Surg Today (2007) 37:325–329DOI 10.1007/s00595-006-3392-5

Reprint requests to: R. AiharaReceived: August 15, 2006 / Accepted: September 21, 2006

Peritoneal Recurrence of Gastric Cancer with Mucin Phenotype 12 Years After Curative Resection: Report of a Case

Ryuusuke Aihara1, Erito Mochiki1, Sayaka Ohotake1, Yoichi Kamiyama1, Teturo Ohono1, Hiroyuki Kuwano1, Kohei Kurokawa2, and Kazuhiro Suzuki2

Departments of 1 General Surgical Science (Surgery I) and 2 Urology, Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan

AbstractWe report a case of peritoneal recurrence of gastric cancer in a 58-year-old man, 12 years after curative surgery. Urinary wall thickness was seen on follow-up computed tomography and magnetic resonance imag-ing scans. We performed total nephroureterectomy and cystectomy for urinary tract cancers, but histological examination of the resected specimen revealed poorly differentiated adenocarcinoma with severe fi brosis, re-sembling the gastric cancer resected 12 years earlier. Immunohistological examination revealed human gas-tric mucin (45M1) and intestinal mucin (MUC2) pheno-type in both the original gastric cancers and the urinary tract cancers. Thus, we concluded that the second can-cer was a peritoneal recurrence of gastric cancer with gastric and intestinal mucin phenotypes. Although peri-toneal recurrence so many years after curative gastrec-tomy is rare, careful long-term follow-up should be done for all patients undergoing surgery for gastric can-cer with mucin phenotype.

Key words Gastric cancer · Mucin phenotype · Gastric and intestinal phenotype · Peritoneal recurrence

Introduction

Peritoneal recurrence of gastric carcinoma after resec-tion is generally associated with a poor prognosis. Ac-cording to one report, peritoneal recurrence was found in 17% of patients who underwent curative resection. In most cases, it was diagnosed in the fi rst 2 years after surgery.1 To our knowledge, there is no report of peri-toneal recurrence of gastric carcinoma developing long term after curative surgery. We report a case of perito-

neal recurrence detected 12 years after curative surgery, in which the origin of the secondary cancer was diag-nosed by mucin immunohistochemistry.

Case Report

A 46-year-old man underwent distal gastrectomy for type 0–IIc advanced gastric cancer in the greater curva-ture of the antrum. Histological examination of the re-sected specimen confi rmed that the depth of tumor invasion was exposed-serosal (se). The tumor showed infi ltrative growth with severe fi brosis (sci). There was moderate lymphatic invasion (ly2), moderate venous invasion (v2), and lymph node metastasis (n2). The tu-mor was diagnosed histologically as poorly differenti-ated adenocarcinoma with partial signet-ring cell carcinomas.2 The patient was followed up on an outpa-tient basis.

At the age of 58 years, 12 years later, he visited our hospital for a follow-up examination. No remarkable abnormalities were found on physical examination or laboratory analysis. The tumor markers carcinoembry-onic antigen (CEA), gastrointestinal cancer antigen 19-9 (CA 19-9), and α-fetoprotein (AFP) were within normal limits. However, abdominal computed tomog-raphy (CT) showed right urinary duct thickness, and a right hydroureter (Fig. 1A). A CT scan of the pelvis showed a mass lesion behind the urinary bladder (Fig. 1B) and magnetic resonance imaging (MRI) of the uri-nary tract supported the CT fi ndings (Fig. 1C,D). As no malignant cells were detected by cytological examina-tion of the urinary tract, the patient was followed up under informed consent. However, abdominal CT, MRI, and cytological examinations performed about 4 weeks later showed that the wall thickness had become worse; thus, 8 weeks later we performed total nephro-ureterectomy and cystectomy to remove the urinary tract tumor.

326 R. Aihara et al.: Late Recurrence of Gastric Cancer

Macroscopic and Pathological Findings

Microscopically, the urinary tract was dilated from the renal pelvis to the middle part. The lower urinary tract and ureterovesical junction were narrowed with severe fi brosis originating from the outside; however, the mu-cosal lesion in the urinary tract and urinary bladder was smooth, and did not appear to be cancerous (Fig. 2A,B). Histological examination of the urinary tract showed no mucosal cancerous features; however, poorly differenti-ated adenocarcinoma with signet-ring cell carcinomas was found in the peritoneum around the urinary tract (Fig. 2C). The gastric tumor resected 12 years earlier showed the same histology as the poorly differentiated adenocarcinoma (Fig. 2D).

Immunohistochemical Findings

Immunohistochemical staining was performed accord-ing to the manufacturer’s instructions with only slight modifi cations as follows: human gastric mucin (HGM) (clone 45M1, 1 : 50, Novocastra, Newcastle, UK) for gas-tric foveola-type mucin, MUC2 (clone Ccp58, 1 : 100, Novocastra) for goblet cells and their precursors, and CD10 (clone 56C6; 1 : 40, Novocastra) for the brush bor-der of small intestinal-type enterocytes. Immunohisto-chemistry with mucin phenotype revealed that both the peritoneal tumor and the gastric carcinoma contained gastric mucin (45M1) and intestinal mucin (MUC2), confi rming that the peritoneal tumor was a metastasis of the gastric tumor (Fig. 3A–D).

