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Background Institutional variation in outcomes is a key factor to ascertain the generalizability of results and reliability of the clinical trial. This study evaluated institutional variation in survival and postoperative complications using data from JCOG0404 comparing laparoscopic colectomy (LAP) with open colectomy (OP). Methods Institutions with fewer than 10 registered patients were excluded from this analysis. Institutional variation was evaluated in terms of early postoperative complications, overall survival, and relapse‐free survival and estimated using a mixed‐effect model with institution as a random effect after adjusting for background factors. Results This analysis included 1028 patients in the safety analysis and 1040 patients in the efficacy analysis from 26 institutions. In the safety analysis, there was no variation in grades 3–4 early postoperative complications (in OP, median 6.3% [range 6.3%–6.3%]; in LAP, median 2.6% [range 2.6%–2.6%]), but some variation in grades 1–4 early postoperative complications was observed (in OP, median 20.8% [range 13.2%–31.8%]; in LAP, median 11.9% [range 7.2%–28.7%]), and that in grades 2–4 was observed only in LAP (median 8.8% [range 4.7%–24.0%]; in OP, median 12.7% [range 12.7%–12.7%]). Two specific institutions showed especially high incidences of postoperative complications in LAP. In the efficacy analysis, there was no institutional variation in OP, although a certain variation was observed in LAP. Conclusions Some institutional variations in safety and efficacy were observed, although only in LAP. We conclude that a qualification system, including training and education, is needed when new surgical techniques such as laparoscopic surgery are introduced in clinical practice., We evaluated institutional variation in survival and postoperative complications (PCs) using JCOG0404 data. Institutional variation was observed in laparoscopic surgery in grades 1–4 and 2–4 early PCs and 5‐y relapse‐free survival. A qualification system through training and education is needed when new surgeries, including laparoscopic surgery, are introduced.

Although non-small cell lung cancer can metastasize to any part of the body, metastasis to the gallbladder is extremely rare. We present a case of acute cholecystitis caused by gallbladder metastasis from non-small cell lung cancer. A 66-year-old man diagnosed with primary stage IV T4N3M1b non-small cell lung cancer was admitted to our hospital to receive chemotherapy, during which he presented with right upper abdominal pain. Abdominal contrast-enhanced computed tomography showed an enhanced mass at the neck of the gallbladder and gallbladder distension with obvious wall thickening. Acute cholecystitis caused by obstruction of the gallbladder neck by malignancy was suspected. Open cholecystectomy, extrahepatic bile duct resection, and Roux-en-Y choledochojejunostomy were performed. Pathological and immunohistochemical examinations revealed gallbladder metastasis originating from non-small cell lung cancer. In conclusion, when a patient with lung cancer presents with acute cholecystitis, the rare possibility of gallbladder metastasis should be considered.

Carcinoembryonic antigen (CEA) has limited value as a standalone predictor of the survival in patients with colorectal cancer (CRC). D-dimer (DD) is a predictor of the survival in patients with metastatic CRC. We aimed to predict the prognosis in patients undergoing curative resection for the treatment of CRC by integrating the evaluation of preoperative CEA and DD concentrations with the pathological classification for stage grouping (pStage). The study enrolled 304 patients between 2007 and 2012. The Combination of DD and CEA Score (CDCS) awarded 1 point each for a CEA concentration of > 5.0 ng/ml and DD concentration of > 1.0 μg/ml. Patients were classified according to the total points: CDCS 2, increased DD and CEA concentrations; CDCS 1, increased concentration of either DD or CEA; CDCS 0, normal concentrations. The overall survival (OS) and relapse-free survival (RFS) were significantly lower in patients with CDCS 2 than in those with CDCS 1 or 0. The pStage and CDCS were not independent prognostic predictors of the OS but were predictors of the RFS. The C-index value of the combination of the pStage and CDCS was better than that of either alone for the OS and RFS. The combination of the pStage and CDCS accurately predicts relapse in patients with CRC.

Background. The practice of leaving the abdomen open after an emergency laparotomy has gained increasing popularity recently. Negative pressure wound therapy (NPWT) is known as an effective technique in the management of an open abdomen (OA). A new device, the ABThera™ Open Abdomen Negative Pressure Therapy System (KCI USA, San Antonio, TX, USA), was specifically designed to achieve a temporary abdominal closure (TAC) in the management of an OA. This study was aimed at presenting a successful experience of treating a case of abdominal wall necrosis caused by a perforated ascending colon using the ABThera System. Case Presentation. A 66-year-old man was admitted to our hospital with complaints of severe pain in the abdomen. On admission, abdominal contrast-enhanced computed tomography (CT) showed fluid collection, an air pocket in the subcutaneous fat layer of the abdominal wall, and edematous changes in the adipose tissue in the peritoneum and abdominal wall. Based on a diagnosis of peritonitis resulting from a perforated ascending colon, emergency surgery was performed. A right hemicolectomy, ileostomy construction, and debridement of the necrotic tissues were performed. However, necrotizing fasciitis rapidly spread; therefore, more necrotic tissue was debrided in a second operation. The abdominal wall defect was left open, and the ABThera System was used in the management of the OA; this device promoted wound healing. A reduction was observed in the size of the open wound with visible granulation tissue. The defect was finally covered with a mesh split-thickness skin graft and anterolateral thigh flap. Conclusions. In the management of a case of a massive wound with infection, it can be of great benefit to treat the wound with NPWT initially to decrease its size. The ABThera System could facilitate early and safe management of an OA by surgeons.

Highlights • Gastric heterotopic pancreas (HP) rarely expands due to inflammation or malignant transformation. • Enlarged gastric HP caused by retention cysts is a rare case. • Symptomatic enlarged gastric HP should be resected for histological diagnosis., Introduction Gastric heterotopic pancreas (HP) is usually asymptomatic and benign; however, it may become evident when it is complicated by pathological changes such as inflammation, bleeding, and malignant transformation. Presentation of case A 43-year old man was diagnosed with gastric HP 18 years prior suffered a haemorrhage from the enlarged gastric HP with multiple cystic lesions. Although endoscopic ultrasonography–guided fine needle aspiration showed no malignancy, he underwent a partial gastrectomy for diagnosis and treatment. Postoperative histological findings revealed ectopic pancreatic tissue with retained cysts that consisted of dilated pancreatic ducts without malignancy. Discussion This is a first report of enlarged gastric HP due to the expansion of retained cysts. Gastric HP is rarely enlarged by pathological changes including inflammation, retention cysts, or malignant neoplasms. Conclusion Symptomatic enlarged gastric HP should be respected and further examined histologically to ensure diagnostic accuracy.

