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To evaluate the right colic vascularity, focusing on the confluences of veins.The subjects of this retrospective study were 100 patients who underwent laparoscopic extended right hemicolectomy (Lap-ERHC) between April 2015 and September 2020, at our hospitals. Veins draining into the superior mesenteric vein (SMV) included the ileocecal vein (ICV), the right colic vein (RCV), the middle colic vein (MCV), and the gastrocolic trunk of Henle (GCT). Veins draining into vessels other than the SMV were defined as accessory colic veins (aICV, aRCV or aMCV).The GCT, aRCV, and aMCV were found in 86, 89, and 15 patients, respectively. In 66 patients with one aRCV, drainage was split as the anterior superior pancreaticoduodenal vein (ASPDV) in 12, the right gastroepiploic vein (RGEV) in 7, and the GCT in 47. In 23 patients with two aRCVs, drainage was split as the ASPDV in 4, the RGEV in 1, the GCT in 11, and the ASPDV and GCT in 7. In 14 patients with one aMCV, drainage was split as the GCT in 8, the splenic vein in 5, and the first jejunal vein (FJV) in 1. One patient had two aMCVs, draining into the GCT and the FJV.The findings of our evaluation of vascular anatomy, focusing on confluences of the colic veins, provides useful information for colorectal surgeons.

Despite having once been extensively used for cosmetics or pain reduction, the use of single-incision laparoscopic cholecystectomy (SILC) has declined in recent years due to technical difficulties and a reported increase in complications. Since the introduction of SILC in 2009, our hospital has been actively involved with this technique. Our experience suggests that SILC is not a difficult procedure and can be safe and useful, with particularly excellent cosmetic outcomes. This study retrospectively details the outcomes of SILC at our hospital.Data on 1469 cases of SILC performed on a waitlist basis at Osaka Police Hospital from May 2009 to December 2020 were collected and retrospectively analysed.The median operative time and blood loss were 96 min and 0 mL, respectively. A total of 46 patients (3.1%) required conversion surgery, including 36 needing additional ports and 10 requiring laparotomy. Intraoperative complications included common bile duct injury in 1 patient (0.07%) and right hepatic artery injury in 1 patient (0.07%), with no other organ injury. Postoperative Clavien-Dindo 3 or higher complications were observed in 18 patients (1.2%). Incisional hernias occurred in 15 patients (1.0%). The median postoperative hospital stay was 3 days.This study showed that SILC can be performed safely without any increase in complications, as reported previously. Granted that it is performed safely, SILC may be a useful technique due to its superior cosmetic outcomes or pain reduction.

Single-port laparoscopic extended right hemicolectomy with complete mesocolic excision and central vascular ligation is technically challenging, and a standardized procedure is needed to minimize technical hazards. As a first step, the hepatic flexure is mobilized from the duodenum, and the third part of the duodenum and pancreatic head was exposed. Next, the ileocecal vessels are divided at the root using a medial-to-lateral approach, and the cecum is separated from the retroperitoneal space. This process completes the mobilization of the right colon. In the second step, the omental bursa is opened, and the inferior border of the pancreas is exposed. The mobilized right colon is turned around to the left of the superior mesenteric vein, continuing to separate the mesentery from right to left side, and the right colic vessels are divided at the roots. The inverted right colon is restored to its original position, and the mesenteric fat is dissected along the left edge of the superior mesenteric artery to the inferior border of the pancreas. A total of 57 consecutive patients with advanced hepatic flexure colon cancer (n = 24) and transverse colon cancer (n = 33) underwent S-ERHC. The conversion rate to open surgery was 5.3%. Operative time, blood loss, and number of harvested lymph nodes were 232 min (interquartile range [IQR], 184–277 min), 5 mL (IQR, 5–66 mL), and 30 (IQR, 22–38), respectively. According to the Clavien–Dindo classification, the grade ≥ 2 complication rate was 10.5%. Median duration of hospitalization was 9 days (IQR, 7–13 days). Single-port laparoscopic extended right hemicolectomy using a right colon rotation technique is safe, feasible, and useful. This technique of repeating the inversion and restoration of the right colon may help avoid bleeding and damage to other organs and facilitate reliable lymph node dissection.

Background/aim The rate of lymph node metastasis (LNM) of colorectal carcinoma (CRC) with a submucosal (SM) invasion depth of 1000 µm or more can reach 12.5%, which is the most common reason for additional resection in daily practice. Other studies have reported that the rate of LNM is less than 2%, regardless of the depth of invasion, if the lesions show good histology, lymphovascular infiltration is negative, and tumor budding is limited. The purpose of this study was to investigate new risk factors for LNM in T1b colorectal cancer. Patients and methods The 239 patients who were diagnosed with pathological T1b CRC after colorectal surgical resection at the Osaka Police Hospital in Japan between January 2008 and December 2018 were retrospectively reviewed in this study. Results The LNM rate was 11.3% (27/239). The variables identified as being significant factors using multivariate analysis were: i) lymphatic invasion (Ly)-positive [odds ratio (OR)=5.97; 95% confidence interval (CI)=2.27-15.74], ii) female gender (OR=3.49; 95%CI=1.38-8.85), and iii) left-sided colorectal involvement (OR=4.98; 95%CI=1.22-20.39). If none of these risk factors were present with T1b, the LNM rate was 0% (0/28). Conclusions Ly-positive, female gender, and left-sided colorectal involvement could be risk factors for LNM in T1b CRC.

