Comprehensive analysis of full-length transcripts reveals novel splicing abnormalities and oncogenic transcripts in liver cancer.

Genes generate transcripts of various functions by alternative splicing. However, in most transcriptome studies, short-reads sequencing technologies (next-generation sequencers) have been used, leaving full-length transcripts unobserved directly. Although long-reads sequencing technologies would enable the sequencing of full-length transcripts, the data analysis is difficult. In this study, we developed an analysis pipeline named SPLICE and analyzed cDNA sequences from 42 pairs of hepatocellular carcinoma (HCC) and matched non-cancerous livers with an Oxford Nanopore sequencer. Our analysis detected 46,663 transcripts from the protein-coding genes in the HCCs and the matched non-cancerous livers, of which 5,366 (11.5%) were novel. A comparison of expression levels identified 9,933 differentially expressed transcripts (DETs) in 4,744 genes. Interestingly, 746 genes with DETs, including the LINE1-MET transcript, were not found by a gene-level analysis. We also found that fusion transcripts of transposable elements and hepatitis B virus (HBV) were overexpressed in HCCs. In vitro experiments on DETs showed that LINE1-MET and HBV-human transposable elements promoted cell growth. Furthermore, fusion gene detection showed novel recurrent fusion events that were not detected in the short-reads. These results suggest the efficiency of full-length transcriptome studies and the importance of splicing variants in carcinogenesis.

Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Neoadjuvant Triplet Chemotherapy with Docetaxel, Cisplatin plus 5-Fluorouracil versus Docetaxel, Cisplatin plus S-1 for Advanced Esophageal Squamous cell Carcinoma: Propensity Score Matched Analysis.

INTRODUCTION: This study examines whether neoadjuvant docetaxel, cisplatin plus S-1 (DCS) therapy is superior to docetaxel, cisplatin plus 5-fluorouracil (DCF) therapy for resectable advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients diagnosed with resectable advanced ESCC at our hospital between January 2010 and December 2019 underwent either neoadjuvant DCF therapy or DCS therapy, followed by radical esophagectomy. Prior to August 2014, we usually used neoadjuvant DCF therapy; we then completely transitioned to using neoadjuvant DCS therapy. RESULTS: A total of 144 patients received one of these triplet regimens as neoadjuvant chemotherapy: DCF therapy to 67 patients and DCS therapy to 77 patients. After propensity score matching, 55 patients in each group were selected as matched cohorts. There was no significant difference between the groups in complete response (DCF = 7.3%, DCS = 9.1%) or in partial response (DCF = 45.4%, DCS = 52.7%). The pathological response rate was 23.8% for grade 2 and 18.2% for grade 3 in the DCF group, compared with 30.9% and 14.5% in the DCS group. Independent predictive factors for recurrence-free survival were poor clinical response and pathological response ≤1b. Independent prognostic factors for overall survival were poor clinical response, anastomotic leakage, and pathological response ≤1b. Duration of hospital stays in the DCS group was significantly shorter than those of the DCF group (6.0 vs. 15.0 days, p < 0.001). Expenses of drug and hospitalization for the neoadjuvant chemotherapy in the DCS group were also significantly lower than those of the DCF group (265.7 vs. 550.3 USD, p < 0.001). CONCLUSIONS: Neoadjuvant DCS therapy for resectable advanced ESCC did not result in significantly higher clinical and pathological response than neoadjuvant DCF therapy. However, neoadjuvant DCS therapy for resectable ESCC required comparatively shorter hospital stays and incurred lower costs, making it an attractive therapeutic option.

Days of the week and 90-day mortality after esophagectomy: analysis of 33,980 patients from the National Clinical Database.

