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Several recent case reports have demonstrated long survival cases of advanced gastric cancer(AGC)patients suffering from peritoneal dissemination(PD)treatedwith effective chemotherapy; however, these AGC patients have poor prognosis in general. We report a case of AGC who hadsurvivedPD over 40 months with locoregional therapies. A 58-year-oldmale underwent distal gastrectomy for AGC with localized PD. Although we recommended postoperative chemotherapy, he chose surveillance as his will. Eighteen months postoperatively, CT scan revealedrecurrence of PD, andPET -CT showedonly one site of recurrent nodule. The patient chose locoregional therapy, ie, resection of the recurrent nodule instead of chemotherapy. Pathological exam confirmedthe recurrence of AGC, andabd ominal lavage cytology was classifiedas V. Even after these pathological findings, the patient refused to receive chemotherapy. At 39 months postoperatively, he developed subileus due to multiple recurrence of PD. At 40 months postoperatively, we performedchemotherapy because locoregional therapy was not supposedto be appropriate for these multiple lesions. However, the patient movedto another hospital after 1 course of chemotherapy because of his continuedrefusal to receive chemotherapy.

We report a case of sigmoid colon cancer that was incidentally found using CT that was performed for upper abdominal pain. An 83-year-old man with a long history of lung tuberculosis and idiopathic pulmonary fibrosis presented with upper abdominal pain. CT findings revealed free gas around the stomach. He was diagnosed with upper gastrointestinal perforation and his condition improved after undergoing conservative treatment. Upper endoscopy revealed an irregular ulcer at the angular incisure of the stomach with thickened folds, but biopsy resulted in a Group 1 classification. CT findings also incidentally revealed sigmoid colonic wall thickness, and colonoscopy showed a type Ⅰ lesion in the sigmoid colon, which biopsy resulted in Group 5, and we performed sigmoidectomy for sigmoid colon cancer under a combination of spine-subarachnoid and epidural anesthesia because of his respiratory dysfunction.

Neonicotinoids and fipronil are the most widely used insecticides in the world. Previous studies showed that these compounds have high toxicity to a wide taxonomic range of non-target invertebrates. In rice cultivation, they are frequently used for nursery-box treatment of rice seedlings. The use of fipronil and neonicotinoid imidacloprid is suspected to be the main cause of population declines of red dragonflies, in particular Sympetrum frequens, because they have high lethal toxicity to dragonfly nymphs and the timing of the insecticides' introduction in Japan (i.e., the late 1990s) overlapped with the sharp population declines. However, a causal link between application of these insecticides and population declines of the dragonflies remains unclear. Therefore, we estimated the amount of the insecticides applied for nursery-box treatment of rice seedlings and analyzed currently available information to evaluate the causality between fipronil and imidacloprid usage and population decline of S. frequens using Hill's causality criteria. Based on our scoring of Hill's nine criteria, the strongest lines of evidence were strength, plausibility, and coherence, whereas the weakest were temporality and biological gradient. We conclude that the use of these insecticides, particularly fipronil, was a major cause of the declines of S. frequens in Japan in the 1990s, with a high degree of certainty. The existing information and our analyses, however, do not allow us to exclude the possibility that some agronomic practices (e.g., midsummer drainage or crop rotation) that can severely limit the survival of aquatic nymphs also played a role in the dragonfly's decline.

We report a case of ascending colon cancer with hepatic metastases that was treated by CapeOX plus bevacizumab with remarkable efficacy. A 40-year-old female patient presented with a medical history of surgery for resection of right breast cancer4 years ago, left-sided transverse colon 2 years ago, and right ovarian cancer 6 months ago. Follow-up computed tomography(CT)found wall thickening from the ascending colon to cecum. She was diagnosed with an ascending colon cancer by colonoscopy, and underwent right hemicolectomy. One month after the surgery, her serum marker carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels were high. She was diagnosed with unresectable multiple hepatic metastases by CT 2 months after the surgery. Her tumor was epidermal growth factor receptor(EGFR)- positive and wild-type for RAS; she received 4 courses of CapeOX plus bevacizumab. Thereafter, liver metastases were remarkably decreased in size, and she could undergo central bisegmentectomy. Pathology examination revealed no tumor and that the center of the tumor was changed to necrotic tissue and the surrounding area was changed to fibrous tissue and lymphocyte infiltration. The patient is disease-free since the last operation.

The relative ability of the NOEC (no-observed-effect concentration) and ECx (the effect concentration corresponding to x-percent response) to determine benchmark toxicant concentrations, which are expected to ensure environmental safety, when there are large uncertainties in data was investigated with Monte Carlo simulations. We assumed a hypothetical true concentration-response function, and examined how random fluctuations of responses around the true responses affected the NOEC and ECx values. For assessment of the relative performances of these endpoints, we adopted two criteria: how large uncertainties were allowed for the minimum requirement for safety to be met, and the probability with which the estimated endpoints exceeded the minimum requirement for safety. The results of simulations indicated that, when there were small uncertainties in the data, performance of the NOEC was comparable with or slightly better than the ECx (EC5 and EC10) in providing benchmark concentrations that satisfied the minimum requirement for safety. With larger random variation of data (the coefficient of variation in responses between replicates within treatments or in the control was noticeably larger than 10 percent), the NOEC performed considerably worse than the ECx in terms of the frequency of simulated runs in which the endpoints exceeded the minimum requirement of safety. We conclude that the NOEC is as relevant as the ECx for risk assessment of chemicals under limited situations., Competing Interests: The authors have declared that no competing interests exist.

Patients and Methods: Four hundred and nineteen patients with colorectal cancer who underwent laparotomy were included in this study. Indicators that reflected immunity, nutrition, and physical function were selected, and risks associated with the presence of postoperative pneumonia were investigated. Cut-off values of factors affecting the occurrence of pneumonia were determined using the receiver-operating characteristic curve approach., Results: Pneumonia was observed in 2.9%of the patients, and PNI(C40.0), CONUT(B2), BMI(<18.5 kg/m2), PS(B1), %VC(<80.0%), and FEV1.0%(<70.0%)were identified as risk factors in multivariate analysis(p<0.05). %VC(<80.0%)was extracted as an independent factor. The cutoff value of %VC was determined to be 80.0%based on the incidence of postoperative pneumonia., Conclusion: Low volume in %VC(<80.0%)may be a risk factor for pneumonia after resection of colorectal cancer.