Background: The clinical impact of single-incision laparoscopic surgery (SILS) for rectal cancer is unclear. However, SILS is a technically challenging procedure for novice surgeons. The aim of this study was to evaluate clinical outcomes of SILS for rectal cancer compared with multi-port laparoscopic surgery (MPLS).Patients and Methods: We retrospectively analyzed 357 consecutive patients with stage I–III rectal cancer located in the rectosigmoid or upper rectum who underwent SILS or MPLS between January 2012 and December 2016, using propensity score-matched analysis.Results: After propensity score-matching, we enrolled 204 patients (n=102 per group). Before matching, significant group-dependent differences were observed in tumor location (p < 0.001). After matching, preoperative clinical factors were similar between groups. SILS was successful in 73.5% of cases, an additional port was required in 23.5% and 2.9% were converted to open surgery. Compared to the MPLS group, the SILS group showed shorter operative time (192 vs. 211 min, p=0.015) and shorter postoperative hospital stay (9 vs. 11 days, p=0.038). Other operative factors and morbidity rates did not differ significantly between groups. The number of harvested lymph nodes was smaller in the SILS group (24) than in the MPLS group (27, p=0.008). Postoperative recurrence did not differ between groups before or after matching. No significant differences in 3-year disease-free, 3-year local recurrence-free or 5-year overall survival were found between groups.Conclusions: SILS is safe, feasible and offers satisfactory oncological outcomes in selected patients with rectosigmoid or upper rectal cancer.

Purpose: Single-incision laparoscopic surgery (SILS) for descending colon cancer (DCC) is a technically challenging procedure with unclear clinical impact. The aim of this study was to evaluate the short-term outcomes of SILS for DCC compared with multi-port laparoscopic surgery (MPLS).Methods: We retrospectively analyzed 137 consecutive patients with stage I–III DCC who underwent SILS or MPLS at two high-volume multidisciplinary tertiary hospitals between April 2008 and December 2018, using propensity score-matched analysis.Results: After propensity score-matching, we enrolled 88 patients (n=44 in each group). Median follow-up period was 48 months. The completion rate for SILS was 98.1% in the overall cohort and 97.7% in the matched cohort. One patient was converted to open surgery in the MPLS group. Compared with the MPLS group, the SILS group showed significantly less blood loss and a greater number of harvested lymph nodes in both the entire patient cohort and the matched cohort. Morbidity rates did not differ significantly between groups before and after matching. R0 resection was achieved in the entire patient cohort. In terms of the incidence of recurrence, both groups were similar before and after matching. No significant differences were found between groups in terms of 3-year disease-free and overall survival rates in either the entire patient cohort or the matched cohort.Conclusions: SILS appears safe and feasible and can provide satisfactory oncological outcomes for selected patients with DCC.

136 Background: Although clinical outcomes of chemotherapy in patients with locally advanced or metastatic colorectal cancer (CRC) have improved over the last decade, the standard-of-care chemotherapy regimens for patients with unresectable RAS wild-type CRC remain to be discussed. The aim of this study was to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated, unresectable, locally advanced, or metastatic CRC with wild-type KRAS. Methods: This phase II, randomized, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated, unresectable, locally advanced, or metastatic CRC with wild-type KRAS. Forty-five patients were enrolled in this study between February 2012 and October 2016. Results: The overall response rate (ORR) for the SOX+B-mab group was 59.1%, whereas that for the SOX+C-mab group was 43.5% (p = 0.29). The disease control rate (DCR) for the SOX+B-mab group was 90.9%, whereas that of the SOX+C-mab group was 91.3% (p = 0.96). For all patients, median OS were 25.3 months (95% CI: 16.5–39.4 months) in the SOX+B-mab group and 15.5 months (95% CI: 7.30–30.4 months, p = 0.167) in the SOX+C-mab group. Median PFS were 11.7 months (95% CI: 7.37–18.2 months) in the SOX+B-mab group and 5.5 months (95% CI: 3.36–10.1 months, p = 0.077) in the SOX+C-mab group. In the SOX+B-mab group, OS and PFS were not significantly different with and without early tumor shrinkage (ETS). However, in the SOX+C-mab group, patients with ETS had significantly better OS (30.4 months [95% CI: 8.0–44.3 months, p = 0.032]) and PFS (12.0 months [95% CI: 5.1–19.7 months, p = 0.003]) than those without ETS. Conclusions: The safety and efficacy of SOX+B-mab and SOX+C-mab as initial treatment for unresectable CRC with wild-type KRAS were almost the same. ETS was more correlated with PFS in the SOX+C-mab group than in the SOX+B-mab group, suggesting consideration of treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. Clinical trial information: UMIN000006706 .

