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A 16-y-old Japanese female was referred to our hospital with a suspicion of infected retroperitoneal cyst. Abdominal CT MRI revealed a 38-mm diameter retroperitoneal cyst under the left diaphragm. Because a retroperitoneal bronchogenic cyst was suspected, total resection was planned. In addition, preoperative 3D reconstruction using multidetector CT provided a detailed location of the lesion. Based on the anatomical position, we decided that single-incision laparoscopic surgery with an anterior approach through the umbilicus would be the optimal choice. The lesion was completely resected without intraoperative complications. Histopathological examination confirmed the diagnosis of bronchogenic cyst. Postoperatively, the surgical wound became completely unnoticeable, and there was no incisional hernia or cyst recurrence at the 2-y follow-up.

Purpose FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. Methods Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). Results Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8–77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. Conclusions FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

We herein report the first case of rectal stenosis that developed after internal hemorrhoid treatment with aluminum potassium sulfate and tannic acid (ALTA) therapy that was successfully treated by laparoscopic surgery. A 72-year-old man suffered from a fever and rectal stenosis after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA at a previous clinic. Three months after ALTA therapy, he developed frequent mucous and bloody stools. Lower intestinal tract endoscopy revealed circumferential severe rectal stenosis. He was therefore referred to our hospital. The patient suffered from frequent stool build-up and difficulty defecating. We performed balloon-dilatation intervention. The stenosis was not improved at all. Five months after ALTA therapy, we performed laparoscopic low anterior resection with diverting ileostomy. Three months after the operation, ileostomy takedown was performed. The patient has experienced no rectal stenosis in the 2 years since his radical operation.

Highlights • Appendicular endometriosis a rare entity which usually presents with symptoms of abdominal pain, melena, and constipation. • Appendicular endometriosis can present as a submucosal tumor in the cecum without any abdominal symptoms. • Single-incision laparoscopic surgery is an useful procedure for cecum tumor resection., Introduction We report the case of characteristic findings of appendicular endometriosis that presented as a submucosal tumor in the cecum without any abdominal symptoms treated with single-incision laparoscopic ileocolectomy. Presentation of case The patient was a 51-year-old woman (body mass index: 21.5) who underwent an examination to investigate the cause of a positive fecal occult blood test. Her laboratory test results were normal, without anemia or tumor marker elevation. Colonoscopy revealed a submucosal tumor in the cecum. Enhanced computed tomography (CT), fluorodeoxyglucose-positron emission tomography-CT and magnetic resonance imaging failed to produce a clear diagnosis. Given the malignant potentiality of the tumor, ileocolectomy was considered potentially necessary, but she wished for minimally invasive surgery. She ultimately underwent ileocolectomy and lymphadenectomy with single-incision laparoscopic surgery. A pathological examination revealed the lesion to be appendicular endometriosis, and 14 lymph nodes with no malignancy were resected. Conclusion Appendicular endometriosis can present as a submucosal tumor in the cecum without any abdominal symptoms. Appendicular endometriosis should be considered in the differential diagnosis of ileocecal submucosal tumor. Single-incision laparoscopic ileocolectomy was useful procedure for cecum tumor resection.

Background: Complicated appendicitis is an indication for emergency surgery. Therefore, the predictive factors for appendicitis based on the patient background needs identification. Previously, factors predicting non-complicated and complicated appendicitis were reported. However, most of those reports were deemed unsuitable as a standard for emergency use, since those comprised too many items as predictors. We previously reported three items that preoperatively predicted complicated appendicitis (body temperature, C-reactive protein, and fluid retention around the appendix). In this study, we re-evaluated different cases to confirm the usefulness of these three items can for accurately predicting complicated appendicitis preoperatively. In addition, we compared the effectiveness of these predictor items with those reported by other researchers.Methods: We retrospectively evaluated 417 adult patients who underwent surgery for acute appendicitis between January 2013 and December 2019, and compared our predictor items with those used in previous reports on the preoperative prediction of complicated appendicitis (criteria A consisting of eight predictor items and criteria B consisting of seven predictor items). Results: The area under the receiver operating characteristic curve (AUC) for the sensitivity to diagnose complicated appendicitis according to our criteria, criteria A, and criteria B were 0.823, 0.839, and 0.856, respectively. The AUC of our criteria and criteria A were similar (P = 0.356); those of criteria A and B were also similar (P = 0.352). However, the AUC of criteria B was statistically higher than that of our criteria (P < 0.05).Conclusion: Diagnostic criteria B were statistically the best predictor items for characterizing complicated and uncomplicated appendicitis. However, like criteria A and B, the AUC of our criteria exceeded 0.8, and only involved three predictor items; therefore, they can be considered useful predictors.

Background/aim Right ventricular cardiac metastasis from colorectal cancer (CRC) is rare and clinically silent. There is no standardised treatment. To date, only twelve cases have been reported in the literature. This is a case report and literature review of right ventricular cardiac metastasis from CRC. Case report A 75-year-old woman with a history of CRC treated with sigmoidectomy followed by liver and lung metastasectomy presented with a right ventricle tumour. Biopsy showed metastatic adenocarcinoma not suitable for resection because multiple lung metastases coexisted. The metastases were controlled for a prolonged duration by chemotherapy with capecitabine plus bevacizumab. According to the review of 13 cases, the median age of metastatic CRC that involves the right ventricle is 71 years and the primary site is half the colon and rectum. Half of cases have non-cardiac metastases at cardiac metastasis diagnosis. Chemotherapy is more suitable than resection in cases with metastases other than heart because resection of the right ventricle has a high risk. Conclusion Cardiac right ventricular metastasis from CRC can be controlled by capecitabine plus bevacizumab.

