佐田 尚宏

BACKGROUND: Patients with esophageal cancer and a history of gastrectomy or concurrent gastric cancer undergo not only esophagectomy but also total gastrectomy. The goal of this study is to evaluate the postoperative quality of life (QOL) and dysfunction of these patients using two postoperative questionnaires. MATERIALS AND METHODS: From 1999 to 2015, 41 patients underwent concurrent esophagectomy and total gastrectomy. A jejunal pedicle with the subcutaneous supercharge technique was used for reconstruction. Patients were divided into two groups, including those undergoing concurrent esophagostomy and gastrectomy (Group 1), and those undergoing esophagectomy alone (Group 2, history of previous gastrectomy). Patients were analyzed by time interval, including patients within three years of surgery (Group A) and those more than three years after surgery (Group B). RESULTS: Eighteen patients completed the questionnaires. The mean DAUGS20 score was 26.4 ± 13.2. The DAUGS20 scores of groups 1 (N = 7) and 2 (N = 11) were 25.4 ± 12.5 and 27 ± 15.4 (p = 0.58), respectively. Global health status scored by the EORTC QLQC-30 were 71.4 ± 18.5 in group 1 and 67.4 ± 22.8 in group 2 (p = 0.85). DAUGS20 scores of group A (N = 10) and B (N = 8) were 28.1 ± 12.4 and 23.3 ± 14.4 (p = 0.35). No significant differences were found between groups A and B regarding the QLQ-C30 scores. CONCLUSION: DAUGS20 and QLQ-C30 scores showed no significant differences between groups 1 and 2 or groups A and B. These results suggest that postoperative QOL and dysfunction may be influenced more by current status than by surgical history and postoperative interval. Previous reports describe a DAUGS 20 score after gastrectomy of 27.8 and after esophagectomy of 36.1. The DAUGS20 score of these 18 patients is lower than DAUGS20 scores for patients undergoing either operation alone. Reconstruction using a subcutaneously placed jejunal segment seems to be reasonable.

Lung cancer is the leading cause of cancer-related deaths worldwide with over 1 million deaths each year. The overall prognosis of lung cancer patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use. Notably, more than half of the lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer (NSCLC) cases, cigarette-smokers have a greater association with squamous cell carcinoma than adenocarcinoma, which is more common in non-smokers. These findings imply that specific molecular and pathological features may associate with lung adenocarcinoma arising in non-smoker female patients. Over the past decade, whole genome sequencing and other '-omics' technologies led to the discovery of pathogenic mutations that drive tumor cell formation. These technological developments may enable tailored patient treatments throughout the course of their disease, potentially leading to improved patient outcomes. Some clinical and laboratory studies have shown success outcomes using epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) in patients with EGFR mutations and ALK rearrangements, respectively. In fact, these 2 mutations are predominantly present in female non-smokers with adenocarcinoma. Immunotherapy has also recently emerged as a major therapeutic modality in NSCLC. In this review, we summarize the current understanding of NSCLC biology and new therapeutic molecular targets, focusing on the pathogenesis of non-smoker female NSCLC patients.

