MULTIDISCIPLINARY APPROACH TO COLORECTAL CANCER TREATMENT

AN NCCS QUARTERLY PUBLICATION July – September 2012

Salubris is a Latin word which means healthy, in good condition (body) and wholesome.

...HELPING R EADERS TO ACHIEVE GOOD HEALTHMEDICAL VERSION

Issue No. 22 • MICA (P) 061/10/2010

FIRST SURGICAL ONCOLOGY CONFERENCE ATTRACTS FULL-HOUSE ATTENDANCE

— NCCS lends its expertise in Oncology at its first regional surgical oncology conference to impart skills to doctors from the region.

Dr Tan Hiang Khoon

In line with global trends, the Southeast Asian region has seen an increase in the number of cancer incidences. According to the American Cancer Society, there was an estimated 1,596,670 new cases in 2011. It also expects an increase in demand for oncology services by 48%. However, the supply of oncologists has not been in tandem with the demand for oncology services due to the shortfall in the supply of doctors by a staggering 34%, or a shortage of close to 3,800 oncologists.

The participants were also encouraged to present and share their own experiences on cancer management in their country, enabling them to be considered for a BNP Paribas Fellowship Programme.

The BNP Paribas Fellowship programme is an extension of NCCS and BNP Paribas’ collaboration, established since 2009, to promote the standard of clinical practice for oncology in the region. Since its inception, four BNP Paribas Fellowships have been awarded to doctors in Vietnam to receive post-graduate training in the various fields of oncology.

Encouraged by the effective learning experiences that these fellows obtained at NCCS, the idea of the conference was then conceived, to reach out to more oncologists in the region to give the standard of surgical oncology a timely boost. After rounds of rigorous judging and competition, 10 fellowships were awarded. The recipients will spend between 3 and 12 months at NCCS to improve their knowledge and hone their skills.

Apart from funding the fellowship programmes, BNP Paribas was also the key sponsor of the conference.

The delegates enjoyed accelerated learning when they were placed under the guidance of world-class NCCS oncologists who were predominantly trained in Singapore, Europe and the US, and who have held teaching positions in local tertiary institutions.

A gainst this backdrop, NCCS held its first ever Surgical Conference from 16 to 18 May 2012, providing a platform for young surgical oncologists to learn, discuss and exchange knowledge and expertise. The

desired outcome was to promote the best practices in surgical oncology in the region. Twenty-nine overseas participants attended the conference all of whom were awarded with a certificate of participation.

The conference explored the synthesis of treatment modalities like chemotherapy and radiation therapy in surgical settings for common cancers within the region such as Head and Neck, Sarcoma, Gastrointestinal, Breast and Colorectal Cancers, and featured hands-on workshops that include surgical techniques such as sentinel lymph nodes biopsy, thyroid ultrasound that were performed on animals or real patients. Participants were also shown how to use the various modules in the simulators in an endoscopy simulation workshop to improve their technique in gastroscopy and colonoscopy.

Dr Tan Hiang Khoon, the conference organising chairman, hopes that such meetings can be held on a regular basis. “The idea of the conference stems from our desire to alleviate the sufferings of those who are afflicted with cancer. We feel that the best way to do this is to train as many doctors as possible so that they can go back and treat their local community.“

Prof Soo Khee Chee, Director of NCCS, has high hopes for the delegates, whom he believed had benefitted greatly from the conference. He said, “We hope that from the extensive exchange of knowledge, our regional colleagues will be able to gain other perspectives of the advances in medicine. When they return to their respective communities, they can in turn train their colleagues and ultimately, all the communities will benefit.”

BY VERONICA LEE

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LINE COMPLICATION IN PATIENT UNDERGOING CHEMOTHERAPY TREATMENTBY ALICE CHUANurse Clinician, NCCS

The National Cancer Centre treats approximately 70% of the cancer population in Singapore. Multimodality treatment is pivotal in the management of cancer. It commonly involves surgery, chemotherapy and radiotherapy in the neoadjuvant or adjuvant setting.