Background Rectovaginal fistula (RVF) following aluminum potassium sulfate hydrate-tannic acid (ALTA) injection therapy for hemorrhoids is a rare complication. We report the first case of RVF after ALTA injection therapy successfully treated by gluteal-fold flap. Case presentation A 49-year-old female suffered from a fever and rectal ulcer after undergoing internal hemorrhoid treatment with a submucosal ALTA injection at a previous clinic. One week after ALTA therapy, she noted obvious passage of flatus and stool through the vagina, and was diagnosed with RVF by anoscope at another clinic. She was referred to our hospital 3 weeks after ALTA therapy. Sigmoid colostomy was performed for fecal diversion as a preliminary step for fistula repair. However, the fistula was scarred and the defect between the rectum and vagina did not improve at all. Ten months after ALTA therapy, we performed fistula repair by gluteal-fold flap. Seven months later, sigmoid-colostomy reversal was performed. The patient has experienced no RVF in the 3 years since sigmoid-colostomy reversal. Conclusions The gluteal-fold flap strategy is a useful option for severe RVF management.

Introduction The number of elderly patients with colorectal cancer has gradually increased. Laparoscopic colorectal surgery is widely used to approach colorectal cancer. The aim of this study was to evaluate long-term outcomes in octogenarians who underwent laparoscopic colorectal surgery for colorectal cancer. Methods This study included 158 patients aged 80 or over who underwent surgery for colorectal cancer between 2010 and 2015. We compared long-term outcomes of a laparoscopic colorectal surgery group with those of an open colorectal surgery group by propensity score matching equalizing factors that could affect prognosis such as prognostic nutritional index and Charlson comorbidity index score. Results Forty-eight pairs were selected after propensity score matching. The cancer-specific 5-year survival rate was 97.1% in the laparoscopic colorectal surgery group and 87.6% in the open colorectal surgery group (P = .17). The overall 5-year survival rate was 77.3% in the laparoscopic colorectal surgery group and 73.9% in the open colorectal surgery group (P = .32). The 5-year recurrence-free survival rate was 95.1% in the laparoscopic colorectal surgery group and 85.4% in the open colorectal surgery group (P = .14). Conclusion Laparoscopic colorectal surgery for octogenarians with colorectal cancer achieves similar oncological outcomes to open colorectal surgery and should be considered as a treatment option.

Rectal tumors are traditionally resected by proctectomy to ensure the achievement of negative margins, an approach associated with an adverse impact on subsequent quality of life due to sequelae such as permanent stoma and urinary and sexual dysfunction. Many studies have now demonstrated that recurrence after local excision of early rectal tumors is significantly higher than would typically be expected. We have developed a new procedure, described herein, that combines local resection with endoscopic submucosal dissection for low rectal tumor. We report four consecutive cases (three submucosal tumors and one tumor with clinical deep submucosal invasion) treated at Hiroshima City Asa Citizens Hospital between January 2009 and March 2018. The mean duration of the procedure was 137 minutes. The en bloc resection and histologically complete resection rates were 100 %. Delayed bleeding and perforation rates were 0 %. Postoperative complications were fever and anal pain (one case each). All patients recovered with conservative therapy. No recurrence was found in any of the four patients during a follow-up period of 56 months. Our combined endoscopic and surgical procedure for low rectal tumors enabled definite negative vertical margins, reduced tumor volume, allowed for accurate pathological diagnosis, preserved rectal function, and aided the decision on additional therapy.

Schwannomas are tumors originating from the Schwann cells of the peripheral nerve sheath. Only 1%-3% of schwannomas reportedly occur in the pelvis. In a 67-year-old man, a pelvic mass that was 52 mm in diameter was incidentally diagnosed during a preoperative CT evaluation for prostate cancer. Preoperative 3-D reconstruction CT showed that the feeding artery to the tumor originated from the internal iliac artery and the drainage vein from the internal iliac vein. Each vessel could be isolated, clipped, and cut with minimal bleeding. The tumor was easily dissected from adjacent structures and was completely resected via laparoscopic surgery. Histopathology and immunohistochemistry of the excised specimen revealed a benign schwannoma. Using 3-D reconstruction to recognize a tumor's positional relation with the supplying vessels is important for avoiding complications during laparoscopic resection in the narrow pelvis. Laparoscopic resection is safe, feasible, and effective for retroperitoneal schwannoma.

Highlights • Intestinal obstructions caused by external compression from the appendix are rare. • Low-grade appendiceal mucinous neoplasm (LAMN) with torsion is rarer still. • LAMN have the potential to lead to pseudomyxoma peritonei. • Surgical resection for LAMN is the standard treatment. • The appropriate surgical procedure, however, remains controversial., Introduction Intestinal obstructions due to appendiceal pathology are rare. Obstructions caused by low-grade appendiceal mucinous neoplasms (LAMNs) are rarer still. Presentation of case A 79-year-old woman was referred to our hospital for mechanical small intestinal obstruction. The patient had undergone prior left oophorectomy via a lower abdominal incision. Physical examination revealed abdominal distension and slight tenderness. Laboratory analysis was unremarkable. Contrast enhanced computed tomography (CT) demonstrated dilation of an obstructed small intestinal loop without evidence of strangulation. There appeared to be a low density mass measuring 3.0 × 1.5 cm with a potential twist in the mesentery near the transition point in the small intestine. The patient was diagnosed with mechanical small intestinal obstruction and was treated conservatively with nasogastric tube decompression for one week. After no clinical improvement, we elected to surgically explore her. Intraoperative findings revealed that the ileum was compressed by the appendix, which had a cystic mass on its tip. There was no evidence of intestinal ischemia. Laparotomy appendectomy alone was performed. Pathology revealed a LAMN measuring 3.0 × 1.5 cm. She remains disease-free with 18 months of postoperative follow-up. Discussion Intestinal obstruction due to external compression by an appendiceal mass is rare, and is often difficult to preoperatively diagnose with CT. Conclusions The etiology of small intestinal obstruction with a transition point in the right lower quadrant of abdomen includes an appendiceal mass on the broad differential for this common problem.

