Surgical Treatment for Biliary Carcinoma Arising After Pancreatoduodenectomy

The clinicopathological features and surgical treatment of biliary carcinoma around the major hepatic duct confluence arising after pancreatoduodenectomy (PD) due to initial bile duct carcinoma are described in three patients. Occurrence of biliary carcinoma more than 12 years after initial surgery and a histological finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma suggested metachronous incidence of biliary carcinoma after PD. Extended right hemihepatectomy with complete removal of the residual extrahepatic bile duct and segmental, resection of the jejunal loop were carried out safely without operative death or severe postoperative complications. Two patients died of tumor recurrence 6 months after surgery, and the remaining patient is currently living a normal life without evidence of recurrence 17 months after surgery. These surgical procedures are a therapeutic option in patients with biliary carcinoma around the major hepatic duct confluence arising after PD

Two Cases of Early Carcinoma of a Reconstructed Gastric Tube after Esophagectomy Treated Extendedly with Endoscopic Submucosal Dissection

We report two cases of gastric tube carcinoma (GTC) treated with endoscopic submucosal dissection (ESD) after esophagectomy. Case 1 was a 47-year-old woman who had received esophagectomy with reconstruction of the gastric tube (GT) for esophageal squamous cell carcinoma. Sixty-seven months later, endoscopy showed a carcinoma in the lower part of the GT. The removed tumor showed a 0-IIc lesion, 10 mm in diameter, diagnosed as a signet ring cell carcinoma limited to the mucosa. Case 2 was an 83-year-old woman who simultaneously underwent lower esophagectomy for basaloid-squamous cell carcinoma of the esophagus and colectomy for ascending colon carcinoma. Sixty-one months later, endoscopy showed a carcinoma in the middle part of the GT. The tumor removed by ESD showed a 0-IIa+IIc lesion, 50 mm in diameter, diagnosed as a moderately differentiated tubular adenocarcinoma limited to the mucosa. The clinicopathologic features of 48 Japanese cases, including Cases 1 and 2, with GTC were reviewed. An extended indication of endoscopic resection for gastric carcinoma was present in 12 (25%) including Cases 1 and 2. In conclusion, ESD may be safe for GTC; however, further investigations may be necessary to confirm the safety and curative potential of ESD for GTC.Article信州医学雑誌 59(2): 81-88(2011)departmental bulletin pape

Microinjection-Based RNA Interference Method in the Water Flea, Daphnia pulex and Daphnia magna

It is well known that most daphnid species have several attractive life history characteristics such as cyclical parthenogenesis, environmental sex determination, and predator-induced defense formation. Recent advances in high-throughput omics technologies make it easy to obtain a huge number of potential candidate factors involved in environmental stimuli-triggered phenotypic alterations. Furthermore, our group has developed a microinjection system to introduce foreign materials such as nucleotides and chemicals into the early-stage (one-cell stage) egg of Daphnia pulex and Daphnia magna. Consequently, we established a microinjection-based RNAi system that allows arbitrary gene functions to be investigated. However, this microinjection system does not seem to have pervaded in the daphnid research community due to its low throughput and high level of skills required. In this chapter, we review the microinjection method and its RNAi system in water fleas, D. pulex and D. magna, providing some technical tips and making challenging proposals for the development of novel high-throughput RNAi methods. Finally, we provide an overview of recently developed gene functional analysis methods such as overexpression and genome-editing systems

Additional Gastrectomy after Endoscopic Submucosal Dissection for Early Gastric Cancer Patients with Comorbidities

Purpose. We investigated the clinicopathologic features of early gastric cancer (EGC) patients who have undergone additional gastrectomy after endoscopic submucosal dissection (ESD) because of their comorbidities. Methods. Eighteen (7.1%) of 252 GC patients were gastrectomized after prior ESD. Reasons for further surgery, preoperative and postoperative problems, and the clinical outcome were determined. Results. The 18 patients had submucosal EGC and several co-morbidities. Other primary cancers were observed in 8 (44.4%). Histories of major abdominal operations were observed in 6 (33.3%). Fourteen patients (77.8%) hoped for endoscopic treatment. Due to additional gastrectomy, residual cancer was suspected in 10, and node metastasis was suspected in 11. A cancer remnant was histologically observed in one. Node metastasis was detected in 3 (16.7%). Small EGC was newly detected in 4. Consequently, additional gastrectomy was necessary for the one third. No patient showed GC recurrence. However, 9 (50%) had new diseases, and 4 (22.2%) died of other diseases. The overall survival after surgery in these patients with additional gastrectomy was poorer than those with routine gastrectomy for submucosal EGC (P = 0.0087). Conclusions. Additional gastrectomy was safely performed in EGC patients with co-morbidities. However, some issues, including presence of node metastasis and other death after surgery, remain