Introduction: There are few reports on the outcome of relapsed cases after curative resection for colorectal cancer(CRC) with adjuvant oxaliplatin-based chemotherapy. Thus, we analyzed such cases., Patients and Method: In total, 48 patients with CRC who received oxaliplatin-based postoperative adjuvant chemotherapy from 2012 were analyzed. The clinical course was examined in 9 cases ofrecurrence., Results: Stages II, III a, and III b(1, 3, and 5 cases, respectively)were judged as recurrence in 9 cases. Metastatic sites were the lungs, local sites, liver, and peritoneum(3, 3, 3, and 1 case[s], respectively). The median time to relapse was 390 days. There were 2 cases ofwild -type RAS and 7 cases ofmutant RAS. Although R0 resection was performed in 1 case, re-relapse was recognized. Another 8 cases involved induced chemotherapy. An oxaliplatin-based regimen was administered as first-line treatment in 4 of8 cases. At present, 5 patients died, and 3 of8 cases could not progress to second-line treatment. The overall survival(OS)after relapse was 475 days, and survival more than 3 years was not observed., Conclusion: Recurrent cases after Cur A resection for CRC with oxaliplatin-based adjuvant chemotherapy were examined. Although the 3-year RFS and 5-year OS were relatively good, the prognosis after relapse was quite poor.

We report a case of effective treatment comprising mFOLFOX6 plus bevacizumab for neuroendocrine carcinoma of the ascending colon. A 60-year-old woman was admitted for diarrhea and abdominal pain. Colonoscopy showed a Type 2 tumor in the ascending colon. She was diagnosed with neuroendocrine cell carcinoma based on biopsy and immunostaining. CT and MRI showed liver metastasis and lymph node #12a metastasis. Right hemi-colectomy, lymphadenectomy, and partial hepatectomy were performed(T4a, N2, M1b, Stage IV). Neuroendocrine cell carcinoma(small-cell type)was finally diagnosed based on a histological examination because the nuclear fission image was 30(/10HPF)and the Ki-67 index was 42%. Three months after the surgery, multiple lymph node metastases were found using CT and MRI. mFOLFOX6 plus bevacizumab was initiated. After 4 courses of the chemotherapy, the metastases responded completely. A total of 10 courses of chemotherapy were administered. About 2 years and 6 months after the surgery, no recurrence is allowed.

We herein report a Stage IV case ofrectal cancer in a patient who achieved stable disease and was treated monthly with fluorouracil(FU)monotherapy plus bevacizumab(Bmab)against relapse after residual tumor resection and withdrawal because ofref usal to continue chemotherapy, even though a marked response was obtained with standard chemotherapy. A 73-year-old woman visited a former hospital in 2014, and was diagnosed with rectal cancer with liver and lung metastases (diagnosed with Rb, T3, M1b[liver, lung]cStage IV). Chemotherapy(mFOLFOX6 plus Bmab)was initiated with a consideration of conversion. After 5 courses, she moved to our hospital. Since she was not aggressive to chemotherapy from the beginning, an imaging examination was performed after 9 courses. The primary lesion and lung metastases had disappeared, and there was only one liver metastasis. Partial hepatic resection was performed to attempt chemotherapy withdrawal following informed consent. Six months after surgery with no therapy, since relapse in the rectum and lungs was confirmed, laparoscopic rectal amputation was performed to control the primary tumor. Chemotherapy containing FU monotherapy plus Bmab was reinitiated after 15 months of withdrawal because liver and lung metastases increased 5 months after rectal amputation. Two months after resuming chemotherapy, the metastatic lesion decreased in size, and the tumor marker level normalized. The same regimen is continued monthly, and the response has been maintained for 17 months(infusions of 5-FU/LV plus Bmab, 18 courses).

The Japan Ministry of Health, Labour and Welfare (MHLW) has published instructions for radiological protection against food after the Fukushima Daiichi nuclear power plant accident in 2011. Following the instructions, the export and consumption of food items identified as being contaminated were restricted for a certain period. We assessed the validity of the imposed restriction periods for two representative vegetables (spinach and cabbage) grown in Fukushima Prefecture from two perspectives: effectiveness for reducing dietary dose and economic efficiency. To assess effectiveness, we estimated the restriction period required to maintain consumers' dose below the guidance dose levels. To assess economic efficiency, we estimated the restriction period that maximizes the net benefit to taxpayers. All estimated restriction periods were shorter than the actual restriction periods imposed on spinach and cabbage from Fukushima in 2011, which indicates that the food restriction effectively maintained consumers' dietary dose below the guidance dose level, but in an economically inefficient manner. We also evaluated the response of the restriction period to the sample size for each weekly food safety test and the instructions for when to remove the restriction. Stringent MHLW instructions seemed to sufficiently reduce consumers' health risk even when the sample size for the weekly food safety test was small, but tended to increase the economic cost to taxpayers., (© 2017 Society for Risk Analysis.)

Three-field lymph node dissection is now performed in operations for advanced thoracic esophageal cancer, with an associated improvement in outcomes. However, reconstructive surgery following resection of the esophagus is frequently associated with the occurrence of anastomotic leakage. Once it occurs, major problems can arise such as decreased quality of life, protracted hospitalization, or even death. This is why there has been a large number of innovations in and modifications to reconstructive surgery. The standard procedures in our Department for advanced thoracic esophageal cancer are subtotal esophagectomy and three-field lymph node dissection. The thin gastric tube along the greater curvature is used as the reconstructed organ in reconstructive surgery, performing a cervical esophagogastrostomy. Innovations have been made to reconstructive surgery in order to prevent anastomotic leakage. This procedure markedly reduces anastomotic leakage, and also reduces anastomotic stricture, which likely makes it an extremely useful procedure that any surgeon can perform., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Necrosis of a reconstructed organ after esophageal cancer surgery is a very serious complication that often occurs soon after the surgery. We report a case of emergency surgery that was performed to treat necrosis of a reconstructed colon 10 years after esophagectomy. A 73-year-old man was admitted to our hospital with complaints of chest pain. His history included a proximal gastrectomy for gastric cancer. His present illness includes endoscopic mucosal resection for superficial esophageal cancer in 1995. Subtotal esophagectomy and right colon interposition through the retrosternal route were performed due to a recurrence in the same lesion in 2005. The patient was immediately hospitalized due to chest pain in 2015. An upper gastrointestinal endoscopy revealed extensive necrosis in the colon. He underwent an emergency operation. The surgical operations included reconstructed colonic resection by longitudinal sternotomy, esophagostomy, gastrostomy, and drainage procedure. The patient is currently under rehabilitation at a referral hospital. There has been no report on the occurrence of necrosis in the reconstructed colon 10 years after esophagectomy.

The patient was 55-year-old woman, undergoing Hartmann operation by the sigmoid colon diverticulum perforation, 2 years later visited our hospital with abdominal pain. Although lower endoscopy and histological examination could not be performed due to stoma stenosis, we diagnosed cecal carcinoma, liver metastasis, distant lymph node metastasis from CT and PET-CT, CapeOX plus Bmabtherapy and IRIS plus Bmabtherapy were performed. After that, repeated intestinal obstruction due to exacerbated stoma stenosis, metastatic lesion increased in CT examination, furthermore the patient had hope of stoma closure, we decided to resect the primacy tumor, performed subtotal colonectomy and stoma closure. Pathological diagnosis revealed RAS wild type. After surgery, Pmabplus CPT-11 therapy was performed and the metastatic lesion was temporarily shrunk but re-exacerbated, the patient died 2 years 2 months after the first treatment started, 7 months after the primary tumor resection. In the treatment of colorectal cancer, when metastatic lesion is unresectable, chemotherapy is often carried out except when the primary tumor is symptomatic. In our case, although the primary tumor was asymptomatic, an intestinal obstruction due to stoma stenosis was developed and it was necessary to examine whether to use anti-EGFR antibody drugs, therefore we performed operation.