A 61-year-old man presenting with abdominal pain and fever refractory to antibiotics underwent diagnostic laparoscopy and non-mass-forming isolated omental panniculitis was identified. He presented with left-upper-quadrant abdominal pain. Laboratory data and the CT findings suggested intraabdominal bacterial disease in the splenic flexure, which we treated with antibiotics and fasting. He clinically improved once, but later relapsed with abdominal pain migration to the left-lower-quadrant. CT re-examination revealed no inflammation in the splenic flexure, but attenuation of adipose tissue in the greater omentum. We partially extracted the greater omentum during diagnostic laparoscopy and diagnosed omental panniculitis and administered steroids. He improved and was discharged three days after starting oral prednisone and is recurrence-free with a close follow-up. The characteristic CT feature of omentum panniculitis is a high-density fatty mass, but we noted only an attenuation of adipose tissue in the greater omentum. Diagnositic laparoscopy is useful for diagnosing this condition.

Highlights • Few cases of splenic hamartomas associated with thrombocytopenia have been reported. • Imaging findings in splenic hamartomas are non-specific, variable, and making definitive preoperative diagnosis difficult. • Surgery is necessary for diagnosis when malignancy cannot be ruled out. • Surgery may also improve symptoms of hypersplenism, including thrombocytopenia., Introduction Hamartomas are rare, benign tumors of the spleen. Few cases of splenic hamartomas associated with thrombocytopenia have been reported. Presentation of case An asymptomatic 64-year-old man with myelodysplastic syndrome was found to have a splenic tumor. Laboratory tests were significant for thrombocytopenia, with a platelet count of 7.8 × 104/μL. Ultrasonography showed splenomegaly (10.8 × 6.6 cm), and a hypoechoic splenic mass (8.0 × 7.0 cm). Color doppler ultrasound revealed blood flow within the mass, and the mass density was homogeneous on abdominal computed tomography (CT). Contrast-enhanced CT showed heterogeneous enhancement of the splenic mass during the arterial phase. Positron emission tomography (PET)-CT showed no significant fludeoxyglucose (FDG) accumulation within the mass. The differential diagnosis included splenic hamartoma, splenic hemangioma, splenomegaly associated with extramedullary hematopoiesis, and malignant tumor, including solitary splenic metastasis. A laparoscopic splenectomy was performed due to the possibility of malignancy, the presence of thrombocytopenia, and the risk of splenic rupture. The resected specimen showed a localized, well-demarcated, 8.0 × 7.0 cm splenic mass. Histological examination revealed abnormal red pulp proliferation and the absence of normal splenic structures. The patient’s post-operative course was uneventful. His platelet count improved on post-operative day 1 and he was discharged on post-operative day 9. He remained in good health with a normal platelet count one month after surgery. Discussion Making definitive preoperative diagnosis is difficult in splenic hamartomas. Surgery is necessary for diagnosis when malignancy cannot be ruled out. Conclusions Surgery may also improve symptoms of hypersplenism, including thrombocytopenia.

Although synbiotics may be effective in maintaining remission of inflammatory bowel disease, their anticarcinogenic effects are still debated. To address this issue, we evaluated the effects of synbiotics, probiotics, and prebiotics on tumorigenesis using a CDX2P-Cre; Apc+/flox mouse model harboring a colon-specific Apc knock out, which develops adenoma and adenocarcinoma of the colon. Dextran sodium sulfate (DSS)-administration promoted colonic tumor development in CDX2P-Cre; Apc+/flox mice, and these tumors were associated with loss of Apc heterozygosity, as confirmed by observation of well-differentiated adenocarcinomas with β-catenin accumulation in tumor cell cytoplasm. Synbiotics-treatment suppressed dextran sodium sulfate-induced colitis in CDX2P-Cre; Apc+/flox mice, thereby reducing mortality, and inhibited tumorigenesis accelerated by DSS-administration. Conversely, neither probiotics nor prebiotics had any effect on inflammation and tumorigenesis. Lactobacillus casei and Bifidobacterium breve were detected in the fecal microbiota of probiotics-treated mice. Synbiotics-treatment suppressed DSS-induced expression of IL-6, STAT-3, COX-2, and TNF-α gene transcripts in normal colonic epithelium, indicating the possibility of suppressing tumor development. Importantly, these genes may be potential therapeutic targets in inflammation-associated colon cancer.

Epithelial ovarian cancer is an aggressive gynecological malignancy with a high mortality rate. Resistance against chemotherapeutic agents often develops in ovarian cancer patients, contributing to high recurrence rates. The multidrug resistance 1 (MDR1/ABCB1) gene encodes P‐glycoprotein, which affects the pharmacokinetic properties of anticancer agents. We previously reported that the Caudal‐related homeobox transcription factor CDX2 transcriptionally regulates MDR1 expression in colorectal cancer. CDX2 is a factor that influences cancer cell differentiation, malignancy, and cancer progression. We hypothesized that profiling of CDX2 and MDR1 expression could be an effective strategy for predicting anticancer drug resistance. We studied the expression of these factors in clinical samples from ovarian cancer patients. We found that endogenous MDR1 expression was positively associated with CDX2 expression in ovarian mucinous adenocarcinoma. Using ovarian mucinous adenocarcinoma cell lines, we also observed decreased MDR1 expression following inhibition of CDX2 by RNA interference. In addition, CDX2 overexpression in MN‐1 cells, which display low endogenous CDX2, resulted in upregulation of MDR1 expression. CDX2 induced MDR1‐dependent resistance to vincristine and paclitaxel, which was reversed by treatment with the MDR1‐specific inhibitor verapamil. Our findings show that CDX2 promotes upregulation of MDR1 expression, leading to drug resistance in ovarian mucinous adenocarcinoma. Therefore, our study demonstrates the potential of novel chemotherapy regimens based on CDX2 status and MDR1 expression in ovarian mucinous adenocarcinoma.