PURPOSE: The effect of the days of the week on the short-term outcomes after elective surgeries has been suggested; however, such data on esophagectomies remain limited. This study aimed to investigate the association between the day of the week and mortality rates after elective esophagectomy using a large-scale clinical database in Japan. METHODS: The data of elective esophagectomies, registered in the National Clinical Database in Japan, for esophageal cancer treatment between 2012 and 2017 were analyzed. We hypothesized that the later days of the week could have higher odds ratios of death after elective esophagectomy. With 22 relevant clinical variables and days of surgery, 90-day mortality was evaluated using hierarchical logistic regression modeling. RESULTS: Ninety-day mortality rates among 33,980 patients undergoing elective esophagectomy were 1.8% (range, 1.5-2.1%). Surgeries were largely concentrated on earlier days of the week, whereas esophagectomies performed on Fridays accounted for only 11.1% of all cases. Before risk adjustment, lower odds ratios of 90-day mortality were found on Tuesday and a tendency towards lower odds ratios on Thursday. In the hierarchical logistic regression model, 21 independent factors of 90-day mortality were identified. However, the adjusted odds ratios of 90-day mortality for Tuesday, Wednesday, Thursday, and Friday were 0.87, 1.09, 0.85, and 0.88, respectively, revealing no significant difference. CONCLUSION: The results imply that the variation in 90-day mortality rates after esophagectomy on different days of the week may be attributed to differing preoperative risk factors of the patient group rather than the disparity in medical care provided.

Induced pluripotent stem cell-derived dendritic cell vaccine therapy genetically modified on the ubiquitin-proteasome system.

We previously reported that dendritic cells (DCs) transduced with the full-length tumor-associated antigen (TAA) gene induced TAA-specific cytotoxic T lymphocytes (CTLs) to elicit antitumor responses. To overcome the issue of quantity and quality of DCs required for DC vaccine therapy, we focused on induced pluripotent stem cells (iPSCs) as a new tool for obtaining DCs and reported efficacy of iPSCs-derived DCs (iPSDCs). However, in clinical application of iPSDC vaccine therapy, further enhancement of the antitumor effect is necessary. In this study, we targeted mesothelin (MSLN) as a potentially useful TAA, and focused on the ubiquitin-proteasome system to enhance antigen-presenting ability of iPSDCs. The CTLs induced by iPSDCs transduced with MSLN gene (iPSDCs-MSLN) from healthy donors showed cytotoxic activity against autologous lymphoblastoid cells (LCLs) expressing MSLN (LCLs-MSLN). The CTLs induced by iPSDCs transduced ubiquitin-MSLN fusion gene exhibited higher cytotoxic activity against LCLs-MSLN than the CTLs induced by iPSDCs-MSLN. The current study was designed that peripheral T-cell tolerance to MSLN could be overcome by the immunization of genetically modified iPSDCs simultaneously expressing ubiquitin and MSLN, leading to a strong cytotoxicity against tumors endogenously expressing MSLN. Therefore, this strategy may be promising for clinical application as an effective cancer vaccine therapy.

Impact of S-1 adjuvant chemotherapy longer than 6 months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data.

BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. METHODS: In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days. RESULTS: The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. CONCLUSIONS: The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.

Liver Resection for Hepatocellular Carcinoma With Tumor Thrombus in the Inferior Vena Cava or Right Atrium: A Large-scale Multicenter Survey Conducted in Japan.

OBJECTIVE: To clarify the short and long-term postoperative outcomes and surgical indications for patients accompanied by hepatocellular carcinoma with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA). BACKGROUND: These patients are known to have an extremely poor prognosis; however, the postoperative outcomes have not been fully verified because of the rarity of this disease. METHODS: We contacted 211 specialized centers in Japan and collected data on liver resection for hepatocellular carcinoma with TT in the IVC or RA from centers with experience performing surgery for such patients. The patient characteristics, operative procedures, and surgical outcomes were then analyzed. RESULTS: A total of 119 patients from 23 institutions were enrolled; 49 patients had TT in the IVC below the diaphragm (type I), 42 had TT in the IVC above the diaphragm (type II), and 28 had TT entering the RA (type III). The severity and frequency of postoperative complications did not differ among the 3 groups. There was one surgery-related death in the type III group. The median survival times were 2.47 years in the type I group, 1.77 years in the type II group, and 1.02 years in the type III group. Multivariate analysis identified an indocyanine green retention rate at 15 minutes >15% and ≥3 tumors as prognostic factors affecting survival, whereas the use of cardiopulmonary bypass and ≥3 tumors were risk factors for recurrence. CONCLUSIONS: As the postoperative prognosis of patients with type I or type II disease and of patients with no risk factors is relatively good, surgery should be considered for these patient populations.

Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study.

OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

Randomized controlled trial comparing cosmetic results of midline incision versus off-midline incision for specimen extraction in laparoscopic colectomy.