Background and Aim: The recommendedind ication of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)is Barcelona Clinic Liver Cancer(BCLC)stage B HCC. But there are some cases in which we do not perform TACE because of liver damage with malnutrition in stage B. So we examined whether branched-chain amino acid (BCAA)improve nutritional status and perform TACE to contribute the prolongation of HCC survival., Methods: This study included8 8 patients treatedfor liver cirrhosis with HCC. All patients initially receivedBCAA granules. In patients with unchangedor decreasedAlb levels, BCAA granules were discontinuedandBCAA enrichednutrient was started. TACE for HCC were performedin those with an improvedChild -Pugh score., Results: TACE were performedfollowing the aggressive intervention with BCAA nutritional education in 66 of 88(75%)patients. Finally, overall survival time was significantly extended in TACE group(p<0.0001)., Conclusion: Timely aggressive nutritional intervention in BCLC stage B HCC, early partial replacement with BCAA enrichednutrient before TACE may consequently contribute to improvement of the treatment outcome of HCC.

Objective: We evaluated the preoperative patient status including nutrition, immunity, and inflammation as a predictive factor of remote infection (RI) in colorectal cancer surgery., Subjects and Methods: A total of 351 patients who underwent colorectal cancer resection were retrospectively analyzed. Factors correlated with RI incidence were identified by logistic analysis and stepwise selection., Results: RI occurred in 27 patients, with an incidence of 7.7%. In univariate logistic analysis, a significantly high incidence of RI was associated with excessive blood loss (>423 mL), long duration of surgery (>279 minutes), ileus, pulmonary dysfunction, performance status (PS) ≥1, American Society of Anesthesiologists (ASA) classification>2, prognostic nutritional index (PNI) ≤40, and controlling nutritional status (CONUT) ≥2, modified Glasgow Prognostic Score (mGPS) (Score 2).In multivariate analysis, pulmonary dysfunction (odds ratio=2.83; 95% CI: 1.14-6.97; p=0.02) and PNI≤40 (odds ratio=3.87; 95% CI: 1.45-10.31; p=0.006) were independent risk factors of RI incidence., Conclusion: RI is caused by poor nutrition, immune system dysfunction and pulmonary dysfunction.

Incisional surgical site infection (SSI) is a leading complication of stoma reversal procedures. This retrospective study was conducted to assess the incidence of incisional SSI and other wound complications when wound closure was achieved by subcuticular suturing and closed suction drainage following stoma reversal. We analyzed data from a total of 49 patients, all of whom had undergone insertion of a 10 Fr closed suction drainage tube in the fascia, following irrigation with approximately 300 mL of physiological saline. We then performed subcuticular suturing with 4-0 monofilament absorbable sutures. The median age of our patient population (34 men and 15 women) was 68 (range, 35-84) years. Six patients had an end stoma and 43 had a loop stoma. The wound category was 'contaminated' in 18 patients, while an incisional SSI was observed in one patient (2.0%). No wound disruptions, seromas, or drain infections were evident. Our data are reliable, but our study is limited in terms of general applicability; however, the low SSI rate indicates that the procedure is acceptable. Further research into this procedure will require a randomized trial design.

Purpose: We analyzed to clarify an outcome of multiple resections of metastases from colorectal cancer., Patients and Method: Total 7 cases who underwent several resections for metastases from colorectal cancer in Saiseikai Kurihashi Hospital after 2010 were enrolled for analysis., Result: Age of patients at the time of the primary site resection was 67(45-78)year-old, including 4males and 3 females. Patients located at cecum/ascending/sigmoid/rectosigmoid/upper rectum were 1/1/2/2/1 respectively. Metachronous metastases were found in 5 patients. There were 1 patient for Stage I , 2 patients for Stage III a and III b each and all Stage III patients received adjuvant chemotherapy. The resected organs were 9 in lung, 8 in liver, 1 case in lymph node, local site and peritoneum and the median resected sites were 3(2-4)lesions. In 17 months median observation periods after latest resection, 5 cases have not been prolapsed including 3 cases with chemotherapy. Two cases were relapsed with unresectble status. One case died for 24 months and one case is under the chemotherapy for 12 months. Five year survival rate was 75% and 2 year prolapse free rate was 66.7%, since the relatively good prognosis was obtained by multiple resections., Conclusion: The cases that multiple resections with R0 were able to perform for the metastases were analyzed. Although cases which become finally to be unresectable exist, it is suggested that the relatively good prognosis might be obtained by multiple resections for metastases.

Objective: The objective of this study is to evaluate whether exogenously induced hyperinsulinemia may increase the development of atherosclerosis., Approach and Results: Hyperinsulinemia, induced by exogenous insulin implantation in high-fat fed (60% fat HFD) apolipoprotein E-deficient mice (ApoE -/- ) mice, exhibited insulin resistance, hyperglycemia, and hyperinsulinemia. Atherosclerosis was measured by the accumulation of fat, macrophage, and extracellular matrix in the aorta. After 8 weeks on HFD, ApoE -/- mice were subcutaneously implanted with control (sham) or insulin pellet, and phlorizin, a sodium glucose cotransporters inhibitor (1/2)inhibitor, for additional 8 weeks. Intraperitoneal glucose tolerance test showed that plasma glucose levels were lower and insulin and IGF-1 (insulin-like growth factor-1) levels were 5.3- and 3.3-fold higher, respectively, in insulin-implanted compared with sham-treated ApoE -/- mice. Plasma triglyceride, cholesterol, and lipoprotein levels were decreased in mice with insulin implant, in parallel with increased lipoprotein lipase activities. Atherosclerotic plaque by en face and complexity staining showed significant reductions of fat deposits and expressions of vascular adhesion molecule-1, tumor necrosis factor-α, interleukin 6, and macrophages in arterial wall while exhibiting increased activation of pAKT and endothelial nitric oxide synthase ( P <0.05) comparing insulin-implanted versus sham HFD ApoE -/- mice. No differences were observed in atherosclerotic plaques between phlorizin-treated and sham HFD ApoE -/- mice, except phlorizin significantly lowered plasma glucose and glycated hemoglobin levels while increased glucosuria. Endothelial function was improved only by insulin treatment through endothelial nitric oxide synthase/nitric oxide activations and reduced proinflammatory (M1) and increased anti-inflammatory (M2) macrophages, which were inhibited by endothelial nitric oxide synthase inhibitor., Conclusions: Exogenous insulin decreased atherosclerosis by lowering inflammatory cytokines, macrophages, and plasma lipids in HFD-induced hyperlipidemia, insulin resistant and mildly diabetic ApoE -/- mice., (© 2017 American Heart Association, Inc.)

