Reovirus inhibits the peritoneal dissemination of pancreatic cancer cells in an immunocompetent animal model.

The prognosis of pancreatic cancer with peritoneal dissemination has not improved. The aim of this study was to clarify whether oncolytic reovirus is effective against the peritoneal dissemination of pancreatic cancer in an immunocompetent animal model. The hamster pancreatic cancer cells HaP-T1 were inoculated into the peritoneal cavity of the hamster and reovirus (1x10(8) plaque-forming units) was administered into the peritoneal cavity on days 1, 3, 5 and 7 after HaP-T1 inoculations. The number and weight of the disseminated nodules in each group were recorded. Reovirus protein in the disseminated nodules was examined by immunohistochemical staining. The tumor volumes of peritoneal dissemination in the treatment group were significantly less than those in the control group (p<0.05). In addition, the amount of ascites was decreased in the treatment group in comparison to the control group. Immunohistochemical examination revealed that reovirus replication was seen only in the disseminated nodules but not in surrounding normal tissues. There were no serious side effects observed in this study. These data suggested that intraperitoneal administration of reovirus might be an effective form of oncolytic viral therapy for peritoneal dissemination of pancreatic cancer.

Groove pancreatic carcinoma.

The groove area is localized between the head of the pancreas, the duodenum, and the common bile duct. Differentiating of groove pancreatitis from pancreatic carcinoma is often difficult. Herein, we report a 54-year-old woman with groove pancreatic adenocarcinoma presenting epigastralgia, jaundice, and vomiting. The diagnosis was confirmed by computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic biopsy. The patient underwent pancreatoduodenectomy. Microscopically, well-differentiated adenocarcinoma was mainly located in Santorini's duct, but there was no invasion to the main pancreatic duct. The patient followed a satisfactory post operative course. She is doing well without recurrence 15 months after the surgery. It is very difficult to differentiate groove pancreatic carcinoma from groove pancreatitis. To avoid unnecessary surgical treatment, endoscopic biopsy and observation of the duodenum are useful for diagnosis. However, keeping in mind the differential diagnosis of pancreatic head carcinoma is necessary.

Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes.

BACKGROUND: The infiltration of lymphocytes in tumor tissue has been associated with a good prognosis for patients with hepatocellular carcinoma (HCC). The purpose of the present study was to estimate the correlation between mRNA expression of chemokines and tumor-infiltrating lymphocytes in HCC. METHODS: A total of 44 HCC were examined. Immunohistochemical staining was performed using antibodies to CD4, CD8, CD68, and L-26. The mRNA expression of each chemokine was investigated: regulated upon activation normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), epithelial-derived neutrophil attractant-78 (ENA78), interferon-inducible protein-10 (IP-10), monokine induced by interferon-gamma (Mig), and interferon-gamma in HCC were quantified via a real-time polymerase chain reaction assay. Chemokine proteins of Mig and IP-10 were examined by immunohistochemistry. RESULTS: The mean number of infiltrating lymphocytes in HCC was 136.9 +/- 32.9/0.25 mm2. Of these infiltrating lymphocytes, CD8-positive T lymphocytes were those predominantly seen around the tumor cells. The mean mRNA expression (copies/10(3) glyceraldehyde-3-phosphate dehydrogenase [GAPDH] mRNA) of the following chemokines was determined to be follows: 3.0 +/- 1.9 copies/10(3) GAPDH mRNA, RANTES; 9.2 +/- 4.9 copies/10(3) GAPDH mRNA, IL-8; 44.6 +/- 24.4 copies/10(3) GAPDH mRNA, ENA78; 215.7 +/- 93.9 copies/10(3) GAPDH mRNA, IP-10; 77.3 +/- 38.5 copies/10(3) GAPDH mRNA, Mig; and 1.7 +/- 0.4 copies/10(3) GAPDH mRNA, interferon-gamma. Significant close correlations were observed between the number of infiltrating lymphocytes in these HCC and the expression of Mig and IP-10 mRNA. In the immunostaining, expression of Mig and IP-10 proteins was found only in the HCC cells in the high-infiltration group. CONCLUSIONS: Some chemokines induced by interferon-gamma, such as Mig and IP-10, may promote lymphocyte recruitment to HCC and may thus play important roles in cancer immunology.

Safety and efficacy of laparoscopic distal pancreatectomy for the treatment of pancreatic disease.

