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MicroRNA (miRNA) expression is dysregulated in human tumors, thereby contributing to tumorigenesis through altered expression of mRNA. Thus, identification of the relationships between miRNAs and mRNAs is important for evaluating the molecular mechanisms of tumors. Additionally, elucidation of the molecular features of serrated lesions is essential in colorectal tumorigenesis. Here, we examined the relationships of miRNA and mRNA expressed in serrated lesions, including 26 sessile serrated lesions (SSLs), 12 traditional serrated adenomas (TSAs), and 11 colorectal cancers (CRCs) with a microsatellite instability (MSI) phenotype using crypt isolation. We divided the samples into the first and second cohorts for validation. Array-based expression analyses were used to evaluate miRNAs and mRNAs with opposite expression patterns in isolated tumor glands. In addition, we validated the relationships of miRNA/mRNA pairs in the second cohort using real-time polymerase chain reaction. We found that the expression of miRNA-5787 was correlated with reciprocal expression of 2 mRNAs, i.e., SRRM2 and POLR2J3, in SSL samples. In TSA samples, 2 pairs of miRNAs/mRNAs showing opposite expression patterns, i.e., miRNA-182-5p/ETF1 and miRNA-200b-3p/MYB, were identified. Ultimately, three pairs of miRNAs/mRNAs with opposite expression patterns, including miRNA-222-3p/SLC26A3, miRNA-6753-3p/FABP1, and miRNA-222-3p/OLFM4, were retained in CRC with an MSI phenotype. Finally, we performed transfection with an miR-222-3p mimic to confirm the expression of SLC26A3 and OLFM4; the results showed that ectopic expression of miR-222-3p moderately suppressed OLFM4 and downregulated SLC26A3 to some extent. Overall, our results provided basic insights into the evaluation of colorectal tumorigenesis of serrated lesions and CRC with an MSI phenotype. This article is protected by copyright. All rights reserved.

Aim Recent reports have described the use and efficacy of several types of transanal tube (TAT) for preventing anastomotic leakage by reducing intraluminal pressure. The aim of this study was to evaluate the safety and efficacy of a newly developed TAT for the prevention of anastomotic leakage after low anterior resection (LAR) for rectal cancer. Method A multicentre confirmatory single-arm trial was designed to evaluate the safety and efficacy of a new TAT after LAR for rectal cancer. A total of 115 patients were registered in the trial at several cancer centres and other hospitals. All patients initially received reconstruction with a stapled anastomosis, but 18 then underwent creation of a diverting stoma. Of the remaining 97 patients, the first 96 were included in the protocol-defined primary analysis set. The primary outcome was the incidence of symptomatic leakage and the secondary endpoint was the incidence of complications associated with use of the TAT. The TAT was placed during LAR without creating a covering stoma and the drain was removed 4 or 5 days postoperatively. Results The rate of symptomatic leakage was 5.2% (95% confidence interval 1.7-11.7), which was significantly lower than the predetermined threshold value of 15.8% (one-sided p-value 0.0013). Only one patient had Grade 3 rectal bleeding that might have been related to use of the TAT. Conclusion This nonrandomized study shows that the TAT appears to be safe and results in lower rates of anastomotic leakage in LAR compared with previous studies.