There is a paucity of evidence pertaining to long-term survival outcomes of laparoscopic versus open surgery for locally advanced rectal cancer.This study aimed to evaluate the long-term survival outcomes of laparoscopic surgery for locally advanced rectal cancer and to investigate the recurrence pattern.This was a prospective analysis of a registered cohort.This study was conducted at 69 institutions across Japan.A total of 1500 patients with clinical stage II-III rectal cancer located below the peritoneal reflection between January 2010 and December 2011 were included. After propensity score matching, all eligible patients, including the matched patients registered in 2014, were prospectively followed up.Five-year relapse-free survival was the primary outcome.The median follow-up period was 5.6 years. Among the 964 matched patients, the 5-year relapse-free survival was 65.1% in the open group versus 63.5% in the laparoscopic group (HR 1.04; p = 0.71). Distant recurrences at rare sites, which were more frequently observed in the laparoscopic group, were significantly less salvaged (adjusted OR 0.74; p = 0.045). Postrecurrence 5-year overall survival was significantly better for patients who underwent salvage surgery than for those who did not; 55.3% vs 29.5% for patients with initial local recurrence ( p = 0.03) and 64.4% vs 30.7% for patients with distant recurrence alone ( p0.001).Potential heterogeneity and influence of unknown confounding.Five-year follow-up data demonstrated that laparoscopic surgery for locally advanced rectal cancer was safely performed in terms of long-term prognosis. In addition, salvage surgery for recurrent lesions was associated with prolonged postrecurrence survival, both in patients with local and distant recurrence. However, recurrence at rare sites may require further investigation. See Video Abstract at http://links.lww.com/DCR/B793 .ANTECEDENTES:Existe una escasez de pruebas relacionadas con los resultados de supervivencia a largo plazo de la cirugía laparoscópica versus abierta para el cáncer de recto localmente avanzado.OBJETIVO:Este estudio tuvo como objetivo evaluar los resultados de supervivencia a largo plazo de la cirugía laparoscópica para el cáncer de recto localmente avanzado e investigar el patrón de recurrencia.DISEÑO:Fue un análisis prospectivo de una cohorte registrada.ENTORNO CLÍNICO:El estudio se llevó a cabo en 69 instituciones en todo Japón.PACIENTES:Se incluyó un total de 1500 pacientes con cáncer de recto en estadio clínico II-III ubicados por debajo de la reflección peritoneal, entre enero del 2010 y diciembre del 2011. Después del pareamiento por puntaje de propensión, se realizó un seguimiento prospectivo de todos los pacientes elegibles, incluidos los pacientes emparejados registrados en 2014.PRINCIPALES MEDIDAS DE VALORACIÓN:La supervivencia sin recaídas a cinco años fue el resultado primario.RESULTADOS:El período de seguimiento medio fue de 5,6 años. Entre los 964 pacientes emparejados, la supervivencia libre de recaída a 5 años fue del 65,1% en el grupo abierto frente al 63,5% en el grupo laparoscópico (cociente de riesgo 1,04; p = 0,71). Las recurrencias a distancia en sitios raros, que se observaron con mayor frecuencia en el grupo laparoscópico, tuvieron menor sobrevida (razón de posibilidades ajustada 0,74; p = 0,045). La supervivencia general a los 5 años después de la recidiva fue significativamente menor en los pacientes sometidos a una cirugía de rescate; 55,3% frente al 29,5% para los pacientes con recidiva local inicial ( p = 0,03) y 64,4% frente al 30,7% para los pacientes con recidiva a distancia sola ( p0,001).LIMITACIONES:Potencial heterogeneidad e influencia de factores de confusión desconocidos.CONCLUSIONES:El seguimiento a cinco años demostró que la cirugía laparoscópica para el cáncer de recto localmente avanzado es segura en términos de pronóstico a largo plazo. Además, la cirugía de rescate de las lesiones recurrentes se asoció con una mayor supervivencia posrecurrencia, tanto en pacientes con recurrencia local como a distancia. Sin embargo, la recurrencia en sitios raros puede requerir una mayor investigación. Consulte Video Resumen en http://links.lww.com/DCR/B793 . (Traducción- Dr. Ingrid Melo ).

Aya Sugiyama,1 Teruhisa Fujii,2,3 Yoshiko Okikawa,4 Fumie Sasaki,5 Masazumi Okajima,3,6 Hidekuni Hidaka,3,7 Koji Iwato,3,8 Kazuyoshi Sato,3,9 Akira Kokubunji,3,10 Noboru Takata,3,11 Masahiro Yamamoto,3,12 Junko Tanaka1,3 1Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 2Division of Transfusion Medicine, Hiroshima University Hospital, Hiroshima, Japan; 3Joint Committee for Blood Transfusion Therapy in Hiroshima Prefecture, Hiroshima, Japan; 4Department of Oncology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan; 5Division of Laboratory, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan; 6Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan; 7Division of Surgical Services, Fukuyama City Hospital, Hiroshima, Japan; 8Department of Hematology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan; 9Division of Laboratory, Shobara Red Cross Hospital, Shobara, Japan; 10Department of Medical Science and Technology, Faculty of Health Sciences, Hiroshima International University, Hiroshima, Japan; 11Oda Internal Medical Clinic, Hiroshima, Japan; 12Hiroshima Red Cross Blood Centre, Hiroshima, JapanCorrespondence: Teruhisa FujiiDivision of Transfusion Medicine, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ward, Hiroshima, 734-8551, JapanTel +81-82-257-5581Email terchan@hiroshima-u.ac.jpPurpose: Given the chronic shortage of blood for transfusion in Japan, promotion of appropriate use of fresh frozen plasma (FFP) urgently needs to be addressed by the national blood project in Japan. Whether FFP transfusions are administered appropriately in Japan is currently unclear. In this study, we aimed to investigate the outcomes of patients who undergo FFP transfusion and the appropriateness of use of FFP.Patients and Methods: This multicentre, prospective, observational cohort study was conducted from September 2017 to April 2019 at the 15 medical institutions in Hiroshima Prefecture that are the top providers of FFP. All patients who underwent FFP transfusion during the study period were included, relevant data being extracted from the medical records. The indications for FFP transfusion were classified in accordance with the Guidelines of the Ministry of Health, Labour and Welfare of Japan. Factors associated with patient outcomes at day 28 after FFP transfusion were subjected to multivariable logistic regression analysis.Results: In total, data of 1299 patients were eligible for analysis. At least 63.8% of indications for FFP were in accordance with the guideline for FFP transfusions. The mortality rate at day 28 after FFP transfusion was 16.2%. Older age (65– 74 years: adjusted odds ratio [AOR]=4.3, ≥ 75 years: AOR=4.1), non-perioperative use (AOR=4.5), coagulopathy associated with liver damage (AOR=2.7), large volume of FFP transfused (AOR=2.5), and lack of improvement in blood coagulation following FFP transfusion were independently and significantly associated with death within 28 days after FFP transfusion.Conclusion: Our findings do not support the simple conclusion that FFP transfusions contribute to prognosis. However, given that coagulopathy in patients with end-stage liver disease is infrequently improved by FFP transfusion, “inappropriate” use of FFP should be avoided. It is important to promote appropriate use of FFP so as not to waste blood resources.Keywords: prognosis, coagulopathy, inappropriate use, compliance with guideline