We report a case of an advanced rectal cancer recurrence that responded completely to chemo-radiotherapy. The patient was an 80-year-old woman. Low anterior resection with D2(prxD3)lymph node dissection was performed. Sixteen months after operation, CEA level elevated but no recurrence foci were found in any image tests. Administration of TS-1 was initiated since recurrence was highly suspected. Twenty seven months after operation, PET-CT detected local recurrence in the posterior wall of the vagina. After construction colostomy, chemo-radiotherapy(60 Gy+oral UFT)was performed and CEA level dropped promptly to the normal value. No relapse was pointed out in CT scans or MRI tests. There were not any signs of recurrence through 112 months after chemo-radiotherapy.

To diagnose postoperative pancreatic fistula(POPF)after pancreaticoduodenectomy(PD)during early post operative days, we evaluatedwhether a change in drain amylase value(DAV), WBC value, or CRP value predicted clinically significant POPF. One hundred thirty patients underwent substomach preserving PD(SSPPD)from 2005 to 2016 in our institution andwe examinedDAV, WBC, andCRP values at POD 1, 3, and 5. Seventy-five patients(57.7%)were equivalent to ISGPF grade A at POD 3.We analyzedthese 75 cases by following 5 factors(DAV at POD 3>1,500 U/L, DAV at POD 5>1,000 U/L,WBC value at POD 5≤9,000/mL, DAV of POD 5 decreased to 1/3 from DAV of POD 3, CRP value not improved≥50%from POD 3 to 5) andwere concernedwith the crisis of the grade B/C POPF at final diagnosis after POD 5. In conclusion, DAV of POD 5 decreased to 1/3 from DAV of POD 3, andthe CRP value having not improved(≥50%from POD 3 to 5)were significant risk factors for POPF grade B andC by Cox proportional hazard models.

Case is a 66-year-old male. He was inserted covered self expandable metallic stent(SEMS)for jejunal stenosis due to gastric cancer recurrence. Migration was occurred after 4 days from stent replacement. We had removed SEMS by endoscopy, and re-inserted non-covered SEMS. Two months later, stent stenosis was occurred by tumor ingrowth. We tried to insert another stent in the stenotic stent. The patient was able to maintain oral intake without complication for 3 months. SEMS placement would improve a quality of life for selected patients with recurrent jejunal stenosis.

The aim of this study was to clarify the prognosis of cases with recurrent colorectal cancer that underwent curative resection in order to determine index for recurrent colorectal cancer treatment. Of the cases that exhibited recurrence after undergoing curative resection for primary colorectal cancer at our hospital between 1993 and 2013, this study targeted the 109 cases for which curative resection was possible. The sites of recurrence were the liver(58 cases), the lungs(27 cases), the peritoneum (11 cases), local sites(9 cases), lymph nodes(8 cases), and the anastomotic sites(6 cases). Of these, 10 cases exhibited metastasis to 2 organs. The median survival time after metastasectomy was 75.3 months, and the 5-year survival rate was 53.8%. The primary lesion histological type being a poorly differentiated adenocarcinoma/mucinous carcinoma, degree of progression upon initial onset being Stage III b or greater, and disease-free interval being less than 2 years were associated with poorpr ognosis. Specifically, histological type and disease-free interval were found to be independent factors that correlated with prognosis. Meanwhile, no differences were observed for prognosis related to the number of recurrent organs, the number of recurrent nodules, or the number of times curative resection was performed after recurrence. While the histological type and disease-free interval determine prognosis in cases with recurrent colorectal cancer performed curative resection, it appears that if curative resection is possible, aggressive resection should be pursued even for cases of multiple or repeated recurrence.

There have been many reports on ERCP for patients with alteredgastrointestinal anatomy(AGA), using balloon-assisted enteroscopy(BAE); however, BAE is not commonly usedin practice because it requires special endoscopic systems and accessories, which are time-consuming to operate. For this reason, patients with AGA who suffer from obstructive jaundice (OJ)might receive PTBD in general practice during emergency situations. We report a case of OJ, caused by recurrent gastric cancer andpreviously treatedwith distal gastrectomy andRoux -en-Y reconstruction(DGRY). The obstruction was relieved by ERCP for AGA, using conventional endoscopes. A 74-year-oldwoman, who hadpreviously undergone DGRY for advanced gastric cancer(AGC)andhadbeen receiving first-line chemotherapy for AGC recurrence, was admitted to our hospital for treatment of OJ, causedby progression of recurrent AGC, in July 2016. ERCP for AGA was performedusing conventional endoscopes, andOJ was successfully relievedby the insertion of a self-expandable metallic stent. Subsequently, second-line chemotherapy was administeredandthe patient enteredPR after 2 courses of chemotherapy.

Rationale: Activation of monocytes/macrophages by hyperlipidemia associated with diabetes mellitus and obesity contributes to the development of atherosclerosis. PKCδ (protein kinase C δ) expression and activity in monocytes were increased by hyperlipidemia and diabetes mellitus with unknown consequences to atherosclerosis., Objective: To investigate the effect of PKCδ activation in macrophages on the severity of atherosclerosis., Methods and Results: PKCδ expression and activity were increased in Zucker diabetic rats. Mice with selective deletion of PKCδ in macrophages were generated by breeding PKCδ flox/flox mice with LyzM-Cre and ApoE -/ - mice (MPKCδKO/ApoE -/- mice) and studied in atherogenic (AD) and high-fat diet (HFD). Mice fed AD and HFD exhibited hyperlipidemia, but only HFD-fed mice had insulin resistance and mild diabetes mellitus. Surprisingly, MPKCδKO/ApoE -/- mice exhibited accelerated aortic atherosclerotic lesions by 2-fold versus ApoE -/- mice on AD or HFD. Splenomegaly was observed in MPKCδKO/ApoE -/- mice on AD and HFD but not on regular chow. Both the AD or HFD increased macrophage number in aortic plaques and spleen by 1.7- and 2-fold, respectively, in MPKCδKO/ApoE -/- versus ApoE -/- mice because of decreased apoptosis (62%) and increased proliferation (1.9-fold), and not because of uptake, with parallel increased expressions of inflammatory cytokines. Mechanisms for the increased macrophages in MPKCδKO/ApoE -/- were associated with elevated phosphorylation levels of prosurvival cell-signaling proteins, Akt and FoxO3a, with reduction of proapoptotic protein Bim associated with PKCδ induced inhibition of P85/PI3K., Conclusions: Accelerated development of atherosclerosis induced by insulin resistance and hyperlipidemia may be partially limited by PKCδ isoform activation in the monocytes, which decreased its number and inflammatory responses in the arterial wall., (© 2017 American Heart Association, Inc.)