BACKGROUND & AIMSThis study investigated whether a circulating tumor DNA (ctDNA) assay using digital PCR (dPCR) could provide early relapse detection and disease-free corroboration at molecular level during postoperative surveillance of colorectal cancer (CRC).METHODSThe ctDNA dynamics of 52 patients with CRC measured by dPCR targeting 87 individual tumor-specific mutations (1-5 per patient) were compared with results for conventional surveillance using serum tumor markers and computed tomography scanning (CTS). The data were collected between March 2016 and June 2018.RESULTSA total of 1,526 prospectively collected plasma samples from 867 timepoints were analyzed. The average number of ctDNA assays per patient was 16.4 and the median follow-up was 1,503 days (range 322-1,951 days). Among patients with Stage II or higher disease who underwent curative resection as their initial surgery (n=47), patients who were ctDNA-positive during the postoperative period (n= 9) showed a higher risk of relapse than those who had sustained ctDNA-negative results (n=38) (hazard ratio 56.3, 95%CI 7.8–407.0, P < 0.0001). Elevated ctDNA levels were observed in nine of 10 clinical-relapse patients (11 of 13 events) with an average lead time from a ctDNA-positive time-point to clinical relapse of 191.9 days (range 0-376 days). Given periodic CTS surveillance with ctDNA, 218 (57.1%) CTSs were presumed to be unnecessary for clinical relapse detection and a ctDNA assay would still provide a lead time of 307 days (range 45–582 days).CONCLUSIONOur findings suggest that the ctDNA assay can reduce the frequency of CTS for relapse diagnosis during postoperative surveillance of CRC. UMIN Clinical Trial Registry number, UMIN000045114

Background Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. Methods We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. Results “Founder” mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, “truncal” mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than “non-founder” and “branch” mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. Conclusions A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.

Background: There are some restrictions in Japan regarding end-of-life care. For example, only physicians can legally issue death certificates. By law, ambulance staff members perform cardiopulmonary resuscitation (CPR) for all patients with cardiopulmonary arrest (CPA). Therefore, it is difficult to transport patients to hospitals without CPR, even in cases of terminal patients with do-not-attempt-resuscitation (DNAR) order. Furthermore, there is no 24-hour home care nursing system in our area. Therefore, terminal patients are unable to spend their last moments at their home in the Kuji area. Objective: To design a system in which terminal patients who wish to spend their final moments at their home can be transported to the hospital without CPR after at-home CPA and a system to avoid confusion between ambulance staff and family members using instructions provided by the physician. Setting/Subjects: The subjects were terminal patients with DNAR order who wanted to stay at home. The instruction to not perform CPR after CPA was created as a document by physicians. Patient information was shared with the fire department; patients were transported to our hospital without CPR after at-home CPA. Results: In total, 26 patients died during the study period; eight received emergency transport to the hospital without CPR after CPA. CPR was not performed for any patient. Conclusion: A system transporting terminal patients without CPR after CPA was necessary in our area. This instruction allows terminal patients to spend their last moments where they wish and avoids unwanted CPR and troubles after CPA.

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome‐wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22‐q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.

Background Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving surgery for the treatment of early gastric cancer in East Asian countries. Therefore, this study aimed to evaluate the feasibility and safety of totally laparoscopic PPG (TLPPG) with intracorporeal anastomosis. Methods A total of 43 patients with early gastric cancer underwent laparoscopy-assisted PPG (LAPPG) with extracorporeal anastomosis between May 2006 and November 2012. The operative outcomes of 22 patients who underwent TLPPG between November 2012 and February 2019 were evaluated, and data were compared with that of the LAPPG group. Results No significant difference in the operative time was observed between the two groups. Blood loss was lower in the TLPPG group (18.5 mL) than in the LAPPG group (30.7 mL, p = 0.008), and the length of abdominal incision was shorter in the TLPPG group (3.8 cm) than in the LAPPG group (4.7 cm, p < 0.001). No significant difference in the complication rate was observed between the two groups (13.6% in the TLPPG vs. 9.3% in the LAPPG group, p = 0.594). No anastomosis-related complications occurred in either group. No significant between-group difference was observed in the delayed gastric emptying (TLPPG, 9.1 vs. LAPPG, 7%, p = 0.762). The initiation of postoperative fluid (TLPPG, 1.0 day vs. LAPPG, 3.0 days, p < 0.001) and meal (TLPPG, 3.0 days vs. LAPPG, 4.0 days, p < 0.001) intake was earlier in the TLPPG group than in the LAPPG group. No significant between-group difference was observed in the postoperative hospital stay. Conclusions The findings of this study suggest that TLPPG with intracorporeal reconstruction not only is as feasible and safe as LAPPG for the treatment of patients with early gastric cancer but also provides certain advantages such as reduced blood loss and wound size.