Background: Repeated intraperitoneal (IP) administration of paclitaxel (PTX) with concurrent systemic chemotherapy is clinically effective for the treatment of peritoneal metastases (PM) from gastric cancer. However, it is unclear how biochemical modifications may affect the pharmacokinetics and bioavailability of IP administered PTX. Methods: In a xenograft PM model using human gastric cancer cells, MKN45, fluorescein-conjugated PTX (OG-PTX) was given IP and the intra-tumor distribution of PTX examined with fluorescein microscopy. Results: After IP injection, PTX was seen to directly infiltrate up to several hundred micrometers from the surface of the PM. Co-injection with 5 % non-animal stabilized hyaluronic acid increased PTX infiltration and suppressed the development of PM more efficiently than PTX alone. PTX solubilized with amphiphilic polymer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate (BMA) efficiently formed a micellar formation 50-100 nm in diameter. IP injection of the nanomicellar PTX (PTX-30W) also showed significantly enhanced tumor infiltration and further inhibition of the growth of PM compared with PTX solubilized with Cremophor-ethanol (PTX-Cre). Finally, IP administration of NK105, another nanomicellar PTX, inhibited the growth of subcutaneous tumors as well as PM, compared with conventional PTX-Cre in the same murine model. Conclusions: PTX administered IP directly infiltrates PM and are thus a useful strategy for the treatment of PM. Drug modification with nanotechnology may further enhance penetration of PM resulting in improved clinical efficacy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a vascular disorder of unknown etiology characterized by severe asthma, eosinophilia, and granulomatous vasculitis. It is sometimes associated with gastrointestinal lesions, although perforations are uncommon. Corticosteroids are commonly used in the treatment of patients with EGPA; however, they may impair tissue repair and induce fibrotic changes in the vascular intima, which can lead to vascular occlusion, ischemia, and perforation. The anti-inflammatory properties of corticosteroids may mask symptoms of gastroduodenal ulcers or other intra-abdominal conditions, which can lead to a delay in diagnosis. From January 1, 2001 to December 31, 2014, 71 patients underwent surgery for small intestinal perforations. Of these, 4 operations were performed on 3 patients with EGPA who were receiving corticosteroids. We retrospectively reviewed the clinical and pathologic features of these patients. All 3 patients with EGPA were men, with a mean age of 56 years. The length of resected intestine ranged from 10 to 60 cm. Histopathologic examination revealed ulcers and perforations of the small intestine associated with vasculitis, compatible with EGPA. All patients had an uneventful postoperative course. Patients with EGPA presenting with abdominal pain must be carefully evaluated for possible intestinal perforation, especially those receiving corticosteroid therapy.

BACKGROUND: To improve prognosis of pancreatic cancer (PC) patients, the discovery of more reliable biomarkers for the early detection is desired. METHODS: Blood samples were collected by 2 independent groups. The 1st set was included 55 early PC and 58 healthy volunteers (HV), and the 2nd set was included 16 PC and 16HV. The 16 targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry together with their corresponding stable isotopes. In the 1st set, the levels of these metabolites were evaluated, and diagnostic models were constructed via multivariate logistic regression analysis, leading to validation using the 2nd set. RESULTS: In the 1st set, model X consisting of 4 candidates based on our previous report possessed higher sensitivity (74.1%) than carbohydrate antigen 19-9 (CA19-9). Model Y, consisting of 2 metabolites newly selected from 16 metabolites via stepwise method possessed higher sensitivity (70.4%) than CA19-9. Furthermore, combining model Y with CA19-9 increased its sensitivity (90.7%) and specificity (89.5%). In the 2nd set, combining model Y with CA19-9 displayed high sensitivity (81.3%) and specificity (93.8%). In particular, it displayed very high sensitivity (100%) for resectable PC. CONCLUSIONS: Quantitative analysis confirmed that metabolomics-based diagnostic methods are useful for detecting PC early.

BACKGROUND: We previously identified 25 intraoperative findings during laparoscopic cholecystectomy (LC) as potential indicators of surgical difficulty per nominal group technique. This study aimed to build a consensus among expert LC surgeons on the impact of each item on surgical difficulty. METHODS: Surgeons from Japan, Korea, and Taiwan (n = 554) participated in a Delphi process and graded the 25 items on a seven-stage scale (range, 0-6). Consensus was defined as (1) the interquartile range (IQR) of overall responses ≤2 and (2) ≥66% of the responses concentrated within a median ± 1 after stratification by workplace and LC experience level. RESULTS: Response rates for the first and the second-round Delphi were 92.6% and 90.3%, respectively. Final consensus was reached for all the 25 items. 'Diffuse scarring in the Calot's triangle area' in the 'Factors related to inflammation of the gallbladder' category had the strongest impact on surgical difficulty (median, 5; IQR, 1). Surgeons agreed that the surgical difficulty increases as more fibrotic change and scarring develop. The median point for each item was set as the difficulty score. CONCLUSIONS: A Delphi consensus was reached among expert LC surgeons on the impact of intraoperative findings on surgical difficulty.

Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5 mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6 mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5 mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.

