[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

Rationale of Treatment for Peritoneal Metastasis.

In 1998, the Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment referred to as comprehensive treatment(COMPT). COMPT involves the complete removal of macroscopic tumors(cytoreductive surgery: CRS) and eradication of micrometastasis(MM)with neoadjuvant chemotherapy(NAC)plus intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC). This article provides a rationale for curative COMPT. Additionally, based on our experience, the selection criteria for treatment will be clarified. RATIONALE: The residual cancer cell burden is lowest immediately following CRS, and intraoperative HIPEC plays a crucial role in the treatment of patients with peritoneal surface malignancy (PSM). COMPT will fail if the number of the MM remaining after CRS exceeds the limit of complete eradication by intraoperative HIPEC(threshold). However, if the residual number of MM is less than the threshold, patients will respond positively to treatment. PATIENTS AND METHODS: To validate the direct effect of HIPEC, laparoscopic HIPEC(LHIPEC)was performed, and changes in the peritoneal cancer index(PCI)were then evaluated. Complete cytoreduction and HIPEC carried out based on the concept of COMPT was performed in 171 gastric cancer(GC)patients with PCI≤12, 183 colorectal cancer(CRC)with PCI≤21 and 460 pseudomyxoma peritonei(PMP)patients with PCI≤28. The postoperative survivals rates were then analyzed. RESULTS: After 1 cycle of LHIPEC, PCIs in GC and PMP were significantly reduced by 1.85 and 2.7 1 month after LHIPEC. However, PCI of CRC increased. Positive cytology at LHIPEC became negative in 57.6%, 42.9% and 60.9% of patients with GC, CRC and PMP, respectively. Median survival time(MST)for GC and CRC was 21.2 and 71.5 months, respectively MST of PMP was not reached. MST of PMP was not reached. Ten-year survival rates were 12.6%, 21.7% and 81.6%, respectively. Grade 5 complications for each disease were 0.8%, 1.0% and 1.1%, respectively. CONCLUSIONS: Complete cytoreductive surgery combined with intraoperative HIPEC may improve the long-term survival of patients with PSM who have PCIs less than the threshold levels, by keeping the mortality rates after CRS plus intraoperative HIPEC within acceptable levels.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience.

BACKGROUND: The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA). METHODS: A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC. RESULTS: Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS. CONCLUSION: The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report).

We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient's performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.

[A case of response to panitumumab as third-line chemotherapy for multiple liver metastases and portal venal tumor embolus of rectal cancer].

A 64-year-old man who underwent rectal amputation for rectal cancer was diagnosed with multiple liver metastases and tumor embolus in the portal vein 6 months after operation. Though the patient underwent chemotherapy, mFOLFOX6, and bevacizumab+FOLFIRI, liver metastases were diagnosed as progressive disease (PD). After panitumumab+FOLFIRI was administered for three months as third-line chemotherapy, the tumor embolus completely disappeared, and liver metastases became cytoreductive on CT. The patient was judged to have achieved a partial response (PR). This case indicated that panitumumab was effective as third-line chemotherapy for unresectable recurrent rectal cancer.

[Local resection of a gangliocytic paraganglioma near the papilla of Vater].

A 69-year-old man was admitted to our hospital with epigastric discomfort. Upper gastrointestinal endoscopy showed a submucosal tumor near the papilla of Vater. Abdominal CT and MRI showed a small, well-enhanced tumor. Endoscopic tumor biopsy was performed before the operation, but pathologic findings showed normal duodenal musosa. Nevertheless, since malignancy could not be ruled out, we resected the tumor with the sphincter of the papilla of Vater, followed by plasty of the orifice for the common bile duct and main pancreatic duct. We identified 3 parts with tumor cells; epithelioid cells, spindle cells, and ganglion-like cells. The tumor was diagnosed as gangliocytic paraganglioma of the duodenum. Treatment by resecting the tumor with the sphincter of the papilla of Vater, followed by the plasty of the orifice for the common bile duct and main pancreatic duct, was selected considering the patient's safety and to achieve radical cure.

[A case of stomach metastasis of pleomorphic carcinoma of the lung with hypercalcemia].