Background Cutaneous metastases of colorectal cancer (CRC) are rare, occurring in 0.7% to 5% of cancer patients. Furthermore, the molecular subtypes of cutaneous metastasis of CRC are unclear. Here, we present a rare case of cutaneous metastasis of high-frequency microsatellite instability (MSI-high)/BRAFV600E-mutant cecum cancer. Case presentation A 77-year-old woman presented at the outpatient clinic with a subcutaneous mass on her left back. An excisional biopsy was performed and metastatic cutaneous adenocarcinoma was diagnosed. A computed tomography scan of the thorax and abdomen showed thickening of the cecum wall, the presence of pericolic lymph nodes, multiple masses in the liver, and a single nodule in the right lung. Right colectomy with D2 lymphadenectomy and functional end-to-end anastomosis was performed because of the almost-complete intestinal obstruction. The expression of KRAS wild type, BRAFV600E mutation, and MSI-high was detected in the cecum cancer using molecular pathological examination. She received chemotherapy with XELOX + BEV regimen (capecitabine + oxaliplatin + bevacizumab). After four administrations, a computed tomography scan showed reduction of distant metastases, which suggested partial response. Conclusions We encountered a rare case of cutaneous metastasis of MSI-high and BRAFV600E-mutant cecum cancer. In the future, it will be necessary to accumulate more cases to identify clinical features and more effective treatments for CRCs with cutaneous metastasis.

Background Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. Recently, it has reported that mCAPIRI is well tolerated and non-inferior to FOLFIRI. In this study, we conducted a multicenter phase II trial to assess the efficacy and safety of biweekly CAPIRI plus bevacizumab as second-line chemotherapy for mCRC with reduced toxicity and preserved efficacy. Methods Patients with mCRC who had received prior chemotherapy, including oxaliplatin-based regimens, were eligible for this study. The treatment protocol administered capecitabine at 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan at 150 mg/m2 on day 1, and bevacizumab at 10 mg/kg on day 1 every 2 weeks. Primary endpoints for this study were progression-free survival (PFS) and safety. Secondary endpoints were overall survival (OS), time to treatment failure, response rate (RR), and disease control rate (DCR). Results Fifty-one patients were enrolled in this study. Median PFS was 5.5 months [95% confidence interval (CI) 4.23–7.40 months], and median OS was 13.5 months (95% CI 11.57–20.23 months). The RR was 14.6% (95% CI 6.5–28.4%), and the DCR was 66.7% (95% CI 51.5–79.2%). Hypertension was the most common Grade 3 adverse event (27.5%), followed by neutropenia (17.6%). Only two patients suffered from grade 3 hand–foot syndrome. Conclusions In mCRC patients, biweekly CAPIRI + bevacizumab appears effective and feasible as a second-line chemotherapy with relatively low toxicities, and has potential as a useful substitute for FOLFIRI + bevacizumab.

Purpose: Harvesting at least 12 lymph nodes (LNs) is recommended for adequate tumor staging in colon surgery. Although preoperative endoscopic tattooing has been used for primary localization of tumors, its impact on LN retrieval in colorectal surgery remains controversial. We aimed to investigate the relationship between preoperative tattooing and LN retrieval after laparoscopic rectal resection.Methods: We reviewed the records of 92 patients with rectal cancer who underwent laparoscopic resection from January 1, 2018 to December 31, 2019. Patients were categorized into 2 groups according to whether preoperative endoscopic tattooing was performed. The rate of adequate LN retrieval (≥12) was compared.Results: The tattooed and non-tattooed groups comprised 49 and 43 patients, respectively. In the tattooed and non-tattooed groups, the rates of adequate LN retrieval were 75.5% and 55.8%, respectively (P=0.046). Univariate analysis revealed that female sex, tattooing, LN metastasis status, pathological pathological stage (p-stage), and LN dissection were predictive factors for adequate LN retrieval. In the multivariate analysis, female sex (odds ratio [OR], 3.34; 95% confidence interval [CI], 1.15–9.73; P=0.027), tattooing (OR, 2.87; 95% CI, 1.03–7.94; P=0.043), and p-stage (OR, 3.34; 95% CI, 1.04–10.75; P=0.043) were independent predictive factors for adequate LN retrieval after surgery.Conclusion: This study revealed that preoperative endoscopic tattooing was statistically significantly associated with adequate LN retrieval in patients with rectal cancer who underwent laparoscopic rectal resection. Preoperative endoscopic tattooing should be considered to improve disease assessment and avoid stage migration.

Anal canal neuroendocrine carcinoma (NEC) with pagetoid spread (PS) is a rare disease, and its treatment strategy remains unclear. The prognosis of anal canal NEC with PS is poor. Resection margin status is very important for anorectal carcinoma because it affects survival. When accompanied by PS, the defect of the resulting perineal wound following radical surgical intervention may be necessarily enlarged to ensure the appropriate margin status. This case report discusses the treatment of a patient with advanced anal canal NEC with PS, inguinal lymph node metastasis and sphincter infiltration in which total pelvic exenteration with plastic surgery was successfully performed. The plastic surgery incorporated a gracilis muscle flap that was useful for the reconstruction of the enlarged perineal defect.

Herniation through a defect of the uterine broad ligament is a rare internal hernia that is difficult to diagnose definitively. Common hernia contents contain ileal loops. Herein, we report a rare case of internal herniation of both the ileum and fallopian tube through a defect of the broad ligament. A 52-year-old woman presented to our hospital with suprapubic pain and vomiting. She had a history of bowel obstruction following cesarean section. On abdominopelvic computed tomography, we suspected a closed-loop obstruction associated with bowel herniation in the right broad ligament. However, we could not identify an area of poor enhancement adjacent to distended small intestines. Emergency laparoscopic exploration revealed a viable ileal loop and incarcerated organ. Therefore, we switched to laparotomy that revealed the right fallopian tube as the ischemic organ. We reduced the hernia, resected necrotic right fallopian tube, and closed the defect of the broad ligament. The patient had an uneventful postoperative course. Rare hernia contents might complicate preoperative clinical diagnosis. Laparoscopy is useful for establishing a definitive diagnosis and treating broad ligament hernias.