This phase II study (MCSGO-1202) aimed to evaluate the initial dose reduction of oxaliplatin in XELOX plus bevacizumab therapy.This was a phase II, multicenter, open-label, single-arm, prospective, study conducted at 14 Japanese institutions. The study included patients with metastatic colorectal cancer (mCRC) with performance status (PS) of 1 or 2 who had not undergone chemotherapy. Patients received oxaliplatin (100 mg/mBetween April 2012 and March 2016, 56 patients were enrolled. The median age was 71 years (range=44-85 years), and the majority (90.6%) had a PS of 1. A complete response was observed in three patients (5.7%), partial response in 24 (45.3%), stable disease in 22 (43.4%), and progressive disease in one (1.9%). The median progression-free survival and overall survival were 11.4 and 26.5 months, respectively. The most common grade 3-4 adverse events were leucopenia (15.1%), neutropenia (9.4%), neuropathy (9.4%).The dose-reduction strategy of oxaliplatin was effective for elderly or vulnerable patients with mCRC.

With the advancement of endoscopic resection(ER)of colorectal cancer, surgical resection after ER has been increasing. This study evaluated the effects of initial ER on short- and long-term outcomes in T1b colorectal cancer. This retrospective cohort study enrolled patients with pathological T1b colorectal cancer who underwent colorectal surgical resection between 2008 and 2018. A total of 239 eligible patients were divided into 2 groups: patients initially treated using surgical resection with lymph node dissection(LND)(surgery alone, n=142)and patients treated using initial ER and additional surgical resection with LND(surgery after ER, n=97). No significant differences were observed in short-term outcomes(ie, operative time, blood loss, or postoperative complications)or the long-term outcomes(ie, recurrence rate, overall survival rate, or recurrence free survival rate)between groups.

Simple Summary The screening methods and therapeutic strategies for gastrointestinal cancer (GIC) have improved, but mortality in GIC patients remains high. Early detection and precise evaluation of GIC are required to further improve treatment outcomes in GIC patients. MicroRNAs (miRNAs), which do not encode proteins, have attracted attention as biomarkers of various diseases. Since the first report revealing the strong correlation between miRNAs and cancer in 2002, numerous studies have illustrated the changes in the expression and the biological and oncological effects of miRNAs in GIC. Furthermore, miRNAs circulating in the blood are reported to be associated with GIC status. These miRNAs are thought to be useful as noninvasive biomarkers because of their stability in blood. Herein, we discuss the potential of miRNAs as noninvasive biomarkers for each type of GIC on the basis of previous reports and describe perspectives for their future application. Abstract Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but do not encode proteins. MicroRNAs (miRNAs) are short ncRNAs that are reported to function as both oncogenes and tumor suppressors. Moreover, several miRNA-based drugs are currently proceeding to clinical trials for various diseases, including cancer. In recent years, the stability of circulating miRNAs in blood has been demonstrated. This is of interest because these miRNAs could be potential noninvasive biomarkers of cancer. In this review, we focus on circulating miRNAs associated with GIC and discuss their potential as novel biomarkers.

Nodular lymphocyte-predominant Hodgkin lymphoma(NLPHL)is a subtype of Hodgkin lymphoma. It is uncommon in Japan, and only a few cases of NLPHL originating from the mesentery have been reported. Most patients with NLPHL present in the early stage, but some patients have malignancy at initial presentation. We should perform staging laparotomy for the diagnosis and treatment of cases in which a lymph node biopsy is difficult.

Robot-assisted laparoscopic surgery(RALS)for rectal cancer has been covered by National Health Insurance in Japan since April 2018. We launched RALS in our hospital in October 2019 and now report the short-term results(up to January 2020). Altogether, 15 consecutive patients(12 men, 3 women: median age 70 years)with rectal cancer underwent RALS during that period. For the first 2 cases, we performed RALS under the instruction of an experienced proctor from another institution. Among the 15 patients, 6 underwent high anterior resection and 9 low anterior resection. Median operating time was 358 min, median intraoperative blood loss was 0 mL, and there were no apparent intraoperative complications. Median postoperative length of hospital stay was 13 days, and only 1 patient developed a high-grade complication(Clavien-Dindo Grade Ⅲb)postoperatively. Hence, RALS for rectal cancer was launched successfully in our institution.

A phase-Ⅱtrial of TAS-102 plus bevacizumab(Bev)combination therapy showed a progression-free survival(PFS)of 3.7-4.6 months. Here, we report 12 cases of unresectable advanced recurrent colorectal cancer treated with TAS-102 plus Bev therapy at our hospital between June 2017 and February 2020. The median PFS was 6 months(2-12). Adverse events greater than Grade 3 were neutropenia(33.3%), febrile neutropenia(8.3%), thrombocytopenia(8.3%), and vomiting (8.3%). The frequency of non-hematotoxicity was low. In conclusion, the TAS-102 plus Bev therapy may be a useful option for the late-line treatment of unresectable advanced recurrent colorectal cancer.