A 69-year-old man was admitted with fatigue, anorexia, and slight fever. Gastroscopy showed a tumor in the stomach, and biopsy revealed a poorly differentiated adenocarcinoma. CT scan revealed a tumor of the stomach, a tumor in the lower lobe of the right lung, and multiple tumors in the liver. Moreover, he was drowsy, probably caused by severe hypocalcemia thought to be caused by parathyroid hormone related protein. We treated him with S-1, but the gastric tumors progressed rapidly and massive pleural effusion developed. He died on the 16th day after admission. At autopsy, the histology of the lung tumor was found to be pleomorphic carcinoma, and that had metastasized to the stomach, the liver, and other abdominal organs. We treated a rare case of pleomorphic carcinoma with hypercalcemia that was discovered due to gastric metastasis.

The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5'-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

RIN1-Ras-ERK pathway plays an important role in carcinogenesis in colon cancer cell line LoVo.

The RIN1 protein has SH2, three domains, and H-Ras binding domains; thus, it is presumed to be an important molecule in an intracellular signaling pathway. We examined the effect of the introduction of a membrane protein-encoding, mutated (S351A)RIN1 gene into a colon cancer. In the LoVo colon cancer cell line, endogenous RIN1 protein was strongly expressed in the cytoplasmic fraction, and the RIN1 protein in the cytoplasmic fraction was strongly bound to the 14-3-3 protein. In the mutated (S351A)RIN1-transfected LoVo cells, the mutated (S351A)RIN1 protein was identified in the cell membrane, and was bound to HRas protein. Also, in vitro the proliferative capacity of the mutated (S351A)RIN1-transfected LoVo cells was significantly inhibited, compared with that of their empty vector-transfected counterparts. In the mutated (S351A)RIN1-transfected LoVo cells, the phosphorylation of ERK1/2 proteins downstream of the H-Ras molecule was inhibited, compared with the counterparts. This study is the first to show that the localization of RIN1 protein plays an important role in the carcinogenesis in colon cancer cells LoVo (i.e., signal transduction in the Ras-ERK pathway).

Ruptured mucinous cystic neoplasm with an associated invasive carcinoma of pancreatic head in a pregnant woman: report of a case and review of literature.

Mucinous cystic neoplasm (MCN) of the pancreas is characterized by mucin-producing columnar epithelium and an ovarian-type stroma. It occurs almost exclusively in women and is almost always located in the pancreatic body or tail. Here, we report a case of large MCN located in the pancreatic head but not in the body nor tail in a 32-year-old pregnant woman, which was thought to have grown rapidly during pregnancy. It was ruptured at 34 weeks of gestation and the patient was admitted to the emergency department of the University of Fukui Hospital with an acute abdomen. Emergency cesarean section followed by pancreaticoduodenectomy was performed. The tumor consisted of many small cysts lined by a single-layer of mucinous epithelium with papillary growth and partial solid parts showing invasive growth and sarcomatoid changes, indicating mucinous cystic neoplasm with an associated invasive carcinoma (previously referred as mucinous cystadenocarcinoma). Thickened septa revealed ovarian-type stroma strongly positive for α-inhibin and partly positive for progesterone receptor immunohistochemically. We also review and discuss previous reports of MCNs including those with an associated invasive carcinoma in pregnant patients.

Atypical metastatic carcinoid of the uterine cervix and review of the literature.

Atypical carcinoid tumors of the uterine cervix represent rare neuroendocrine tumors and are highly aggressive, showing early lymphatic invasion and hematogenous distant metastases. Because of the small number of cases, there are currently no recommendations regarding treatment, and little is known about the response to chemotherapeutic agents. A 39-year-old woman was diagnosed with a primary atypical carcinoid of the uterine cervix with numerous metastases to the liver. After radical hysterectomy, she underwent hepatic arterial chemoembolization with streptozotocin and 5-fluorouracil. Complete response was achieved in numerous liver metastases. At the 2-year follow up of chemotherapy, the patient remains alive. Treatment for atypical carcinoid tumors remains elusive, however hepatic arterial chemoembolization with streptozotocin and 5-fluorouracil was effective in the present primary atypical carcinoid with liver metastases. A review of the previous reports is also presented.

The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI.

BACKGROUND: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). METHODS: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. RESULTS: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2-7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0-2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2-2.6) years. CONCLUSIONS: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.