Aim To reveal systemic chemotherapy outcomes and the suitable first-line regimens for elderly (≥75 years) metastatic colorectal cancer (mCRC) patients. Methods We retrospectively compared systemic chemotherapy outcomes between elderly (≥75 years) and adult (≤74 years) patients with mCRC who were treated between January 2007 and December 2012 at Hiroshima University Hospital and analyzed the outcomes of elderly patients after treatment with single-agent oral 5-fluorouracil chemotherapy (oral FC) or intravenous combination chemotherapy (IV CC) as the first-line regimen. Results A total of 140 patients with mCRC were enrolled. The median age of adult patients was 60 years, compared to 77 years for elderly patients. There were no significant differences between the two groups in terms of patient characteristics and the stage of cancer progression. Overall survival (OS) (median, 20.7 vs 26.5 months; P = 0.65) and first-line progression-free survival (PFS) (median, 11.0 vs 9.8 months; P = 0.36) did not differ significantly between elderly patients and adult patients. Among elderly patients, first-line PFS (median, 10.3 months vs. 11.8 months; P = 0.85) and the incidence of grade 3 adverse events (22.2% vs. 44.4%; P = 0.31) were similar in the oral FC and IV CC groups. Conclusion The results of this study suggest that elderly patients with mCRC who can receive chemotherapy derive an equivalent survival benefit to adult patients. First-line oral FC may be better suited for elderly patients with mCRC.

Highlights • Single-incision laparoscopic surgery has been performed for resection of benign and malignant gastrointestinal tumors in recent years; however, its safety and feasibility is still controversial, and there have been no reports of its use in resecting mesenteric cysts. • This report deals with the first case of a mesenteric chylous cyst successfully treated by single-incision laparoscopic surgery., Introduction Chylous mesenteric cysts are rare intra-abdominal lesions located in the mesentery of the gastrointestinal tract and may extend from the base of the mesentery into the retroperitoneum. The treatment is the complete removal of the cyst Presentation of case A 49-year-old female presented with abdominal pain. Abdominal computed tomography showed a 5.0-cm-diameter intraabdominal, homogenous cystic lesion located on the mesentery of the small intestine. Single-incision laparoscopic surgery was performed for complete resection. Discussion Only a handful of cases of laparoscopic surgery for a mesenteric cyst have been reported, and no reports have been published regarding single-incision laparoscopic surgery for a mesenteric cyst. Conclusion We report the first known case of a chylous mesenteric cyst that was successfully treated by single-incision laparoscopic surgery.

134 Background: FOLFOXIRI-Bmab has been recognized as one of the standard first-line treatments for mCRC. We conducted a single arm, multicenter, phase II study to assess the efficacy and safety of FOLFOXIRI-Bmab in pts with untreated mCRC harboring UGT1A1(*6 and *28) wild or single hetero genotype. Methods: Pts received FOLFOXIRI-Bmab (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin 200mg/m2, fluorouracil 3200 mg/m2 and Bmab 5mg/kg repeated biweekly) up to a maximum of 12 cycles, followed by the sequential therapy which consisted of the remaining drugs if any of the individual drugs were discontinued at the investigator’s discretion. Protocol therapy was continued until progressive disease, an unacceptable adverse event, tumor resection or consent withdrawal. The primary endpoint was ORR evaluated by central reviewers. Secondary endpoints include TTF, PFS, OS, R0 resection rate, relative dose intensity (RDI) and safety. The exploratory objectives were early tumor shrinkage (ETS), depth of response (DoR). Results: 47 pts were enrolled from 16 centers between April 2015 and May 2017, of whom 1 was excluded for not meeting the inclusion criteria. The full analysis set consisted of 44 pts because 2 had no target lesions that were considered measurable lesion by central reviewers. 46 pts had the following characteristics: median age 58 (29-68), 57% male, 76% PS0, 22% right-sided tumors and 52% UGT1A1 wild. RAS status was 37% wild, 52% mutant, 11% unknown. Primary endpoint was met. The ORR was 63.6% (95% CI, 47.8-77.6). ETS and DoR was 70.5%, 43.9%, respectively. R0 resection rate was 23%. Median PFS was 15.5mo (95% CI, 11.5-23.4). Median TTF was 8.1mo (95% CI, 5.3-10.1). Median OS was 34.4mo (95% CI, 26.4-not reached). The mean RDI of fluorouracil, irinotecan and oxaliplatin were 71%, 67%, and 64%, respectively. Grade 3 or higher adverse events (≥10%) were neutropenia (65.2%), febrile neutropenia (FN) (26.1%), anorexia (10.9%), nausea (10.9%), and diarrhea (10.9%). No treatment-related deaths were observed. Conclusions: Our results of FOLFOXIRI-Bmab in Japanese pts showed to be beneficial and manageable although caution to FN is required. Clinical trial information: NCT02497157.

Highlights • Non-perforating acute appendicitis with septic DIC is extremely rare. • Nowadays, interval appendectomy has become popular. • However, judging the limit of conservative treatment for acute appendicitis is a critically important matter. • Appendectomy should be performed for non-perforating acute appendicitis with septic DIC., Introduction Perforating appendicitis and abscess-forming appendicitis may cause septic disseminated intravascular coagulation (DIC). However, non-perforating acute appendicitis with septic DIC is extremely rare. Presentation of case A 67-year-old man was referred to our hospital one day after starting oral antibiotic treatment for acute appendicitis. Physical examination revealed only slight spontaneous abdominal pain without tenderness and peritoneal irritation. Contrast-enhanced computed tomography demonstrated an enlarged appendix (10 mm in diameter) without fecalith, ascites, intraperitoneal free air, and abscess. There was no evidence of perforating appendicitis. Laboratory analysis revealed septic DIC. The patient was diagnosed with non-perforating acute appendicitis with septic DIC. The patient was distressed regarding whether he should be treated conservatively with an antibiotics-first strategy or undergo an appendectomy. Ultimately, a laparoscopic appendectomy was performed. Histopathological examination showed non-perforating gangrenous appendicitis. He required DIC therapy for 2 days postoperatively. He was discharged on postoperative day 9, and remained in good health 1 month after surgery. Discussion There is no absolute index of conversion to surgery with an antibiotics-first strategy of appendicitis treatment. Judging the limit of conservative treatment and determining the best moment to perform surgery is a critically important matter for patients with acute appendicitis. Conclusions The incidence of conservative treatment preceding an antibiotics-first strategy for acute appendicitis is increasing. However, it is thought that appendectomy should be performed when acute appendicitis is complicated with septic DIC, even if it is a non-perforating appendicitis in which improvement with conservative treatment is anticipated.