A dministration of chemotherapy is more evident in the outpatient setting as the trend of chemotherapy administration moves away from the inpatient setting. Regimes for cancer treatment can be complicated and involves administration of multiple drugs which requires repeated venous access.

Central Venous Catheter (CVC) is commonly used in the centre to minimise any administration-related complications for patients with difficult veins and those treated with vesicant drugs or regimes involving administration through a pump. Despite advances in modern technology and oncology care, infection remains a major cause of morbidity and mortality among patients with cancer. Immunosuppression caused by underlying malignancy and chemotherapy are main factors contributing to increased risk of infection. In retrospect, CVC placement is not without its complications. It is associated with site infection, catheter damage, occlusion, dislodgement, migration, and skin allergies. Complications can lead to treatment delays and may potentially affect the efficiency and overall treatment outcome. Thus, healthcare professionals must be vigilant in the prevention of catheter-related complication by constantly monitoring, observing and providing appropriate management if they arise.

At the National Cancer Centre, nurses involved in the care of patients with lines are trained on basic care aspects. Additionally, identification and management of line complications are included in their training during the induction period. We have a nurse specially trained in the management of CVC-related complications and she manages any complication in collaboration with the oncologists. Her role includes pre-counselling of patients scheduled for line placement and post placement care and management teaching. During the pre-placement counselling session, the CVC Nurse can identify any potential issues the patient may encounter after the placement. For patients who are unable to manage their line due to personal, physical or lack of caregiver issues, they will be directed to the Specialist Outpatient Clinic or Ambulatory Treatment Unit for the care of their lines. To further facilitate their learning on the care of the lines, the Department of Nursing has devised a CVC care booklet and DVD for patients. It consists of information that is taught during the teaching session. We commonly involve the family members or caregivers in the teaching sessions too. The materials are designed to cater to the needs of different learners who have different learning curves and modes e.g., auditory learners, visual learners and kinaesthetic learners (hands-on). All learning materials are available at clinical areas in the Centre. Thus, remaining vigilant in our care and adhering to the best practices in preventing complication is the best treatment we can render to our patient.

Pre-insertion counselling materials

Post insertion counselling materials

DVD

POTENTIAL COMPLICATIONS OF COLORECTAL CANCER TREATMENT BY DR MELISSA TEO Senior Consultant, Department of Surgical Oncology, NCCS

AND DR JOELLE WONG Resident Physician, Department of Surgical Oncology, NCCS

Colorectal cancer is the most common cancer in many developed countries. It is also the leading cancer in Singapore. The stage of the disease at diagnosis often determines the prognosis and survival rate of a patient with colorectal cancer, with the best outcomes seen in patients diagnosed at an early stage.

COMPLICATIONS OF TREATMENT:

S urgery is the mainstay treatment for colorectal cancer and may be the only modality required if the disease is at an early stage. Chemotherapy and radiation therapy are additional treatment modalities that can be used before surgery (neoadjuvant), after surgery (adjuvant) or for palliative treatment.

Although advances in these treatment modalities have improved survival rates significantly over the years, there remain short and long term complications and adverse effects of each of these modalities.

SURGERY

Surgery for colorectal cancer is performed under general anaesthesia. The risks of the general anaesthesia itself are low (less than 3%), especially in patients without significant co-morbidities. Complications like perioperative cerebral vascular accident, acute myocardial infarct, pulmonary embolism, deep vein thrombosis and pneumonia can happen. The risk is higher with age, poor physical health and pre-existing commodities. An underlying condition may be exacerbated during perioperative period; evaluate each patient pre-operatively to ensure optimisation of their medical condition.

Common side effects that may also happen immediately after general anaesthesia are nausea, vomiting, dizziness, acute urinary retention and temporary nerve injury secondary to positioning during surgery. However most side effects do not last long and can usually be treated effectively with oral or intravenous medications and physiotherapy.

Specific complications related to surgery would include bleeding, pain, wound infection and anastomotic leak. Bleeding after surgery that requires a repeat operation happens infrequently. More often, a patient with stable parameters but blood-stained discharge seen in the drain may merely require a blood transfusion and close observation. Post-operative pain is often managed with the provision of patient-controlled analgesia (PCA), allowing the patient control over his/ her pain management.