Gastric cancer is a common malignancy and remains potentially lethal. The prognosis of patients with stage IV gastric cancer is thought to be poor, but new molecular targeted therapy may benefit patients with advanced gastric cancer. Currently, conversion surgery after chemotherapy with a trastuzumab-containing regimen is reported to be effective in these patients. We present 3 patients with human epidermal growth factor receptor 2 (HER2)–positive advanced gastric cancer who underwent conversion surgery after receiving a trastuzumab-containing chemotherapy regimen. Interestingly, the primary lesion acquired resistance to the trastuzumab-containing regimen, although the metastatic lesions maintained a complete response. The reason why the primary lesions became resistant to trastuzumab remains unclear. More studies are needed to clarify the mechanism of resistance. Conversion surgery, made possible by the use of molecular-targeted therapy, may improve the prognosis of patients with stage IV gastric cancer, particularly if metastatic lesions show a complete response to therapy.

BACKGROUND: Long-term term survival in patients with pancreatic neuroendocrine tumors has been reported, even in patients with metastatic disease. Metastases to the spleen are extremely rare, but have been reported from a number of primary malignancies, such as breast cancer, lung cancer, melanoma and ovarian cancer. This is the first report of a splenic metastasis from a primary pancreatic neuroendocrine tumor. CASE PRESENTATION: The patient presented as a 53 years old white male with anemia and fatigue. Physical examination revealed a left upper quadrant fullness and computed tomography showed a 24 cm left upper quadrant mass with multiple liver metastases, splenomegaly and a 1 cm mass in the spleen. Resection of the primary pancreatic tumor (T4N0M1) was accompanied by gastrectomy, splenectomy and resection of adherent bowel. The spleen contained a metastatic lesion 1.0 cm in diameter, consistent with a primary neuroendocrine tumor of the pancreas. This operation was followed 8 months later, by delayed resection of liver metastases. The patient receives monthly administration of somatostatin long-acting analogue and has undergone several ablations of liver lesions with percutaneous radiofrequency ablation as well as a second liver resection. The patient is alive seven years after initial presentation, with no evidence of disease on imaging studies. CONCLUSIONS: This is the first report of a splenic metastasis from a primary pancreatic neuroendocrine tumor. The patient initially presented with synchronous multiple liver metastases and a single splenic metastasis. After resection of the primary tumor and spleen, the patient has undergone aggressive cytoreductive surgery/ablation of liver lesions and somatostatin therapy with resulting long-term survival.

BACKGROUND: Generally, surgeons' perceptions of surgical safety are based on experience and institutional policy. Our recent pilot survey demonstrated that the acceptable duration of surgery and criteria for open conversion during laparoscopic cholecystectomy (LC) vary among workplaces. METHODS: A web-based survey was distributed to 554 expert LC surgeons in Japan, Korea, and Taiwan. The questionnaire covered LC experience, safety measures and recognition of landmarks, decision-making regarding conversion to open/partial cholecystectomy and the implications of this decision. Overall responses were compared among nations, and then stratified by LC experience level (lifetime cases 200-499, 500-999, and ≥1,000). RESULTS: The response rate was 92.6% (513/554); 67 surgeons with ≤199 LCs were excluded, and responses from 446 surgeons were analyzed. We observed significant differences among nations on almost all questions. Differences that remained after stratification by LC experience were on questions related to acceptable duration of surgery, adoption rates of intraoperative cholangiography, the "critical view of safety" technique, identification of Rouvière's sulcus, recognition of the SS-Inner layer theory, and intraoperative judgment to abandon conventional LC. CONCLUSIONS: Even among experts, surgeons' perceptions during LC are workplace-dependent. A novel grading system of surgical difficulty and standardized LC procedures are paramount to generate high-level evidence.