Highlights • Appendiceal neurofibromas (AN) in Neurofibromatosis type (NF) 1 are rare. • AN in NF1 with Low-grade appendiceal mucinous neoplasms (LAMNs) are extremely rare. • AN and LAMNs have potential for malignant transformation. • Surgical resection is the standard treatment for patients with AN and LAMNs. • However, appropriate surgical procedure remains controversial., Introduction Neurofibromas are a characteristic of the autosomal dominant disorder Neurofibromatosis type 1 (NF1), also known as von Recklinghausen’s disease. Appendiceal neurofibromas are extremely rare, and low-grade appendiceal mucinous neoplasms (LAMNs) have not previously been reported in NF1. Presentation of case A 62-year-old man with NF1 was scheduled for elective surgical treatment of an asymptomatic, enlarged and diffusely thickened appendix that remained after curative antimicrobial treatment of acute appendicitis. Laboratory analysis revealed all normal. Colonoscopy showed thickened appendiceal mucosa projecting into the cecum. A sample of the mucosa was found to be pathologically benign. The patient was preoperatively diagnosed with treated acute appendicitis with chronic appendiceal inflammation versus appendiceal neoplasms. Laparoscopic cecectomy was performed. Multiple neurofibromas were observed in the muscle layer, submucosa, and mucosa of the appendix on histopathological examination. Immunohistochemical examination showed positive staining for S-100. Pathologically, the patient was diagnosed with appendiceal neurofibroma consistent with NF1 with LAMNs. His postoperative course was unremarkable. He was discharged on post-operative day 3 and remained in good health 7 month after surgery. Conclusions Appendiceal neurofibromas are often preoperatively diagnosed as appendicitis. Appendiceal neurofibromas should be considered in patients with NF1 who are suspected of having appendicitis.

We conducted this study to establish whether drinking alcohol alters the risk of early-onset colorectal cancer (CRC) in Japanese patients with Lynch syndrome (LS). The subjects were 66 LS patients with pathogenic mutation of mismatch repair genes (MLH1, MSH2, and MSH6) from the nationwide Japanese retrospective multicenter study. Cox proportional hazards modeling was used to investigate the factors correlating with early-onset CRC diagnosis, using clinical data such as gender, tobacco use, alcohol consumption, body mass index, gene mutation (MLH1, MSH2 vs MSH6), and family cancer history. Alcohol was significantly correlated with an increased risk of early-onset CRC [HR 2.44, 95% CI 1.13-5.16 (p = 0.02)], but tobacco use was not [HR 0.8, 95%CI 0.38-1.62 (p = 0.53)]. These findings suggest that alcohol consumption is correlated with an earlier onset of CRC in Japanese patients with LS.

KRAS gene mutations are found in 40–50 % of colorectal cancer cases, but their functional contribution is not fully understood. To address this issue, we generated genetically engineered mice with colon tumors expressing an oncogenic Kras G12D allele in the context of the Adenomatous polyposis coli (Apc) deficiency to compare them to tumors harboring Apc deficiency alone. CDX2P9.5-G22Cre (referred to as G22Cre) mice showing inducible Cre recombinase transgene expression in the proximal colon controlled under the CDX2 gene promoter were intercrossed with Apc flox/flox mice and LSL-Kras G12D mice carrying loxP-flanked Apc and Lox–Stop–Lox oncogenic Kras G12D alleles, respectively, to generate G22Cre;Apc flox/flox ;Kras G12D and G22Cre;Apc flox/flox ;KrasWT mice. Gene expression profiles of the tumors were analyzed using high-density oligonucleotide arrays. Morphologically, minimal difference in proximal colon tumor was observed between the two mouse models. Consistent with previous findings in vitro, Glut1 transcript and protein expression was up-regulated in the tumors of G22Cre;Apc flox/flox ;Kras G12D mice. Immunohistochemical staining analysis revealed that GLUT1 protein expression correlated with KRAS mutations in human colorectal cancer. Microarray analysis identified 11 candidate genes upregulated more than fivefold and quantitative PCR analysis confirmed that Aqp8, Ttr, Qpct, and Slc26a3 genes were upregulated 3.7- to 30.2-fold in tumors with mutant Kras. These results demonstrated the validity of the G22Cre;Apc flox/flox ;Kras G12D mice as a new mouse model with oncogenic Kras activation. We believe that this model can facilitate efforts to define novel factors that contribute to the pathogenesis of human colorectal cancer with KRAS mutations.

The number of elderly patients with colorectal cancer (CRC) treated with surgery has gradually increased. The aim of this study was to evaluate the short-term outcomes in patients ≥80 years of age who underwent laparoscopic or open surgery for CRC using a propensity score-matched analysis to make uniform the patient background characteristics affecting the postoperative morbidity and mortality. We compared the short-term outcomes of open vs. laparoscopic surgery in patients with CRC ≥80 years of age between 2010 and 2015. Fifty-two patients undergoing laparoscopic colectomy for CRC were matched to 52 patients undergoing open colectomy with respect to gender, age, body mass index, performance status, prognostic nutritional index, Charlson Comorbidity Index score, tumor-node-metastasis stage, and tumor location. The operative time, blood loss, length of hospital stay, and postoperative complications were investigated. Blood loss was less during laparoscopic surgery than during open surgery (40 vs. 140 ml, p

Few studies have investigated the risk factors in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) who die within 3 months of undergoing surgical intervention and systemic chemotherapy. This study aimed to identify the risk factors associated with the post-treatment 3-month mortality rate. Retrospectively collected data from Hiroshima University were analyzed for patients presenting with synchronous PC from CRC between 1992 and 2012. The clinical, histological and survival data were evaluated and correlated with the overall survival rate at 3 months after surgical intervention. In patients who underwent surgical intervention with systemic chemotherapy for synchronous PC from CRC (N = 65), a Kaplan–Meier analysis and the log-rank test revealed that systemic chemotherapy (P = 0.023) and the modified Glasgow Prognostic Score (mGPS) (P = 0.00001) were associated with the 3-month mortality rate. Multivariate analyses using these two factors revealed that the mGPS (0/1, 2) (odds ratio 8.087; 95 % CI 1.512–43.25; P = 0.015) was an independent risk factor for the 3-month mortality rate. The mGPS is an important independent predictor of the 3-month mortality rate in patients who undergo surgical intervention with systemic chemotherapy for synchronous PC from CRC. The mGPS could aid surgeons in choosing the appropriate treatment strategy and best care for patients.