We aimed to clarify usefulness of the modified Frailty Index 11 (mFI-11) for assessing risk of postoperative complications (POCs) and effectiveness of perioperative management team (POMT) intervention for improving postoperative status of frail aged patients requiring colorectal cancer (CRC) surgery.We compared, retrospectively, surgical outcomes among 151 consecutive CRC surgery patients aged ≥80 years. Patients were grouped by mFI-11 scores and by POMT intervention (vs. no POMT intervention).POCs were more prevalent, postoperative stays were longer, and discharge status was poorer among high-risk (mFI-11 ≥ 3/11) patients without POMT intervention than among low-risk (mFI-11 ≤ 2/11) patients (p = 0.04, p = 0.02, p 0.01). Multiple POCs occurred less frequently and performance of activities of daily living was better for high-risk patients with (vs. those without) POMT intervention (p = 0.04, p = 0.03).POMT intervention appears beneficial for frail aged patients scheduled for CRC surgery.

Long-term outcomes of single-incision laparoscopic colectomy (SILC) for colon cancer (CC), as practiced in real-world settings, especially in relation to disease stage, have not been established. We examined, retrospectively, both short- and long-term outcomes of SILC versus those of multiport laparoscopic colectomy (MPLC) performed for CC in a propensity-score-matched cohort. The study involved 263 patient pairs matched 1:1 from among 691 patients who, between January 2008 and May 2014, underwent either SILC or MPLC for a primary solitary CC at our hospital. Short-term and long-term operative outcomes were compared between the two groups. Operation time was the only surgical outcome that varied significantly between the two groups (p = 0.0004). Overall 5-year cancer-specific survival (CSS) in the SILC group was 93.7 (95% CI 89.6–96.2)%, and CSS per pathological stage (I, II and III) was 98.5 (90.0–99.8)%, 96.0 (88.2–98.7)%, and 88.3 (79.6–93.6)%, respectively, whereas overall 5-year CSS in the MPLC group was 93.3 (89.4–95.9)%, and CSS per pathological stage was 100%, 95.4 (88.3–98.3)%, and 84.1 (74.1–90.8)% (p = 0.5278, 0.2679, 0.7666, and 0.9073), respectively. Overall 3-year disease-free survival (DFS) in the SILC group was 94.0 (90.2–96.4)%, and 3-year DFS per pathological stage was 98.6 (90.4–99.8)%, 90.1 (81.4–95.0)%, and 79.0 (69.4–86.2)%, respectively, whereas overall 3-year DFS in the MPLC group was 93.2 (89.4–95.7)%, and 3-year DFS per pathological disease stage was 100%, 94.5 (87.4–97.7)% and 75.5 (64.7–83.8)% (p = 0.2829, 0.7401, 0.4335 and 0.8518), respectively. Thus, oncological outcomes did not differ significantly between groups. Incisional hernia occurred in 21 (8.0%) SILC group patients and 17 (6.5%) MPLC group patients, without a significant between-group difference (p = 0.6139). Our data indicate that perioperative and oncological outcomes of SILC performed for CC are comparable to those of MPLC performed for CC.

The standard treatment for unresectable or recurrent gastrointestinal stromal tumor(GIST)is tyrosine kinase inhibitor(TKI). It is reported that resection of metastatic lesions after TKI administration prolongs progression free survival, but its influence on overall survival is not clarified. We experienced a case of GIST with peritoneal dissemination for which TKI administration and 2 local resections were effective. The patient was a man in his 70's. We started chemotherapy with imatinib for GIST with peritoneal dissemination. However, it was discontinued due to the occurrence of interstitial pneumonia. Dissemination was evaluated as radically resectable on the images. After the interstitial pneumonia was alleviated, surgery was performed. Although sunitinib was introduced at 2 months postoperatively, recurrent peritoneal dissemination was detected at 32 months postoperatively, and treatment was then changed to regorafenib. Regorafenib treatment reduced the tumor size; however, Grade 3 albuminuria was detected 16 months after treatment initiation and, thus, this treatment was discontinued. Subsequently, the tumor enlarged again. Because there was only 1 recurrent lesion, we performed radical resection. Postoperatively, a reduced dose of regorafenib was re-administered. At present, 9 months after the re-surgery, the patient is alive without recurrence.

A 67-year-old woman presented with bloody stools to a local physician. Lower gastrointestinal endoscopy revealed a type 3 all-circumferential tumor at descending colon. She was diagnosed with descending colon cancer and referred to our hospital for surgery. Preoperative computed tomography(CT)revealed a horseshoe kidney. We performed single-incision laparoscopic colectomy for descending colon cancer(cT3cN0cM0, cStageⅡa)complicated by a horseshoe kidney. The surgery was performed safely without any additional injuries. In patients with horseshoe kidneys, abnormalities have been reported in the running of the blood vascular system and the renal pelvis and ureter systems. Thus, sufficient understanding of the anatomic abnormality by preoperative examinations, such as 3D-CT, is essential for performing surgery safely.