Introduction Recent studies have reported that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) is an effective treatment for unresectable, locally advanced esophageal cancer. The aim of this study was to investigate the safety and feasibility of thoracoscopic esophagectomy (TE) after DCF for initially unresectable esophageal squamous cell carcinoma (ESCC). Methods Twenty-three patients with initially unresectable T4 thoracic ESCC underwent TE after induction DCF. Results The neighboring organs with tumors were the tracheobronchus in nine patients, thoracic aorta in 13, and pericardium and diaphragm in three each (concurrent overlapping invasion occurred in five patients). The mean total operation time was 556.3 ± 107.2 minutes, and the mean time of the thoracic procedure was 258.9 ± 83.9 minutes. The mean total blood loss was 166.2 ± 117.8 mL, and the loss during the thoracic procedure was 33.5 ± 24.6 mL. All patients achieved complete R0 resection under TE. No conversions to open thoracotomy were performed. The postoperative morbidity rate was 34.8%. The postoperative hospital stay was 24.3 (range, 13-38) days. Five patients had recurrence: four had distant metastasis (lung, two; liver, three; and one with overlap), and one had mediastinal lymph node recurrence. No local recurrence was noted at the site of the primary T4 tumor. Conclusions TE was safely performed in 23 patients after DCF therapy for locally advanced unresectable ESCC. Induction DCF, followed by TE, could be an alternative treatment for unresectable T4 ESCC.

Highlights • ECS is a rare tumor often treated in the same manner as esophageal cancer. • ECS often presents as a polypoid tumor continuous with the superficial lesion. • We encountered an ECS case in which a polypoid lesion sloughed off before surgery. • Polypoid tumor exfoliation in ECS may lead to an incorrect diagnosis., Introduction Most esophageal carcinosarcoma (ECS) tumors present as a polypoid tumor that is continuous with the superficial lesion and suspended by a pedicle. Here, we report a case of ECS in which a polypoid lesion sloughed off before surgery. Presentation of case A 76-year-old man with dysphagia was admitted to our hospital. Esophagogastroscopy revealed a 20-mm polypoid tumor continuous with a superficial lesion and attached to the lesion by a thin pedicle in the mid-thoracic esophagus. Histopathological examination of the endoscopic biopsy showed that the superficial lesion was a moderately differentiated squamous cell carcinoma and that the polypoid tumor contained a sarcomatous element. He was diagnosed with ECS and underwent radical esophagectomy with three-field lymph node dissection. In the resected specimen, no polypoid tumor was found, and only a superficial lesion was observed. The histopathological findings revealed only squamous cell carcinoma, and the pathological diagnosis was esophageal squamous cell carcinoma, pT1bN0M0, pathological stage I. The patient was discharged from the hospital 22 days after surgery and did not experience any complications. He is currently alive and remained cancer-free for three years since surgery was performed. Discussion Due to the distinctive configuration in which the polypoid lesion was connected to the superficial cancerous lesion by a very thin pedicle, researchers suggested that the polypoid tumor, which consisted of a sarcomatous element, was sloughed off before surgery. Conclusion We encountered a rare case of ECS in which the sarcomatous element sloughed off prior to surgical resection.

Highlights • Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. • There are few reports of treatment with the anti-programmed cell death 1 antibody, nivolumab for PMME. • We report a case of retroperitoneal recurrence of PMME successfully treated with nivolumab., Introduction Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. Here, we report a case of retroperitoneal recurrence of PMME successfully treated with the anti-programmed cell death 1 antibody, nivolumab. Presentation of case A 70-year-old male with dysphagia was referred to our hospital. Esophagogastroscopy showed an elevated tumor in the lower thoracic esophagus. A histopathological examination of the biopsy revealed poorly differentiated squamous cell carcinoma. The patient was diagnosed with clinical T3N1M0 stage III esophageal squamous cell carcinoma and was treated with neoadjuvant chemotherapy followed by radical esophagectomy. A postoperative histopathological examination revealed that atypical cells with a brown pigment were scattered in the tumor. Immunohistochemical staining demonstrated positive expression of human melanoma black 45, melan A, and S100. A pathological diagnosis of PMME was confirmed. Sixteen months after surgery, abdominal computed tomography revealed solitary retroperitoneal recurrence in the lateral portion of the ascending colon. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) showed hypermetabolic accumulation with a maximum standardized uptake value of 5.8. The patient was treated with nivolumab (240 mg) every two weeks. After eight courses of nivolumab, abnormal accumulation of the retroperitoneal mass disappeared on PET, and this therapeutic effect continued for 20 months. Conclusions Nivolumab was effective for recurrence of PMME in our case. There are few reports of treatment with nivolumab for PMME. Further studies are necessary to establish the usefulness of nivolumab for PMME in the future.