A sporadic colon cancer mouse model with conditional mutations in adenomatous polyposis coli (Apc) is biologically relevant for human colorectal cancer (CRC). This study aimed to determine the utility and limitations of colonoscopy for evaluating colon tumors in this mouse model. We compared the estimates of location, size, and miss rate of tumors detected during colonoscopy with those determined by necropsy. Sixty-six CPC-Apc mice originating from Apc F/wt mice harbor a Cdx2-Cre transgene in which colorectal tumorigenesis was driven by Apc allelic loss. The sensitivity and specificity of colonoscopy for detecting tumors in a mouse CRC model were investigated. A strong positive correlation was found between tumor location as measured by colonoscopy and the location determined by necropsy (p

Purpose Surgical site infection (SSI) is a frequent complication of elective surgery for colorectal cancer. The classical clinical markers of infection—elevations in white blood cell count, C-reactive protein (CRP) level, and body temperature—do not precisely predict SSI after elective colorectal resection. The objective of this study was to evaluate the efficacy of procalcitonin (PCT) as a tool for diagnosis of SSI in elective surgery for colorectal cancer.

Micropapillary carcinoma was originally reported to be an aggressive variant of breast carcinoma, and it is associated with frequent lymphovascular invasion and a dismal clinical outcome. It has subsequently been found in other organs; however, at present, only a limited number of cases of colorectal micropapillary carcinoma have been reported. We present a case of early colon cancer with extensive nodal metastases in a Japanese patient. An 82-year-old man was found by colonoscopy to have a 20-mm pedunculated polyp in his sigmoid colon. Endoscopic resection of the sigmoid colon tumor was performed, and pathological examination of the resected specimen revealed a poorly differentiated adenocarcinoma component and a micropapillary component. Despite the tumor being confined within the submucosa, massive lymphatic invasion was noted. Thereafter, the patient underwent laparoscopic sigmoidectomy with lymph node dissection, and multiple lymph node metastases were observed. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for early colorectal cancer, surgical resection with adequate lymph node dissection would be required because of the high potential for nodal metastases.

In the present study, we observed that the adenocarcinoma component in the mucosa was continuous with neuroendocrine carcinoma (NEC) in the deeper layers; this suggests the normal course of NEC carcinogenesis at the histological level. A 72-year-old man was admitted to our hospital with a chief complaint of tarry stools. Endoscopic examination of the upper gastrointestinal tract revealed a 2-cm tumor, with a deep central depression, surrounded by a smooth elevated area, in the middle of the stomach body. A biopsy showed that the tumor was a moderately differentiated gastric adenocarcinoma. The patient underwent total gastrectomy and standard lymph node dissection. The resected tumor was a 3.5 × 2.5 cm type 2 lesion. It comprised two elements at the histological level: (i) a moderately differentiated adenocarcinoma in the superficial portion of the mucous membrane layer, and (ii) NEC-like cells with dark, round nuclei and scant cytoplasm, presenting a solid and trabecular pattern, in the submucosal and muscularis propria layers. Immunohistochemical findings showed that the NEC-like cells were diffusely positive for chromogranin A, synaptophysin, neural cell adhesion molecule, and neuron-specific enolase, but were negative for carcinoembryonic antigen. The Ki-67 labeling index was 95%. The final pathological diagnosis was gastric NEC with an adenocarcinoma component and a high cellular proliferative potential.

症例は57歳の女性で，約3年前より脾嚢胞性病変を指摘されていた．2度の上腹部疝痛発作を主訴に来院した．発作時腹膜刺激症状および血清CA19-9の異常高値，CTでは脾嚢胞を認めたが嚢胞壁の形態変化なく腹水はなかった．保存的加療にて一時軽快したが，症状が再燃したため腹腔鏡下脾臓摘出術を行った．組織学的には脾類上皮嚢胞と診断され，嚢胞壁の一部に出血，壊死巣を認めた．嚢胞内のCA19-9は高値で，免疫組織学的には類上皮に一致してCA19-9がびまん性に陽性であった．術後経過は良好で，術後1か月で血清CA19-9値は正常化した．嚢胞壁一部の出血，壊死により腹部疝痛発作，血清CA19-9値の上昇を来したと考えられた．血清CA19-9が高値を示した脾嚢胞の本邦報告例は28例で，これらに自験例を加えて検討した．

近年，肝細胞癌症例の高齢化に伴い，高齢者手術症例は増加傾向にある．それに伴い，術前から様々な併存症を有する症例も増加傾向にある．これら併存症を有する症例をより安全に手術することを目的に当科での肝細胞癌初回手術症例を対象に全身状態，肝局所因子の両面から術後合併症発生の予測を行った． 2002年7月から2008年12月に当科にて経験した肝細胞癌初回手術例131例のうち，何らかの処置を必要とする術後合併症を認めた51例を合併症群，合併症の無い80例を非合併症群として検討を行った． 背景肝機能の単変量解析では合併症群でコリンエステラーゼ，アルブミン，ヘパプラスチンが有意に低く，総ビリルビン，AST，ZTT，ICG-R15値が有意に高かった．多変量解析ではアルブミンが有意な因子であった．腫瘍因子では両群間に差を認めなかった．治療因子では術中出血量に有意差を認め500 g以上が合併症発生の危険因子であった．幕内基準を基に手術適応を決定していること，アルブミンが有意な因子であったことからこれらを含む肝障害度を背景肝機能因子とし，出血量を含むH-POSSUMを全身状態評価・手術因子評価とし多変量解析した結果，肝障害度BまたはC，H-POSSUM合併症発生予測50%以上はともに合併症発生の危険因子であった． これらを用い症例を4群に分類すると，予測術後合併症発生率50%未満かつ肝障害度BまたはCの症例での合併症発生率は60.0%，予測術後合併症発生率50%以上かつ肝障害度Aの症例での合併症発生率は50.0%，予測術後合併症発生率50%以上かつ肝障害度BまたはCの症例での合併症発生率は80.0%であり，予測術後合併症発生率50%未満かつ肝障害度Aの症例での合併症発生率21.6%と比較して有意に合併症発生は高率であった． 標準的な検査で算定できる肝障害度とH-POSSUMの組み合わせにより，肝切除の術前状態を正確に把握し，術後合併症を予測することが可能で，肝疾患以外の合併症を有する症例でも，術前肝障害度AでH-POSSUM 50%未満の症例では安全に肝切除手術を施行することが可能である．

