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An unusual case of a jejunal mesenteric pseudocyst treated by laparoscopic resection is reported. A 44-year-old woman was admitted to our hospital with intermittent upper abdominal pain and diarrhea. Physical examination revealed slight periumbilical tenderness, and no masses were palpable. Contrast-enhanced computed tomography showed a 4-cm-sized nonenhancing high-density mass with a heterogeneous pattern on a proximal small bowel loop. Based on these findings, a gastrointestinal stromal tumor accompanied by hemorrhagic and cystic change, a mesenteric hematoma, or a desmoid tumor was diagnosed. Laparoscopy was performed to obtain an accurate diagnosis. Exploration of the abdominal cavity identified a 4-cm mass originating from the mesentery of the jejunum. Segmental resection of the jejunum and its mesentery, including the mass, was performed. Macroscopically, the mass appeared to be a cystic mass of the jejunal mesentery. The mass within the cyst lumen consisted of white clayish material with no specific pathology. The final pathological diagnosis was a mesenteric pseudocyst. The patient had an uneventful postoperative course.

Castleman's disease (CD) is an uncommon benign lymphoproliferative disorder of unknown etiology. A rare case of cervical CD diagnosed at lymph node dissection for esophageal carcinoma is reported. An esophageal tumor was identified in a 67-year-old man during a follow-up examination after surgery for oral carcinoma. Esophagoscopy revealed a type 1 tumor in the cervical esophagus. Histology of esophagoscopic biopsies indicated squamous cell carcinoma. Contrast-enhanced computed tomography revealed swollen lymph nodes of the right cervical region. No distant metastasis was detected. Esophageal carcinoma, T2N2M0, Stage IIIA was diagnosed. Neoadjuvant chemotherapy was recommended, but the patient rejected the chemotherapy. The patient underwent laparoscopic-assisted transhiatal esophagectomy. The histopathological diagnosis was moderately differentiated squamous cell carcinoma with pT1bN0M0, Stage IA. On histology, the swollen lymph nodes of the right cervical region revealed CD. The patient's postoperative course was relatively good.

BACKGROUND Patients with tetraplegia can achieve independent gait with lateral-type powered exoskeletons; it is unclear whether medial-type powered exoskeletons allow for this. OBJECTIVE To investigate gait training with a medial-type powered exoskeleton wearable power-assist locomotor (WPAL) in an individual with incomplete cervical (C5) and complete thoracic (T12) spinal cord injury (SCI). METHODS The 60-session program was investigated retrospectively using medical records. Upon completion, gait performance was examined using three-dimensional motion analyses and surface electromyography (EMG) of the upper limbs. RESULTS The subject achieved independent gait with WPAL and a walker in 12 sessions. He continuously extended his right elbow; his left elbow periodically flexed/extended. His pelvic inclination was larger than the trunk inclination during single-leg stance. EMG activity was increased in the left deltoid muscles during ipsilateral foot-contact. The right anterior and medial deltoid muscle EMG activity increased just after foot-off for each leg, as did the right biceps activity. Continuous activity was observed in the left triceps throughout the gait cycle; activity was unclear in the right triceps. CONCLUSIONS These results suggest the importance of upper limb residual motor function, and may be useful in extending the range of clinical applications for robotic gait rehabilitation in patients with SCI.

Gastrointestinal stromal tumors of the duodenum are rare. For benign tumors, premalignant lesions, or malignant potential tumors located in the second portion of the duodenum close to the papilla of Vater, pancreaticoduodenectomy is sometimes performed. A case of laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor at the second portion of the duodenum is reported. The surgical procedure was performed as follows: first, the second portion of the duodenum was separated from the pancreatic head; second, the duodenum was cut off with the linear stapler after having confirmed preservation of the papilla by intraoperative endoscopy; and third, reconstruction was carried out by a side-to-side duodenojejunostomy. Laparoscopic segmental duodenectomy for duodenal gastrointestinal stromal tumors is thought to be advantageous compared with pancreaticoduodenectomy in terms of low burden and organ function preservation. The present procedure is feasible for benign or low-malignant tumors that do not infiltrate outside of the duodenal walls.