INTRODUCTION: Pancreatic neuroendocrine tumors are rare. Treatment includes aggressive local management of the primary lesion and metastases, and systemic somatostatin. This is the first report of an isolated metachronous metastasis to the adrenal gland from a pancreatic neuroendocrine tumor that presented 90 months after the primary tumor. PRESENTATION OF CASE: The patient presented as a 53yo man with a left upper quadrant mass and synchronous metastases to the spleen and liver (pancreatic neuroendocrine tumor T4N0M1, Stage IV), which were resected (CD56-, synaptophysin+, chromogranin+, Ki-67<1%). Over the next 90 months, he underwent five procedures to treat hepatic recurrences (2 liver resections and 3 percutaneous radiofrequency ablations). Serum PIVKA levels were elevated prior to treatment of four of six lesions and returned to baseline after therapy. He presents now, asymptomatic, with a right adrenal mass found on routine imaging and no other lesions. Serum PIVKA was elevated to 44mg/dL. The adrenal gland was resected and shown to be a metastasis (CD56+, synaptophysin+, chromogranin+, Ki-67 15-20%). DISCUSSION: This patient's clinical course reflects aggressive local therapy of the primary lesion and multiple metastatic lesions to three organs (liver, spleen, adrenal) over nearly eight years. The utility of serum PIVKA levels in patients with pancreatic neuroendocrine tumors is not previously reported and needs further investigation. CONCLUSION: This patient has a pancreatic neuroendocrine tumor with metastases to the spleen, liver and adrenal gland and elevated PIVKA levels with recurrent disease. These unique clinical features add to the diversity of clinical presentation of these rare tumors.

INTRODUCTION: The aim of this study was to compare the clinical outcomes of single-incision transumbilical laparoscopy-assisted appendectomy performed by surgical residents and attending surgeons. METHODS: We reviewed the clinical outcomes of 131 transumbilical laparoscopy-assisted appendectomies performed from January 2011 to June 2014. During the study period, 13 residents and 6 board-certified attending surgeons performed the procedures. For all operations performed by residents and attending surgeons, we reviewed and compared gender, age, BMI, body temperature, white blood cell count, C-reactive protein serum level, and the presence of a fecalith or abscess. Clinical outcomes including operative time, estimated blood loss, need for additional ports, conversion to open surgery, intraoperative complications, postoperative complications, and postoperative hospital stay were compared between the two groups. RESULTS: The mean preoperative white blood cell count in the resident-operated group was significantly higher than in the attending-operated group (14.0 vs 10.8 ×103 /mm3 , P = 0.007). There were no other significant differences in clinical variables between the two groups. Outcomes show that estimated blood loss was significantly higher (23.4 vs 9.8 mL, P = 0.031) and operative time tended to be longer (86.0 vs 72.0 min, P = 0.056) in the resident-operated group. No other significant differences were observed. CONCLUSION: Transumbilical laparoscopy-assisted appendectomy performed by residents is feasible and safe. It is an acceptable as a part of routine surgical training.

Utilizing the opened round ligament as venous grafts during liver transplantation is useful but controversial, and there are no pathological analyses of this procedure. Herein, we describe the first reported case of a pathological analysis of an opened round ligament used as a venous patch graft in a living donor liver transplantation (LDLT). A 13-year-old female patient with biliary atresia underwent LDLT using a posterior segment graft from her mother. The graft had two hepatic veins (HVs), which included the right HV (RHV; 15 mm) and the inferior RHV (IRHV; 20 mm). The graft RHV and IRHV were formed into a single orifice using the donor's opened round ligament (60 mm × 20 mm) as a patch graft during bench surgery; it was then anastomosed end-to-side with the recipient inferior vena cava. The recipient had no post-transplant complications involving the HVs, but she died of septic shock with persistent cholangitis and jaundice 86 d after LDLT. The HV anastomotic site had no stenosis or thrombus on autopsy. On pathology, there was adequate patency and continuity between the recipient's HV and the donor's opened round ligament. In addition, the stains for CD31 and CD34 on the inner membrane of the opened round ligament were positive. Hepatic venous reconstruction using the opened round ligament as a venous patch graft is effective in LDLT, as observed on pathology.

