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Supplementary Table 1 from CDX2 Regulates Multidrug Resistance 1 Gene Expression in Malignant Intestinal Epithelium

The caudal-related homeobox transcription factor CDX2 has a key role in intestinal development and differentiation. CDX2 heterozygous mutant mice develop colonic polyps, and loss of CDX2 expression is seen in a subset of colon carcinomas in humans. Ectopic CDX2 expression in the stomach of transgenic mice promotes intestinal metaplasia, and CDX2 expression is frequently detected in intestinal metaplasia in the stomach and esophagus. We sought to define CDX2-regulated genes to enhance knowledge of CDX2 function. HT-29 colorectal cancer cells have minimal endogenous CDX2 expression, and HT-29 cells with ectopic CDX2 expression were generated. Microarray-based gene expression studies revealed that the Multidrug Resistance 1 (MDR1/P-glycoprotein/ABCB1) gene was activated by CDX2. Evidence that the MDR1 gene was a direct transcriptional target of CDX2 was obtained, including analyses with MDR1 reporter gene constructs and chromatin immunoprecipitation assays. RNA interference–mediated inhibition of CDX2 decreased endogenous MDR1 expression. In various colorectal cancer cell lines and human tissues, endogenous MDR1 expression was well correlated to CDX2 expression. Overexpression of CDX2 in HT-29 cells revealed increased resistance to the known substrate of MDR1, vincristine and paclitaxel, which was reversed by an MDR1 inhibitor, verapamil. These data indicate that CDX2 directly regulates MDR1 gene expression through binding to elements in the promoter region. Thus, CDX2 is probably important for basal expression of MDR1, regulating drug excretion and absorption in the lower gastrointestinal tract, as well as for multidrug resistance to chemotherapy reagent in CDX2-positive gastrointestinal cancers. Cancer Res; 70(17); 6767–78. ©2010 AACR.

Supplementary Figure 1 from CDX2 Regulates Multidrug Resistance 1 Gene Expression in Malignant Intestinal Epithelium

Supplementary Figure 1 Legend from CDX2 Regulates Multidrug Resistance 1 Gene Expression in Malignant Intestinal Epithelium

Supplementary Table 2 from CDX2 Regulates Multidrug Resistance 1 Gene Expression in Malignant Intestinal Epithelium

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 some studies have reported on the relationship between appendiceal stump closure methods and postoperative complications, there is no fixed method for this procedure. This study aimed to compare treatment outcomes of the existing procedures.We retrospectively analyzed the records of 200 patients who underwent urgent laparoscopic surgeries and investigated whether the difference in the appendiceal stump closure method was a risk factor for surgical site infection. The patients were divided into the Endoloop and endostapler groups, and 45 propensity score-matched patients were included. The treatment outcomes of the two groups were compared.The patients with high body temperature showed significantly developed surgical site infection in multivariate analysis (P = .036). There was no significant difference in the appendix stump methods (Endoloop vs endostapler). Regarding postoperative complications, superficial and deep incisional surgical site infection, organ/space surgical site infection, ileus, and complications of Clavien-Dindo grade IIIa or higher; there was no significant difference between the endoloop and endostapler groups after propensity score matching (P = .725, 1.000, .645 and .557, respectively).By properly using the Endoloop and endostapler according to the severity of inflammation, the Endoloop can be safely performed in many cases. Inexpensive Endoloop as an option for stump closure methods should positively impact medical costs.

The prevalence of colonic diverticular disease has been on the increase in Japan due to an increase in westernized diet and a rapidly aging population. However, solitary cecal diverticulum is rare and considered congenital in etiology. Solitary cecal diverticulitis with calcified fecaliths is even rarer. Herein, we report a case of cecal colon diverticulitis caused by a calcified fecalith in a 38-year-old woman treated with single-incision laparoscopic surgery. To the best of our knowledge, this report describes the first case of cecal colon diverticulitis caused by a calcified fecalith that was successfully treated with single-incision laparoscopic ileocolectomy.