Colorectal adenocarcinoma (CRA) is characterized by marked heterogeneity and may be composed of an admixture of various histologic patterns, including well-formed gland and cribriform types. Although tumors displaying a prominent or predominant cribriform feature are frequently found in CRA, this type may contain specific histologic variants with a characteristic molecular alteration. We investigated the molecular features of 51 primary CRAs with a predominant cribriform histology using array-based analyses [somatic copy number alterations (SCNAs); mRNA expression]. Mutations (TP53, KRAS, PIK3CA and BRAF) and DNA methylation status were also analyzed. The crypt isolation method was used to obtain isolated tumor glands of each type separately. All patients were classified by their CRA histologic subtype into two groups: well-formed gland and cribriform. Next, we performed cluster analysis to stratify SCNA and mRNA expression patterns between the two subtypes. Two distinctive subgroups were stratified based on patterns of SCNA and mRNA expression and were correlated with each histologic subtype. The cribriform type was characterized by a high frequency of SCNA compared with that of the well-formed gland type and was closely associated with the expression of specific mRNAs. In addition, the frequency of KRAS mutation was significantly higher in the cribriform type than in the well-formed gland type. Finally, there was no difference in DNA methylation status between the two subtypes. Overall, these data suggest that the cribriform type provides important insights into colorectal carcinogenesis, suggesting specific potential histologic implications based on the molecular profile.

Introduction Rectal and prostate cancers are common cancers occurring globally, and both can metastasize to the pelvic lateral lymph nodes (LLNs). Presentation of case A 69-year-old man, presenting with blood in stool, was diagnosed with rectal cancer. Computed tomography revealed a 7-mm LLN in the right internal iliac artery region, leading to the suspicion of metastasis. The patient underwent laparoscopic low anterior resection and LLN dissection. Histopathological findings of the metastatic tissue in the LLN were different than that of rectal cancer, and endocrine tumor was suspected. Immunostaining performed based on high serum prostate-specific antigen (PSA) level revealed positivity for PSA and α-methylacyl-CoA racemase in the dissected LLN. Thus, he was diagnosed with synchronous rectal and prostate cancers and received hormonal therapy for stage IV prostate cancer, which led to a dramatic reduction in PSA level after three months. He was followed regularly and did not relapse or experienced disease progression for either cancer for approximately four years after the initial diagnosis. Discussion Few studies reported synchronous rectal and prostate cancers, both of which can metastasize to pelvic LLNs. However, preoperative diagnosis of the primary cancer metastasizing to the LLNs is challenging. Treatment of synchronous rectal and prostate cancers requires a strategy to diagnose each tumor stage and corresponding degree of progression because lymph node metastases affect staging in both cancers. Conclusion Lymph node dissection may be useful in determining progression and treatment plan in cases of concurrent rectal and prostate cancers with suspected LLN metastasis., Highlights • Lateral lymph node (LLN) metastasis is rarely reported in synchronous rectal and prostate cancer. • LLN metastasis impacts staging in synchronous rectal and prostate cancer. • Preoperative identification of the origin of LLN metastasis is difficult in such cases. • LLN dissection may be useful to assess progression and treatment of synchronous cancers.