BACKGROUND: Serious complications continue to occur in laparoscopic cholecystectomy (LC). The commonly used indicators of surgical difficulty such as the duration of surgery are insufficient because they are surgeon and institution dependent. We aimed to identify appropriate indicators of surgical difficulty during LC. METHODS: A total of 26 Japanese expert LC surgeons discussed using the nominal group technique (NGT) to generate a list of intraoperative findings that contribute to surgical difficulty. Thereafter, a survey was circulated to 61 experts in Japan, Korea, and Taiwan. The questionnaire addressed LC experience, surgical strategy, and perceptions of 30 intraoperative findings listed by the NGT. RESULTS: The response rate of the survey was 100%. There was a statistically significant difference among nations regarding the duration of surgery and adoption rate of safety measures and recognition of landmarks. The criteria for conversion to an open or subtotal cholecystectomy were at the discretion of each surgeon. In contrast, perceptions of the impact of 30 intraoperative findings on surgical difficulty (categorized by factors related to inflammation and additional findings of the gallbladder and other intra-abdominal factors) were consistent among surgeons. CONCLUSIONS: Intraoperative findings are objective and considered to be appropriate indicators of surgical difficulty during LC.

BACKGROUND: Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival. METHODS: We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I-III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m(2), intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan-Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0.87 with a non-inferiority margin of 1.25 (power 80%; one-sided type I error 2.5%). This trial is registered at UMIN CTR (UMIN000000655). FINDINGS: 385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0.57 (95% CI 0.44-0.72, pnon-inferiority<0.0001, p<0.0001 for superiority), associated with 5-year overall survival of 24.4% (18.6-30.8) in the gemcitabine group and 44.1% (36.9-51.1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group. INTERPRETATION: Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients. FUNDING: Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.

A 61-year-old woman underwent surgical resection of rectal cancer (SI, N3, Stage Kb) and received 12 courses of adjuvant mFOLFOX6 chemotherapy. Six months after completion of adjuvant chemotherapy, she was found to have pulmonary metastases, and was treated with FOLFIRI plus bevacizumab. After 6 courses of chemotherapy, the pulmonary nodules showed central cavitation without any change in size. After 6 additional courses of chemotherapy, pulmonary lesions increased in and had consolidated. She was treated with regorafenib as second-line chemotherapy for recurrent disease. After 6 courses of regorafenib, the pulmonary nodules became cavitated. According to the RECIST criteria, the tumor response was stable disease. However, the morphology was significantly changed and tumor growth had been controlled for a long time. Assessment of tumor response depends not only on size according to the RECIST criteria, but also on the morphologic response when we assess tumor response to molecular targeted drugs.

Metastatic squamous cell carcinoma (SCC) from an unknown primary site to the colon has not been reported previously. A 75-year-old woman presented with a mass in the left submandibular region. Biopsy revealed a Class V lesion, but the histologic type was undetermined. Surgical resection of the left submandibular gland with cervical lymph node dissection was performed. However, SCC was seen in the lymph nodes only, with no tumor in the submandibular gland. Three months after surgery, computed tomography revealed that the preoperatively diagnosed lesion in the transverse colon had grown considerably. A laparoscopic right hemicolectomy was performed. Histological examination showed features of SCC, similar to the findings in the cervical lymph nodes. We report a rare case of synchronous metastatic SCC to the colon and cervical lymph nodes from a carcinoma of unknown primary site.

Background In small infants, left lateral segment grafts are sometimes too large to overcome the problems of large-for-size grafts in the abdominal compartment. To address this problem, we have developed a safe living donor graftectomy for neonates, a so-called "S2 monosegment graft" to minimize graft thickness. We reviewed our single-center experience to evaluate the feasibility of this technique for reducing graft size. Methods Eleven living-donor liver transplants using S2 monosegment grafts were performed between October 2008 and September 2014 at our institution. Medical records of both donors and recipients were reviewed and data collected retrospectively. Results The mean age of recipients at the time of transplantation was 125.3 days, including 3 neonates. The average S2 monosegment graft weight was 127.4 g, and the graft-to-recipient body weight ratio was successfully reduced to 3.5%. The graft livers were reduced to 4.1 cm in thickness. Two recipients with grafts larger than 5 cm could not undergo primary abdominal closure. Portal vein stenosis and biliary stenosis was observed in 1 recipient, and hepatic artery complications were seen in 2 recipients the clinical course for all donors were uneventful. Liver regeneration was seen in every patient. The graft and patient 1-year survival rate was 100%. Conclusions Living-donor liver transplantation using S2 monosegment grafts offers a safe and useful option for treating smaller infants. Here, we introduce our method of S2 monosegment graft emphasizing the donor harvest and graft thickness.