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.

Desmoid tumors are a very rare disease associated with familial adenomatous polyposis, surgical trauma and hormonal factors. Surgical trauma is a critical trigger for sporadic desmoid tumors. Tumor development has been reported, and laparoscopic surgery has become more widely performed than the conventional open surgery. However, a few cases of desmoid tumors have developed after robot-assisted surgery. When desmoid tumors develop after cancer surgery, they are often difficult to distinguish from cancer recurrence. This differentiation is important for patients with bladder cancer because it helps determine the treatment plan. However, very few cases of mesenteric desmoid tumors after cystectomy for bladder cancer have been reported. Herein, we present a case of desmoid tumor that developed following robot-assisted laparoscopic cystectomy for bladder cancer. The tumor was resected via minilaparotomy with laparoscopic assistance for diagnostic treatment.

There is a wide variety of vessel types in the transverse colon region. Among them, it is very rare that the accessory middle colonic artery(A-MCA)is branched from the splenic artery. We found a transverse colon cancer. The dominant vessel of the cancer was the A-MCA branched from the splenic artery. This vessel type was confirmed by preoperative 3D-CT. We performed a laparoscopic left hemicolectomy for the cancer. In this study, we report a case of safe laparoscopic surgery in which we separate the A-MCA branched from the splenic artery using the preoperative 3D-CT image.

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.

The case involved a female in her 70s. Six years prior, she had undergone an abdominoperineal rectal resection for rectal cancer. Local recurrence was observed during follow-up so preoperative chemoradiotherapy was performed to shrink the tumor, followed by a total pelvic exenteration, bilateral ureterocutaneous fistula, and perineal reconstruction with a gracilis myocutaneous flap. She was discharged from hospital 39 days following surgery with no major complications. We herein report on a case of a good postoperative course due to surgery including a total pelvic exenteration and perineal reconstruction with a gracilis myocutaneous flap for postoperative local recurrence.

Case 1: A 51-year-old man with advanced gastric cancer and peritoneal metastasis was referred to our hospital. He received fourth-line chemotherapy with nivolumab, but it became PD. Next, he received S-1 plus docetaxel therapy as fifth- line therapy. After 2 courses of S-1 plus docetaxel, erythema and blisters appeared on his limbs, with erosions of the oral mucosa and penis. We diagnosed Stevens-Johnson syndrome(SJS)based on the clinical and pathological findings. He received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue the chemotherapy because of the SJS. Case 2: A 75-year-old woman with recurrence of peritoneally disseminated gastric cancer received third-line chemotherapy with nivolumab. After 1 course of nivolumab, erythema appeared on her body and limbs, with erosion of the lips and oral mucosa. We diagnosed SJS based on the clinical findings. She received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue chemotherapy because of the SJS. It should be noted that the onset of serious irAEs, such as SJS, might make continuous chemotherapy difficult.

The clinical efficacy of nivolumab has been shown as a third-line treatment for advanced gastric cancer; however, nivolumab sometimes causes immune-related adverse events(irAEs). We retrospectively examined the clinical features and influence on treatment in cases of irAEs after nivolumab treatment.We retrospectively examined 43 patients who received nivolumab treatment at our institution between October 2017 and December 2019.The incidence of irAEs was 23.2%(10/43), and Grade 3 or higher irAEs included interstitial pneumonia, hypoadrenalism, Stevens- Johnson syndrome(SJS), and type 1 diabetes. Three patients showed long-term disease control after irAE onset. Meanwhile, SJS prevented patients from continuing treatment for gastric cancer.Nivolumab is effective in some patients with gastric cancer, while irAEs made subsequent treatment difficult. Trifluridine/tipiracil or irinotecan are also known to be effective as therapeutic drugs after third-line treatment for gastric cancer in addition to nivolumab; therefore, the choice of the third-line drug and management of irAEs owing to individual cases are considered desirable.Long-term efficacy is expected with nivolumab, but it may be necessary to recognize that the onset of serious irAEs might make subsequent treatment difficult.