A 55-year-old-man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Preoperative barium enema showed a slightly medial displacement of the descending colon, and the sigmoid colon was quite long. The operative findings showed that the descending colon was not fused with the retroperitoneum and shifted to the midline and the left colon adhered to the small mesentery and right pelvic wall. Thus, a diagnosis of persistent descending mesocolon (PDM) was made. The left colon, sigmoid colon, and superior rectal arteries often branch radially from the inferior mesenteric artery. The sigmoid mesentery shortens, and the inferior mesenteric vein is often close to the marginal vessels. By understanding the anatomical feature of PDM and devising surgical techniques, laparoscopic sigmoidectomy for sigmoid colon cancer with PDM could be performed without compromising its curative effect and safety.

Recent study has shown that there is a close association of desmoplastic reactions (DRs) with the survival of patient with colorectal cancer (CRC). Here, we examined the correlation of DR classification with disease-free survival and overall survival of CRC. Moreover, we also investigated the association of the histological transition of the DR with the expression of cancer-associated fibroblast (CAF)- and epithelial-mesenchymal transition (EMT)-related proteins in CRC in stages II and III. We examined 157 cases of stage II CRC and 163 cases in stage III. We classified DRs into mature, intermediate, and immature types and examined the correlation of the DR patterns with patient survival. Next, the expression of CAF- and EMT-related markers was examined in CRC samples using immunohistochemistry. In stage II CRC, we found a significant correlation of disease-free survival with DR subtype (immature vs mature) in univariate and multivariate analyses. In stage III CRC, however, such association was not identified. Finally, the DR was closely associated with two EMT-related markers in stages II and III CRC. Our findings suggest that classification of the DR may help to predict patient prognosis in CRC. Furthermore, classification of the DR is correlated with the expression of EMT-related proteins.

Although microRNAs (miRNAs) play an important role in invasive tumor lesions, which involve cancer tissues mixed with stromal tissues, the differences in miRNA expression between cancer and stromal cells remain unclear. We selected 13 miRNAs and examined their differential expression patterns in cancer gland cells and surrounding stromal cells isolated from 24 colorectal cancer (CRC) specimens using a crypt isolation method. Although six miRNAs were upregulated in gland cells, only three were upregulated in the corresponding stromal cells, in the cancer compared with non-cancer specimens. Next, we examined the differences in miRNA expression between isolated cancer gland and stromal cells. Five miRNAs showed statistical differences in their cancer-related differential expression patterns between isolated cancer gland and stromal cells. We then compared these miRNA expression patterns in isolated cancer gland and stromal cells with those in fresh intact tumor tissues, consisting of cancer nests and stromal tissue, obtained from the 24 CRCs. The expression patterns of three miRNAs in the intact cancer tissue samples did not correspond with those in the isolated components. Identification of the expression patterns of miRNAs in both the cancer gland and stromal cell components of the tumor microenvironment greatly contributes to evaluating epigenetic regulation in CRC.

Aim Laparoscopic liver resection (LLR) is increasingly carried out worldwide. However, there are concerns regarding ischemia‐reperfusion injury caused by pneumoperitoneum and the Pringle maneuver. It is not clear whether perioperative use of glucocorticoids lowers the risk of ischemia‐reperfusion hepatic injury in LLR as has been reported for open liver resection. The aim of the present study was to investigate the role of perioperative glucocorticoid use in improving hepatic function and surgical outcomes after LLR. Methods In this double‐blind, randomized controlled trial (UMIN000013823), we enrolled 130 patients who presented to our institution for LLR between April 2014 and October 2018. Six patients were excluded, resulting in 124 patients being randomized to either the glucocorticoid or the control group. Preoperatively, patients in the glucocorticoid group received 500 mg methylprednisolone in saline solution, patients in the control group saline solution only. Surgical outcomes and blood parameters were compared between the two groups. Results The Pringle maneuver could not be carried out in 24 patients, resulting in 50 patients in each group being included in the analysis. Postoperatively, total, direct and indirect bilirubin, and C‐reactive protein and interleukin‐6 levels were significantly lower, albumin levels were significantly higher, and prothrombin time was significantly shorter in the glucocorticoid than in the control group. Surgical outcomes were not significantly different between the groups. Conclusion This first report on preoperative glucocorticoid use in LLR showed that it significantly improved postoperative liver function and thus might enhance the safety of LLR., In this single‐center, double‐blind, randomized controlled trial, we show the effect of a single bolus of methylprednisolone on hepatic function as evidenced by postoperative bilirubin and albumin levels, and prothrombin time after laparoscopic liver resection. We conclude that perioperative glucocorticoid use may enhance the safety of this procedure.