BACKGROUND: Decrease in appetite and weight after total gastrectomy in patients with gastric cancer leads to a decrease in quality of life, increased mortality, and may necessitate discontinuation of adjuvant chemotherapy. The aim of this study is to determine whether rikkunshito, a Japanese herbal medicine, increases food intake and weight after gastrectomy in rats. METHODS: Male rats underwent gastrectomy followed by roux-en-Y reconstruction or sham operation and were then treated with rikkunshito for 14 days starting on postoperative day 3. Daily food intake, weight, plasma glucagon-like peptide-1 (GLP-1), and ghrelin levels were measured. A pilot study to measure pre- and postoperative plasma GLP-1 levels was conducted in patients who underwent total gastrectomy for gastric cancer. RESULTS: Administration of rikkunshito after gastrectomy in rats significantly increased food intake and weight, which continued for at least 2 weeks after treatment. Both fasting and postprandial plasma GLP-1 levels were increased markedly after gastrectomy compared with sham-operated animals. Increased GLP-1 levels in rats after gastrectomy were suppressed markedly by rikkunshito. rikkunshito had no significant effect on plasma ghrelin levels after gastrectomy. Treatment with a GLP-1 receptor antagonist significantly improved food intake and weight after gastrectomy. Plasma fasting GLP-1 levels in patients with gastric cancer were increased greatly after gastrectomy on postoperative day 1. CONCLUSION: Administration of rikkunshito suppresses plasma GLP-1 levels after total gastrectomy, which is associated with recovery from reduced food intake and weight in rats.

A 48-year-old man underwent laparoscopic sigmoid colon resection for cancer and surveillance colonoscopy was performed annually thereafter. Five years after the resection, a submucosal mass was found at the anastomotic staple line, 15 cm from the anal verge. Computed tomography scan and endoscopic ultrasound were not consistent with tumor recurrence. Endoscopic mucosa biopsy was performed to obtain a definitive diagnosis. Mucosal incision over the lesion with the cutting needle knife technique revealed a creamy white material, which was completely removed. Histologic examination showed fibrotic tissue without caseous necrosis or tumor cells. No bacteria, including mycobacterium, were found on culture. The patient remains free of recurrence at five years since the resection. Endoscopic biopsy with a cutting mucosal incision is an important technique for evaluation of submucosal lesions after rectal resection.

PURPOSE: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. METHODS: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. RESULTS: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. CONCLUSION: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.

INTRODUCTION: Isolated vaginal metastases from colorectal cancer are extremely rare. There are only a few reported cases in the English literature, and the characteristics of such cases of metastasis remain relatively unknown. PRESENTATION OF CASE: We present a case of isolated vaginal metastasis from rectal cancer in a 78-year-old female patient. The patient had no symptoms related to vaginal tumor. Magnetic resonance imaging (MRI) showed thickening of the middle rectum and a vaginal tumor. Biopsy from the vaginal tumor showed adenocarcinoma, similar to the rectal lesion. Low anterior resection with ileostomy, hystero-oophorectomy, and transvaginal tumor resection was performed. After nineteen months, computed tomography scan revealed multiple lung metastases and recurrent tumor in the pelvis. The patient refused chemotherapy and is alive three months after developing recurrent disease. DISCUSSION: Most cases of primary vaginal carcinoma are squamous cell carcinoma. Other histologic types such as adenocarcinoma are usually metastatic lesions. Primary lesions associated with metastatic vaginal adenocarcinoma are most often the uterus, and are very rarely from the colon or rectum. We review previous case reports of isolated vaginal metastases from colorectal cancer and discuss their symptoms, treatments, and outcomes. CONCLUSION: We should keep the vagina within the field of view of pelvic MRI, which is one of the preoperative diagnostic tools for colorectal cancer. If female patients show gynecological symptoms, gynecological examination should be recommended. Isolated vaginal metastases are an indication for surgical resection, and adjuvant chemotherapy is also recommended.