今回われわれは梅の種子が原因でイレウスをきたした1例を経験したので報告する．症例は82歳，女性．8年前に子宮癌で放射線療法施行歴があった．嘔吐，腹痛を主訴に当院を受診した．イレウスと診断しイレウス管減圧による保存的加療を2週間施行したが，軽快しなかったため手術を施行した．回腸全体に放射性腸炎を認め，回腸末端の狭窄部位に梅の種子が嵌頓し穿孔しており同部位を切除した．植物種子によるイレウスの本邦報告例は自験例を含めて15例のみで非常に稀である．原因となった異物としては梅の種子が11例と圧倒的に多かった．また，13例は原因となる器質的疾患が存在していた．大腸の場合は大腸癌，小腸の場合は放射性腸炎が多かった．何らかの腸管狭窄を伴う場合は，異物が梅の種のように比較的小さくてもイレウスの原因となりうることを十分考慮する必要がある．また全例術前に異物誤嚥を確認できておらず繰り返しの問診が重要であると考えられた．

74歳，女性．当院整形外科入院中に粘血便を主訴に当科紹介受診となった．直腸診にて肛門縁より約6cmの部位に弾性硬の腫瘤を触知した．腹部CTで直腸にmulti concentric ring signを呈する腫瘤を指摘され，直腸腫瘍による腸重積が疑われた．注腸造影では腫瘍は蟹の爪様の陰影欠損として描出され，先進部はRa，Rbの境界部にありRsより重積している直腸粘膜が描出された．整復を試みたが不可能であった．以上より，腸重積症を合併した直腸癌と診断し手術を施行した．術中所見ではRsからRbにかけて腸重積が確認された．用手的整復を試みたが，重積腸管が損傷する危険性があったため整復を断念しハルトマン手術を行った．組織学的診断は高分化腺癌，SE，N1 StageIIIaであった．成人の直腸S状部癌を先進部とする成人腸重積症は非常に稀である．成人の腸重積症例は，症状・所見に乏しい慢性の経過を取ることが多く，診断時には整復困難な状態に陥っておることが予想される．そのため，無理な保存的整復には固執せずに手術を施行するべきであると考えられた．

Introduction: Previous study showed that Synbiotics might have beneficial effect in human and animal colitis like ulcerative colitis. However, it is not well known that the influence of Synbiotics for tumorigenesis in colon cancer. The aim of present study was to investigate the influence of Synbiotics in colon cancer mouse model and colitis associated cancer mouse model. Methods: Mouse stains carrying colon epithelium-preferential Apc mutation (CPC;Apc mice), that show sporadic colorectal adenomas and carcinomas are used in this study. We also used CPC;Apc mice consumed 1%Dextran Sulfate Sodium (DSS) as colitis associated colon cancer model, developing apploximately fourfold more adenomas and adenocarcinomas than CPC;Apc not consumed. At first, 9 of CPC;Apc mice were administerated symbiotics (Probiotics (Lactobacillus) 0.1g + Prebiotics (Oligosaccharide) 10mg/0.3ml/body) between 7 and 20 age in weeks and 10 was not administerated. Secondaly, using 9 of CPC;Apc consumed 1%DSS was administrated Symbiotics, 8 of not administrated, 7 of only Probiotics, and 7 of only Prebiotics. Body weight was measured weekly. Fecal microbial analysis was performed. At sacrifice in 21 age in weeks, the small and large bowel were histologically assessed. Results: Synbiotics administration group has no differences of tumorigenesis comparing to control group (tumor incidence rate(88.9%(8/9) vs. 62.5% (5 / 8); control vs. Synbiotics; p = 0.21)average tumor number(3.2 vs. 2.1; p = 0.38), average tumor greatest diameter 5.8 vs. 5.1 mm; p = 0.51). Using CPC;Apc consumed 1%DSS, Symbiotics administration group showed inhibiting morbidity (50% (8 / 16) vs. 80% (8 / 10); control vs. Synbiotics; p = 0.04) and weight loss, and less tumor incidence than control (18.8 vs. 9.6; control vs. Synbiotics; p = 0.01). On the other hands, administration of probiotics or prebiotics alone had no significant differences of tumorigeneis. Conclusion: This data suggest that Synbiotics administration may have influence of inhibiting tumorigenesis in the colitis associated colon cancer. Citation Format: Yasufumi Saito, Takao Hinoi, Tomohiro Adachi, Manabu Shimomura, Masashi Miguchi, Hiroaki Niitsu, Masatoshi Kochi, Hideki Ohdan, Kazuhiro Sentani, Naohide Oue, Wataru Yasui. Impact of synbiotics administration on tumorigenesis of colon cancer mouse model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2303. doi:10.1158/1538-7445.AM2015-2303

