Pseudomyxoma peritonei accompanied by intraductal papillary mucinous neoplasm of the pancreas.

We describe a case of pseudomyxoma peritonei (PMP) successfully managed with intraperitoneal hyperthermic chemoperfusion. This case is unique due to the concurrent presence of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The patient presented with abdominal fullness. Abdominal computed tomography revealed massive ascites, thickened peritoneum, and a cystic lesion of the pancreas. Cytological examination of ascitic fluid sample showed mucin-rich atypical cells. Endoscopic retrograde pancreatography revealed a cystic lesion with the defect probably due to mural nodule and mucin, communicating with the pancreatic duct. At exploratory laparotomy, massive ascites and multiple nodules were identified within the peritoneal cavity. No primary tumour, including mucinous neoplasm of the appendix, was found. Histopathological examination of the omentum showed mucinous adenocarcinoma in pools of mucoid material, consistent with PMP. The relation between PMP and IPMN of the pancreas was possible, but not conclusive. The patient received intraperitoneal perfusion of saline heated to 42 degrees C containing cisplatin, etoposide, and mitomycin C, followed by 24 courses of postoperative chemotherapy with gemcitabine. The patient remains in good general condition with no signs of progression of PMP for 2 years, but with a gradual and progressive enlargement of the pancreatic cystic lesion.

Tumor dihydropyrimidine dehydrogenase expression is a useful marker in adjuvant therapy with oral fluoropyrimidines after curative resection of colorectal cancer.

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluoropyrimidine (5-FU) catabolism. We examined whether tumor DPD expression is an effective marker in adjuvant therapy with oral fluoropyrimidines after curative resection of colorectal cancer. METHODS: We studied 89 patients with stage II-III colorectal cancers who had undergone curative resections and received oral 5-FU-based adjuvant chemotherapy. The levels of DPD expression in tumor and normal colonic mucosa were measured by an enzyme-linked immunosorbent assay. In 53 tumor samples, DPD enzymatic activity was also analyzed in order to evaluate the relationship between DPD expression and enzymatic activity. RESULTS: DPD expression significantly correlated with DPD enzymatic activity in these 53 tumors ( r=0.56; P<0.001). DPD expression in the tumors was significantly lower than in normal mucosa (47.1+/-30.8 and 56.4+/-18.5 U/mg protein, respectively; P<0.05). We designated the cut-off value of tumor DPD as its median value (46.0 U/mg protein). Patients with low DPD expression had longer disease-free intervals than those with high DPD expression according to univariate analysis ( P=0.026). In a multivariate analysis, low DPD expression was significantly and independently associated with better survival. CONCLUSIONS: Tumor DPD expression is a useful marker for use with adjuvant chemotherapy with oral fluoropyrimidines after curative resection of colorectal cancer.

Tumor dihydropyrimidine dehydrogenase in stage II and III colorectal cancer: low level expression is a beneficial marker in oral-adjuvant chemotherapy, but is also a predictor for poor prognosis in patients treated with curative surgery alone.

The aim of this study was to evaluate the prognostic significance of tumor dihydropyrimidine dehydroganase (DPD) in curatively resected colorectal cancer patients who received or did not receive oral 5-FU based-adjuvant chemotherapy. Among 182 patients with stage II-III colorectal cancers, 89 patients (adjuvant chemotherapy group) received oral 5-FU based-adjuvant chemotherapy, and 93 patients (surgery alone group) did not receive 5-FU. DPD expressions in the tumors and in the normal colonic mucosa were measured by enzyme-linked immunosorbent assays. The mean DPD expression of the tumors was significantly lower than that of the normal mucosa (54.4 +/- 40.4 versus 72.3 +/- 23.3 Unit/mg protein, P < 0.01). For survival analyses, we designated the cut-off value of tumor DPD as its median value (46.3). In the adjuvant chemotherapy group, high tumor DPD levels were associated with poor survival (HR, 5.24; P = 0.03). In the surgery alone group, high tumor DPD levels were associated with better survival (HR, 0.32; P = 0.02). In conclusion, tumor DPD level is an efficacious marker in oral 5-FU based-adjuvant chemotherapy for colorectal cancer; however, low tumor DPD predicts reduced survival in patients treated with curative surgery alone.

Polymorphism in the thymidylate synthase promoter enhancer region is not an efficacious marker for tumor sensitivity to 5-fluorouracil-based oral adjuvant chemotherapy in colorectal cancer.

Thymidylate synthase (TS) is the target enzyme of 5-fluoropyrimidines. The TS gene promoter enhancer region (TSER) possesses tandem, repeated, regulatory sequences that are polymorphic in humans. This polymorphism has been reported to influence TS expression in vitro and in vivo. In this study, we assessed whether or not the TSER genotype is an efficacious marker for tumor sensitivity to 5-fluorouracil (5-FU)-based oral adjuvant chemotherapy for colorectal cancer. One hundred and thirty-five Japanese patients who received curative resection and 5-FU-based oral adjuvant chemotherapy were studied. TSER genotypes of the tumors were analyzed by PCR. The numbers of repeated sequences of representative bands were determined by direct sequence. The genotypes of two-/two-repeats (TSER 2/2), two-/three-repeats (TSER 2/3), three-/three-repeats (TSER 3/3), and three-/five-repeats (TSER 3/5) were found in 11 (8.1%), 32 (23.7%), 85 (63.0%), and 7 (5.2%) tumors, respectively. Patients were classified into two groups: TSER 2/2 or 2/3 group; and the TSER 3/3 group. The relationship between the TSER genotype group and disease-free intervals was analyzed by univariate and multivariate analyses. Five-year disease-free survivals of the TSER 2/2 or 2/3 group and the TSER 3/3 group were 77% and 75%, respectively (P = 0.89). Multivariate analysis revealed that stage was the only independent prognostic factor and that the TSER genotype did not have a prognostic significance (hazard ratio for TSER 3/3, 0.91; P = 0.84). In conclusion, TSER genotype is not an efficacious marker for tumor sensitivity to 5-FU-based oral adjuvant chemotherapy for Japanese colorectal cancer patients after curative resection.