PURPOSE: A notable advantage of laparoscopic colorectal surgery is that only a small incision at the extraction site is necessary, which is considered to be cosmetically beneficial. Meanwhile, the optimal extraction site for the resected specimen in laparoscopic colectomy is controversial in terms of cosmetic benefit. This randomized controlled trial compares midline and off-midline extraction sites in laparoscopic colectomy in patients with colon cancer, with consideration of cosmetic benefits as the primary endpoint. METHODS: Included were patients that underwent elective laparoscopic colectomy at WMUH between October 2014 and February 2017. Patients were randomly assigned to either midline incision group or off-midline incision group. Prospectively collected data included cosmetic results (patients and observer assessment scale) and complications including incidence of incisional hernia, SSI, and pain. This trial was registered with UMIN Clinical Trials (UMIN000028943). RESULTS: Finally, 98 patients with colorectal cancer were analyzed. No significant differences were found between the two groups in patient and observer assessment scales of cosmetic results (midline 8 ± 1.1 vs off-midline 11 ± 5.9 p = 0.16, midline 13.5 ± 6.6 vs off-midline 15 ± 11 p = 0.58, respectively) or in postoperative pain. However, incisional hernia occurred in four cases in the midline group (8%), which was significantly higher than that in the off-midline group (no cases, 0%). CONCLUSION: There was no significant difference in terms of cosmetic benefit, the primary endpoint, between the two groups. In this study, only the extraction site location was compared; future studies will examine differences depending on the incisional direction, including the incidence of incisional hernia.

Laparoscopic reconstruction in McKeown esophagectomy is a risk factor for postoperative diaphragmatic hernia.

Diaphragmatic hernia is a very rare but high-risk complication after esophagectomy. Although there are many studies on the Ivor Lewis esophagectomy procedure for diaphragmatic hernia, there are fewer studies on the McKeown procedure. The present study aimed to estimate the incidence of diaphragmatic hernia after esophagectomy, describing its presentation and management with the McKeown procedure. We retrospectively evaluated the 622 patients who underwent radical esophagectomy between January 2002 and December 2020 at the Wakayama Medical University Hospital. Statistical analyses were performed to evaluate risk factors for diaphragmatic hernia. Emergency surgery for postoperative diaphragmatic hernia was performed in nine of 622 patients (1.45%). Of these nine patients, one developed prolapse of the small intestine into the mediastinum (11.1%). The other eight patients underwent posterior mediastinal route reconstructions (88.9%), one of whom developed prolapse of the gastric conduit, and seven of whom developed transverse colon via the diaphragmatic hiatus. Laparoscopic surgery was identified in multivariate analysis as the only independent risk factor for diaphragmatic hernia (odd's ratio [OR] = 9.802, p = 0.034). In all seven cases of transverse colon prolapse into the thoracic cavity, the prolapsed organ had herniated from the left anterior part of gastric conduit. Laparoscopic surgery for esophageal cancer is a risk factor for diaphragmatic hernia. The left anterior surface of gastric conduit and diaphragmatic hiatus should be fixed firmly without compromising blood flow to the gastric conduit.

The degree of satisfaction and level of learning in male and female surgical residents: a nationwide questionnaire survey of graduating residents in Japan.

PURPOSE: Since 2002, the Japan Surgical Society has established a board certification system for surgeons to be certified for a specialty. Surgery remains a male-dominated field in Japan. This study aimed to clarify if the Japanese surgical residency training system is equally suitable for female and male residents. METHODS: The Japan Surgical Society conducted the first questionnaire survey regarding the system of surgical training for the residents in 2016. The questionnaire included the degree of satisfaction with 7 aspects of the training system, including the number and variety of cases experienced and duration and quality of instruction, and the learning level for 31 procedures. The degree of satisfaction and level of learning were compared between female and male residents. RESULTS: The degree of satisfaction was similar for all items between female and male residents. Female residents chose breast surgery as their subspecialty more frequently than male residents and were more confident in breast surgery procedures than male residents. Conversely, fewer female residents chose gastrointestinal surgery and were less confident in gastrointestinal surgery procedures than male residents. CONCLUSION: Female residents were as satisfied with the current surgical training system as male residents. However, there may be room for improvement in the surgical system, considering that fewer applications for gastrointestinal surgery come from female residents than from males.

Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.

Risk Factors of Postoperative Intra-Abdominal Infectious Complications after Robotic Gastrectomy for Gastric Cancer.