Wound infection may occur especially in cases where the tumour has resulted in the perforation of the intestine, resulting in a contaminated surgical field. Although peri-operative intravenous antibiotics are always used in this scenario, a worsening infection may require drainage and daily dressing.

Anastomotic leaks are serious complications that occur in less than 5% of all colorectal cancer operations. If they do occur, the most common time would be between five and seven days after the operation. An anastomotic leak is suspected if the patient has increased pain compared to the preceding days, develops a temperature and becomes clinically unstable, has increased abdominal tenderness and guarding and is associated with clinical signs of peritonitis.

Continued on page 6.

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A drain that is left in-situ after the initial surgery may contain faeculent or bilious discharge. If an anastomotic leak occurs, a second operation will be required to repair any leak at the surgical site. In this second surgery, a stoma may be required if the peritoneal cavity is contaminated.

Stomas may occasionally be required in the original surgery, if the anastomosis is low (as in some low anterior resections for rectal cancer) or if the operative field is contaminated (perforated tumour). In these situations, the stoma is usually temporary and is reversed when the reason for fashioning them no longer exists; usually 6 weeks after the surgery. In the event that the tumour involves the anal sphincters or if clear distal margins cannot be obtained without resection of the anal sphincters, an abdomino-perineal resection and a permanent stoma would be required. Complications relating to stomas would include short-term problems of bleeding and high stomal output whilst longer-term issues include stoma prolapse/ retraction/ herniation. These surgical related complications can substantially prolong the duration of hospitalization of the patients.

Other mid to long term complications are mostly related to bowel and anorectal problems, urinary or sexual dysfunctions.

Patients who are prone to suffering from these dysfunctions are those who have undergone low or ultra-low anterior resections. These patients are known to be experiencing the “anterior resection syndrome”. They make up approximately 10-20% of those who had undergone the named surgery. These complications can be explained by the removal of a segment of the rectum and hence the loss of effective storage and reabsorption functions. Post bowel resection patients may experience bowel and anorectal problems such as frequency, urgency, fragmentation of stools, diarrhoea and incontinence. These bowel patterns take a while to settle and may take up to 1–2 years before patients discover what is normal for them. During this period, symptomatic treatment with oral anti-diarrhoeal or bulk forming medication, adequate oral rehydration and dietary modifications might help with the situation.

The treatment consists of twice daily doses of oral Xeloda, either alone or in combination with intravenous irinotecan or oxaliplatin. Some common side effects of Xeloda are diarrhoea, hand-foot syndrome and stomatitis.

In addition to chemotherapy, targeted agents like bevacizumab and cetuximab are also increasingly used in the management of metastatic colorectal cancer. These agents typically have a much lower toxicity profile.

RADIOTHERAPY

Radiation therapy has been shown to improve local control rates in locally advanced rectal cancers when applied pre-operatively or post-operatively. Patients are treated daily (Mondays to Fridays) over 5 to 6 weeks, and usually with concurrent chemotherapy (5-fluorouracil or capecitabine). It can also be used in the palliative setting.

Side effects of treatment may be divided into acute and late effects. Acute effects happen during a course of treatment and include skin reactions, abdominal cramps, diarrhoea and urinary frequency or urgency. Local skin reaction usually appears as dry erythematous skin in the region of treatment, and aqueous cream may be applied should the patient be bothered by itch. Bowel and urinary complaints may also be treated symptomatically and will usually settle after completion of treatment.

Late effects however, are potential complications which manifest only months to years in the future. These include rectal bleeding, haematuria, decreased bladder capacity, strictures, pedal oedema and infertility/impotency. Fortunately, such complications are not common and their severity varies with individuals. Mild cases may not need treatment at all but more severe ones might require compression stockings (for pedal oedema), steroid enemas (for rectal bleeding) or even hyperbaric oxygen therapy.