Although esophageal stricture after acute esophageal necrosis (AEN) is often refractory to dilation therapy, there have been few reports of surgical intervention. We report two rare cases of successful subtotal esophagectomy and esophagogastrostomy for esophageal strictures after AEN using indocyanine green (ICG) fluorescence imaging. In case 1, emergent esophagogastroduodenoscopy (EGD) in a 56-year-old man with coffee-ground emesis revealed black esophageal mucosa in the middle to lower esophagus, indicating AEN. Despite conservative therapy, an esophageal stricture developed after 2 weeks. Repeated endoscopic balloon dilation (EBD) did not resolve the stenosis; esophagectomy was thus performed approximately 6 months after AEN onset. We evaluated the blood flow to the esophagus using ICG fluorescence imaging to determine the proximal surgical resection line. The postoperative course was uneventful. In case 2, an 81-year-old woman with upper gastrointestinal bleeding with hematemesis and chest pain was diagnosed with AEN by EGD and was treated with conservative therapy. An esophageal stricture developed after 3 weeks, and repeated EBD was ineffective. Approximately 2 months after AEN onset, she underwent esophagectomy using ICG fluorescence imaging. The postoperative course was uneventful. Considering that AEN is a blood flow disorder, ICG fluorescence imaging is a useful technology to prevent surgical morbidity.

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.

Background Six months of adjuvant chemotherapy is regarded as the standard of care for patients with stage III colon cancer. However, whether longer treatment can improve prognosis has not been fully investigated. We conducted a phase III study comparing 6 and 12 months of adjuvant capecitabine chemotherapy for stage III colon cancer, and report here the results of our preplanned safety analysis. Methods Patients aged 20–79 years with curatively resected stage III colon cancer were randomly assigned to receive 8 cycles (6 months) or 16 cycles (12 months) of capecitabine (2500 mg/m2/day on days 1–14 of each 21-day cycle). Treatment exposure and adverse events (AEs) were evaluated. Results A total of 1304 patients (642 and 636 in the 6-month and 12-month groups, respectively) were analyzed. The most common AE was hand-foot syndrome (HFS). HFS, leukocytopenia, neutropenia, and hyperbilirubinemia (any grade) occurred more frequently in the 12-month group than in the 6-month group. HFS was the only grade ≥3 AE to have a significantly higher incidence in the 12-month group (23 vs 17%, p = 0.011). The completion rate for 8 cycles was 72% in both groups, while that for 16 cycles was 46% in the 12-month group. HFS was the most common AE requiring dose reduction and treatment discontinuation. Conclusions Twelve months of adjuvant capecitabine demonstrated a higher cumulative incidence of HFS compared to the standard 6-month treatment period, while toxicities after 12 months of capecitabine were clinically acceptable. Trial registration UMIN-CTR, UMIN000001367.

Highlights • Gastric carcinoma with features of a submucosal tumor is a rare condition. • Gastric carcinoma with features of a submucosal tumor has unique features. • Tissue sampling must be performed if gastric malignant submucosal tumor is suspected., Introduction Gastric cancer with features of a submucosal tumor (GCSMT) is rare, and the preoperative diagnosis is very difficult. We present a case of GCSMT diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and boring biopsy (deeper biopsy), successfully treated with distal gastrectomy and lymph node dissection. Presentation of case An 81-year-old man with a history of myocardial infarction and type 2 diabetes mellitus was admitted to our hospital for further examination of a gastric submucosal tumor. Endoscopic examination of the gastrointestinal tract showed a 30-mm submucosal tumor at the lower gastric body. Enhanced computed tomography revealed a tumor located at the lower body of the stomach and pyloric lymph node swelling. EUS-FNA and boring biopsy from the tumor revealed adenocarcinoma. Accordingly, distal gastrectomy with lymph node dissection was performed. Histopathological examination showed a poorly differentiated adenocarcinoma. Postoperative diagnosis was GCSMT with lymph node metastasis (T2, N1, M0, stage IIA). Conclusion We report a rare case of GCSMT with lymph node metastasis. Preoperative diagnosis of GCSMT is necessary to guide surgical management. EUS-FNA and boring biopsy could aid in obtaining adequate quantities of the specimens for histopathological and immunohistochemical diagnosis.

Objective Skeletal muscle loss (sarcopenia) is a prognostic factor in patients undergoing gastrointestinal surgery. However, the influence of muscle quality on prognosis remains unclear. We retrospectively examined preoperative skeletal muscle quantity and quality impact on survival of elderly patients undergoing curative resection of colorectal cancer. Methods We examined data from 142 patients aged ≥75 years who underwent curative resection of colorectal cancer between 2007 and 2012. We determined the size and quality of skeletal muscles, represented by the psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), respectively, using a preoperative computed tomography image. Overall survival (OS) and relapse-free survival (RFS) rates were determined according to values of PMI, IMAC, and other prognostic factors. Results OS and RFS rates in patients with low PMI were lower than those in patients with normal PMI. The OS and RFS rates in patients with high IMAC were also lower than those in patients with normal IMAC. PMI and IMAC were independent prognostic factors for OS (hazard ratio [HR], 3.81, and 3.04, respectively); IMAC was an independent factor for RFS (hazard ratio [HR], 3.03). Conclusion Preoperative sarcopenia, indicating low quality and size of skeletal muscle, predicts mortality after curative resection of colorectal cancer in the elderly.