Here we report a case in which a locally advanced ascending colon cancer was successfully treated with anti-EGFR immunotherapy combined with chemotherapy and curative resection, and recurrent cancer was treated with the same chemotherapy. A 71-year-old man was diagnosed with ascending colon cancer in our department. No distant metastasis was observed, but curative resection was considered impossible because of extensive local cancer invasion. Because a genetic analysis revealed the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab were administered. A cPR was obtained and curative resection was performed. The final diagnosis was ypT3N1M0, ypStage III a colon cancer, and chemotherapy improved the cancer stage to Grade 1b. Six courses of FOLFOX6 were then administered, followed by observation. After 2 years 6 months, a tumor of approximately 5 cm in size was noted in the right buttock using surveillance CT and was diagnosed as recurrent colon cancer. We considered further curative resection difficult and therefore 6 courses of mFOLFOX6 plus panitumumab were administered, a cPR was obtained, and right hip tumor extirpation surgery was performed. These results suggest that chemotherapy combined with anti-EGFR antibody immunotherapy is effective in treating recurrent colon cancer.

Paitients and methods: We retrospectively reviewed a database of 188 patients who underwent resection for colorectal cancer with laparoscopic surgery between July 2007 and March 2015. The prognostic nutrition index(PNI), modified Glas- gow prognostic score(mGPS), controlling nutritional status(CONUT), and neutrophil/lymphocyte ratio(N/L)were measured in these patients. We examined the association between postoperative complications and clinicopathological factors., Results: The study included 110 men and 78 women. Median age was 68 years. The site of the primary lesion was colon in 118 and rectum in 70 patients. Postoperative complications higher than Grade II(Clavien-Dindo classification)were reported in 24(12.8%)patients: Surgical site infection(SSI)in 12, remote infection in 7, ileus in 5, and others in 2 patients. Clinicopathological factors related to complications were rectal surgery, large amount of intraoperative bleeding, and long operative time. The related immunologic and nutritional factors were mGPS 2, PNI below 40, and N/L above 3. CONUT was not associated with complications in ourcases., Conclusions: mGPS, PNI, and N/L are predictive factors for complications in laparoscopic colorectal surgery.

Aim: We examined the outcome of treatment with first-line chemotherapy with bevacizumab(Bmab)formetastatic colorectal cancer in our hospital to clarify the outcome for RAS mutant patients., Subjects and Methods: From January 2013 to April 2016, 28 patients who initiated standard chemotherapy(2 chemotherapeutic agents)with Bmab as the first-line regimen for metastatic colorectal cancer were enrolled in this retrospective study. Time to treatment failure(TTF)and overall survival(OS)were analyzed., Results: The median age was 66.5(46-81)years old, including 16 men and 12 women, 11 cases with RAS wild type, and 17 cases with mutant type. The response rate was 30.8% in 2 cases of CR, 6 cases of PR, 14 cases of SD, 4 cases of PD, and 4 cases with conversion surgery after chemotherapy. TTF was 6.5 months and OS was 32.1 months. Among those with RAS mutations, 3 cases received conversion surgery. TTF of the mutant and wild type were 6.3 and 5.6 months, respectively, and OS was 35.8 and 32.1 months, respectively, without any significant difference. In addition, excluding conversion cases, the OS of mutant and wild type patients was 22.7 and 29.5 months, respectively., Conclusion: The outcome of treatment using first-line chemotherapy with Bmab for metastatic colorectal cancer with RAS mutations was retrospectively analyzed. There was no difference in therapeutic effect between RAS mutated and not, and it seems that an OS of more than 20 months can be expected for those with RAS mutations with this choice of treatment.

Introduction: We investigated whether the prognostic nutritional index(PNI), controlling nutritional status(CONUT), modified Glasgow prognostic score(mGPS), and the neutrophil count/lymphocyte number ratio(NLR)could be prognostic factors for fStage II/III colorectal cancer., Subjects and Methods: The subjects were 115 patients with fStage II/III colorectal cancer who underwent curative resection. We studied the relationship with 3-year disease-free survival(DFS)and 5-year survival rate(OS)., Results: DFS and OS were 75.6% and 84.4%, respectively, and 81.3% and 69.6% for DFS and 82.4% and 84.4% for OS were in fStage II and III, respectively. Univariate analysis of DFS showed significant differences for sex, age, PNI, and NLR, but there was no difference in PS, location, adjuvant chemotherapy, CONUT, or mGPS. In multivariate analysis, sex(male)and NLR(>2)were independent prognostic factors(p=0.006 and p=0.01, respectively). As for OS, although significant differences were recognized for sex, age, PS, PNI, NLR, and CONUT, there was no difference in location, adjuvant chemotherapy, or mGPS. In multivariate analysis, PS(≥1)and NLR(>2)were independent prognostic factors(p=0.009 and p=0.006, respectively)., Conclusions: NLR(>2)was an independent prognostic factor for DFS and OS among prognos- tic factors based on inflammation, nutrition, and immunity in fStage II/III colorectal cancer patients.

We examined the relationship between risk factors for surgical site infections(SSIs)and prognosis in 440 patients who underwent colon cancer surgery. We evaluated factors related to SSIs(GradeB II)and compared survival rates by stage. SSIs were observed in 36 patients. An increased SSI incidence was associated with pulmonary dysfunction, mGPS=2, CONUT≥2, PNI≤40, NLR>4.3, location(rectum), depth of tumor invasion(Bsubserosa, SS), lymph node metastasis, laparotomy, resection of other organs, colostomy, blood loss(large), and operative time(long). Survival rates were lower in Stage II/III patients with SSIs. Preoperative risk judgment is important in colorectal cancer surgery.

Background/aim: Pancreaticoduodenectomy (PD) treatment outcomes in elderly patients have been reported to be acceptable, but the eligibility criteria are not clear. To elucidate the importance of PD in octogenarians in particular, we set five eligibility criteria for elderly patients based on preoperative cardiac and pulmonary function, nutritional status, daily activity status, and psychological independence status for the first time and evaluated prospectively whether the validity of patient selection was adaptable., Patients and Methods: The study population consisted of 222 patients with pancreaticobiliary cancer aged over 70 years. The patients were divided into two groups: 192 patients as septuagenarians and 30 as octogenarians. Postoperative morbidity and long-term outcome were compared between the two groups, and prognostic factors relating to survival time were identified., Results: Octogenarians had a significantly higher frequency of two or more comorbidities (p<0.0001). The difference in the mortality rates between the two groups was not significant, being 3.3% and 4.2%, respectively. No difference between the two groups was found in overall survival rate, including deaths due to other diseases, for any type of pancreaticobiliary cancer. Independent prognostic factors relating to survival duration were intraoperative blood loss (p=0.0004) and duration of surgery (p=0.0093)., Conclusion: These five eligibility criteria for PD in elderly patients are also satisfactorily applicable to octogenarian patients. These criteria may be helpful when uncertainties arise regarding the selection of PD., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6)., Methods: Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m 2  + leucovorin at 200 mg/m 2  + fluorouracil as a 400 mg/m 2 bolus followed by infusion of 2400 mg/m 2 over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician., Results: mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable., Conclusions: The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.