Due to the proximity of the femoral heads to the region of radiation treatment, patients are theoretically at a higher risk of avascular necrosis as well and may be more prone to hip fractures. Very rarely, radiation has also been known to induce secondary malignancies (usually sarcomas) in the pelvis. This tends to occur 10 years or more after exposure to radiation and is unlikely to affect the vast majority of adult patients.

PSYCHOSOCIAL ISSUES

In addition to managing the various risks of treatment-related complications, colorectal cancer patients are often prone to significant psychosocial distress. They experience depression secondary to fear of recurrence, adjustment to physical changes (e.g. presence of a stoma, irregular bowel movement, sexual dysfunction etc.) and death. Recurrence can happen after a period of time at local (site of original tumour), regional (near primary tumour), distal (in other parts of the body) or metachronous (a second primary colonic cancer) sites.

These psychosocial issues are most frequently experienced by patients in the treatment stage, those who require adjuvant treatment other than surgery and those with a permanent stoma. It is important to support all colorectal cancer survivors in the first five years of survivorship and beyond. Appropriate referral to psychologists, rehabilitative facilities (e.g. stoma nurse), social services and support groups should be made when necessary to help facilitate reintegration.

SUMMARY

Whilst it may seem that the treatment of colorectal cancer may potentially cause many complications, the simple truth is that many cancer survivors are able to overcome most if not all of these problems. Doctors, nurses, social workers and many other support staff are always present to help. Crucially, support groups and family always play the biggest roles in survivorship, transforming the victim into a victor in the fight against cancer.

ADDITIONAL INPUTS BY DR ONG SIN JEN, DR SIOW TIAN RUI AND MS DEANNA NG

Due to the frequent visits to the toilet, perianal skin can be inflamed and proper skin care is important to prevent painful excoriation and infection.

Damage sustained by the surrounding nervous plexus or vascular network during bowel resection and pelvic dissection could result in urinary and sexual dysfunction. Stress urinary incontinence has been shown to be correlated with the extent of pelvic dissection in patients. Those who have undergone abdominalperineal resections are more likely to develop urinary dysfunction as compared to those who have undergone only a low anterior resection. Sexual dysfunction like erectile dysfunction and sexual arousal disorder may affect both man and woman. Multimodality treatment with combined surgical and radiotherapy treatment for rectal cancers has been shown to improve cure rates but increases the incidence of voiding and sexual disorders.

CHEMOTHERAPY

Complications from chemotherapy depend on the agents used, and may include fatigue, nausea, vomiting, diarrhea, bone marrow suppression with increased susceptibility to infections (febrile neutropenia), mucositis, hand-foot syndrome, neuropathy and cardiotoxicity. However, these side effects are usually reversible once chemotherapy is stopped.

In colorectal cancer, common agents used are 5-fluorouracil (5-FU), folinic acid, oxaliplatin and irinotecan. Side effects attributable to 5-FU include diarrhoea, stomatitis, neutropenia and cardiotoxicity. Oxaliplatin related peripheral neuropathy is also a common side effect and can affect up to 90% of patients to varying degrees. The symptoms of numbness, tingling and cold-induced pain is often reported and may persist for years even after treatment. Opioid-based analgesia and gabapentin are useful to treat severe cases.

Oral chemotherapy with capecitabine (Xeloda) is now frequently part of the first line therapy for metastatic colorectal cancer. Compared to intravenous 5FU, it is more convenient for a patient and has similar therapeutic benefits.

Continued from page 5.

HUNGARY-SINGAPORE CANCER CENTRE TIE UP IN THE OFFINGVisit by Prof Miklos Kasler opens doors for collaborations

Decades ago, it would have been hard to imagine Professor Miklos Kasler as the internationally renowned advocate of cancer control programmes that he is now. Trained as a surgeon specialising in oral, plastic and reconstruction surgery, he subsequently went into the field of oncology where he took a keen personal interest in cancer control.

A nd, ever since then he has been working relentlessly for

his cause to keep cancer at bay, not just in his homeland in Hungary, but across the globe.