Background The C-cubed study investigates the optimal treatment strategy in patients with untreated metastatic colorectal cancer (mCRC). We tested the superiority of a sequential treatment of FP+BEV followed by OX+FP+BEV (arm A: OX “wait & go”) at first progression to a combination treatment of OX+FP+BEV (arm B: OX “stop & go”), trial information: UMIN000015405. Methods The Primary endpoint was time-to-failure of strategy (TFS). A target sample size of 304 patients was considered sufficient to validate an expected Hazard Ratio (HR) for TFS of arm A compared with arm B with 80% power and 2-sided 5% α in case of a true HR value of Results Between Dec 2014 and Sep 2016, 311 patients were enrolled, and 302 patients were randomized either to receive the arm A (n = 151) or B (n = 151) as a full analysis set (FAS). Superiority of TFS in the arm A was established in this study (HR, 0.475; 95% CI, 0.362–0.623; p Table . 571P Table Endpoint Arm A, “wait & go” (n = 151) Months (95%CI) Arm B, “stop & go” (n = 151) Months (95%CI) p-value (log rank) TFS (FAS) 15.2 (12.5 – 17.2) 7.6 (6.2 – 9.5) OS (FAS) 27.5 (24.4 – 32.7) 29.4 (24.1 – 36.0) 0.6692 Factor RAS WT (n = 112) Months (95%CI) RAS MT (n = 167) Months (95%CI) p-value (log rank) TFS Arm A 14.0 (11.2 – 19.0) 15.3 (12.4 – 17.2) 0.3126 Arm B 7.8 (7.0 – 10.5) 7.4 (5.2 – 9.6) 0.1615 OS Arm A 27.5 (22.6 – NC) 28.0 (23.4 – 32.7) 0.3143 Arm B 34.7 (24.5 – NC) 24.3 (19.1 – 32.8) 0.0265 Conclusions The sequential “wait & go” strategy for OX was superior in TFS compared with the combinational “stop & go” accompanying with the equal survival benefit of nearly 30 months. Thus, the sequential approach with FP+BEV followed by OX is deemed an acceptable treatment strategy for patients with mCRC. Clinical trial identification UMIN000015405. Legal entity responsible for the study Japan South West Oncology Group (JSWOG). Funding Chugai Pharmaceutical Co., Ltd. Disclosure T. Nagasaka: Speaker Bureau / Expert testimony: Eli Lilly Japan. Y. Shindo: Research grant / Funding (institution): Chugai; Research grant / Funding (institution): MSD; Research grant / Funding (self): Ono; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Lilly. A. Tsuji: Honoraria (institution): Daiichi Sankyo; Honoraria (institution), Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau / Expert testimony: Chugai Pharma; Honoraria (institution), Speaker Bureau / Expert testimony: Merck Serono; Honoraria (institution), Speaker Bureau / Expert testimony: Takeda Pharmaceutical; Honoraria (institution): Bristol-Myers Squibb Japan. Y. Tsuji: Honoraria (institution): Bayer Co. Ltd; Honoraria (institution): Merck Serono Co. Ltd; Honoraria (institution): Eli Lilly Japan; Honoraria (institution): Chugai Pharmaceutical Co. Ltd; Honoraria (institution): Taiho Pharmaceutical Co. Ltd; Honoraria (institution): Ono Pharmaceutical Co. Ltd; Honoraria (institution): Takeda Pharmaceutical Co. Ltd; Honoraria (institution): Medicon Co. Ltd. H. Mishima: Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd. All other authors have declared no conflicts of interest.

Highlights • Adrenal cortical carcinoma (ACC) is rare, often recurring, and has a poor prognosis. • Surgery remains the optimal treatment for ACC, due to chemotherapy’s ineffectiveness. • Our patient developed 2 liver metastases after right adrenalectomy (1.5 and 4 years). • Therefore, complete surgical resection should be considered in similar cases., Introduction Adrenal cortical carcinoma (ACC) is a very rare type of tumor that generally has a poor prognosis. Little has been reported on repeated liver resections with recurrent metastasis still confined to the liver. In this report, we describe a case of functioning ACC in a 65-year-old woman with 2 liver metastases of the ACC (at 1.5 and 4 years) after the right adrenalectomy. Presentation of case A 65-year-old woman was referred to our hospital based on a suspicion of hyperaldosteronism. Abdominal computed tomography revealed a lesion at the right adrenal gland; therefore, we performed right adrenalectomy and subsequently diagnosed the lesion as ACC. However, follow-up computed tomography at 1.5 and 4 years after the right adrenalectomy revealed liver metastasis of ACC; liver resection was performed for both metastases. Discussion Complete surgical resection is the established approach for the treatment of ACC. The prognosis of ACC is usually dismal, and recurrence rates of up to 85% have been reported. However, the appropriate treatment for recurrent ACC is not well established, and the effectiveness of other modalities, such as chemotherapy and radiotherapy, is not proven. Therefore, surgical resection may currently be the most appropriate treatment modality, as the patient achieved a disease-free interval of 2.5 years after the first liver resection. Conclusion In selected patients with recurrent or metastatic ACC, resection is likely to be associated with prolonged survival. However, a full cure is generally not achievable, and a multidisciplinary approach is likely needed to achieve long-term disease-free status and survival.

Background Guidelines for rectal cancer treatment differ in Japan, Europe, and the United States. Neoadjuvant chemoradiotherapy (CRT) has been used to control lateral lymph nodes (LLNs) in the West. The usefulness of LLN dissection (LLND) has been discussed in Japan, and a randomized study stated the possible advantage of local control. However, it is still unclear whether adding LLND to CRT is beneficial. Methods To investigate the effectiveness of LLND on rectal cancer patients who underwent neoadjuvant CRT, we retrospectively collected magnetic resonance images (MRIs) in a cohort of 1500 patients with cStage II/III lower rectal cancer below the peritoneal reflection and centrally reviewed MRIs. We measured short-axis LLN sizes on pre- and post-CRT images and evaluated patients’ prognosis according to LLN size and whether LLND was performed. Results MRIs were collected from 752 patients, of whom 189 underwent neoadjuvant CRT. Both pre- and post-CRT MRIs were available in 155 patients, of whom 66 underwent LLND (LLND group) and 89 did not (non-LLND group). The LLND and non-LLND group showed the following differences: positive circumferential resection margin by MRI after CRT: 53.0% vs. 32.6%; positive extramural venous invasion: 36.4% vs. 24.7%; laparoscopic surgery: 39.4% vs. 88.8%; and mean pre-CRT LLN size: 5.2 mm vs. 3.6 mm. Five-year relapse-free survival (5y-RFS) was 73.8% and 66.1% in the LLND and non-LLND groups, respectively (p = 0.38). Two local recurrences occurred in the LLND group. In stratified analysis, 5y-RFS of 40 patients whose LLN size was ≥5 mm in pre-CRT images was 77.8% in the LLND group and 46.2% in the non-LLND group (p = 0.06). On the other hand, 115 patients whose LLN size was Conclusions Our data indicated that adding LLND to CRT may have survival benefits on those who had LLN size of ≥ 5 mm before CRT. Stratification by short-axis LLN size using pre-CRT MRIs may facilitate optimal multidisciplinary treatment strategies for low rectal cancer. Legal entity responsible for the study Department of Surgery, Kyoto University Graduate School of Medicine. Funding The Japanese Foundation for Research and Promotion of Endoscopy, The Japan Society of Clinical Oncology, and Kondou Kinen Medical Foundation. Disclosure All authors have declared no conflicts of interest.