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

症例は54歳の女性．近親者の大腸癌罹患による不安から近医を受診した．大腸内視鏡検査は挿入困難であった．注腸検査で上行結腸癌を疑われ精査加療目的に当院へ紹介となった．ダブルバルーン内視鏡検査で上行結腸癌と診断された．3D-CT angiographyではSMV rotation signを認め，腸回転異常症を伴う上行結腸癌の診断で開腹回盲部切除術を施行した．手術所見では，上行結腸は後腹膜に固定されておらず，小腸は十二指腸尾側より肝下面に内ヘルニアをきたし，paraduodenal hernia typeの腸回転異常症と診断された．郭清は回結腸動脈を根部で切離してD3とした．内ヘルニアの小腸は右上腹部で後腹膜に強固に癒着しており，これまで無症状であったことから整復は行わなかった．内ヘルニアを伴う腸回転異常症に併存する大腸癌は稀であり，文献的考察を含めて報告する．

INTRODUCTION: Laparoscopic gastric devascularization of the upper stomach in patients with gastric varices has rarely been reported. Perioperative clinical data were compared with patients who underwent open surgery. PRESENTATION OF CASES: From 2009 to 2012, we performed laparoscopic gastric devascularization without splenectomy for the treatment of gastric varices in eight patients. The patients included four males and four females. Peri-gastric vessels were divided using electrical coagulating devices or other devices according to the diameter of the vessels. Two patients underwent conversion to open surgery due to intraoperative bleeding. DISCUSSION: Intraoperative blood loss in patients who accomplished laparoscopic devascularization was very small (mean 76ml). However, once bleeding occurs, there is a risk of causing massive bleeding. CONCLUSION: With further improvement of laparoscopic devices, laparoscopic gastric devascularization without splenectomy must be an effective and less-invasive surgical procedure in the treatment of gastric varices.

BACKGROUND: Pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) has been regarded as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS) of patients with breast cancer. No consensus regarding the definition of pCR has been established; there are several definitions according to a variety of classifications. Eradication of cancer cells in both breast and lymph nodes has been better associated with improved prognosis than in the breast alone. Even in patients diagnosed as having clinically node-negative cancer before NAC, postoperative pathological examination often shows axillary lymph node metastases. PATIENTS AND METHODS: Of the 771 patients with breast cancer who underwent NAC in the Cancer Institute Hospital between January 2000 and May 2009, 146 patients preoperatively diagnosed as having node-negative breast cancer were retrospectively evaluated. We have made the definition of clinically lymph node-negative (N0) as follows: first, ultrasonography before NAC did not show any lymphadenopathy. Second, a cytological procedure confirmed negative study for each patient when ultrasonography suggested lymphadenopathy. RESULTS: The median observation period was 79.7 months, and the median age of the subjects was 51 years. Pathological examination at the time of the surgery showed lymph node metastases (ypN+) in 46 patients (31.5%). Histological therapeutic effects revealed ypT0/is in 9 patients (6.2%) and ypTinv in 137 (93.8%). Multivariate analysis demonstrated that younger age (49>), large tumor size, NG3, and ypN+ were significant poor prognostic factors for DFS (p = 0.020, p = 0.008, P = 0.022 and p = 0.010, respectively). Moreover, ypN+ was the only significant poor prognostic factor for OS (p = 0.022). The predictive factors of ypN+ in clinically lymph node-negative breast cancer were ypTinv (p = 0.036) and the luminal type (HR+ and HER2-) (p = 0.029). CONCLUSION: The prognosis of clinically lymph node negative breast cancer depended on ypN+, which was associated with ypTinv and luminal subtype.