Purpose: Fluorouracil and folinic acid with irinotecan (FOLFIRI) plus bevacizumab (BV) is widely used as second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, oxaliplatin, and BV. FOLFIRI requires a CV catheter and an infusion pump, which are inconvenient for patients. Sufficient data are not available for characterizing the effectiveness of fluoropyrimidines beyond first disease progression. In this study, we evaluated the efficacy and safety of irinotecan (CPT-11) plus BV as second-line therapy., Methods: Patients with mCRC previously treated with at least four courses of a fluoropyrimidine, oxaliplatin, and BV were designated to receive 150 mg/m 2 of CPT-11 and 10 mg/kg of BV every 2 weeks as second-line therapy. The primary endpoint was progression-free survival (PFS), and secondary endpoints included response rate (RR), overall survival (OS), and adverse events., Results: Thirty patients from six institutes were enrolled from March 2011 to January 2014. The median PFS was 5.7 months (95% CI 4.2-7.3 months), and the RR was 6.7% (range 0.8-22.1%). Grades 3-4 adverse events included leucopenia (36.7%), neutropenia (50%), thrombocytopenia (26.7%), anemia (30%), diarrhea (3.3%), anorexia (6.7%), and hypertension (3.3%). Relative dose intensities were 94.5 and 96.3% for CPT-11 and BV, respectively. The median OS was 11.8 months (6.3 months-not reached)., Conclusions: Administration of CPT-11 plus BV to patients with mCRC achieved comparable efficacies with relatively lower toxicities compared with the results of previous studies using FOLFIRI plus BV as second-line therapy. The dose intensity of CPT-11 was judged as satisfactory., Clinical Trial Information: UMIN000005228.

Postoperative chylothorax after surgery for esophageal cancer is a rare but serious complication. Treatment initially consists of conservative therapy and, if it fails to provide improvement, it is important to perform surgical treatment without delay. We report on a recent case of intractable chylothorax. This report describes a 72-year-old man with Stage III esophageal squamous cell carcinoma. Subtotal esophagectomy, through a right thoracoabdominal approach with two-field lymphadenectomy, and cervical esophagogastric anastomosis via the retrosternal route, were performed. On the 12th postoperative day, a diagnosis of chylothorax was made. Conservative treatment was initiated, but it proved to be ineffective. Therefore, ligation of the thoracic duct via a thoracotomy was performed, but this was not effective, either. Lymphangiography undertaken to identify the site of the leak in the thoracic duct enabled a diagnosis of an extremely rare double thoracic duct and identification of the site of the leak in the thoracic duct, thereby allowing curative direct ligation of the site. This case underscores the remarkable usefulness of lymphangiography in dealing with intractable postoperative chylothorax.

Objective: The modified Glasgow Prognostic Score (mGPS) is an inflammation-based measure of malnutrition that reflects a state of cachexia in cancer patients. We evaluated mGPS as an index to predict surgical site infection (SSI) incidence in patients undergoing colorectal cancer surgery., Subjects and Methods: We retrospectively analyzed 351 patients who underwent colon cancer resection. Factors correlated with the incidence of SSIs were identified by logistic analysis and stepwise selection., Results: SSIs were observed in 32 patients, with an incidence of 9.1%. Univariate logistic analysis revealed mGPS (Score 2), laparotomy, resection of other organs, colostomy, excessive blood loss (>423 mL), long duration of surgery (>279 minutes), pulmonary dysfunction, prognostic nutritional index (PNI) ≤40, neutrophil lymphocyte ratio (NLR)(>4), and controlling nutritional status (CONUT) ≥2 to be associated with an increased incidence of SSIs. Multivariate analysis with variables selected by the stepwise procedure also revealed mGPS (Score 2) (Odds ratio (OR) =3.55, 95% Confidence interval (CI) 1.30-9.56; p=0.01), colostomy (OR=6.56, 95%CI 1.60-31.38; p=0.01), excessive blood loss (OR=3.20, 95%CI 1.23-8.42; p=0.02), and NLR (>4)(OR=3.24, 95%CI 1.31-8.17; p=0.01) to be independent risk factors., Conclusion: mGPS is an independent risk factor for SSIs. Our results suggest that cachexia before surgery in patients with colorectal cancer might predict the incidence of SSIs.

A 57-year-old woman with von Recklinghausen's disease presented with epigastralgia. Gastroduodenoscopy revealed swelling of the ampulla of Vater in the ventral and caudal direction, forming a hard, elastic mass. She was diagnosed with a tumor of the ampulla of Vater, and a subtotal stomach-preserving pancreaticoduodenectomy and D2 lymph node dissection were performed. The isolated specimen showed an intra-ampullary tumor of the ampulla of Vater and a submucosal tumor in the descending duodenum, which were diagnosed as a somatostatin-producing neuroendocrine tumor and gastrointestinal stromal tumor, respectively, on pathological examination. We believe that the neuroendocrine tumor of the ampulla of Vater and gastrointestinal stromal tumor of the duodenum are common gastrointestinal lesions in von Recklinghausen's disease.

Patients and Methods: From 2001, cases of 76 patients who underwent Cur A resection for colorectal cancer and preoperative prognostic nutritional index (PNI) assessment were analyzed in terms of clinicopathological factors, surgical outcomes, and prognosis., Results: Median age of the 36 men and 40 women included in the study was 83 years. Median PNI was 42.1. Twenty-four patients had a PNI below 40. There were 36 patients with pulmonary dysfunction, and 60 patients with D2 or wider LN dissection. Median operating time was 177 minutes. Postoperative complications were reported in 48 patients and SSI in 15 patients. Postoperative hospital stay was 16 days. During a median 30 month follow-up period, there were 16 deaths, including 8 from cancer-related causes and 8 from other disease-related causes. Patients with a PNI below 40 often had fewerD2 LN dissections(p=0.082)and significantly shorter operating times(p=0.015). First gait and first flatus were observed significantly later(p=0.0051, 0.0307). There were no significant differences in postoperative complication rates, SSI, postoperative hospital stay, cause of death, or survival., Conclusions: In the elderly aged over 80-years-old, because those with a PNI below 40 underwent resection with fewer LN dissections and shorter operating time, there were no significant differences in postoperative complications, cause of death, or prognosis. These results suggest that PNI could be a selection factor for surgical procedure in elderly patients aged over 80 years.