565 Background: We have previously reported biweekly XELIRI + bevacizumab 10 mg/kg as second-line chemotherapy in metastatic colorectal cancer (mCRC). In this study, we investigated relationships between efficacy/toxicity and biomarkers (polymorphisms of UGT1A’s, somatic mutations of RAS, BRAF and PIK3CA). Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin based regimen were eligible for this study. Treatment protocol administrated capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan 150mg/m2 on day 1, and bevacizumab 10 mg/kg on day 1 every 2 weeks. Results: Between January 2013 and July 2015, 51 patients were enrolled in this study. The patients’ characteristics were as follows (N=51): median age, 66 years (range 41–82); male/female, 29/22; the median PFS was 5.47 months (95% CI, 4.23–7.40 months), the median OS was 13.5months (95%CI, 11.57– 20.23months), and the median TTF was 4.5 months (95%CI, 3.97–6.93 months). The response rate was 16% (95%CI, 7.2–29.1), and the disease control rate was 76% (95%CI, 61.8-86.9). Grade 3 or higher adverse events were mainly febrile neutropenia in two patients and hypertension in 14 patients (28.6%). The patients with UGT1A7 (387G

Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (p = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.

Summary Background Although benefits of laparoscopic surgery compared with open surgery have been suggested, the long-term survival of patients undergoing laparoscopic surgery for colon cancer requiring Japanese D3 dissection remains unclear. We did a randomised controlled trial to establish non-inferiority of laparoscopic surgery to open surgery. Methods We did an open-label, multi-institutional, randomised, two-arm phase 3 trial in 30 hospitals in Japan. Patients aged 20–75 years who had histologically proven colon cancer; tumours located in the caecum or ascending, sigmoid, or rectosigmoid colon; T3 or deeper lesions without involvement of other organs, node stages N0–2, and metastasis stage M0; and tumour size of 8 cm or smaller were included. Only accredited surgeons did surgery as an operator or instructor. Patients were randomly assigned (1:1) preoperatively to undergo D3 resection either by an open route or a laparoscopic route, via phone call or fax to the Japan Clinical Oncology Group (JCOG) Data Center. Randomisation used a minimisation method with a biased-coin assignment according to tumour location (caecum, ascending vs sigmoid, rectosigmoid) and institution. The primary endpoint was overall survival and was analysed by intention to treat. The non-inferiority margin for the hazard ratio (HR) was set at 1·366. This study is registered with UMIN Clinical Trials Registry, number C000000105, and ClinicalTrials.gov, number NCT00147134. Findings Between Oct 1, 2004, and March 27, 2009, 1057 patients were randomly assigned to either open surgery (n=528) or laparoscopic surgery (n=529). 5-year overall survival was 90·4% (95% CI 87·5–92·6) for open surgery and 91·8% (89·1–93·8) for laparoscopic surgery. Laparoscopic D3 surgery was not non-inferior to open surgery for overall survival (HR 1·06, 90% CI 0·79–1·41; p non-inferiority =0·073). 65 (13%) patients in the open surgery group and 53 (10%) patients in the laparoscopic surgery group had grade 2–4 adverse events. Grade 2–4 adverse events included diarrhoea (15 [3%] in the open surgery group vs 14 [3%] in the laparoscopic surgery group), paralytic ileus (six [1%] vs nine [2%]), and small intestine bowel obstruction (16 [3%] vs 11 [2%]). Two treatment-related deaths occurred in the open surgery group: one patient died 7 days after surgery (probably due to myocardial infarction), and one patient died from febrile neutropenia, pneumonia, diarrhoea, and gastrointestinal haemorrhage during postoperative chemotherapy. Interpretation Laparoscopic D3 surgery was not non-inferior to open D3 surgery in terms of overall survival for patients with stage II or III colon cancer. However, because overall survival in both groups was similar and better than expected, laparoscopic D3 surgery could be an acceptable treatment option for patients with stage II or III colon cancer. Funding National Cancer Center Research and Development Fund, Grant-in-Aid for Cancer Research, and Health and Labour Sciences Research Grant for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

The aim of the present study was to examine the technical and oncological feasibility of laparoscopic surgery (LAP) in elderly patients with a history of abdominal surgery. We conducted a propensity score-matched case–control study of colorectal cancer (CRC) patients aged ≥80 years that were treated at 41 hospitals between 2003 and 2007. We included 601 patients who had a history of abdominal surgery and underwent curative and elective surgery for stage 0 to III CRC. After the matching procedure, 153 patients were included in each cohort. The surgical outcomes of LAP and open surgery (OS) were compared. P-values of

Background Laparoscopic surgery has spread quickly during the past twenty years, and has become one of the important treatments in the field of colorectal surgery. Recently, natural orifice transluminal endoscopic surgery (NOTES) has been studied as the next generation of minimally-invasive surgery, but the feasibility and safety of the NOTES method have not been evaluated. In such a situation, single-incision laparoscopic surgery has attracted interest from surgeons worldwide. However, single-incision laparoscopic colorectal surgery has not yet been standardized. Methods From February 2010, single-incision laparoscopic colectomy was performed for 7 patients presenting with early colon cancer. All procedures were performed by two experts with the License of Endoscopic Surgical Skill Qualification System (ESSQS) of Japan Society for Endoscopic Surgery (JSES) in the field of colorectal Surgery. Results We used the Gelport system (Applied Medical, Rancho Santa Margarita, CA, USA) as the access port and 3 trocars of different sizes (Ethicon, Inc., Cincinnati, OH, USA). Using this technique, we did not experience any difficulties or use any articulated instruments. All of the present 7 patients underwent the single-incision laparoscopic colectomy successfully and had no complications. Conclusion: Single-incision laparoscopic surgery using the Gelport was performed safely in the present cases. The use of the Gelport as an access port can address the technical difficulty associated with this new technique.

Two nomograms are available for predicting patient survival after hepatic resection for metastatic colorectal cancer (CRC). However, they have not been externally validated using other databases, and so their universal applicability has not been established. We aimed to examine the validity of these nomograms for predicting patient survival after hepatic resection for metastatic CRC in different institutions. We analyzed the cases of 113 patients who underwent hepatic resection for metastatic CRC at Hiroshima University Hospital between 1995 and 2006. In this patient set, we assessed the predictive value of the Kattan nomogram of the Memorial Sloan-Kettering Cancer Center (MSKCC) (United States) and the Kanemitsu nomogram from the Aichi Cancer Center (Japan). The concordance index was used as an accuracy measure for comparing these two nomograms. The predictive accuracy of these nomograms was compared with that of conventional predictive models. The 3-, 5-, and 10-year overall survival rates in our cohort were 66.3%, 52.4%, and 42.7%, respectively. The concordance indexes of the pre- and postoperative Kanemitsu nomogram and that of the Kattan nomogram were 0.70, 0.69, and 0.68, respectively. These values were higher than those obtained using other models for hepatic metastatic CRC, including the clinical risk score of the MSKCC and the grading system of the Japanese Society for Cancer of the Colon and Rectum. The high predictive accuracy of both nomograms shows that these predictive tools can be used in different institutions. Patient counseling and adjuvant therapy decision-making should benefit from use of these nomograms.