Background: Proximal early gastric cancer is a good indication for totally laparoscopic proximal gastrectomy (TLPG) with double-tract reconstruction (DTR). However, when most of the dietary intake passes through the escape route of the jejunum, the functional benefits of proximal gastrectomy might be similar to those after total gastrectomy. Our DTR procedure was improved for easy passage through the remnant stomach. The purposes of this study were to present a novel technique for intracorporeal DTR using linear staplers after TLPG and to investigate surgical outcomes. Methods: DTR was performed using linear staplers only. A side-to-side jejunogastrostomy with twisting of both the remnant stomach and the anal jejunum was performed for the purpose of passing meals through the remnant stomach (an oblique jejunogastrostomy technique). The ten patients who underwent TLPG with DTR from January 2011 to August 2016 in Hokkaido University Hospital were retrospectively reviewed. Their clinicopathological characteristics and surgical and postoperative outcomes were collected and analyzed. Results: The median duration of operation was 285 (range 146-440) min. No patients required blood transfusions. The number of dissected lymph nodes was 32 (range 22-56). There were no intraoperative complications, and no cases were converted to open surgery. All the patients were pT1N0M0 stage IA. No anastomotic leakage or complications were detected. Postoperative gastrography after reconstruction showed that contrast medium flowed mainly to the remnant stomach. The average percentage body weight loss was 14.0 +/- 7.1% at 10 months. The average percentage decrease in serum hemoglobin was 5.4 +/- 10.4% at 12 months. Conclusions: This novel technique for intracorporeal DTR provided a considerable advantage by the passage of dietary intake to the remnant stomach after LPG.

Purpose: The tumor-node-metastasis (TNM) classification defines R1 as the presence of tumor cells at the resection margin, while the current Royal College of Pathologists guidelines for pancreaticoduodenectomy specimens regard the presence of tumor cells within 1 mm from the resection margin as R1 (the "1-mm rule"). The aims of this study were to investigate the resection margin status of pancreatic head cancer retrospectively according to both the TNM and 1-mm rule classifications, and to evaluate the postoperative survival and tumor recurrence patterns. Methods: A total of 117 patients with pancreatic head cancer were the subjects of this study. Results: R1^1-mm rule resection was associated with a significantly worse disease-free survival (DFS) than R0^1-mm rule resection (p = 0.0259), while R1^TNM had no impact on DFS. R1^1-mm rule resection margin status correlated with the incidence of tumor recurrence in the liver (p = 0.0483). In a multivariate analysis, R1^1-mm rule resection was the independent variable for predicting poor DFS (hazard ratio 1.71; p = 0.0289). Conclusions: R1 resection margin status determined by the 1-mm rule may be an independent indicator for predicting disease recurrence, especially liver metastasis. These results may be useful for selecting the appropriate adjuvant therapy protocol and conducting strict surveillance in PDAC patients.

Aim To examine the efficacy of postural strategy training using a balance exercise assist robot (BEAR) as compared with conventional balance training for frail older adults. Methods The present study was designed as a cross-over trial without a washout term. A total of 27 community-dwelling frail or prefrail elderly residents (7 men, 20 women; age range 65–85 years) were selected from a volunteer sample. Two exercises were prepared for interventions: robotic exercise moving the center of gravity by the balance exercise assist robot system; and conventional balance training combining muscle-strengthening exercise, postural strategy training and applied motion exercise. Each exercise was carried out twice a week for 6 weeks. Participants were allocated randomly to either the robotic exercise first group or the conventional balance exercise first group. Main outcome measures: preferred and maximal gait speeds, tandem gait speeds, timed up-and-go test, functional reach test, functional base of support, center of pressure, and muscle strength of the lower extremities were assessed before and after completion of each exercise program. Results Robotic exercise achieved significant improvements for tandem gait speed (P = 0.012), functional reach test (P = 0.002), timed up-and-go test (P = 0.023) and muscle strength of the lower extremities (P = 0.001–0.030) compared with conventional exercise. Conclusions In frail or prefrail older adults, robotic exercise was more effective for improving dynamic balance and lower extremity muscle strength than conventional exercise. These findings suggest that postural strategy training with the balance exercise assist robot is effective to improve the gait instability and muscle weakness often seen in frail older adults. Geriatr Gerontol Int 2017; 17: 1982–1990.

PURPOSE We developed laparoscopic-assisted rectus sheath block (LRSB) as a novel technique and report on its safety and effectiveness. METHODS Patients were randomly enrolled to an LRSB or control group (n=19 each). In the LRSB group, after the umbilical wound was closed, local anesthetic was injected transcutaneous at each of 4 sites (3 cm above and below the umbilicus bilaterally) with 10 mL of 0.25% levobupivacaine, laparoscopically. The control group received conventional postoperative pain management. The primary endpoint was visual analogue scale (VAS) pain score at the end of surgery. Secondary endpoints were VAS and Prince Henry pain scale after surgery, number of administrations of analgesics, and side effects of anesthesia. RESULTS No significant differences in background were seen between groups. VAS at the end of surgery was significantly lower in the LRSB group than in controls (P