BACKGROUND/PURPOSE: There are a few reports of laparoscopic distal pancreatectomy in the literature. We describe our experience with laparoscopic distal pancreatectomy and evaluate the safety and efficacy of the procedure in light of other reported findings. METHODS: A retrospective study was performed of all patients who underwent laparoscopic distal pancreatectomy between April 1996 and December 2002 at Oita University Faculty of Medicine. RESULTS: Laparoscopic distal pancreatectomy was attempted in seven patients (three men and four women) with a mean age of 65 years. One patient was converted to open surgery, and two patients required a hand-assistance procedure. There were no complications in any patients. Median operation time for all seven patients was 300 min, and median blood loss was 330 ml. Median postoperative hospital stay was 12 days (range, 7 to 21 days). CONCLUSIONS: Our limited results, together with reported outcomes, suggest that laparoscopic distal pancreatectomy is safe and effective for selected patients. The potential advantages of this procedure include reduced morbidity and reduced hospital stay.

Consensus interferon enhances the anti-proliferative effect of 5-fluorouracil on human hepatoma cells via downregulation of dihydropyrimidine dehydrogenase expression.

BACKGROUND/AIMS: The effectiveness of 5-fluorouracil (5-FU) treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate whether interferon (IFN)-alpha influences expression of 5-FU catabolic or target-related enzymes in human hepatoma cells. METHODS: HepG2 cells were treated with 0, 0.15, 1.5, 15, and 150 ng/ml of consensus interferon (C-IFN). Expression of mRNAs encoding dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase, and thymidylate synthase was examined by reverse transcription-polymerase chain reaction before and after C-IFN treatment. To determine the effect of pretreatment with C-IFN on 5-FU+C-IFN combination therapy, we performed WST-1 cell proliferation assays. RESULTS: A significant reduction in the level of DPD mRNA was observed when HepG2 cells were pretreated with C-IFN (P<0.05). This reduction occurred in a time-dependent manner. Cell proliferation was reduced most significantly when HepG2 cells were treated with 5-FU and C-IFN. Furthermore, when cells were pretreated with C-IFN for 3 days, the anti-proliferative effect of 5-FU+C-IFN combination therapy was augmented significantly (P<0.05). CONCLUSIONS: C-IFN likely improves the anti-tumor effect of 5-FU via downregulation of DPD enzyme in hepatoma cells. Pretreatment with C-IFN may increase the anti-cancer effect of 5-FU+C-IFN combination therapy.

Malignant serous cystic neoplasm of the pancreas: report of a case and review of the literature.

BACKGROUND: In general, serous cystic neoplasms of the pancreas are thought to be benign. Malignant serous cystic neoplasm of the pancreas is a rare clinical entity. CASE REPORT: We report the case of an 87-year-old woman with a serous microcystic neoplasm in the tail of the pancreas that behaved in a malignant fashion. The neoplasm had also invaded the colonic mesentery and splenic hilum. The pancreatic lesion was diagnosed as a large malignant serous cystic neoplasm, and the patient underwent distal pancreatectomy with splenectomy and segmental colectomy. The resected specimen contained a large tumor, 12 x 9 x 8 cm, which occupied the body and tail of the pancreas. Histologically, the tumor was indistinguishable from serous cystadenoma. However, the tumor had invaded surrounding tissues including the splenic vein, and there were splenic invasion and a regional lymph node metastasis. The postoperative course was uneventful. DISCUSSION: There are few reported cases of malignant serous cystic neoplasm, in which malignancy was histologically confirmed in the resected specimen. There are no reports of a negative outcome with complete resection of the tumor. Surgical treatment should be considered for serous cystic neoplasms, especially large ones, because of the malignant potential.

Microsatellite distribution and indication for locoregional therapy in small hepatocellular carcinoma.

BACKGROUND: Intrahepatic disease recurrence is observed frequently after locoregional therapies for patients with hepatocellular carcinoma (HCC). However, the indication for locoregional therapy is still unclear. To clarify the indication for locoregional therapy for small HCC tumors, the authors measured the distance of microsatellites from the main tumor and analyzed the relation between this distance and clinicopathologic factors. METHODS: The authors retrospectively analyzed 100 patients with small HCC tumors ( 5 mm) and clinicopathologic factors, as well as overall and disease-free survival rates after hepatectomy. RESULTS: Of the 100 patients, 46 had microsatellites with a mean distance of 9.9 mm (median, 5.0 mm). Of the clinicopathologic factors investigated, tumor grade and preoperative alpha-fetoprotein level significantly correlated with the presence of a microsatellite. Tumor size and distance to the microsatellite were significantly correlated. All but 1 tumor associated with a microsatellite distance > 5 mm was a high-grade tumor > 25 mm in greatest dimension. The overall survival rate of patients with a microsatellite distance of > 5 mm was lower than that of patients with a microsatellite distance < 5 mm. CONCLUSIONS: Locoregional therapy, including limited resection and ablation therapies, was appropriate for patients with low-grade HCC tumors or with tumors < 25 mm in diameter.

Factors influencing recurrence after surgical treatment for T2 gallbladder carcinoma.