Claudin-18 plays a key role in constructing tight junctions, and altered claudin-18 expression has been documented in various human malignancies; however, little is known about the biological significance of claudin-18 in colorectal cancer (CRC). The aim of this study is to investigate the significance of claudin-18 expression in CRC and its association with clinicopathological factors. We performed clinicopathological analysis of claudin-18 expression in a total of 569 CRCs by immunohistochemistry. Moreover, we investigated the association between claudin-18 and various markers including gastric/intestinal phenotype (MUC5AC, MUC6, MUC2 and CD10), CDX2, claudin-3, claudin-4, p53 and Ki-67. Claudin-18 expression was detected in 21 of the 569 CRCs (4%) and was seen exclusively on the cell membrane. Positive expression of claudin-18 showed a significant correlation with positive expression of MUC5AC (P < 0.0001) and negative expression of CDX2 (P= 0.0013). The prognosis of patients with positive claudin-18 expression was significantly poorer than in negative cases (P= 0.0106). Multivariate analysis revealed that T grade, M grade and claudin-18 expression were independent predictors of survival in patients with CRC. We revealed that claudin-18 expression correlates with poor survival in patients with CRC and is associated with the gastric phenotype.

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue, and especially on the cell membrane, will be useful molecular markers for diagnosis and may also be good therapeutic targets. To identify genes that encode transmembrane proteins present in GC, we generated Escherichia coli ampicillin secretion trap (CAST) libraries from two GC cell lines and normal stomach. By sequencing 4320 colonies from CAST libraries, we identified 30 candidate genes that encode transmembrane proteins present in GC. Quantitative reverse transcription-polymerase chain reaction analysis of these candidates revealed that ZDHHC14, BST2, DRAM2, and DSC2 were expressed much more highly in GC than in 14 kinds of normal tissues. Among these, DSC2 encodes desmocollin 2, which is one of three known desmocollins. Immunohistochemical analysis demonstrated that 22 (28%) of 80 GC cases were positive for desmocollin 2, and desmocollin 2 expression was observed frequently in GC with the intestinal mucin phenotype. Furthermore, desmocollin 2 expression was correlated with CDX2 expression. These results suggest that expression of desmocollin 2, induced by CDX2, may be a key regulator for GC with the intestinal mucin phenotype. Our results provide a list of genes that have high potential as a diagnostic and therapeutic target for GC. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

TPS872 Background: Less intensive regimens, focusing on survival and disease control, may be better first-line treatments in unresectable metastatic colorectal cancer (mCRC). Several randomized trials suggested that sequential cytotoxic agents in mCRC may improve overall survival compared with combination chemotherapy. This study investigated whether sequential treatment with Bmab-based first-line therapy with oxaliplatin has superior efficacy to combination treatment for unresectable mCRC. Methods: This study is a two-arm, multicenter, open-label, randomized phase III trial in Japan, comparing the efficacy and safety of sequential Cape/5-FU+Bmab with escalation to CapeOX/mFOLFOX6+Bmab versus combination CapeOX/mFOLFOX6+Bmab as the first-line treatment of mCRC. The primary endpoint is Time to failure of strategy (TFS). In the sequential arm (Arm A: oxaliplatin ‘wait-and-go’), treatment escalation from Cape/5-FU+Bmab to CapeOX/mFOLFOX6+Bmab is recommended for progressive disease. In the combination arm (Arm B: oxaliplatin ‘stop-and-go’), de-escalation from CapeOX/mFOLFOX6+Bmab to Cape/5-FU+Bmab is possible after 12 weeks of treatment. Re-escalation to CapeOX/mFOLFOX6+Bmab after progressive disease is considered only for patients who received de-escalation of oxaliplatin, not caused by oxaliplatin-associated toxicity, after 12 weeks of treatment. A target sample size of 304 evaluable patients is considered sufficient to detect a hazard ratio of 0.69 for the TFS of the sequential ‘wait-and-go’ approach compared with the combination ‘stop-and go’ approach with 80% power and a 2-sided significance level of 5%. From December 2014 to September 2016, 311 patients were enrolled across 81 centers in Japan. The follow-up period is until March 2018, and results are expected in 2019, and results are expected in 2019. Clinical trial information: 000015405.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. We previously performed Serial Analysis of Gene Expression (SAGE) on four primary gastric cancer samples and identified several gastric cancer-specific genes. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC-1) is a candidate gene for cancer-specific expression. In the present study, we examined the expression and distribution of olfactomedin 4 in CRC by immunohistochemistry. Of the 176 CRC cases, 59 (34%) were positive for cytoplasmic staining of olfactomedin 4. Olfactomedin 4-positive CRC cases showed earlier T classification (P=0.0180), N classification (P=0.0149) and stage (P=0.0144) than olfactomedin 4-negative CRC cases. In the 176 CRC patients, those with olfactomedin 4-positive CRC had a better survival rate than patients with olfactomedin 4-negative CRC (P=0.0092). Multivariate analysis indicated that T classification, M classification and negative olfactomedin 4 expression were independent predictors of survival in patients with CRC. In addition to cytoplasmic staining of olfactomedin 4, stromal staining at the invasive front was observed. In total, 29 (16%) of the 176 CRC cases were positive for stromal olfactomedin 4; however, stromal olfactomedin 4 staining was not correlated with any clinicopathologic characteristic or with patient survival. These results indicate that olfactomedin 4 is a valuable marker for long-term survival in patients with CRC.

Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.

Intramucosal neutrophil infiltration is related to the activity of ulcerative colitis, and Th1 immunity is responsible for the onset of Crohn's disease. We examined the therapeutic effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in the two types of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis of five rat strains. SD and DA rats showed much lower mRNA expression levels of endogenous G-CSF in lipopolysaccharide (LPS)-stimulated splenocytes than did Lewis, F344, and BN rats. On day 7 after anal instillation of TNBS, SD and DA rats demonstrated massive lymphocyte infiltration with an interferon-gamma (IFN-gamma) mRNA upregulation, whereas Lewis, F344, and BN rats showed an intense submucosal neutrophil accumulation with high tumor necrosis factor-alpha (TNF-alpha) mRNA levels. A 5-day course of rHuG-CSF pretreatment (250 microg/kg/day, s.c.) reduced the elevated levels of both cytokines. The treatment improved the survival rate of DA and reduced the degree of body weight loss of SD, while not significantly influencing the wasting disease of other strains. Interleukin-10 (IL-10) mRNA levels were highly upregulated by rHuG-CSF treatment on day 1 in the neutrophil-dominant lesions of F344 but not in the Th1-type lesions of SD, and IL-12p35 mRNA levels were downregulated in both. A supply of G-CSF prevents the onset of Th1-type TNBS colitis and does not deteriorate neutrophil-dominant chronic colitis in hosts showing higher expression of endogenous G-CSF.