MicroRNAs (miRNAs) are potential biomarkers of neoplastic lesions, but additional information on dysregulated miRNA expression during progression of the adenoma-adenocarcinoma sequence may be helpful to identify the role of miRNAs in this sequence. We examined the expression levels of 13 miRNAs (hsa-miRNA-19a-3p, hsa-miRNA-21-5p, hsa-miRNA-27a-3p, hsa-miRNA-27b-3p, hsa-miRNA-31-5p, hsa-miRNA-34b-3p, hsa-miRNA-125b-5p, hsa-miRNA-143-3p, miRNA-191-5p, hsa-miRNA-193b-3p, hsa-miRNA-195-5p, hsa-miRNA-206 and hsa-let-7a-5p) that are closely associated with colorectal carcinogenesis in 40 conventional adenomas (tubular and tubulovillous adenomas), 20 intramucosal carcinomas (IMCs) and 60 invasive colorectal cancers (iCRCs) using reverse-transcription polymerase chain reaction. These 120 tumors were divided into two cohorts, that is, cohort 1 (60 cases) and cohort 2 (for validation; 60 cases). We analyzed the expression levels of these miRNAs in the first step (adenoma→IMC) and second step IMC→iCRC) of the adenoma-carcinoma sequence in both cohorts. Although no significant differences in the expression of any of the 13 miRNAs were found between adenomas and IMCs consistently in both cohorts, the expression levels of hsa-miRNA-125b-5p, hsa-miRNA-143-3p, and hsa-miRNA-206 were significantly upregulated in iCRC in both cohorts compared with those in IMC. The current results suggest that certain miRNAs, including hsa-miRNA-125b-5p, hsa-miRNA-143-3p and hsa-miRNA-206, are candidate markers that play critical roles in the progression of IMC to iCRC.

Background Indications for laparoscopic liver resection (LLR) are continuously expanding. The Japanese Society of Hepato-Biliary-Pancreatic Surgery defines highly difficult hepatectomy as a procedure involving one or more sections (except for left lateral sectionectomy) or anatomical segmentectomy. This study aimed to assess the outcomes of complex LLR procedures and compare their technical difficulties, about which only a little is known to date. Methods We performed a retrospective review of the operative outcomes of 118 consecutive patients who underwent pure laparoscopic complex hepatectomy. The surgical outcomes, including operative times, blood loss amounts, and postoperative morbidity rates, were compared among complex LLR procedures. Results The overall median operative time was 280 minutes, and the median intraoperative blood loss was 86 mL. Two patients required conversion to open laparotomy (1.7%). The postoperative major morbidity rate was 11.0% Posterosuperior segmentectomy, right hemihepatectomy, and anterior sectionectomy required the longest operative times. Anterior and posterior sectionectomy resulted in the highest blood loss, and right hemihepatectomy and anterior sectionectomy resulted in the most complications. Conclusions The surgical difficulties associated with complex LLR procedures vary. It is critical to recognize the specific risks and cautionary points to ensure patient safety and provide proper systemic training to surgeons.