A 66-year-old woman admitted for nausea was found to have a type 2 tumor with stenosis at the fourth portion of the duodenum by upper gastrointestinal series and endoscopy, which was diagnosed as an adenocarcinoma by endoscopic biopsy. Abdominal computed tomography(CT)showed an irregular thick wall at the fourth portion of the duodenum but without metastasis or invasion to the adjacent vessels. We examined the lymph nodes around the pancreatic head intraoperatively and partially resected the duodenum and jejunum based on the diagnosis of negative swollen nodes. The definitive diagnosis was primary tubular adenocarcinoma of the fourth portion of the duodenum, T3, N0, M0, Stage ⅡA. Reports of primary cancer of the fourth portion of the duodenum are very rare, and we include a discussion of the current literature.

A 71-year-old woman with advanced ascending colon cancer was admitted to our hospital. Abdominal computed tomography( CT)revealed locally advanced sigmoid colon cancer with suspected invasion of the liver and duodenum. The clinical stage of the disease was cT4bN3M1a, cStage Ⅳa, with wild-type RAS and UGT1A1 expression. An ileostomy was performed because of bowel obstruction. The patient received 6 courses of FOLFOXIRI plus bevacizumab(Bev). The only adverse event was Grade 3 neutropenia. Laparoscopic right hemicolectomy with lymph node dissection was performed. The pathological diagnosis was the absence of viable, Grade 3 carcinoma cells. This result suggested that preoperative FOLFOXIRI plus Bev chemotherapy is useful for the treatment of locally advanced colon cancer.

Background/Aim: If both distant metastases and the primary tumour of colorectal cancer (CRC) are resectable, resection of the distant metastases is considered. The aim of this retrospective study was to determine the efficacy of curative resection of both primary and metastatic lesions in organs other than liver or lung in CRC patients. Patients and Methods: The medical records of 23 CRC patients who received R0 resection for primary and metastatic regions between 2009 and 2018 were retrospectively analyzed. Results: The 3-year overall survival (OS) in all 23 cases was 80.0%. There was no clinicopathological factor associated with OS on univariate analysis. Conclusion: Curative surgical resection appears to be useful for distant CRC metastases to organs other than liver or lung.

Most cases of adult intussusception are caused by neoplastic lesions, and idiopathic adult intussusception is very rare. We present a case in which laparoscopic surgery was performed for idiopathic adult intussusception initially reduced by colonoscopy. A 53-year-old woman presented to the emergency department of our hospital with intermittent lower abdominal pain. Contrast-enhanced computed tomography and ultrasonography of the abdomen showed a concentric structure in the ascending colon. We diagnosed intussusception. Colonoscopy achieved successful reduction before surgery. Twelve days after this reduction, laparoscopic surgery was performed. Histopathological examination did not reveal any causative pathology; therefore, idiopathic adult intussusception was diagnosed. The postoperative course was uneventful, and the patient was discharged on postoperative day 14. Preoperative colonoscopy should be utilized to diagnose the main lesion and may be useful for reducing adult intussusception. Laparoscopic surgery is both minimally invasive and safe and can be performed following endoscopic reduction.

Chemoradiation was performed at Osaka Police Hospital's department of respiratory medicine on a 70-year-old male with small cell lung carcinoma(cT4N3M0, cStage ⅢC). Subsequent to secondary chemotherapy for multiple bone metastases that had been observed, he received care to control the disease. He arrived at the hospital complaining of epigastric pain. He got CT-scan and was referred to our department because of a suspected hematoma around the right gastroepiploic artery. He was treated conservatively because circulatory dynamics were steady and there was no indication that anemia had progressed. However, when a test laparotomy was performed the day after the start of treatment because he presented with decreased blood pressure and progressive anemia, a massive hematoma was found around the right gastroepiploic artery. The hematoma was removed, and hemostasis was performed. Based on the pathological findings of the excised specimen, he was diagnosed with abdominal metastasis of small cell lung carcinoma. This is a report on our experience and a literature review on a case of mesenteric hematoma caused by abdominal metastasis of small cell lung carcinoma.

A 75-year-old man presented with a fever. Computed tomography revealed a 10 cm solid tumor under the duodenum. A pre-operative diagnosis of liposarcoma was established using biopsy. Pancreaticoduodenectomy was performed, and the pathological examination led to the diagnosis of dedifferentiation type liposarcoma. Two years later, the liposarcoma recurred at the remnant pancreas. A total remnant pancreatectomy was performed. The pathological examination revealed dedifferentiated type liposarcoma and positive surgical margins. Therefore, radiotherapy of 59.4 Gy in 33 fractions was performed at the recurrence area. The patient has been recurrence-free from 1 year 6 months since the second operation.