The activation of Proteinase-Activated Receptor-1 (PAR1) mediates gastric cancer cell proliferation and invasion.

BACKGROUND: In addition to regulating platelet function, the G protein-coupled sub-family member Proteinase-activated receptor-1 (PAR1) has a proposed role in the development of various cancers, but its exact role and mechanism of action in the invasion, metastasis, and proliferation process in gastric cancer have yet to be completely elucidated. Here, we analyzed the relationship between PAR1 activation, proliferation, invasion, and the signaling pathways downstream of PAR1 activation in gastric cancer. METHODS: We established a PAR1 stably transfected MKN45 human gastric cancer cell line (MKN45/PAR1) and performed cell proliferation and invasion assays employing this cell line and MKN28 cell line exposed to PAR1 agonists (alpha-thrombin and TFLLR-NH2). We also quantified NF-kappaB activation by electrophoretic mobility shift assay (EMSA) and the level of Tenascin-C (TN-C) expression in conditioned medium by ELISA of MKN45/PAR1 following administration of alpha-thrombin. A high molecular weight concentrate was derived from the resultant conditioned medium and subsequent cultures of MKN45/PAR1 and MKN28 were exposed to the resultant concentrate either in the presence or absence of TN-C-neutralizing antibody. Lysates of these subsequent cells were probed to quantify levels of phospholyrated Epidermal Growth Factor Receptor (EGFR). RESULT: PAR1 in both PAR1/MKN45 and MKN28 was activated by PAR1 agonists, resulting in cell proliferation and matrigel invasion. We have shown that activation of NF-kappaB and EGFR phosphorylation initially were triggered by the activation of PAR1 with alpha-thrombin. Quantitative PCR and Western blot assay revealed up-regulation of mRNA and protein expression of NF-kappaB target genes, especially TN-C, a potential EGFR activator. The suppressed level of phosphorylated EGFR, observed in cells exposed to concentrate of conditioned medium in the presence of TN-C-neutralizing antibody, identifies TN-C as a putative autocrine stimulatory factor of EGFR possibly involved in the sustained PAR1 activation responses observed. CONCLUSION: Our data indicate that in gastric carcinoma cells, PAR1 activation can trigger an array of responses that would promote tumor cell growth and invasion. Over expression of NF-kappaB, EGFR, and TN-C, are among the effects of PAR1 activation and TN-C induces EGFR activation in an autocrine manner. Thus, PAR1 is a potentially important therapeutic target for the treatment of gastric cancer.

Survivin-3B gene decreases the invasion-inhibitory effect of colon cancer cells with 5-fluorouracil.

The expression of survivin molecules has been confirmed in many types of cancer cells, including colon cancer cells, and they are considered important antiapoptotic molecules. Recent studies have revealed the existence of different splicing forms of survivin molecules; however, no studies have examined their expression in gastrointestinal cancers. In 2004, we reported the existence of the survivin-3B gene, a novel splice variant of survivin. In this study, we investigated the relationship between human colon cancer and our recently cloned survivin-3B gene with a coding region of 594 bp. In the first examination, survivin-3B expression was analyzed by RT-PCR in human colon cancer and adjacent normal mucosal tissues. The associations of its expression status with clinicopathological parameters and the prognosis were also examined. Survivin-3B mRNA expression was observed in 37 (46.3%) of 80 primary colon cancers, but not in the adjacent normal colonic mucosal tissue. The rate of survivin-3B gene expression was significantly higher in colon cancer with serosal invasion. The 5-year survival rate of patients with survivin-3B gene-positive primary colon cancer was significantly poorer, at 48.7%, than that (75.4%) of survivin-3B gene-negative patients. In the second examination, after the introduction of the survivin-3B gene into cells of the colon cancer cell line DLD-1, 5-fluorouracil-induced changes in their invasive capacity was examined. The invasion-inhibitory effect of 5-fluorouracil on survivin-3B gene-transfected DLD-1 cells was significantly lower than their empty vector gene-transfected counterparts. We speculate that survivin-3B expression in colon cancer is an important factor involved in the invasive capacity of cancer cells in the presence of anticancer drug.

The effectiveness of transverse coloplasty in patients with ultra-lower rectal cancer.