PurposeCirculating tumor DNA (ctDNA) analysis has been proposed as an approach for prediction of post-treatment patient outcomes. However, whether a single platform will provide optimal information in all patients or alternatively a patient-specific monitoring approach based on assessment of mutations in the primary tumor from that patient remains an urgent question. Experimental Design: We conducted multiregional sequencing of 42 specimens of 14 colorectal tumors (Stage III and more) from 12 patients, including two double cancer cases, to identify the full spectrum of mutational heterogeneity and identify aberrations that could be used to develop personalized ctDNA assays.Results“Founder” mutations that occur in all regions of the sample were identified in 12/14 (85.7%) tumors. Subsequent phylogenetic analysis of each tumor showed that 12/14 tumors (85.7%) carried at least one “truncal” mutation. Most founder and truncal mutations exhibited higher variant allele frequency (VAF) than “non-founder” and “branch” mutations. In addition, both founder and truncal mutations were more likely to be detected as ctDNA than non-founder and branch mutations. Synchronized ctDNA dynamics of multiple mutations suggested those mutations from the same clonal origin. For 10/12 patients (83.3%) with nearly 1,000 days of post-operative observation, the validity of frequent personalized ctDNA monitoring was confirmed in terms of early relapse prediction, treatment efficacy, and non-relapse corroboration.ConclusionsPersonalized ctDNA monitoring based on aberrations with a high VAF in the primary tumor site should be explored in larger prospective clinical trials to determine the full clinical validity.Translational relevanceCirculating tumor DNA (ctDNA) has been reported to be a new class of tumor-specific personalized biomarkers, but the selection criteria of index gene mutations from heterogeneous tumors as well as the achievement of sufficient sensitivity remain a challenge. Among mutations detected by multiregional sequencing, we monitored mutations with high variant allele frequencies (VAFs) from advanced colorectal cancers. Clinical validity of longitudinal ctDNA monitoring using highly-sensitive digital PCR was evaluated in terms of: (a) early relapse prediction; (b) treatment efficacy evaluation; and (c) no relapse corroboration. We found that ctDNA from high VAF mutations of a tumor are likely to be founder/truncal mutations. Based on rigorous longitudinal monitoring, our results suggest that sensitivity required the VAF to be 0.01-0.1%. The ctDNA from high VAF mutations strongly reflects tumor burden in a timely manner, thereby establishing clinical validity as a new class of tumor-specific personalized biomarkers.

Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p

Aim As a procedure, major laparoscopic liver resection (LLR) remains in the exploration phase. Previous studies have assessed major LLR en bloc, including hepatectomies of varying complexities; however, the number of segments alone does not convey the complexity of a resection. This study aimed to assess operative outcomes of LLR procedures with more than one sectionectomy, and to identify the best procedure as a first step when learning to carry out major LLR in order to make LLR a safer, more widely used procedure. Methods We carried out a retrospective review of the operative outcomes of 120 consecutive patients who underwent pure LLR with more than one sectionectomy. Operative outcomes were compared according to the complexity classification recently published, and the learning curve for each LLR procedure was assessed and compared. Results Operative outcomes, including operative time, blood loss, and the comprehensive complication index, were significantly stratified according to complexity. There were significant differences in operative outcomes among the medium complexity procedures. The operative time for left hemihepatectomy was the shortest, and the amount of blood loss was the lowest among the medium complexity LLR. Operative times for left hemihepatectomy shortened significantly with time and experience (r = -0.639), and the slope of the learning curve was steeper than for right hemihepatectomy and right posterior sectionectomy. Conclusion Left hemihepatectomy is suitable as a first step in pure laparoscopic major hepatectomy and, given its safety and rapid learning curve for surgeons, it could become the gold standard procedure.

Background Reduced port laparoscopic surgery (RPLS) is comparable to conventional multiport laparoscopic surgery and has the potential to provide improved cosmesis and decreased pain; as such, it satisfies a growing demand for less invasive surgical procedures. Moreover, a zigzag incision of the umbilicus results in a less visible scar in plastic surgery. Here we report a series of two cases with bilateral organ tumors treated by single-stage RPLS using a combination of a transumbilical approach and a zigzag incision. Case presentation Case 1: A 63-year-old man was diagnosed with right renal cell carcinoma (RCC) (clear cell carcinoma, pT1a, venous invasion (−)) and a splenic tumor (cavernous hemangioma). Case 2: An 84-year-old woman was diagnosed with concurrent left RCC (clear cell carcinoma, pT1b, 65 × 65 mm, venous invasion (+)) and ascending colon cancer (adenocarcinoma pT3 with no nodal involvement (0/48)). The perioperative course was uneventful in both cases. However, an additional incision was required in Case 2 for specimen excision. Therefore, the scars were more obvious in Case 2 than in Case 1. Conclusions Although more cases are required to evaluate the superiority of this technique, this novel procedure could be considered for patients with bilateral lesions.