He has pioneered conceptualization of national cancer control programmes in vital areas such as screening, treatment protocol, professional education and research. Recognizing NCCS’s dominant role in cancer prevention in Singapore, Prof Kasler accepted an invitation from NCCS Director, Prof Soo Khee Chee, to share his expertise with the oncologists of NCCS. Prof Miklos Kasler

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“Perhaps more attention could be directed at increasing the physical activity of the population as obesity is known to increase the risk of cancer. It is likewise important to rule out the harmful effects of chemical agents and monitor water contamination, and we have to do our best to protect the environment we are living in.”

He notes that Singapore has been effectively keeping abreast with times in the implementation of screening and prevention programmes, particularly in the area of vaccinations against Human Papilloma Virus (HPV) and Hepatitis B and C. He reckons that the results in HPV vaccination would take effect in 10-15 years, where HPV-induced cancers in the oral cavity, pharynx, larynx, esophagus and rectum would see significant reductions. Noting that HPV vaccinations are targeted at girls, he believes that more can be done to encourage vaccination for boys.

Despite the early introduction of cancer screening programmes in Singapore, greater efforts should be induced to improve screening compliance. He said, “All around the world, nation-wide screenings are carried out for cancer in the breast, cervix and colorectal, like Singapore. Efforts need to be made to increase compliance rate to over 80 percent.”

Prof Kasler gave an insightful presentation “Cancer Control: A useful paradigm of success for emerging countries”. He met several key NCCS staff members and the meetings will pave the way for potential mutual collaborations, particularly in research and education.

Prof Kasler feels that there is much that NCCS and the National Institute of Oncology (NIO) in Hungary, of which he is director of, can work together on by leveraging on NIO’s expertise in education. “In Hungary, more than 50 percent of the medical students are foreigners. They may attend lectures in Hungarian, English or German. NIO is the only accredited comprehensive cancer centre in Europe and the syllabus is based on standards acknowledged in the USA and Europe,” he said.

The NIO is well known at the international level, having fostered cooperation with Comecon (Council for Mutual Economic Assistance) member states and various international organisations. It had partnered the World Health Organization to launch the Cancer Control Programme, participated in the evaluation of these programmes, and developed the European Code against cancer. The Code focuses on measures to reduce smoking and alcohol consumption, and promoting healthy lifestyle and avoiding obesity. NIO was also involved in the International Union against Cancer, anti-smoking campaign, among others.

Prof Kasler has high praise for NCCS. “I feel that the NCCS plays a dominant role in Southeast Asia as it is functioning at a very high level, like how the National Institute of Oncology is like in Central-Eastern Europe. A deeper insight into each other’s potentialities may open up new vistas in collaboration.”

Examining Singapore’s success in cancer prevention, public education and screening, he said that Singapore is in an advantageous position, armed with a very good control on tobacco and alcohol consumption. He feels what needs to be addressed is the sedentary lifestyles of our citizens and the use of harmful chemicals.

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Like Hungary, Singapore is actively seeking out new treatment modalities and research to advance the quality of cancer care for patients. Sharing insights about proton therapy which Hungary has pioneered successfully, he said that collaboration with neighbouring countries like Austria has ensured that there was effective utilisation. “A proton beam irradiating unit is suitable for the care of 30-40 million people. Since Central Eastern European countries are usually small, the effective use of such equipment can only be reached through collaborations.”

As a first move towards formal tie-up between Singapore and Hungary, plans for exchange programmes are in the pipeline.

BY VERONICA LEE

8 SALUBRIS APRIL – JUNE 2012

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Editorial Advisors

Prof Kon Oi Lian Prof Soo Khee Chee Dr Tan Hiang Khoon

Medical Editor

Dr Richard Yeo

Members, Editorial Board

Mr Mark Ko Ms Sharon Leow Dr Shiva Sarraf-Yazdi Ms Jenna Teo

Executive Editors

Ms Charissa Eng Ms Veronica Lee Mr Sunny Wee

Members, Medical Editorial Board

Ms Lita Chew Dr Mohd Farid Dr Melissa Teo Dr Teo Tze Hern Dr Deborah Watkinson