Background & Aims Most cholesterol gallstones have a core consisting of inorganic and/or organic calcium salts, although the mechanisms of core formation are poorly understood. We examined whether the paracellular permeability of ions at hepatic tight junctions is involved in the core formation of cholesterol gallstones, with particular interest in the role of phosphate ion, a common food additive and preservative. Methods We focused on claudin-3 (Cldn3), a paracellular barrier-forming tight junction protein whose expression in mouse liver decreases with age. Since Cldn3-knockout mice exhibited gallstone diseases, we used them to assess the causal relationship between paracellular phosphate ion permeability and the core formation of cholesterol gallstones. Results In the liver of Cldn3-knockout mice, the paracellular phosphate ion permeability through hepatic tight junctions was significantly increased, resulting in calcium phosphate core formation. Cholesterol overdose caused cholesterol gallstone disease in these mice. Conclusion We revealed that in the hepatobiliary system, Cldn3 functions as a paracellular barrier for phosphate ions, to help maintain biliary ion homeostasis. We provide in vivo evidence that elevated phosphate ion concentrations play a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease under cholesterol overdose. Lay summary Herein, we reveal a new mechanism for cholesterol gallstone formation, in which increased paracellular phosphate ion permeability across hepatobiliary epithelia causes calcium phosphate core formation and cholesterol gallstones. Thus, altered phosphate ion metabolism under cholesterol overdose plays a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease.

Introduction In intraperitoneal-onlay-mesh repair with hernia defect closure (IPOM-plus), the abdominal cavity can be reliably approached through the hernial orifice. Adhesions can then be detached, and the hernial orifice can be closed by direct visual manipulation. Presentation of cases IPOM-plus via the hernial orifice approach was performed in 49 patients. First, an incision is made just above the hernial orifice to reach the abdominal cavity. Under direct visualization, the adhesions are dissected, and the mesh is inserted after laparoscopic manipulation. After closing the hernial orifice under direct visual manipulation, the mesh is fixed again under laparoscopic guidance. Conclusions This technique has the advantages of an easy intra-abdominal approach and direct visual manipulation. No mesh infections were observed in this study, suggesting that it may be useful as a hybrid procedure.

Background Rectal metastasis from pulmonary adenocarcinoma is rare, and it has been regarded as an end-stage phenomenon. Recently, however, advances in lung cancer treatment have improved the chance of long-term survival of patients with unresectable distant metastases. We describe the occurrence and management of metastatic spread of a pulmonary carcinoma to the rectum. Case presentation The patient was a 79-year-old woman who had undergone thoracoscopic left lobectomy for pulmonary adenocarcinoma and then, over the next 11 years, various drugs (carboplatin + paclitaxel (as adjuvant therapy), gefitinib, gemcitabine + vinorelbine, S1 (an oral 5-fluorouracil-based drug), carboplatin + pemetrexed + bevacizumab, erlotinib, nivolumab, afatinib, and carboplatin+ S1) were administered, especially for hilar and mediastinal lymph node recurrences. During the eleventh postoperative year, left and right iliac bone metastases were detected, and radiation therapy was undertaken for local control of these lesions. When 18F-fluorodeoxyglucose positron emission tomography was performed for evaluation of the disease, tracer accumulation in the upper rectum was seen. Colonoscopic examination of the rectum revealed an intramural mass with central ulceration, and the mass was diagnosed histologically as an adenocarcinoma. The bone metastases appeared to be controlled, and the patient’s performance status was good, but she had suffered constipation for about a year and desired treatment. Thus, laparoscopic low anterior resection was performed. Histopathologic analysis revealed a moderately differentiated adenocarcinoma existing mainly between the submucosa and serosa, and immunohistochemical analysis showed the tumor to be positive for cytokeratin (CK) 7, negative for CK20, positive for thyroid transcription factor-1, and negative for special AT-rich sequence-binding protein 2 and caudal type homeobox 2, confirming the diagnosis of rectal metastasis from the primary pulmonary adenocarcinoma. The patient recovered well without any change in her functional status. Systemic chemotherapy was resumed, and she continues to do well, now 6 months after surgery. Conclusions Surgery may be a good option for the management of an isolated rectal metastasis from pulmonary cancer in patients whose functional status is good.

We report a case of myeloid sarcoma(MS)that primarily developed in the spleen. The patient was a 60s man with a chief complainant of low-grade fever following a dental implant. Although he underwent intensive antibiotic treatment, including levofloxacin, meropenem, and vancomycin, no significant decline in fever was observed. Abdominal contrast-enhanced CT revealed an LDA occupying the majority of his spleen, which was diagnosed as a splenic abscess. Although a CT-guided biopsy and drainage for the spleen were considered, a puncture of the spleen was not performed due to the substantial concern of bleeding. Subsequently, a splenectomy was performed and HE staining revealed mitosis of tumor cells and massive necrosis. Immunohistochemical analysis revealed that the tumor cells were positive for myeloperoxidase, CD43, CD45, and CD68. Finally, the splenic LDA was diagnosed as MS instead of a splenic abscess. He was treated with systemic chemotherapy. MS primarily develops in the spleen is quite rare: we found only 2 case reports of this disease. The prognosis of MS is poor due to the complications of AML. Accordingly, MS should be considered as a differential diagnosis for accurate diagnosis and treatment of splenic LDA.