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.

Previous reports have demonstrated that repeated surgical resections of resectable hepatic and pulmonary metastases from colorectal cancer contribute to a better prognosis. We retrospectively assessed the outcomes of 19 patients with colorectal cancer who underwent repeated resections of hepatic and pulmonary metastases between February 2007 and February 2017. The median observation period was 69.9 months, and 26 liver and 27 lung resections were performed. The cumulative 5-year survival rates after resection of the last metastasis was 75.1% and the median disease-free survival after resection of the last metastasis was 34.7 months. Although 7 patients showed recurrence and 4 patients died, 7 patients exhibited long-term survival. Univariate analysis revealed that simultaneous liver and lung metastases were significantly predictor of poor prognosis(p=0.039). Progress of the patients in the present study were comparable to those in previous reports. Therefore, we propose that repeated surgical resection of hepatic and pulmonary metastasis from colorectal cancer could improve patient prognosis. Further studies should examine to identify more accurate prognostic factor with large series.

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.

The splenic artery and vein are important to the remnant stomach after distal gastrectomy(DG). Hence, total gastrectomy is recommended when performing gastrectomy and distal pancreatectomy(DP)with splenectomy(S). In the present case, a man in his 70s was diagnosed with early gastric cancer. Abdominal CT detected a dilated main pancreatic duct. Chronic pancreatitis was suspected, but malignancy could not be completely ruled out. Thus, DG with Roux-en-Y reconstruction and DP with S were performed simultaneously. The remnant gastric blood flow was evaluated with intraoperative indocyanine green(ICG)fluorography and the blood flow was confirmed. Finally, the remnant stomach was preserved. The postoperative course was uneventful, except for the occurrence of anastomosis edema. This result suggests that ICG fluorescence is useful to evaluate remnant gastric blood flow and that it may be possible to perform DG and DP with S simultaneously depending on the case.

Pembrolizumab and nivolumab are anti-programmed death receptor-1(PD-1)antibodies. The use of pembrolizumab for unresectable or metastatic cancer with microsatellite instability-high(MSI-High)has been recently approved. However, there were few clinical reports on MSI in gastric cancer.We examined the clinicopathological features and MSI for 37 patients who underwent chemotherapy for unresectable gastric cancer in January 2019.MSI-High was observed in 3 patients(8.1%). Among the MSI-High patients, there was a tendency towards older age, female sex, undifferentiated type, distal-located lesions and lymphatic vessel invasions, but the differences were not significant. Eleven patients underwent chemotherapy with nivolumab, 4 of them had partial response(PR). Three out of the 4 patients (75%)were MSI-High.These results suggested that anti-PD-1 antibody could be effective as a secondary treatment for unresectable or metastatic gastric cancer among MSI-High patients.

This is a first report of gastrectomy after nivolumab immunotherapy. We describe a case in an elderly woman with gastric cancer diagnosed with cT4bN3M1(LYM), cStage ⅣB disease. Although she was administered 2 courses of SOX chemotherapy as the primary treatment, she could not continue the treatment to due to bone marrowsuppression. The second-line treatment was weekly PTX therapy, but she experienced Grade 3 neutropenia and thrombocytopenia in the first course and could not continue treatment. Nivolumab as the next treatment was effective but was discontinued for suspected druginduced pneumonia. During that time, tumor hemorrhage occurred and we performed total gastrectomy. Postoperatively, nivolumab chemotherapy was resumed. There were no adverse events and the patient has had a continued partial response for 30 courses. Gastrectomy was necessary in this case, allowing observation of the pathological findings of this highly effective case.

Purpose Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer. Methods 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m2/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate. Results The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15–2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97–2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007). Conclusion The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.

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.