The human peritoneal cavity contains a small number of free cells of mesenchymal cell lineage. Intraperitoneal mesenchymal cells (PMC) play supportive roles in metastasis formation on the peritoneum. In this study, we found that PMC, when co-cultuerd with human gastric cancer cells, MKN45, enhanced the proliferation of MKN45 when cultured at low, but not high, cellular density. Also, PMC suppressed apoptotic cell death of MKN45 only under low density culture conditions. Time-lapse videoanalysis clearly demonstrated that PMC randomly migrated more vigorously than did MKN45, and strongly enhanced the migration behavior of co-cultured MKN45. In fact, the majority of MKN45 migrated together in direct physical contact with PMC, and the sum of migration lengths from original position of co-cultured MKN45 for 48 hours was approximately 10 times longer than that of MKN45 cultured alone. Our data suggest that enhanced migration can increase the chance of direct contact or positional proximity among sparcely distributed MKN45, which may bring survival advantages to tumor cells. This may be one of the important mechanisms of peritoneal metastasis, since only a small number of tumor cells are considered to be disseminated in the early step of metastasis formation on the peritoneum.

Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor-binding protein (IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19-9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of IDACP patients.

INTRODUCTION: Gastric volvulus is torsion of the stomach and requires immediate treatment. The optimal treatment strategy for patients with gastric volvulus is not established, because of significant variations in the cause and clinical course of this condition. PRESENTATION OF CASES: We describe our experience with six elderly patients with gastric volvulus caused by different conditions using various approaches. This includes two patients managed with endoscopic reduction, followed by endoscopic or laparoscopic gastropexy. DISCUSSION: Endoscopy is a necessary first step to determine the optimal treatment strategy, and endoscopic reduction is often effective. The indications for surgical repair of gastric volvulus depend on the patient's overall condition, and several options are available. In some elderly patients with severe comorbidities, major surgery may have an unacceptably high risk. We propose a novel treatment strategy for gastric volvulus in the elderly and a review of the literature. CONCLUSION: Early endoscopy is necessary in patients with gastric volvulus. Endoscopic or laparoscopic gastropexy may be adequate therapy in selected elderly patients.

INTRODUCTION: Spontaneous esophageal perforation, or Boerhaave's syndrome, is a life-threating condition which usually requires emergent surgery. An upside down stomach is defined as a gastric volvulus in a huge supradiaphragmatic sac. In general, this condition can result in ischemia and perforation of the stomach. This is the first report of a patient with Boerhaave's syndrome and an upside down stomach. CASE PRESENTATION: A 79-year-old woman presented with sudden epigastric pain following hematemesis. Evaluation of the patient showed both an esophageal perforation and an upside down stomach. Surgical drainage and irrigation of the mediastinum and pleural cavities were undertaken emergently. Due to the concurrent gastric volvulus, a gastrostomy was placed to fix and decompress the stomach. The patient had an uneventful hospital course and was discharged. DISCUSSION AND CONCLUSION: Boerhaave's syndrome is a rare but severe complication caused by excessive vomiting, due to a sudden elevation in intraluminal esophageal pressure resulting in esophageal perforation. Acute gastric volvulus can result in ischemia and perforation of the stomach, but has not previously been reported with esophageal perforation. The most likely mechanism associating an upside down stomach with Boerhaave's syndrome is acute gastric outlet obstruction resulting in vomiting, and subsequent esophageal perforation. Perforation of the esophagus as well as perforation of the stomach must be considered in patients with an upside down stomach although both upside down stomach and Boerhaave's syndrome are rare clinical entities.

INTRODUCTION: Neuroendocrine tumors of the colon and rectum are relatively rare compared to sporadic colorectal carcinoma. There are few reports of neuroendocrine tumors of the colon and rectum in patients with ulcerative colitis. PRESENTATION OF CASE: A patient with sigmoid colon carcinoma with focal neuroendocrine features is presented. A 32-year-old man, who had been followed for ulcerative colitis for 14 years, was found to have carcinoma of the sigmoid colon on routine annual colonoscopy, and he underwent laparoscopic total colectomy. Pathologic examination showed sigmoid colon adenocarcinoma with focal neuroendocrine features. DISCUSSION: Most colorectal carcinomas associated with inflammatory bowel disease are histologically similar to the sporadic type, and tumors with neuroendocrine features are very unusual. CONCLUSION: Very rare case of sigmoid colon carcinoma with neuroendocrine features arising in a patient with UC was described.