Despite its spread and advances, laparoscopic gastrectomy (LG) for advanced gastric cancer (AGC) remains controversial. The aim of this study was to evaluate the oncologic outcomes and to identify the potential risk factors for recurrence and survival after LG in AGC patients. The medical records of patients who underwent radical LG for histopathologically diagnosed stage IB or more advanced gastric cancer from 2004 to 2012 were collected. The clinicopathologic factors and outcomes were evaluated retrospectively. LG was performed for 300 patients, with a median operative time of 278 min and blood loss of 46 ml. Postoperative morbidity was defined as Clavien-Dindo grades III and IV and occurred in 13 patients (6.3%) in the laparoscopic distal gastrectomy group. The pathologic stage was IB in 109 patients (36.3%), IIA in 77 patients (25.7%), IIB in 48 patients (16.0%), IIIA in 31 patients (10.3%), IIIB in 19 patients (6.3%), and IIIC in 16 patients (5.3%). Median follow-up period was 55.2 months. The 3-year relapse-free survival (RFS) rate was 92.7% for stage IB, 87.0% for IIA, 68.8% for IIB, 64.5% for IIIA, 47.4% for IIIB, and 43.8% for IIIC. The 5-year actual overall survival rate was 91.1% for stage IB, 72.7% for II, and 62.5% for III. Multivariate analysis revealed postoperative complication as an independent risk factor for RFS. LG for AGC was feasible and provided comparable oncologic outcomes with those previously reported. Postoperative complications correlated with poor prognosis. Randomized control trials should be conducted to confirm these results of LG for AGC in the general population.

Background: Postoperative liver failure is a serious complication after major hepatectomy, and perioperative prediction of its incidence using current technology is still very difficult. Near-infrared (NIR) fluorescence imaging allows quantitative assessment of the fluorescent signal from indocyanine green (ICG) in regions of interest on the liver surface. This method might offer a new promising modality for evaluating regional liver reserve. However, data are lacking regarding the relationship between liver function and fluorescent signals on the liver surface after intravenous ICG injection. This study was conducted to obtain the data necessary to apply NIR fluorescence imaging as a modality for measuring liver function. Materials and Methods: This study included 16 patients who underwent open hepatopancreatobiliary surgery between March 2011 and March 2012. After laparotomy, ICG was injected intravenously at 2.5 mg/L of liver volume, then the fluorescence intensity (FI) and signal-to-background ratio (SBR) in the lateral segment of the liver were assessed for 15 min. Intraoperative blood samples were also obtained to measure the plasma clearance rate of ICG (ICGK). Correlations between ICGK, liver volume, and SBR, as well as between ICGK, liver volume, and rate of change of FI were analyzed. Results: The experimental procedure was performed in all 16 patients. The FI of the liver increased rapidly after ICG injection, then became more gradual, reaching a near-plateau after 15 min. A significant correlation was seen between ICGK and the rate of change of FI up to 15 min (|rS| = 0.5725, p < 0.05). Conclusion: This is the first report to show a relationship between liver function and fluorescent signals on the liver surface after intravenous ICG injection. Intraoperative NIR fluorescence imaging with ICG may be useful as a new method for assessing liver function.

[Purpose] To clarify the changes in postural strategy by evaluating leg joint motion and muscle activity before and after continuous exercise against perturbation using the Balance Exercise Assist Robot (BEAR). [Subjects and Methods] Nine healthy subjects (male 7, female 2; mean age 23 ± 1 years) performed a postural perturbation coping exercise only. In the task, the robot leaned and moved automatically. Participants were instructed to maintain their default upright position and they performed the exercise five times in a row (1 minute/trial). Changes in total movement distance, range of motion of each joint (hip, knee, ankle), and mean activity of each muscle for the first and fifth trials were compared. [Results] The total movement distance of BEAR and range of motion in the hip decreased significantly from the first trial to the last trial. No change in muscle activity was observed in the rectus femoris, biceps femoris, tibialis anterior or gastrocnemius. [Conclusion] The results for exercise against perturbation using BEAR in this study suggest that BEAR may be a promising method to improve the ankle strategy for maintaining a standing posture.