The objectives of the present study were to investigate the treatment outcomes of curative resection in patients with peritoneal metastases from colorectal cancer and to clarify the significance and limitations thereof. The study included 38 patients with colorectal cancer who underwent curative resection of peritoneal metastases between 1996 and 2014. Peritoneal metastases were classified as follows: metachronous(n=9)and synchronous(n=29); P1(n=13)and P2(n=25); and ovarian(n=5). Thirty patients received postoperative chemotherapy, includingoxaliplatin -based regimens(n=14)and other regimens, such as 5-FU/Leucovorin(n=16). The 3-year survival rate amongall patients was 59.9%. There were no differences in survival rates accordingto gender, serum CEA levels, location, differentiation, depth of invasion of tumor, number of organs with distant metastases, severity of peritoneal metastasis, and types of postoperative chemotherapy. However, poor outcomes were observed in patients with more advanced lymph node disease and in patients with metachronous metastases compared to those with synchronous metastases. Although curative resection can contribute to long-term survival in colorectal cancer patients with peritoneal metastases, the therapeutic effect may be limited in patients with lymph node metastases and those with metachronous metastases.

Aim: In general, transcatheter arterial chemoembolization(TACE)can obtain a high therapeutic effect on hypervascular tumors, but the definition of"hypervascular"is unclear. In this study, stainedtumor images on enhancedcomputedtomography( CT)were assessedaccord ing to CT-attenuation value. We investigatedwhether it is possible to estimate the treatment effect(TE)of TACE for hepatocellular carcinomas(HCCs)., Study Population and Methods: We studied 50 patients with unresectable HCCs who underwent TACE. A total of 141 tumors were diagnosed as HCC on enhanced CT. We measured andcalculatedthe ratios of CT-attenuation values of HCCs in the arterial phase to normal enhancedliver parenchyma in the portal phase(CT value ratio). We then evaluatedTE on each target nodule by enhancedCT, to examine the correlation between TE andthe CT value ratio., Results: The CT-attenuation values were 119(range 61-180)hounsfieldunits(HU)for HCC and8 3(49-141)HU for liver parenchyma, andthe CT value ratio was 1.47(0.7-2.6). TE was positively correlatedwith the CT value ratio(p=0.0005). The cut-off value that suggestedfavorable results for TACE was 1.7 by receiver operating characteristic(ROC)analysis., Conclusion: The CT value ratio is useful for recognition of hypervascular tumors. We obtained favorable results in cases with a CT value ratio of 1.7 or more.

There are several reasons for failure in the insertion of a self-expandable metallic stent(SEMS)into a malignant colonic obstruction(MCO)including difficulty in insertion of the catheter or guidewire through the stenotic lumen into the oral side or perforation relatedto the technique. Herein, we report a case of MCO bearing another synchronous obstructive lesion in the anal side of the colon that couldhave explainedthe difficulty in the insertion of the SEMS into the stenosis locatedin the oral side, which might have indicated the need for an emergency operation for relieving the obstruction. A 76-year-oldman with epigastralgia andmelena was admittedto our hospital andhe was diagnosedwith a MCO in the ascending colon. A series of examinations performedafter admission revealedthat the patient hadanother synchronous obstructive lesion in the descending colon, which made colonoscope insertion at the oral side difficult. The next day after admission, we observed that fasting relievedthe patient from abdominal pain causedby obstruction; therefore, we performedSEMS insertion into the MCO of the descending colon followed by SEMS insertion into the ascending colon after 6 days. These serial SEMS insertions facilitated the oral administration of the diet and the patient was discharged 15 days after admission. The patient was readmittedto our hospital andhe underwent a radical operation for both lesions in June 2015.

A 78-year-old man visited our hospital with a prolapsed hemorrhoid. He was referred to the dermatology unit due to the thickness and redness of the perianal skin. He was diagnosed as having extra mammary Paget's disease by skin biopsy. After a biopsy of the anal polyp was performed to investigate the primary site, he was diagnosed with early anal canal cancer with Pagetoid spread and underwent a radical operation. Abdominoperineal resection with skin(D2 prx D3 lymphadenectomy) was performed with perineal reconstruction using a gracilis muscle graft. Postoperative surveillance without adjuvant therapy was performed because the pathological stage was stage I. Two years and 2 months after surgery, multiple liver metastases were found, and the patient was diagnosed with multiple liver, bone, and lymph node metastases(K-ras and UGT1A1 wild type)on PET. XELOX plus bevacizumab was used as first-line treatment and the liver metastases showed remarkable shrinkage; however, disease progression occurred in the bone. IRIS plus bevacizumab was started as second-line therapy but grade 3 hematotoxicity was observed during the first course. After 4 courses, it was difficult to maintain the therapy due to toxicity and cancer-related pain. The liver metastases had almost disappeared but the patient died 11 months after the initiation of chemotherapy.

Three hundred and fourteen patients with pT3 or deeper, Stage II/IIIcolorectal carcinoma who underwent curative operation were divided into two groups: age 75 years and more(elderly)and 74 years and less(non-elderly), to identify prognostic factors and risk factors for postoperative complications. Higher comorbidity rates and poorer nutritional status where found in the elderly group, which led to a shorter operation time and less lymph node dissection. There were no significant differences in 5-year OS and 3-year RFS between the two groups. These results suggest that elderly patients with colorectal carcinoma can achieve outcomes equal to the non-elderly group by curative resection even if it is not standard radical resection.

Background: We examined the significance of neutrophil lymphocyte ratio(NLR)in gastric cancer and colon cancer in the perioperative period., Method: There were 46 patients(21 with gastric cancer and 25 with colon cancer). We examined the association between preoperative NLR and other indicators of nutritional status, as well as the relationship between preoperative NLR and the incidence of postoperative complications(all complications/infectious complications)., Result: NLR was higher in those with zinc<65 mg, prognostic nutritional index(PNI)≤40, and modified Glasgow prognostic score(mGPS)of 2 (p<0.05). NLR showed no difference among all patients with complications(12 cases), but was higher in patients with infectious complications(p<0.05)., Conclusion: Preoperative NLR is correlated with PNI as a predictor of infectious complications.

We investigated the significance of serum p53 antibody in colorectal cancer. The subjects included 239 patients with colorectal cancerwithout any history of priortr eatment. Patients with multiple cancerordouble cancerwer e excluded. Serum p53 antibodies and relationships with clinicopathological factors and prognosis were examined. The preoperative positive rate of serum p53 antibody was 28.9%. There was no relationship between p53 antibody and clinicopathological factors or degree of progression. Examination of a possible relationship with prognosis revealed that p53 antibody was not related to whether recurrence occurred, and there was no difference observed for survival rate. Examination of the cases in which serum p53 antibody was measured continuously after curative resection revealed that there was a tendency to find a low incidence of cancer recurrence in cases in which serum p53 antibody became negative postoperatively. Furthermore, cancer recurred at a low incidence in the cases in which p53 antibody was on the decrease postoperatively(p=0.0008). Thus, ourr esults show that serum p53 antibody in colorectal cancer cases is not related to clinicopathological factors or prognosis. However, in cases positive for preoperative serum p53 antibody, changes in postoperative levels of the titer could be a marker for recurrence.