Rectal cancer accounts for 40% of colon cancer, and postoperative defecatory function is considered to markedly affect the patients' quality of life. We performed transverse coloplasty in 33 patients with rectal cancer who had undergone an anal function preservation operation in which the anastomotic site was within 1 cm of the dentate line (ultra-low anterior resection) and evaluated its effectiveness in controlling the patients' defecatory function. The average daily defecation frequency 1, 6, and 12 months postoperatively was 7.8, 5, and 3.6 times daily following straight colorectal reconstruction (the anastomotic site was more than 5 cm from the dentate line) and 7.5, 3.5, and 2.4 times daily following transverse coloplasty, respectively. Concerning postoperative complications, anastomotic leakage, soiling, and constipation were observed in 1, 1, and 1 cases, respectively. Transverse coloplasty can be performed in a short time, and it is considered a safe and useful method to manage defecatory

Multicystic peritoneal mesothelioma treated with complete cytoreductive surgery, peritonectomy and hyperthermic intra-peritoneal chemotherapy-A case report.

BACKGROUND: Multicystic Peritoneal mesothelioma is a rare and distinct variety of peritoneal mesothelioma with borderline malignant potential. Conventional Tumor bulking has been associated with recurrence of 45-50 %. Hence a comprehensive treatment with Complete cytoreductive surgery with involved field peritonectomy (CRS) and Hyperthermic Intra-peritoneal chemotherapy (HIPEC) is being increasingly adopted for MCPM. CASE PRESENTATION: A 47 year old lady evaluated for peri-menopausal disturbance was diagnosed to have a multicystic lesion in the pelvis. With a preoperative suspicion of diagnosis of pseudomyxoma peritonei, CRS with HIPEC was planned. On exploration a diffuse multicystic mass was found in omentum and pouch of douglas with typical morphological features of MCPM. Complete cytoreduction was achieved with anterolateral and sub-diaphragmatic peritonectomy, omentectomy and panhystrectomy. HIPEC was performed with cisplatin 50 mg/m2 for 40 min. Pathological examination revealed MCPM of omentum and uterine surface with focal clusters of mesothelial proliferation. However there was low proliferative activity 1-2 %. DISCUSSION: MCPM presents with wide spread peritoneal spread but with relative sparing of visceral invasion. Literature review suggests the disease spread is similar to PMP and treatment with CCRS and HIPEC has yielded long term survivals in MCPM. CONCLUSIONS: This patient with voluminous disease burden in abdomen required surgical management and HIPEC for her condition. Whether CCRS alone without HIPEC can be an alternative for limited disease will be interesting research for future clinical reports.

Complete pathological response of high grade appendicular neoplasm induced Pseudomyxoma Peritonei (PMP) after neoadjuvant intra-peritoneal chemotherapy: A case report.

BACKGROUND: Pseudomyxoma Peritonei (PMP) is clinical syndrome characterized by mucinous ascites and gelatinous tumor deposits in the peritoneal cavity. Complete Cytoreduction and Hyperthermic intraperitoneal perfusion is the contemporary standard of care for PMP. A novel treatment approach with Intraperitoneal (IP) chemotherapy has been developed for patients with disease not amenable for complete cytoreduction. CASE PRESENTATION: A 72 year old lady had PMP arising from high grade appendicular neoplasm with extensive intraabdominal spread not suitable for complete cytoreduction (PCI -19; multiple mesenteric deposits). Novel approach with tumor debulking and Neoadjuvant Intraperitoneal chemotherapy was done. Excellent clinical response was obtained after 12 sessions of IP chemotherapy with cisplatin and docetaxel. Subsequently she underwent Complete cytoreductive surgery with peritonectomy and Hyperthermic intraperitoneal chemotherapy. Pathological examination of surgical specimens revealed only acellular mucin with no viable tumor cells indicating a complete response. DISCUSSION: Complete pathological response after IP chemotherapy in extensive PMP is rare. Nevertheless the results are encouraging as the systemic therapy hasn't yielded successful outcomes. IP chemotherapy has the advantage of achieving high intraperitoneal concentrations and down staging the tumor spread. CONCLUSION: Neoadjuvant Intra-peritoneal chemotherapy is a promising neoadjuvant strategy in patients who are poor candidates for upfront resection due to extent of disease or performance status, perhaps better than systemic therapy.

Cloning of a novel splicing variant of RIN1 and its expression in gastric and colon cancer.