Benign biliary strictures have a broad spectrum of etiologies. There have been no reported cases, however, of a biliary stricture secondary to a migrated suture after laparoscopic distal gastrectomy (LDG). Here, we report one such case. The patient was a 60-year-old man who underwent LDG with Roux-en-Y reconstruction for early gastric cancer. Pathology revealed early cancer (T1N0M0) with a curative resection. Two years after LDG, the patient was found to have elevated hepatobiliary enzymes. After further workup, the new diagnosis was invasive cholangiocarcinoma (T2N0M0), and the patient underwent pancreaticoduodenectomy. Intraoperatively, a monofilament nylon suture was found in the center of a biliary stricture; this suture was previously used for duodenal closure during LDG. Histologically, the bile duct with stricture showed chronic inflammation and fibrosis. Despite no evidence of invasive carcinoma on pathology, a small lesion of adenocarcinoma in situ was found in the superior common hepatic duct.

The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes.

Highlights • Laparoscopic perineal hernia repair using a soft and large synthetic mesh is useful. • Using a large mesh could cover the hernial orifice with a sufficient margin. • Cone-shaped implantation is easy by folding a large mesh in the pelvic cavity., Introduction Perineal hernia after abdominoperineal resection (APR) is a rare complication, and no standard surgical procedures are established. We describe a simple laparoscopic mesh implantation technique utilizing a large synthetic flat mesh. Presentation of Case We report a case of perineal hernia after APR. We performed laparoscopic repair using a soft and large synthetic mesh with simple technique. The essence of this technique is that mesh is inserted into the abdominal cavity without trimming and it forms in a conical shape to better adjust to the pelvic cavity. Discussion The perineal and laparoscopic approaches for perineal hernia repair have been performed most commonly in recent years, but the recurrence rate after repair remains high (24.1%). Using a large mesh could cover the hernial orifice with a sufficient margin, reducing a risk of recurrence caused by shrinkage and slippage of the mesh. Conclusion Our technique utilizing a large, lightweight, synthetic mesh can be practical and useful for perineal hernia repair after laparoscopic APR.

A 67-year-old woman was diagnosed with Stage ⅡA breast cancer(T2N0M0)in 2003. She underwent mastectomy and lymph node dissection. Oral fluoropyrimidine was administered for 3 years as adjuvant chemotherapy. In 2008, the patient was diagnosed with multiple bone metastases and left supraclavicular lymph node metastasis. Radiotherapy was performed on the left first rib and left supraclavicular lymph node. She was treated with chemotherapy and endocrine therapy and bone metastasis therapeutic agent. In 2013, multiple liver metastases were noted and treated with chemotherapy. Liver metastases were well-controlled. Endocrine therapy was continued for bone metastases without visceral metastasis. In 2016, the patient was diagnosed with bone marrow carcinomatosis and died 2 weeks later due to bone marrow carcinomatosis.

Purpose To evaluate the self-assessed competency of graduating residents (GRs) in Japan upon completion of their residency and to identify the gap between their competency and the competency expected by their program directors (PDs). Method A list of 31 essential surgical procedures was compiled according to the consensus of surgical educators from around the country. A survey with this list was sent to all 909 GRs and their 611 PDs in 2016. The GRs rated their competency to perform these procedures and the PDs were asked to evaluate the expected competency of their GRs using the Zwisch Scale. Result The response rate was 56.3% for the GRs and 76.8% for the PDs. Fewer than half of the GRs who responded felt confident performing ten (32%) of the surgical procedures evaluated. For most procedures, the GRs' self-reported competency was lower than the expectation reported by their PDs. This gap was more than 10% for 13 of the procedures. Conclusion More than half of the GRs in Japan lacked the confidence in their skill to perform one-third of the surgical procedures selected for evaluation in this study. These findings should be used to update the surgical education curriculum in Japan.

Background The right external iliac vein (REIV) is often used for portal vein reconstruction in patients undergoing pancreatoduodenectomy with portal-superior mesenteric vein resection. We report a case of cardiac arrest caused by acute lower leg compartment syndrome as a result of REIV resection. Case presentation A 53-year-old man underwent pancreatoduodenectomy with portal vein resection. Hyperkalemia progressed during surgery due to intestinal reperfusion injury, which caused recurrent ventricular arrhythmia required for cardio-pulmonary resuscitation. The surgery was discontinued after resuscitation, and portal vein reconstruction using the REIV was performed 2 days post-operatively. Acute compartment syndrome was diagnosed immediately following the surgery. Hyperkalemia progressed, causing pulseless ventricular tachycardia. Emergent fasciotomy was performed, but right leg dysfunction persisted after discharge. Conclusion REIV resection can cause lower-extremity acute compartment syndrome. The status, including intracompartmental pressure, of the lower extremity should be carefully observed after REIV resection during and after surgery.