A 57-year-old woman had been diagnosed with sigmoid colon cancer at surgery for ovarian cancer, and underwent simultaneous radical resection. Because of the pathological diagnosis of sigmoid cancer with ovarian metastasis, adjuvant chemotherapy was scheduled, with Leucovorin(LV)25 mg. This was immediately followed with 5-fluorouracil(5-FU)500 mg, via a 2-hour systemic intravenous infusion daily for 5 consecutive days, with courses repeated at 5 weeks, followed by maintenance once every 1 or 2 weeks for 2 years. There had been no evidence of recurrence for 10 years after surgery; however, peritoneal recurrence and a thyroid tumor were found using computed tomography(CT)at the 10-yearsur veillance. Chemotherapy with mFOLFOX6+bevacizumab was initiated because the peritoneal recurrence was determined to be unresectable and because of the metastasis to the thyroid. Chemotherapy was maintained, except for oxaliplatin(L-OHP)due to toxicity, with shrinkage of the peritoneal tumor; however, it was difficult to maintain the chemotherapy due to toxicity. Eleven months after initiation of chemotherapy, lung and bone metastases were detected, and she subsequently died.

The effect of enhancing insulin's actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet-induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice. Increased angioblasts and EC numbers in GT of ECIRS1 mice were due to proliferation in situ rather than uptake. GT in HF-fed diabetic mice exhibited parallel decreases in insulin and VEGF-induced pAkt and EC numbers by >50% without changes in angioblasts versus WT mice, which were improved in ECIRS1 TG mice on normal chow or HF diet. Thus, HF-induced diabetes impaired angiogenesis by inhibiting insulin signaling in GT to decrease the differentiation of angioblasts to EC, which was normalized by enhancing insulin's action targeted to EC, a potential target to improve wound healing in diabetes and obesity., (© 2016 by the American Diabetes Association.)

Background: In decompensated liver cirrhosis, hypoalbuminemia still persists even after they have been treated with branched-chain amino acid (BCAA) granules. We prospectively evaluated whether BCAA enriched nutrient switched from BCAA granules would increase the serum albumin level, and consequently extend the survival time after hepatocellular carcinoma (HCC) treatment., Methods: This study included 77 patients treated for liver cirrhosis with HCC. After the nutritional assessment, all patients initially received BCAA granules. In patients with unchanged or decreased serum albumin levels, BCAA granules were discontinued and BCAA enriched nutrient was started. Transcatheter arterial chemembolization (TACE) for HCC were performed in those with an improved Child-Pugh score., Results: TACE were performed following the aggressive intervention with BCAA nutritional education in 54 of 77 (70.1%) patients. Finally, survival time was significantly extended in the TACE group (P<0.0001)., Conclusion: Timely aggressive nutritional intervention in Barcelona Clinic Liver Cancer stage B HCC, namely, early partial replacement with BCAA enriched nutrient may consequently improve the treatment outcome of HCC.

Application of herbicides to paddy fields in Japan has strong seasonality, and their environmental concentrations exhibit clear spatiotemporal variation. The authors developed an approach that combines a multimedia environmental exposure model (Grid-Catchment Integrated Modeling System) and density dynamics models for algae. This approach enabled assessment of ecological risk when the exposure concentration shows spatiotemporal variation. First, risk maps of 5 herbicides (pretilachlor, butachlor, simetryn, mefenacet, and esprocarb) were created from the spatial predictions of environmental concentrations and 50% inhibitory concentrations of the herbicides. Simulations of algal density dynamics at high-risk sites were then conducted by incorporating the predicted temporal dynamics of the environmental concentration of each herbicide at the sites. The results suggested that the risk of pretilachlor was clearly the highest of the 5 herbicides, in terms of both the spatial distributions and the temporal durations. The present study highlights the importance of integrating exposure models and effect models to clarify spatial and temporal risk and to develop management plans for chemical exposure that shows high spatiotemporal variation., (© 2015 SETAC.)

Background: Although neuroendocrine tumors are most commonly found in the digestive system, neuroendocrine tumors originating from the bile duct are rare, and neuroendocrine carcinomas derived from the perihilar bile duct are extremely rare. This report presents the clinical course and clinicopathological features of neuroendocrine carcinomas arising from the extrahepatic bile duct., Case Presentation: A 70-year-old Japanese woman was preoperatively diagnosed with perihilar cholangiocarcinoma, and a radical resection with an extended left hepatic lobectomy and a choledochojejunostomy was performed. From the histopathological findings, we diagnosed the tumor as a neuroendocrine carcinoma of the bile duct (small cell type) with lymph node metastasis. The patient was treated with the same adjuvant chemotherapy as that used for small cell carcinoma of the lung. At 10 months after surgery, there was no recurrence of the disease., Conclusion: Neuroendocrine carcinoma of the extrahepatic biliary tracts is a very rare and highly malignant disease with a poor prognosis. A multidisciplinary approach could improve the prognosis for this neoplasm.

We report a case of restenosis after performing stenting twice for ileus caused by peritoneal dissemination that occurred after surgery for sigmoid colon cancer, in which colostomy was performed to improve the patient's QOL. The patient was a 58-year-old woman who underwent sigmoidectomy for sigmoid colon cancer. She presented with a peritoneal recurrence 3 times, and the third surgery was a non-curative resection. Chemotherapy was administered but was discontinued because of severe adverse events, and the patient was followed up with the best supportive care. An anastomotic stricture occurred 4 years after the initial surgery, and despite performing stenting twice, stenosis occurred 3 times within a few months. The third stenosis occurred shortly after the second episode, and colostomy was therefore performed. The patient died from cancer 4 months after colostomy without having another episode of stenosis. Although stenting is effective for patients with malignant colon stenosis, colostomy appears to be more effective for repeated post-stenting stenosis, when the patient is in an eligible general condition.

Patients with Lugol-voiding lesions of the esophagus are frequently affected with multiple cancers. Basaloid carcinoma of the esophagus is a very rare disease characterized by growth in the submucosal layer that exhibits a submucosal tumor-like shape. There have been some reports that this type of carcinoma is biologically high-grade. We report a case of metachronous squamous cell carcinoma in situ and superficial basaloid carcinoma in the esophagus with Lugol-voiding lesions. A 63-year-old man underwent gastrectomy for gastric cancer at the age of 45 years. The subsequent surveillance endoscopy found a type 0-Ⅱc lesion in the esophagus in 2000. EMR was thus performed. The pathology showed squamous cell carcinoma in situ. Dysplasia was diagnosed based on the Lugol-voiding lesions, and EMR was performed twice. In 2014, a fourth EMR was performed after a high-grade intraepithelial neoplasia was diagnosed. The pathology showed squamous cell carcinoma in situ and a basaloid carcinoma in the lamina propria, T1a-LPM, ly0, v0, pHMX, pVM0. The patient has had no recurrence for approximately 1 year after the fourth EMR.