BACKGROUND/AIMS: The overall outcome of T2 gallbladder carcinoma has not been favorable, although there is a modest hope for long-term survival after radical resection. The aim of this study was to examine factors influencing postoperative disease-free survival of patients with T2 gallbladder carcinoma to clarify optimal treatment. METHODOLOGY: Of 53 patients with gallbladder carcinoma who had undergone surgical resection from 1985 to 2000, 22 had T2 carcinoma histologically proved. The significance of variables for disease-free survival was examined retrospectively by the Kaplan-Meier method and the log-rank test. RESULTS: There were 16 patients with stage II (T2N0M0), 6 with stage III (T2N1M0) disease. Eleven patients were treated by extended cholecystectomy with resection of the extrahepatic bile duct, 10 patients underwent extended cholecystectomy without resection of the extrahepatic bile duct, and 1 patient underwent cholecystectomy. All patients underwent lymph node dissection in the hepatoduodenal ligament, below the pancreatic head, and along the common hepatic artery. Lymph node metastasis was present in 6 patients. Lymphatic, venous, and perineural invasions were found in 9, 4, and 4 patients, respectively. The absence of lymphatic invasion was a significant factor related to good postoperative disease-free survival (5-year disease-free survival rate, 88.9% vs. 31.3% in the presence of lymphatic invasion). Lymph node, venous, or perineural invasion, and surgical procedure were not significant factors to good postoperative disease-free survival. CONCLUSIONS: For patients with T2 gallbladder carcinoma, the presence of lymphatic invasion is an unfavorable prognostic indicator that calls for additional treatment after radical surgery.

[mRNA expression of chemokine receptors in hepatic and pancreatic tumor cell lines].

Chemokines represent a large family of polypeptide signaling molecules that are notable for their role in chemotaxis, leukocyte homing, and directional migration. Recent observations have indicated that the expression of chemokine receptors on cancer cells may play a role in tumor progression and metastasis. In this study, the expression of mRNA for chemokine receptors in various human tumor cell lines was analyzed by multiplex-polymerase chain reaction (M-PCR). Strong expression of CCR6 mRNA in 3 of 3 hepatoma cell lines was observed. In the 3 pancreatic cancer cell lines, no specific expression of chemokine receptors was observed. Raji (lymphoma cell line) strongly expressed CCR7 and CXCR4. We further investigated CCR6 mRNA expression in these cell lines by real-time quantitative-PCR. Similar results were obtained by both the PCR methods. Because human liver constitutively express liver and activation-regulated chemokine (specific ligand for CCR6), hepatoma cells may selectively root and spread in the liver. Strong CCR7 and CXCR4 expressions in the lymphoma cell may explain the organ specificity of lymphoma for lymphoid organs as well. These findings probably indicate that some cancer cells have organ specificity via expression of chemokine receptors.

Laparoscopic resection for nonfunctioning small glucagon-producing tumor: report of a case and review of the literature.

Glucagonoma is a relatively rare type of pancreatic endocrine tumor, and is often well-developed and malignant at detection. We report a case of nonfunctioning small glucagon-producing tumor that was successfully resected by laparoscopic surgery. A 63-year-old woman was admitted to our hospital for further examination of a pancreatic tumor that had been detected incidentally. Hematological data and hormone concentrations were within normal ranges. Abdominal ultrasonography and computed tomography showed a small mass in the body of the pancreas. Laparoscopic distal pancreatectomy was done. Macroscopically, the resected tumor was a yellowish-white, solid mass measuring 8 x 8 x 7 mm. The tumor cells showed positive immunohistochemical staining for chromogranin A and glucagon. The postoperative course was uneventful. To the best of our knowledge, this is the first report of laparoscopic surgery for a nonfunctioning small glucagon-producing tumor. Because of recent improvements in laparoscopic surgery technique, use of this approach for resection of pancreatic benign small endocrine tumors will likely increase in the future.

Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: To determine the optimal management of the intraductal papillary mucinous neoplasms (IPMNs) according to the morphologic type based on distinguishing between benign and malignant diseases. BACKGROUNDS: IPMNs are increasingly recognized clinicopathologic entity. Extended pancreatic resection with radical lymph node dissection has been recommended for treatment. STUDY: A retrospective clinicopathologic study was carried out of the 57 cases with IPMNs who were treated between 1985 and 2001. Forty-three patients with IPMNs underwent resection, and 14 patients with small IPMNs were observed without resection. RESULTS: Among the 43 resected IPMNs, 25 were benign and 18 were malignant. Malignant tumors were significantly greater in diameter than benign tumors (52.9 vs. 30.2 mm, P< 0.05). All main duct type tumors with mural nodules were malignant. All branch duct type tumors less than 30 mm in diameter and without mural nodules were benign. Twelve branch duct type IPMNs size less than 30 mm were not resected and have not progressed. CONCLUSION: These results suggest that the branch duct type IPMNs less than 30 mm and without mural nodules is benign and might be treatable with limited resection or careful observation.