Fig. 1. A Computed tomography scan of the upper abdomen showed right urinary duct thickness and a right hydro ureter (arrow). B Computed tomography scan of the pelvis showed

a mass lesion behind the urinary bladder (arrow). C,D Mag-netic resonance imaging of the pelvis showed a mass lesion behind the urinary bladder (arrow)

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Discussion

Peritoneal recurrence of gastric carcinoma is one of the major reasons for a poor prognosis after resection, with an average survival time of only 6 months after its detection.1,3,4 Peritoneal recurrence is thought to be related to a diffuse histological type, infi ltrative growth

pattern, and lymph node metastasis.3,4 Recurrence is generally detected within 2 years after surgery.1 Iwanaga et al. compared the incidences of early and late recurrence of gastric carcinoma after surgery and found that peritoneal recurrence developed early, usually within 22 months.5 To our knowledge, there are no other reports of the peritoneal recurrence of

Proper Muscle

Fig. 2A–D. Pathological fi ndings of the resected urinary tract and urinary blad-der. A The urinary tract was narrowed with severe fi brosis from the outside (ar-row). B The ureterovesical junction was narrowed with severe fi brosis (arrow). C,D Histological examination revealed poorly differentiated adenocarcinoma of the peritoneum and stroma around the urinary tract (C). The gastric carcinoma resected 12 years before had the same histology (D). Both specimens also con-tained signet ring cell carcinomas. (C,D H&E stain, ×100)

Fig. 3A–D. Immunohistochemical fi nd-ings. Both the urinary tract (A,B) and gastric tumors (C,D) revealed gastric (45M1) and intestinal (MUC2) pheno-type poorly differentiated adenocar-cinoma (A,B ×100; C,D ×50)

328 R. Aihara et al.: Late Recurrence of Gastric Cancer

gastric carcinoma developing as long as 12 years after surgery.

Peritoneal recurrence of gastric carcinoma is very diffi cult to detect. Our hospital established follow-up guidelines after gastrectomy according to the clinical stages of carcinoma. In general, patients are followed up by laboratory analysis, endoscopic examination, and CT and MRI for 5 years after surgery; however, detect-ing the peritoneal recurrence of gastric carcinoma in the early phase is still very diffi cult. Recently, Mochiki et al. reported the usefulness of 18F-2-deoxy-2-fl uoro-d-glucose positron emission tomography (FDG-PET) for detecting the peritoneal recurrence of gastric carcino-ma.6 We did not perform FDG-PET in this patient because the imaging fi ndings suggested urinary tumor rather than gastric cancer recurrence. The correct diag-nosis of peritoneal recurrence is very important because it is usually unresectable and must be treated chemotherapeutically.

Mucins are heavily glycosylated glycoproteins with a protein backbone, called apomucin. To date, 12 types of apomucin (MUC1 to 12) have been identifi ed,7,8 and the cell type specifi city of mucin in non-neoplastic con-ditions has been determined as follows: M1 (45M1) for gastric foveolar cells;9,10 MUC6 for gastric pyloric glan-dular cells, fundic mucous neck cells, and Brunner gland cells;11,12 and MUC2 for an intestinal marker of goblet cells and their precursor cells.13,14 M1 and MUC6 are generally classifi ed as the gastric phenotype and MUC2, as the intestinal phenotype. These mucins have been used to study the development and progression of gastric carcinoma.12,15,16 The diagnosis in this case was undifferentiated tubular adenocarcinoma, consisting of both gastric and intestinal phenotypes. This suggests that the mucin phenotypic expression is useful for in-vestigating the development of gastric carcinoma and the origin of gastric cancer metastasis.

According to recent reports, undifferentiated gastric carcinoma expressing gastric and intestinal phenotypes is more invasive and metastatic than other phenotypic undifferentiated gastric carcinomas.17,18 However, to our knowledge, a correlation between the mucin phenotype of undifferentiated gastric carcinoma and peritoneal recurrence has never been investigated. Identifying the risk factors for peritoneal recurrence after gastric carcinoma surgery is important. Several authors have reported factors predictive of peritoneal recurrences, such as histological type,3,19 serosal invasion,3,20 and lymph node involvement;20,21 a biological marker of peritoneal recurrence of gastric carcinoma has not been found. Thus, identifying the mucin phenotype as a pre-dictive factor of peritoneal recurrence after curative surgery may be of great clinical importance. Further study on the correlation between the mucin phenotype of gastric carcinoma and peritoneal recurrence is war-

ranted. In summary, we reported a rare case of perito-neal recurrence of gastric carcinoma detected 12 years after curative surgery, the diagnosis of which was con-fi rmed by the mucin phenotype.

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