Small bowel obstruction (SBO) arises on various backgrounds, and the surgical procedure is often modified intraoperatively as needed. Single-incision laparoscopic surgery (SILS) is less invasive than conventional multiport laparoscopic surgery (MPS) and reported to be equally safe and efficient. We have been applying SILS to SBO requiring surgical treatment, and we conducted a retrospective study to clarify the role of SILS in the management of SBO. Thirty-four consecutive patients were identified for inclusion in the study through a review of hospital records of patients having undergone surgery for SBO between May 2013 and June 2018. Patients with tumor- or hernia-related SBO were excluded. We also identified, for comparison, a group of patients who had undergone open surgery for SBO during the preceeding 5-year period. The primary study endpoint was the SILS completion rate, and analyses were performed to identify risk factors for conversion to open surgery and perioperative complications. The SILS completion rate was 70.6% (24/34 patients), with conversion open surgery required for the remaining 10 (29.4%) patients. Conversion was necessitated by limited working space in 5 (50%) patients, discovery of massive necrosis in 3 (30%), and non-detection of the responsible lesion in 2 (20%). Univariable analysis showed an American Society of Anesthesiologists Physical Status score (p = 0.020) and severe intra-abdominal adhesions (p = 0.007) to be risk factors for conversion. Conversion to open surgery (vs complete SILS) was significantly associated with increased operation time (p = 0.018), blood loss (p = 0.021), postoperative stay (p = 0.010), and postoperative complications (p = 0.004). Open surgery was significantly associated with increased postoperative stay (p = 0.026) and postoperative complications (p = 0.011). SILS appears to be a reasonable surgical treatment option for selected patients with SBO.

Highlights • Isolated splenic sarcoidosis is difficult to diagnose due to its rarity. • Laparoscopic splenectomy has become the gold standard in patients presenting with solid splenic lesions. • Laparoscopic splenectomy is less invasive and useful as part of the diagnostic approach., Introduction Isolated splenic sarcoidosis is difficult to diagnosis due to its rarity. Laparoscopic splenectomy has become the gold standard for therapeutic diagnosis in patients presenting with solid splenic lesions because needle biopsy can lead to bleeding and tract seeding. Presentation of case A 59-year-old female was referred to our hospital due to abnormal accumulation in the spleen on abdominal ultrasonography. Enhanced computed tomography showed three heterogeneously enhanced nodules. Magnetic resonance imaging showed hypointense nodules on T2-weighted images. The initial diagnosis was a fibrous hamartoma or an inflammatory pseudotumor. At follow-up 4 months later, the splenic nodules had increased in size, and diagnostic laparoscopic splenectomy was performed without complications. Histopathologically, the splenic nodules contained noncaseating granulomas comprising epithelioid cells, multinucleated giant cells, and asteroid inclusion bodies. Postoperatively, examinations found no other organ involvement, and the final diagnosis was isolated splenic sarcoidosis. There was no evidence of recurrence at 2 years postoperatively, and systemic treatment was not required. Conclusion Radiological imaging studies are insufficient for the differential diagnosis of splenic lesions in sarcoidosis from other diseases, whereas laparoscopic splenectomy is less invasive and useful as part of the diagnostic approach.

A 44-year-old woman was admitted to our hospital because of an abdominal mass. Blood examination showed no elevation of hepatic enzyme levels but did show a slight increase in the levels of tumor marker CA19-9. An abdominal contrastenhanced CT scan showed a large pedunculated tumor(15 cm)growing from the S5 to the extrahepatic area, with a pattern of earlyenhancement and wash out. Fortunately, organ invasion and tumor dissemination were not observed. Upon FDG-PET examination, marked uptake of FDG was observed in the tumor. S5 hepatic subsectionectomywas performed. The final pathological finding of this tumor was moderatelydifferentiated cholangiocarcinoma. Intrahepatic cholangiocarcinoma with exophytic growth is quite rare, and is reported to have a poor prognosis. Therefore, strict follow-up, including follow-up CT and examination for tumor markers(CA19-9 and CEA), is required.

This phase II clinical trial compared the efficacy and safety of second-line irinotecan and panitumumab treatment (IRI + Pmab) with that of irinotecan, fluoropyrimidines and panitumumab treatment (control) in patients with KRAS wild-type mCRC. The primary endpoint was progression-free survival. In addition, early predictive markers of treatment efficacy were explored. Eighty patients were planned to be recruited. Due to a slow accrual rate, only 48 patients were recruited from 2012 to 2016, of which 23 were allocated to the control group and 25 were allocated to the IRI + Pmab group. The median progression-free survival was 254 days (95% confidence interval, 159–306) for control, and 190 days (95% confidence interval, 159–213) for IRI + Pmab (log-rank test, P = 0.26). The response rate without confirmation was 21.7% (5/23) for control and 40.0% (10/25) for IRI + Pmab. Neutropenia, leukopenia, and anorexia were the most common Grade 3/4 adverse events, and several early drop-outs from the treatment protocol were observed in the control group. As for the biomarkers, carcinoembryonic antigen and lactate dehydrogenase (LDH) smoothly declined immediately after the initial dosing in patients with a partial response or stable disease. After starting treatment, LDH-1 and − 2 increased, while LDH-4 and − 5 decreased, irrespective of tumor response. However, exceptions were frequent. In conclusion, this study failed to prove the safety and efficacy of irinotecan and panitumumab treatment due to insufficient patient accrual. Although LDH and its isozymes changed after initiation of treatment, their ability to predict the tumor response may not surpass that of carcinoembryonic antigen levels. The University Hospital Medical Information Network Clinical Trial Registry: UMIN000007658.

