUMMARY / CONCLUSION

A case of a 33-year-old female with intestinalobstruction secondary to midgut malrotation waspresented. Incidence of midgut malrotation in adultpopulation is rare. It presents with non-specificsymptoms and signs, hence, usually presents as adiagnostic dilemma. Delay in the diagnosis may leadto development of bowel ischemia and perforation.Incidental finding intra-operatively of midgutmalrotation requires Ladd's procedure to beperformed. Prompt surgical intervention is necessaryto minimize complications.

REFERENCES

1. Torres AM, Ziegler MM: Malrotation of the intestine. WorldJ Surg. 1993, 17: 326-31.

2. Von Flue M, Herzog U, Ackermann C, et al. Acute and chronicpresentation of intestina l nonrotation in adult. Dis ColonRectum 1994, 37: 192-8.

3. Brunicardi C. Schwart'z Principles of Surgery 10th editionUSA, 2014; 1616-7.

4. Moldrem AW, Papaconstantinou H, Broker H, Megison S,Jeyarajah DR. Late presentation of intestinal malrotation:an argument for elective repair. World J Surg 2008, 32: 1426-31.


5. Fisher JK: Computer tomographic diagnosis of volvulus inintestinal malrotation. Radiology 1981; 140: 145-6.

6. Matzke GM, Dozois EJ, Larson DW, Moir CR. Surgicalmanagement of intestinal malrotation in adults: comparativeresults for open and laparoscopic Ladd procedures. SurgEndosc 2005; 19: 1416-9.

7. Fu T, Tong WD, He YJ, Wen YY, Luo DL, Liu BH. Surgicalmanagement of intestinal malrotation in adults. World Journalof Surgery 2007; 31: 1797-1803.

8. Matzke GM, Moir CR, Dozois EJ. Laparoscopic Laddprocedure for adult malrotation of the midgut with cocoondeformity: report of a case. J Laparoendosc Adv Surg TechA 2003; 13: 327-9.

9. Bax NM, van der Zee DC: Laparoscopic treatment ofintestinal malrotation in children. Surg Endosc 1998; 12 (11):1314-6.

10. Kalfa N, Zamfir C, Lopez M, Forgues D, Raux O, GuibalMP, Galifer RB, Allal H: Conditions required for laparoscopicrepair of subacute volvulus of the midgut in neonates withintestinal malrotation: 5 cases. Surg Endosc 2004; 18: 1815-7.

11. Stanfill AB, Pearl RH, Kalvakuri K, Wallace LJ, VeguntaRK: Laparoscopic Ladd's procedure: treatment of choice formidgut malrotation in infants and children. J LaparoendoscAdv Surg Tech A 2010; 20 (4): 369-72.

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