In this paper, we propose a system to determine authenticity using image matching. This system uses feature point matching to detect objects. We compare the corresponding points between images using local features and image size to improve the detection accuracy. Consequently, the detection accuracy improved by magnifying the target images to the size of the template image when the KAZE feature was used.

The high expression of human equilibrative nucleoside transporter‐1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5‐fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S‐1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S‐1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S‐1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S‐1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S‐1 arm., In the S‐1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = .007). In contrast, there were no significant differences in OS between DPD low and high groups in the S‐1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm.

Significance Pancreatic ductal carcinomas (PDACs) have been extensively studied regarding their genomic alterations, microenvironmental intercommunication, and metabolic reprogramming. However, identification of the protein machinery of tumor cells that eventually drives malignancy as a result of driver mutations, and their associated events, is highly anticipated toward the development of precision medicine. The lack of such information regarding PDACs has hindered the elucidation of mechanisms driving malignancies, leaving them incurable. Here we demonstrated that the 2 well-known pancreatic driver mutations cooperatively activate a specific signaling pathway that promotes tumor invasion and immune evasion properties. Our results provide insights into the molecular basis by which malignancies often develop in parallel with oncogenesis and PDAC cell growth, as well as druggable targets for immunotherapies., Although KRAS and TP53 mutations are major drivers of pancreatic ductal adenocarcinoma (PDAC), the incurable nature of this cancer still remains largely elusive. ARF6 and its effector AMAP1 are often overexpressed in different cancers and regulate the intracellular dynamics of integrins and E-cadherin, thus promoting tumor invasion and metastasis when ARF6 is activated. Here we show that the ARF6–AMAP1 pathway is a major target by which KRAS and TP53 cooperatively promote malignancy. KRAS was identified to promote eIF4A-dependent ARF6 mRNA translation, which contains a quadruplex structure at its 5′-untranslated region, by inducing TEAD3 and ETV4 to suppress PDCD4; and also eIF4E-dependent AMAP1 mRNA translation, which contains a 5′-terminal oligopyrimidine-like sequence, via up-regulating mTORC1. TP53 facilitated ARF6 activation by platelet-derived growth factor (PDGF), via its known function to promote the expression of PDGF receptor β (PDGFRβ) and enzymes of the mevalonate pathway (MVP). The ARF6–AMAP1 pathway was moreover essential for PDGF-driven recycling of PD-L1, in which KRAS, TP53, eIF4A/4E-dependent translation, mTOR, and MVP were all integral. We moreover demonstrated that the mouse PDAC model KPC cells, bearing KRAS/TP53 mutations, express ARF6 and AMAP1 at high levels and that the ARF6-based pathway is closely associated with immune evasion of KPC cells. Expression of ARF6 pathway components statistically correlated with poor patient outcomes. Thus, the cooperation among eIF4A/4E-dependent mRNA translation and MVP has emerged as a link by which pancreatic driver mutations may promote tumor cell motility, PD-L1 dynamics, and immune evasion, via empowering the ARF6-based pathway and its activation by external ligands.

Background The malignant transformation of an ectopic pancreas in the duodenum is extremely rare. Herein, we report a case of an adenocarcinoma that arose from an ectopic pancreas. We also reviewed 14 cases of malignant transformations arising from an ectopic pancreas in the duodenum that were previously published. Case presentation An 81-year-old man with a 1-month history of vomiting was admitted to our institution. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) scans revealed an obstruction at the first part of the duodenum. A distal gastrectomy was performed for diagnostic and therapeutic purposes. The histopathological examination of the resected specimen showed adenocarcinoma that arose from an ectopic pancreas (Heinrich type 1). The patient is alive without relapse at 18 months of follow-up. Conclusions Adenocarcinoma that arises from an ectopic pancreas should be considered when an obstruction is identified in the duodenum.

Background/Aim: Pemetrexed plus platinum followed by pemetrexed maintenance has been one of the standard first-line treatments in advanced nonsquamous non-small cell lung cancer (NSCLC), but little is known regarding its safety and efficacy for patients with interstitial lung disease (ILD). Patients and Methods: The medical records of 24 patients with advanced nonsquamous NSCLC and preexisting ILD who received pemetrexed and platinum doublet therapy with and without pemetrexed maintenance in the first-line setting between December 2009 and June 2016, were retrospectively reviewed. Results: The median progression-free survival time was 4.7 months, and the median overall survival time was 9.5 months. Of the 24 patients analyzed, six received pemetrexed maintenance. Acute exacerbation of ILD (AE-ILD) occurred in five (20.8 %) of 24 patients, including two fatal cases. Conclusion: The treatment with pemetrexed plus platinum has a high risk of AE-ILD in patients with advanced nonsquamous NSCLC and preexisting ILD.