The regular RIN1 gene is a molecule located on chromosome 1lq13.2, and contains a coding region of 2352 bp with a 3' domain that binds to H-Ras protein, suggesting that it is an important molecule in the intracellular signaling pathway. In this study, we confirmed the existence of a novel form of the RIN1 gene with a different splicing pattern, successfully cloned it, and examined its expression in gastric and colon cancer cell lines. A 612-bp band (the RIN1 variant mRNA) was identified in the RT-PCR product from the colon cancer cell line Colo320D. (A 2352-bp band representing the regular RIN1 gene in HT29 cell line.) The 612-bp band was sequenced and compared with that of the regular RIN1 gene. As a result, the 612-bp product was found to contain a tyrosine phosphorylation site on the 5' side and Ras and 14-3-3 binding domains on the 3' side, indicating that it is a product with a different splicing pattern. The expression of the RIN1 variant mRNA was observed in two of six gastric cancer cell lines and four of five colon cancer cell lines. We identified a novel RIN1 gene with a splicing pattern different from that of the regular RIN1 gene. Comparison of both genes revealed that the novel RIN1 products had a structure conserving the Ras and 14-3-3 binding domains, but lacking two tyrosine phosphorylation sites. Novel RIN1 variant protein was expressed primarily in the cytoplasm and no expression in the cell membrane, and RIN1 variant protein was bound to 14-3-3 protein. In addition, the novel RIN1 mRNA was found to be expressed in gastric and colon cancer cell lines, suggesting that it is an important gene for the function of cancer cells.

Rat islet culture in serum-free medium containing silk protein sericin.

BACKGROUND: The development of islet cultures is desirable for successful clinical islet transplantation. Fetal bovine serum (FBS) has been used as a supplement in islet culture medium, but it may be an unsuitable supplement due recent animal health problems. We have evaluated the use of the silk protein, sericin, derived from Bombyx mori as a replacement for FBS in islet culture medium. METHODS: Twenty rat islets were cultured in medium containing either sericin or FBS, or no supplement, for 14 days, during which time viable islets were counted in order to evaluate islet survival. Insulin secretion was measured in vitro by static incubation on days 3 and 7. In vivo function of cultured islets was tested by syngeneic transplantation. The islets were evaluated histologically and immunohistochemically after culture and transplantation. RESULTS: Ninety-five percent of islets were viable after culture for 14 days in culture medium supplemented with either FBS or sericin, while no islets survived beyond 7 days in culture without supplement. No significant differences in stimulated insulin secretion were noted between two groups of islets grown on supplemented media. Following transplantation, islets cultured in FBS or sericin rapidly reversed hyperglycemia and maintained normal glycemic control. Histologically, islets cultured with sericin displayed a well-preserved structure and strong insulin staining before and after transplantation. CONCLUSION: Serum-free medium containing sericin appears to be useful for islet culture.

Biliopancreatic fistula and abscess formation in the bursa omentalis associated with intraductal papillary mucinous cancer of the pancreas.

We describe an unusual case of biliopancreatic fistula, free perforation, and subsequent abscess formation within the lesser peritoneal sac associated with intraductal papillary mucinous carcinoma (IPMC). A 71-year-old man presented with general fatigue and loss of appetite that had persisted for 1 month. Abdominal computed tomography (CT) revealed findings consistent with an intraductal papillary mucinous neoplasm (IPMN) of the pancreas, accompanied by abscess formation in the bursa omentalis. Gastrointestinal fiberscopy revealed a swollen papilla of Vater expanded by sticky mucus, and a communication between the pancreatic duct and bile duct was demonstrated by the injection of indigo carmine solution into the pancreatic duct. Percutaneous transhepatic abscess drainage (PTAD) was performed on the day of admission. After this procedure, the patient was managed for 1 month and supported nutritionally with glycemic control for diabetes mellitus. After admission, the patient had an episode of obstructive jaundice that was treated by retrograde biliary drainage. Pancreaticoduodenectomy with lymph node dissection was then performed. Pathological examination revealed IPMN with patchy, scattered carcinoma of the pancreatic head and uncinate process with the formation of a biliopancreatic fistula. Bile duct epithelium in the area of the biliopancreatic fistula demonstrated atypical papillary epithelium suggestive of tumor invasion.