Background & Aims In the small intestine, the paracellular transport of Na + is thought to be critical for luminal Na + -homeostasis and the transcellular absorption of nutrients by Na + -driven transporters. Na + is supplied to the intestinal lumen from the submucosa and serum through tight junctions, which form a paracellular barrier between the cells of epithelial sheets. However, the molecular basis for this paracellular transport of Na + is not well understood. Here, we examined this mechanism by performing loss-of-function studies of claudin-2 and claudin-15, two tight-junctional membrane proteins that are specifically and age-dependently expressed in the villi and/or crypts of small intestinal epithelia. Methods Knockout mice for claudin-2 or claudin-15 were subjected to histologic, cell biologic, electrophysiologic, and physiologic analyses. Results Examination of the knockout mice revealed that both claudin-2 and claudin-15 play crucial roles in the transepithelial paracellular channel-like permselectivity for extracellular monovalent cations, particularly Na + , in infants and adults. Especially in Cldn15 −/− adults, the luminal Na + concentration in the small intestine measured directly in vivo was abnormally low, and glucose absorption was impaired, as assessed by the oral glucose tolerance test and estimation of unabsorbed glucose. Conclusions We propose that the "Na + -leaky" claudin-15 is indispensable in vivo for the paracellular Na + permeability, luminal Na + -homeostasis, and efficient glucose absorption in the small intestine, but claudin-2 is indispensable for only the first of these functions. Claudin-15 knockout leads to Na + deficiency and glucose malabsorption in the mouse adult small intestine.

Background Areolar injection for sentinel lymph node biopsy (SLNB) in breast cancer surgery has been adopted by many institutions. However, only one study has reported the follow-up results for patients whose SLNB was performed with this injection method alone. Methods Three hundred eighty patients with breast cancer underwent SLNB with periareolar injection of both blue dye and radiotracer. The follow-up consisted of a physical examination every 3 months and annual mammography. Results Of 380 patients with SLNB, 261 were found to have negative sentinel lymph nodes so that no ALND was performed. At a median follow-up of 39 months (range 13–74), 2 of the 261 patients developed axillary recurrence for an axillary relapse incidence of .77%. Five-year distant disease-free survival was 96.9%, and overall survival was 99.4%. Conclusions The incidence of axillary recurrence for the areolar injection method was low and consistent with that reported in other observational studies using other injection methods.

Lipomas are found very rarely in the stomach, where they account for only 3% of benign gastric tumors. Here, we report a case of large gastric lipoma removed successfully by laparoscopic intragastric surgery. A 45-year-old woman with no symptoms was incidentally diagnosed with a yellowish submucosal gastric tumor, about 3 cm in diameter, in the prepyloric antrum by upper gastrointestinal endoscopy. Pathological findings of biopsy specimens showed no evidence of malignancy. Computed tomography showed an ovoid and well-circumscribed intramural mass, measuring 35 mm, which was of fat density. These findings suggested that the tumor was a lipoma that we felt should be treated, because large lipomas can give rise to gastrointestinal bleeding. We performed a laparoscopic intragastric enucleation for this tumor. Postoperatively, the tumor was confirmed pathologically to be a lipoma of the stomach. This laparoscopic procedure for benign non-epithelial gastric tumors, such as lipomas, presented here is technically feasible, safe, and less stressful for the patient than gastrectomy.

血液,脾疾患に対する腹腔鏡下脾摘出術25例の有効性を検討するため,それ以前に施行した8例の開腹下脾摘出術とretrospectiveに比較した.平均手術時間 (145分 vs 163分),平均出血量 (80g vs 136g)は腹腔鏡下手術の方がともに少なかったが有意差はなかった.術後の排ガス期間 (1.8日 vs 5.2日),第1歩行期間 (1.2日 vs 2.3日),経口摂取開始期間 (1.2日 vs 3.5日),硬膜外麻酔使用期間 (3.4日 vs 4.3日),在院日数 (9.6日 vs 16.3日) はすべて腹腔鏡下手術の方が短く,硬膜外麻酔使用期間以外は有意差が認められた.合併症は腹腔鏡下手術に術後一過性に肺水腫が1例認められるのみであった.以上より血液,脾疾患に対する腹腔鏡下脾摘出術は開腹下手術に匹敵する程安全な手術術式と言える.術後回復は開腹下手術に比べ有意に早く,患者のquality of lifeの向上に貢献していると思われた.