症例は43歳,女性.左腋窩腫瘤を主訴に当科を受診した.理学的所見では左腋窩に2.5cm大の弾性硬腫瘤を触知したが,両側乳腺内に腫瘤は触知せず.マンモグラフィーでは両側乳腺内に明らかな腫瘤陰影,石灰化は認めなかった.エコー上,両側乳腺内には低エコー陰影を多発性に認め,乳腺症の存在が考えられた.左腋窩腫瘤の穿刺吸引細胞診(ABC)の結果は低分化型腺癌の腋窩リンパ節転移と診断され,原発巣検索のため消化管検査,全身のCT検査を行ったが異常所見は認めなかった.乳腺のMRI検査では左乳腺D領域に7mm大の早期濃染する結節状陰影を認めたため同部位のエコーを再度行い,低エコー病変部のABCを行ったところ,悪性所見を認め,本症例は左乳癌を原発巣とする潜在性乳癌と診断した.乳房温存療法を行い,病理組織学的には浸潤性乳管癌(papillotubular type, g, pT1c, pN1, ER(+), PgR(+), HER2(2+))であった.術後は化学,内分泌療法を行い現在まで無再発生存中である.

われわれは直腸原発GISTの術後7年目の肩甲骨転移に対して,メシル酸イマチニブ(商品名グリベック)を使用した症例を経験した.症例は67歳男性で, 1996年直腸粘膜下腫瘍で腹会陰式直腸切断術を行い,病理診断はleiomyosarcomaであった. 1998年肝転移に対して切除術を実施した. 2002年10月右上肢のしびれを自覚し,胸部写真,胸部CTで右第2肋骨に腫瘍を認めた.直腸腫瘍の骨転移と診断し,前方アプローチで1, 2肋骨を含め腫瘍切除術を施行し,病理診断はc-kit陽性のmalignant GISTであった.術後骨シンチグラフィーなどで右肩甲骨へも転移が疑われたため,現在外来でメシル酸イマチニブを投与している.術後1年経過しているが,転移巣の増大は認めていない.

It is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and beta-catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alteration of the components in the Wnt signaling pathway in colorectal cancer (CRC) with microsatellite instability (MSI) has not been elucidated. In order to assess the status of the Wnt signaling components in CRC with MSI, mutational analyses of the beta-catenin, APC, Axin 1, and T cell factor 4 (TCF4) genes were performed. Three of 33 samples had mutations in exon 3 of the beta-catenin gene and two in the APC gene. Eight mutations in seven samples were detected by single-strand conformation polymorphism and subsequent direct sequence analysis of the entire coding region of the Axin 1 gene. Furthermore, TCF4, which is one of the transcriptional factors in the Wnt signaling pathway and has a mononucleotide repeat sequence (a nine- adenine repeat, (A)9) in its C-terminal region, was mutated in 13 of the 33 samples. Thus, alteration in the Wnt signaling pathway is frequently observed in CRC with MSI, including hereditary nonpolyposis colorectal cancer, as well as in familial adenomatous polyposis and sporadic CRC without MSI.

We report a rare case of synchronous multiple carcinomas of the colon. A 65-year-old man visited our hospital because of anal bleeding. Colonoscopy disclosed an ulcerative lesion in the sigmoid colon and 10 polypoid lesions in the ascending and sigmoid colon. After endoscopic polypectomy of the 10 polypoid lesions, anterior resection with lymph node dissection was performed for the ulcerative lesion. Histological study revealed one advanced carcinoma with invasion of the subserosa, 5 early carcinomas with invasion of the mucosa or submosa, and 3 adenomas with moderate to severe atypia. The genetic instability of these 9 lesions was examined using microsatellite assay. In all of these lesions, no replication errors were detected at any of the microsatellite loci analyzed.

The safety of laparoscopic surgery (LAP) in elderly patients with colorectal cancer has not been demonstrated. The aim of this study was to compare the outcomes of LAP and open surgery (OP) and estimate the feasibility of LAP in colorectal cancer patients aged ≥80 years. We conducted a propensity scoring matched case–control study of colon and rectal cancer patients aged ≥80 years using data from 41 hospitals between 2003 and 2007. A total of 1,526 colon cancer patients and 282 rectal cancer patients underwent surgery and were included in the analysis. The primary end point was 3-year overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and postoperative complications. LAP and OP were compared in 804 colon cancer patients (402 pairs) and 114 rectal cancer patients (57 pairs) after all covariates were balanced, and no significant differences were observed, except for tumor size in colon cancer. OS, DFS, and CSS did not differ between the groups for either colon cancer (P = 0.916, 0.968, and 0.799, respectively) or rectal cancer (P = 0.765, 0.519, and 0.950, respectively). In colon cancer cases, LAP was associated with fewer morbidities than was OP (24.9 vs. 36.3 %, P

パーキンソン病とは, 錐体外路症状である振戦, 筋硬直, 無動を3徴とする慢性進行性疾患である.パーキンソン病を基礎疾患に持つ患者に消化管手術を行った場合, 術後の一定期間は抗パーキンソン剤の内服が困難となるため, 術後にパーキンソン病症状の悪化を来し, 術後管理に難渋することが多い.パーキンソン病患者3例に消化器手術を施行し, 2例に術後麻痺性イレウスを認め, そのうち1例で, パーキンソン病の悪化により呼吸管理に気管切開を要した症例を経験した.これらの症例の術前後の経過について述べ, パーキンソン病に対する周術期管理について検討を加えた.術後パーキンソン病症状を抑え, 早期離床をはかり, 呼吸器合併症, 腸管麻痺を予防することが重要で, そのために十分な抗パーキンソン剤を用いる必要があると考えられた.

In rectal cancer, lateral lymphatic spread is considered to worsen the prognosis. Therefore, accurate determination of lymph node involvement preoperatively is helpful in assessing the malignant character of the tumor and in determining resectability. The present study was performed to evaluate the accuracy, limitations, and usefulness of endoluminal ultrasonography in preoperatively diagnosing the localization of lymph node metastasis in rectal cancer. Seventy-six patients with rectal cancer underwent preoperative endoscopic ultrasonography. Three of these patients had lateral lymphatic spread and all could be distinguished on endoscopic ultrasonography by the detection of involvement of lymph nodes in the anterior rectal space. These findings suggest that endoscopic ultrasonography plays a potentially useful role in the strategy for dealing with rectal cancer prior to surgery.