A 70's male was admitted to our hospital with complaints of anorexia and abdominal pain. CT showed thickening of the ascending colon. Colonoscopy revealed multiple diverticula of the ascending colon, but no tumor on the mucosa. The patient was diagnosed as a case of diverticulitis of the ascending colon and was advised laparoscopic ileocecal resection. The resected specimen showed wall thickening; however, no remarkable findings were observed, with the exception of multiple diverticula on the mucosal surface. Histological examination showed well-differentiated tubular adenocarcinoma extending into the serosa probably arising from the diverticulum. Chemotherapy was performed after surgery. The patient died due to peritoneal dissemination from the ascending colon cancer 14 months after surgery.

It has been clear that the clinical responses by applying immune checkpoint inhibitor alone are limited. To better improve this limited clinical response, combinational therapy has been focused. We recently reported the association between EMT related factors and PD-L1 expression in the extrahepatic hilar cholangiocarcinoma, and its role as a surrogate biomarker for patient prognosis. We here report clinical relevance of combinational therapy of HDAC inhibitors and anti-PD-L1 antibody as an immune checkpoint inhibitors.

The aim of this study was to clarify the association between expression of human leukocyte antigen (HLA) class I in non-small-cell lung cancer (NSCLC) cells and patient survival. To address this, immunohistochemical staining for HLA class I was performed on specimens from 111 patients with NSCLC, and overall survival curves were compared using the log-rank test. In addition, multivariate analyses were performed using Cox's proportional hazard model. The cases were divided into 5 classes based on the expression of HLA class I heavy chain and β2-microglobulin. The overall survival rate for patients with tumors lacking HLA class I heavy chain (30 cases; 27.0%) was significantly decreased. The multivariate analysis demonstrated that the absence of HLA class I heavy chain was an independent predictor of poor prognosis. There was a trend towards an unfavorable prognosis for patients whose tumors did not express β2-microglobulin (57 cases; 51.4%). Downregulation of HLA class I heavy chain expression was significantly associated with the downregulation of β2-microglobulin. Cases lacking HLA class I heavy chain as well as β2-microglobulin expression (23 cases; 20.7%) had a statistically significant unfavorable prognosis compared with other cases. The present findings demonstrate that the lack of HLA class I heavy chain expression in tumor cells is an independent prognostic factor for poor NSCLC survival, and is likely to exert an important influence on immune surveillance in patients.

BACKGROUND Since there is no reliable evidence on the safety of pancreaticoduodenectomy (PD) in chronic hepatic dysfunction (CHD) including liver cirrhosis (LC), the effects of CHD on patients undergoing PD were investigated. METHODS This multi-institutional retrospective study analyzed 529 patients with CHD, including 105 patients diagnosed with LC, who underwent PD at 82 high-volume institutions between 2004 and 2013. RESULTS The in-hospital mortality rate was 5.9%. The incidence of postoperative hepatic decompensation upon discharge and refractory ascites was 10.2% and 8.9%, respectively. For hepatic decompensation, the serum aspartate aminotransferase (AST) of more than 50 IU/l and portal hypertension (PHT) were independent significant risk factors. For refractory ascites, prothrombin activity of

There is a lack of patient-reported outcome measures (PROMs) with robust measurement properties to assess postoperative recovery and support patient-centered care after abdominal surgery. The aim of this study was to establish a conceptual framework of recovery after abdominal surgery to support the development of a conceptually relevant and psychometrically sound PROM. Patients from four different countries (Canada, Italy, Brazil, and Japan) participated in qualitative interviews focusing on their lived experiences of recovery after abdominal surgery. Interviews were guided by a previously developed hypothesized conceptual framework established based on a literature review and expert consensus. Interviews were analyzed according to a modified grounded theory approach and transcripts were coded according to the International Classification of Functioning, Disability and Health (ICF). Codes for which thematic saturation was reached were classified into domains of health that are relevant to the process of recovery after abdominal surgery. These domains were organized into a structured diagram. 30 Patients with diverse demographics and surgical characteristics were interviewed (50% female, age 57 ± 18 years, 66% major or major extended surgery). 39 Unique domains of recovery emerged from the interviews, 17 falling under the ICF category of “Body Functions” and 22 under “Activities and Participation”. These domains constitute the conceptual framework of recovery after abdominal surgery. This study provides comprehensive insight into patients’ perspectives of the recovery process after abdominal surgery. This conceptual framework will support content validity and provide the pivotal basis for the development of a novel PROM to inform quality improvement initiatives and patient-centered research in abdominal surgery.