INTRODUCTION: Robotic surgery is regarded as an evolved type of laparoscopic surgery. Few studies have undertaken detailed analysis of complications following robotic gastrectomy for gastric cancer. METHODS: This is a single-center retrospective study of 149 consecutive patients with gastric cancer who underwent robotic gastrectomy. It examines in detail the postoperative complications in robotic gastrectomy for gastric cancer, focusing on intra-abdominal infectious complications including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess. We also aim to identify the related risk factors. RESULTS: The median operation time was 299 min and the median bleeding was 25 mL. The incidence of overall complications higher than grade II was 8.7%. Clinically serious complications higher than grade IIIa occurred in 6.7% of cases. The incidence of intra-abdominal infectious complications that were higher than grade II was 4.0%. Mortality in our consecutive series was zero. Multivariate logistic regression analysis indicated that postoperative intra-abdominal infectious complications were significantly associated with history of abdominal surgery (p = 0.043), with odds ratios of 17.890 (95% confidence interval 1.092-293.150) and with non-curative resection (p = 0.025), with odds ratios of 58.629 (95% confidence interval 1.687-2,037.450). DISCUSSION/CONCLUSION: Robotic gastrectomy was shown to be a safe and effective treatment for gastric cancer when performed by experienced surgeons. Attention should be paid to the risk of developing postoperative complications when performing robotic gastrectomy in gastric cancer patients with a history of abdominal surgery and in patients with advanced gastric cancer in whom there is expected to be difficulty in curative resection.

Laparoscopic sleeve gastrectomy for morbid obesity improves gut microbiota balance, increases colonic mucosal-associated invariant T cells and decreases circulating regulatory T cells.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) for morbid obesity may improve gut microbiota balance and decrease chronic inflammation. This study examines the changes in gut microbiota and immune environment, including mucosal-associated invariant T cells (MAIT cells) and regulatory T cells (Treg cells) caused by LSG. METHODS: Ten morbidly obese patients underwent LSG at our institution between December 2018 and March 2020. Flow cytometry for Th1/Th2/Th17 cells, Treg cells and MAIT cells in peripheral blood and colonic mucosa and 16S rRNA analysis of gut microbiota were performed preoperatively and then 12 months postoperatively. RESULTS: Twelve months after LSG, the median percent total weight loss was 30.3% and the median percent excess weight loss was 66.9%. According to laboratory data, adiponectin increased, leptin decreased, and chronic inflammation improved after LSG. In the gut microbiota, Bacteroidetes and Fusobacteria increased after LSG, and indices of alpha diversity increased after LSG. In colonic mucosa, the frequency of MAIT cells increased after LSG. In peripheral blood, the frequency of Th1 cells and effector Treg cells decreased after LSG. CONCLUSIONS: After LSG for morbid obesity, improvement in chronic inflammation in obesity is suggested by change in the constituent bacterial species, increase in the diversity of gut microbiota, increase in MAIT cells in the colonic mucosa, and decrease in effector Treg cells in the peripheral blood.

Dorsal vs ventral approach to the middle hepatic vein during laparoscopic left hemihepatectomy: multicenter retrospective observational study.

BACKGROUND: Left hemihepatectomy requires exposure of the middle hepatic vein (MHV) at the cutting-surface. Two procedures are used to approach the MHV: a conventional ventral approach and a laparoscopy-specific dorsal approach. This multicenter retrospective observational study aimed to evaluate the perioperative outcomes of these two procedures. METHODS: Clinical records of 38 consecutive patients that underwent laparoscopic left hemihepatectomy in four university hospitals between 2016 and 2021 were retrospectively reviewed. Outcome measurements were operative blood loss, operating time, trend of postoperative laboratory data within 7 days after hepatectomy, and postoperative complications. Quality of MHV exposure was also evaluated and compared by three-grade evaluation (excellent/good/poor) using recorded still images of the cut-surface of the remnant liver (n = 35). RESULTS: Dorsal and ventral approaches were performed in 9 and 29 patients, respectively. Median operating time was 316 min (dorsal) and 314 min (ventral) (P = 0.71). Median operative blood loss was 45 ml (dorsal) and 105 ml (ventral) (P = 0.10). Two patients in the ventral approach group had bleeding in excess of 500 ml, which was not seen in the dorsal approach group. Excellent/good/poor MHV appearance on the cutting-surface was observed in 5/3/1 patients in the dorsal approach group, respectively, and in 7/8/11 patients in the ventral approach group, respectively (P = 0.03). In the ventral approach group, significant increases of aspartate aminotransferase (on postoperative day 1 and day 4/5) and of alanine aminotransferase (on postoperative day 2/3 and 4/5) were observed (P < 0.05). Postoperative complications were observed only in the ventral approach group (n = 3). CONCLUSIONS: The dorsal approach could achieve safe and precise anatomical left hemihepatectomy with operation time and operative blood loss comparable to the conventional ventral approach.

New diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for patients with colorectal cancer.

BACKGROUND: Accurate tumor stage diagnosis during laparoscopic surgery remains difficult. We clarify the impact of new diagnostic strategy using narrow-band imaging (NBI) during laparoscopic surgery for colorectal cancer compared with other strategies. METHODS: We defined angiogenesis (Ag) and fibrosis (Fib) grades using NBI laparoscopy (lap-NBI), and assessed the clinicopathological features associated with these grades for 67 patients with colorectal cancer who underwent surgery. We assessed vessel density and gray scale with computer software. RESULTS: NBI-Ag-grade and NBI-Fib-grade of the serosal surface of cancer lesions and peritoneal nodules correlated with vessel density and gray scale of those assessed by Image J computer software. NBI-Fib-grades of liver nodules also correlated with gray scale. NBI-Ag- grade and Fib-grade of the serosal surface of cancer lesions correlated with pathological depth of invasion. These NBI grades of pathological metastatic peritoneal nodules were higher than those of pathologically benign peritoneal nodules. NBI- Fib grades of pathological metastatic liver nodules were higher than those of pathologically benign liver nodules. In multivariate analysis, lap-NBI was associated with different diagnosis for T3, T4 and non-T3, and non-T4. Moreover, lap-NBI was associated with different diagnosis for T4 and non-T4. Predictive value for T4 by lap-NBI showed high sensitivity (85%) specificity (87%), positive predictive value (74%), negative predictive value (93%), and overall accuracy (87%). Sensitivity and overall accuracy of lap-NBI was superior to that of other diagnostic modalities. CONCLUSION: We clarified the usefulness of the new diagnostic strategy using lap-NBI during laparoscopic surgery for colorectal cancer in comparison with other strategies.

High visceral to subcutaneous fat area ratio predicts early postoperative small bowel obstruction after surgery for colorectal cancer.

PURPOSE: Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO. METHODS: Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed. RESULTS: Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p < 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p < 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p < 0.001) were independent risk factors for EPSBO. CONCLUSION: Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Neonatal congenital mesoblastic nephroma that caused respiratory oncologic emergency early after birth: a case report.

BACKGROUND: Congenital mesoblastic nephromas mainly present as asymptomatic abdominal masses, but some present hematuria, hypertension or hypercalcemia. Neonatal dyspnea in an early-birth neonate due to rapid tumor growth is reported here for the first time. CASE PRESENTATION: A renal tumor and polyhydramnios were detected by ultrasonography of a male fetus at 32 weeks and 3 days of gestation. The mother had abdominal distension due to the polyhydramnios and signs of imminent premature birth. Amniocentesis was performed and the signs of imminent preterm birth subsided, but growth of the renal tumor was noted as a potential cause of respiratory dysfunction. Cesarean section was performed at 36 weeks and 2 days of gestation. His birthweight was 2638 g and his 1 and 5 min APGAR scores were 2 and 4 points, respectively. There was no spontaneous breathing at birth and he had remarkable abdominal distention. He underwent cardiopulmonary resuscitation. After circulation stabilized, emergency surgery was performed because of progressive hypoxemia and respiratory acidosis. Laparotomy revealed a huge tumor arising from the right kidney and right nephrectomy was performed. Histopathological examination led to diagnosis of congenital mesoblastic nephroma. The respiratory condition and circulatory dynamics stabilized after the pressure on the thorax from the tumor was relieved by surgery. The postoperative course was uneventful. No recurrence or complications have been observed in the 36 months since the surgery. CONCLUSIONS: Congenital mesoblastic nephroma can rapidly increase in size from the fetal period and may cause respiratory oncologic emergency, although there is relatively good prognosis.