Emergency Operation for Non-Hodgkin Lymphoma of the Small Intestine

We report 5 cases of non-Hodgkin lymphoma of the small intestine (S-NHL) treated with emergency operation. These cases showed three reasons for emergency operation :［1］massive hemorrhage with shock before diagnosis of S-NHL (Case 1),［2］obstruction of the small intestine before and during chemotherapeutic treatment for S-NHL (Cases 2 and 3),and［3］spontaneous perforation with peritonitis before diagnosis of SNHL or iatrogenic perforation following chemotherapy (Cases 4 and 5).For tumor discovery,double-balloon endoscopy of the small intestine was employed in 3 cases.Three tumors were histologically diagnosed before treatment,while 2 were histopathologically diagnosed using the resected specimens after emergency operation. An advanced stage of NHL was frequently observed.No surgical mortality accurred.We always consider the possibility of emergency operation before, during, and after the diagnosis and treatment of patients with SNHL. Shinshu Med J 60 : 21-25, 2012Article信州医学雑誌 60(1): 21-25(2012)departmental bulletin pape

Transabdominal Preperitoneal Repair for Obturator Hernia

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第889号）・横山隆秀Background A laparoscopic surgical approach for obturator hernia (OH) repair is uncommon. The aim of the present study was to assess the effectiveness of laparoscopic transabdominal preperitoneal (TAPP) repair for OH. Methods From 2001 to May 2010, 659 patients with inguinal hernia underwent TAPP repair at in our institutes. Among these, the eight patients with OH were the subjects of this study. Results Three of the eight patients were diagnosed as having occult OH, and the other five were diagnosed preoperatively, by ultrasonography and/or computed tomography, as having strangulated OH. Bilateral OH was found in five patients (63%), and combined groin hernias, either unilaterally or bilaterally, were observed in seven patients (88%), all of whom had femoral hernia. Of the five patients with bowel obstruction at presentation, four were determined not to require resection after assessment of the intestinal viability by laparoscopy. There was one case of conversion to a two-stage hernia repair performed to avoid mesh contamination: addition of mini-laparotomy, followed by extraction of the gangrenous intestine for resection and anastomosis with simple peritoneal closure of the hernia defect in the first stage, and a Kugel hernia repair in the second stage. There was no incidence of postoperative morbidity, mortality, or recurrence. Conclusions Because TAPP allows assessment of not only the entire groin area bilaterally but also simultaneous assessment of the viability of the incarcerated intestine with a minimum abdominal wall defect, we believe that it is an adequate approach to the treatment of both occult and acutely incarcerated OH. Two-stage hernia repair is technically feasible in patients requiring resection of the incarcerated intestine.ArticleWORLD JOURNAL OF SURGERY. 35(10):2323-2327 (2011)journal articl

Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells

信州大学博士（医学）・学位論文・平成24年6月11日授与（甲第929号）・桂安萍Background: Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling. Methods: We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling. Results: Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), were also observed in RBE cells. Conclusion: In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular-targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of cholangiocarcinoma.ArticleBMC Cancer. 2012, 12:179journal articl

Relationships of obesity and diabetes mellitus to other primary cancers in surgically treated gastric cancer patients

AbstractBackgroundOther primary cancers (OPC) have been reported in gastric cancer (GC) patients. Recent studies have shown relationships of obesity and diabetes mellitus to cancer development in several organs. The purpose of this study was to investigate the relationships of obesity and diabetes mellitus (DM) to the prevalence of OPC in GC patients.MethodsWe reviewed 435 GC patients who were treated surgically and followed their outcomes after surgery. Patients with body mass index (BMI) ≥ 25 kg/m2 were defined as obese. Fasting plasma glucose (FPG) and HbA1c levels were examined before surgery.ResultsOPC was observed in 109 GC patients (25.1%): 40 (9.2%) with synchronous OPC and 76 (18.2%) with metachronous OPC. The most common OPC was colorectal cancer (22.8%). OPC was frequently observed in patients with DM (p = 0.0022), and DM was an independent risk factor for the occurrence of OPC (odds ratio, 2.215; 95% confidence interval, 1.2007–4.0850; p = 0.011). Synchronous OPC was frequently observed in patients with obesity (p = 0.025), and obesity was an independent risk factor for the occurrence of synchronous OPC (odds ratio, 2.354; 95% confidence interval, 1.1246–4.9279; p = 0.023). Metachronous OPC was frequently observed in patients with DM (p = 0.0071), and DM was an independent risk factor for the occurrence of OPC (odds ratio, 2.680; 95% confidence interval, 1.0291–6.9780; p = 0.044).ConclusionThere is a need to be aware of the possibility of OPC in GC patients with DM/obesity. They should undergo intensive screening for OPC before and after gastrectomy

Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

Alpha-fetoprotein-producing carcinoma (AFPC)/hepatoid adenocarcinoma (HAC) and neuroendocrine carcinoma (NEC) are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component