Photodynamic diagnosis/therapy (PDD/PDT) are novel modalities for the diagnosis and treatment of cancer. The photosensitizer protoporphyrin IX is metabolized from 5-aminolevulinic acid (5-ALA) intracellularly, and PDD/PDT using 5-ALA have been approved in dermatologic malignancies and gliomas. However, the molecular mechanism that defines the efficacy of PDD/PDT is unknown. In this study, we analyzed the functions of ATP-binding cassette (ABC) transporters in PDD using 5-ALA. Most of the human gastrointestinal cancer line cells examined showed a homogenous staining pattern with 5-ALA, except for the pancreatic cancer line PANC-1, which showed heterogeneous staining. To analyze this heterogeneous staining pattern, single cell clones were established from PANC-1 cells and the expression of ABC transporters was assessed. Among the ABC transporter genes examined, ABCG2 showed an inverse correlation with the rate of 5-ALA-positive staining. PANC-1 clone #2 cells showed the highest level of ABCG2 expression and the lowest level of 5-ALA staining, with only a 0.6% positive rate. Knockdown of the ABCG2 gene by small interfering RNAs increased the positive rate of 5-ALA staining in PANC-1 wild-type and clone cells. Interestingly, PANC-1 clone #2 cells showed the high sphere-forming ability and tumor-formation ability, indicating that the cells contained high numbers of cancer stem cells (CSCs). Knockdown or inhibition of ABCG2 increased the rate of 5-ALA staining, but did not decrease sphere-forming ability. These results indicate that gastrointestinal cancer cell lines expressing high levels of ABCG2 are enriched with CSCs and show low rates of 5-ALA staining, but 5-ALA staining rates can be improved by inhibition of ABCG2.

Background: Perihilar cholangiocarcinoma (PHC) often requires extensive surgery which is associated with substantial morbidity and mortality. This study aimed to compare an Eastern and Western PHC cohort in terms of patient characteristics, treatment strategies and outcomes including a propensity score matched analysis. Methods: All consecutive patients who underwent combined biliary and liver resection for PHC between 2005 and 2016 at two Western and one Eastern center were included. The overall perioperative and long-term outcomes of the cohorts were compared and a propensity score matched analysis was performed to compare perioperative outcomes. Results: A total of 210 Western patients were compared to 164 Eastern patients. Western patients had inferior survival compared to the East (hazard-ratio 1.72 (1-23-2.40) P < 0.001) corrected for age, ASA score, tumor stage and margin status. After propensity score matching, liver failure rate, morbidity, and mortality were similar. There was more biliary leakage (38% versus 13%, p = 0.015) in the West. Conclusion: There were major differences in patient characteristics, treatment strategies, perioperative outcomes and survival between Eastern and Western PHC cohorts. Future studies should focus whether these findings are due to the differences in the treatment or the disease itself.

Background: Postoperative pancreatic fistula (POPF) is a harmful complication after pancreaticoduodenectomy (PD). Grade C POPF, as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication. This study aims to evaluate risk factors for Grade C POPF after PD. Methods: This is a prospective, multicenter collaboration study based in Japan and Taiwan. Between 2014 and 2017, 3,022 patients were enrolled in this study and 2,762 patients were analysed after 260 patients were excluded (discontinuation of protocol treatment: n=241, incomplete information: n=19). We analysed risk factors of Grade C POPF based on the 2005 ISGPF scheme (sepsis, organ dysfunction, haemorrhage, reoperation, and/or death) and then separately by the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death). Findings: Among 2,762 patients that underwent PD, 93 patients (3∙4%) developed Grade C POPF as defined by 2005 ISGPF and 46 patients (1∙7%) developed Grade C POPF as defined by 2016 ISGPF. We found eight independent risk factors associated with Grade C POPF as defined by 2005 ISGPF on multivariate analyses; male sex, body mass index (BMI) ≥25∙0 kg/m2, chronic steroid use, preoperative serum C-reactive protein ≥1∙0 mg/dL, soft pancreas, main duct size