Purpose Non-steroidal anti-inflammatory drugs (NSAIDs) have shown potential as chemopreventive agents against cancer formation, especially colorectal cancers. However, the mechanisms by which these drugs act are not fully understood. In this study, CPC;Apc mice, a human colorectal cancer mouse model treated with sulindac, were evaluated according to tumor initiation and prognosis and gene expression profile of the tumors were analyzed. Methods CPC;Apc mice, originating from ApcFlox/wt mice harbor a Cdx2-Cre transgene in which colorectal tumorigenesis was driven by Apc allelic loss and represent a genetic model of human colorectal cancer (CRC) were treated with control (n=20) or sulindac (160ppm, n=22) for 12 weeks and their colorectal tumors were evaluated. Gene expression analysis was performed to identify genes differentially expressed in tumor cells from sulindac-treated mice. The gene expression was validated through quantitative real-time polymerase chain reaction in vivo. Results Body weight of mice with control or sulindac was no significantly difference ( P = 0.801). However, we observed that sulindac significantly suppressed the tumor progression relative to untreated controls (the colon tumors size per mouse: median of 4.2mm, range 2.3-5.9 versus 5.0mm, range 3.1-8.7, respectively ; P = 0.007 ), but not the initiation (the colon tumor numbers per mouse: median of 1.5, range 0-5 versus 1.0 tumors, range 0-8 respectively ; P = 0.979) in CPC;Apc mice. We identified some upregulated (n = 6, >1.4 fold ) and downregulated (n = 5, >1.4 fold) target genes by microarray assay. We validated expression of these candidate genes in human colorectal cancer. Conclusion We have identified for the first time that sulindac affected tumor progression by delayed and suppressing it, but had no effect on the initiation of tumor in CRC mice model. Citation Format: Tomohiro Adachi, Takao Hinoi, Yuu Sasaki, Manabu Shimomura, Yasufumi Saito, Masashi Miguchi, Hiroaki Niitsu, Yuusuke Sotomaru, Naohide Oue, Wataru Yasui, Hideki Ohdan. Sulindac delayed and suppressed the tumor progression, was not effective on inhibition of tumor initiation in a human colorectal cancer mouse model (CPC;Apc mouse). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 250. doi:10.1158/1538-7445.AM2014-250

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue tumors that arise from a peripheral nerve or exhibit nerve sheath differentiation. Most of these tumors arise on the trunk, extremities, or head and neck regions; they are very rarely located in the abdominal cavity. The patient was a 71-year-old man who was referred to our hospital for a mass and pain in the right lower abdomen. Abdominal computed tomography revealed a large (9 × 9 cm), well-circumscribed, lobulated, heterogeneously enhanced mass in the pelvis. Exploratory laparotomy revealed a large mass in the greater omentum, and the tumor was completely excised. Histopathological analysis revealed that the tumor was composed of spindle cells with high mitotic activity. On staining the tumor, positive results were obtained for S-100 but negative results were obtained for c-kit, cluster of differentiation (CD)34, α-smooth muscle actin, and desmin. These findings strongly supported a diagnosis of MPNST primarily arising from the greater omentum. To the best of our knowledge, this is the first reported case of an MPNST arising from the greater omentum. In this report, we have described the case of a patient with an MPNST arising from the greater omentum and have discussed the clinical characteristics and management of MPNSTs.

The standard operation for colitic cancer in ulcerative colitis (UC) is restorative proctocolectomy; however, sporadic colorectal cancer (CRC) can coincidentally arise in patients with UC and the optimal procedure remains controversial. Therefore, it is crucial to preoperatively determine whether the CRC in UC is a sporadic or colitic cancer. We report a case of avoiding proctocolectomy for sporadic CRC in a patient with UC based on preoperative diagnosis involving p53 immunostaining. A 73-year-old man with CRC in UC had undergone sigmoid colectomy with lymphadenectomy because of the submucosal deep invasion pathologically after endoscopic mucosal resection. The cancer was diagnosed sporadic cancer preoperatively not only based on the endoscopic, clinical, and histological patterns but also that the colon epithelium was unlikely to develop dysplasia as the circumference and unaffected UC mucosa did not detect p53 protein overexpression. Recent reports have shown that the immunohistochemical detection of p53 protein overexpression can be useful for a differential diagnosis and as a predictor of dysplasia and colitic cancer. The analysis of p53 mutation status based on immunostaining of p53 protein expression in the unaffected UC mucosa can be useful for the decision regarding a surgical procedure for CRC in patients with UC.

Lynch syndrome (LS) is a disorder caused by mismatch repair gene mutations, which have been recognized to be associated with an increased frequency of colorectal and extracolorectal tumors. However, it remains controversial as to whether total or segmental colectomy should be performed to treat colorectal cancer in patients with LS. A 58-year-old male underwent total colectomy with ileostomy for advanced transverse colon cancer. He was also found to have LS based on his characteristic family history and the findings of a preoperative examination, including a microsatellite instability analysis of past multiple metachronous cancers. The postoperative histological findings showed mucinous adenocarcinoma without lymph node metastasis, and the loss of the MSH2 protein expression was confirmed on an immunohistochemical examination. The present case provided important information on the clinical management of multiple developing metachronous colorectal cancers in patients with LS.

Background In stage IV colorectal cancer (CRC) with unresectable metastases, whether or not resection of the primary tumor should be indicated remains controversial. We aim to determine the impact of primary tumor resection on the survival of stage IV CRC patients with unresectable metastases. Methods We retrospectively investigated 103 CRC patients with stage IV colorectal cancer with metastases, treated at Hiroshima University Hospital between 2007 and 2013. Of these, those who had resectable primary tumor but unresectable metastases and received any chemotherapy were included in the study. We analyzed the overall survival (OS) and short-term outcomes between the patients who received up-front systemic chemotherapy (USC group) and those who received primary tumor resection followed by chemotherapy (PTR group). Results Of the 57 included patients, 15 underwent USC and 42 PTR. The median survival times were 13.4 and 23.9 months in the USC and PTR groups, respectively (P = 0.093), but multivariate analysis for the overall survival showed no significant difference between the two groups (hazard ratio, 1.30; 95% confidence interval (CI), 0.60 to 2.73, P = 0.495). In the USC group, the disease control rate of primary tumor was observed in 12 patients (80.0%), but emergency laparotomy was required for 1 patient. Morbidity in the PTR group was observed in 18 cases (42.9%). Conclusions The overall survival did not differ significantly between the USC and PTR groups. USC may help avoid unnecessary resection and consequently the high morbidity rate associated with primary tumor resection for stage IV CRC with unresectable metastases.