Pseudomyxoma peritonei is a rare disease with a reported prevalence of about 1-3 per million people annually. Cytoreductive surgery and perioperative hyperthermic intraperitoneal chemotherapy are considered as treatment options improving disease control or long-term survival. However, for patients with incomplete cytoreduction or debulking surgery, outcomes are significantly poorer compared with patients who have obtained complete or optimal cytoreduction. In cases of high-grade pseudomyxoma peritonei that are considered inoperable and/or unresectable, combination chemotherapy regimen with a neo-angiogenesis inhibitor such as bevacizumab is recommended. In this report, a 62-year-old Japanese man presented with abdominal distention. Examination of ascites demonstrated a jelly-like consistency and peritoneal pseudomyxoma was suspected. To relieve progressive symptoms, palliative debulking surgery with total colectomy was performed. Postoperative pathology confirmed high-grade appendiceal mucinous neoplasm with high-grade pseudomyxoma peritonei. In our case, combination chemotherapy with trifluridine/tipiracil (TAS-102) and bevacizumab was initiated after palliative debulking surgery. As a result, carcinoembryonic antigen level was kept stable and the volume of ascites remained almost the same as at the beginning of treatment for more than 2 years. In conclusion, combination chemotherapy comprising TAS-102 and bevacizumab in patients with palliative debulking could be a useful option for patients with high-grade mucinous appendiceal neoplasm and high-grade pseudomyxoma peritonei.

Introduction Necrotizing soft tissue infection (NSTI) of the chest wall is a rare, rapidly spreading, highly lethal surgical disease. Radical debridement interferes with the important anatomical function of the chest wall. We report a case of chest wall NSTI that was successfully managed with early diagnosis and serial debridement. Presentation of case A 43-year-old, previously healthy woman presented with severe malaise and worsening right axillary pain. She was severely lethargic and had a painful, large, pale lesion with surrounding erythema of the right chest and trunk. Computed tomography revealed NSTI, with diffuse soft tissue inflammation extending from the axilla to the lower abdomen. There was no obvious entry portal. Prompt surgical drainage was established. Group A streptococcus infection was diagnosed. During her 3-month postoperative course, she underwent four more surgeries, including two debridements. This treatment proved successful and avoided the need for complicated muscle flap reconstruction. She was discharged on postoperative day 109. Discussion Group A streptococcus can cause NSTI even in immunocompetent patients without an entry portal. Radical debridement is recommended for infection control. Preserving anatomical chest wall function, however, is also important. Serial debridement with close follow-up solved the problem in this patient. Conclusions Serial debridement with close follow-up enabled to avoid large tissue deficits and complicated reconstruction in the case of NSTI of the chest wall., Highlights • Necrotizing soft tissue infection of the chest wall is rare and lethal. • Radical debridement could interfere with the anatomical function of the chest wall. • Adequate drainage with minimum skin incision avoids large tissue defects. • Serial debridement with close follow-up enabled to avoid complicated reconstruction

Simple Summary Gallbladder cancer (GBC) is a rare but lethal cancer. Molecular characterization of GBC is insufficient so far, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. Clustering analysis of RNA expression revealed two subclasses of 36 GBCs, which reflects the status of the tumor microenvironment (TME) and poor prognosis of GBC, including epithelial-mesenchymal transition (EMT), immune suppression, and the TGF-beta signaling pathway. The knockout of miR125B1 in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutations of the genes related to the TGF-beta signaling pathway were enriched in the poor-prognosis/TME-rich cluster of GBCs. This comprehensive molecular analysis provides a new classification of GBCs based on the TME activity, which is involved with EMT and immune suppression for poor prognosis of GBC. This information may be useful for GBC prognosis and therapeutic decision-making. Gallbladder cancer (GBC), a rare but lethal disease, is often diagnosed at advanced stages. So far, molecular characterization of GBC is insufficient, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. We performed a transcriptome analysis of both coding and non-coding RNAs from 36 GBC fresh-frozen samples. The results were integrated with those of comprehensive mutation profiling based on whole-genome or exome sequencing. The clustering analysis of RNA-seq data facilitated the classification of GBCs into two subclasses, characterized by high or low expression levels of TME (tumor microenvironment) genes. A correlation was observed between gene expression and pathological immunostaining. TME-rich tumors showed significantly poor prognosis and higher recurrence rate than TME-poor tumors. TME-rich tumors showed overexpression of genes involved in epithelial-to-mesenchymal transition (EMT) and inflammation or immune suppression, which was validated by immunostaining. One non-coding RNA, miR125B1, exhibited elevated expression in stroma-rich tumors, and miR125B1 knockout in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutation profiles revealed TP53 (47%) as the most commonly mutated gene, followed by ELF3 (13%) and ARID1A (11%). Mutations of ARID1A, ERBB3, and the genes related to the TGF-beta signaling pathway were enriched in TME-rich tumors. This comprehensive analysis demonstrated that TME, EMT, and TGF-beta pathway alterations are the main drivers of GBC and provides a new classification of GBCs that may be useful for therapeutic decision-making.