Preoperative chemotherapy with cisplatin and 5-fluorouracil (CF) has become the standard treatment for resectable stage II/III thoracic esophageal carcinoma in Japan. Recently, preoperative triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) has been reported to be effective for locally advanced esophageal cancer. Thoracoscopic esophagectomy (TE) has been increasingly accepted worldwide for the treatment of esophageal cancer. We conducted a retrospective study to evaluate the safety and outcomes of TE after DCF therapy for patients with advanced esophageal cancer. The medical records of 63 consecutive patients with esophageal squamous cell carcinoma who underwent thoracoscopic surgery after chemotherapy were reviewed. Thirty-four patients received neoadjuvant chemotherapy with CF, and 29 received DCF as first-line chemotherapy. The clinical T stage was significantly higher in the DCF group than in the CF group (p

We aimed to evaluate the effectiveness of intervention by a perioperative multidisciplinary support team for radical esophagectomy for esophageal cancer. We retrospectively reviewed 85 consecutive patients with esophageal cancer who underwent radical esophagectomy via right thoracotomy or thoracoscopic surgery with gastric tube reconstruction. Twenty-one patients were enrolled in the non-intervention group (group N) from May 2011 to September 2012, 31 patients in the perioperative rehabilitation group (group R) from October 2012 to April 2014, and 33 patients in the multidisciplinary support team group (group S) from May 2014 to September 2015. Morbidity rates were 38, 45.2, and 42.4% for groups N, R, and S, respectively. Although there were no significant differences in the incidence of pneumonia among the groups, the durations of fever and C-reactive protein positivity were shorter in group S. Moreover, postoperative oral intake commenced earlier [5.9 (5–8) days] and postoperative hospital stay was shorter [19.6 (13–29) days] for group S. The intervention by a perioperative multidisciplinary support team for radical esophagectomy was effective in preventing the progression and prolongation of pneumonia as well as earlier ambulation, oral feeding, and shortening of postoperative hospitalization.

Introduction Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic and open colectomies, except for cases involving transverse colon and splenic flexure colon cancer. The objective of this study was to confirm the oncological safety and advantages of the short-term results of laparoscopic surgery for transverse and descending colon cancer in comparison with open surgery. Methods The study data were retrospectively collected from the databases of 45 hospitals. Patients with transverse or descending colon cancer who underwent laparoscopic or open R0 resection were registered. The primary end-points were the 3-year overall survival and relapse-free survival rates according to pathological stage. The secondary end-points were the short-term results, including blood loss, operative time, diet intake, hospital stay, and postoperative complications. Results Of the 1830 eligible patients, 872 underwent open colectomy and 958 underwent laparoscopic colectomy. The median follow-up period was 38.4 months. The conversion rate to open resection was 4.5%. The 3-year overall survival rate of the laparoscopic group was significantly higher than that of the open group for stage I patients (96.2% vs 99.2%; P = 0.04); it was also higher for stage II (94.0% vs 95.5%) and stage III (87.4% vs 90.2%) patients, but there were no significant differences. The 3-year relapse-free survival rate of the laparoscopic group was significantly higher than that of the open group for stage I patients; there were no differences between the open and laparoscopic groups among the stage II and III patients. In the multivariate analyses, laparoscopic resection was a significant factor in relapse-free survival. Laparoscopic patients had significantly lower blood loss and a significantly longer operative time than the open groups. Also, postoperative hospital stay was significantly shorter and postoperative morbidity was significantly lower in the laparoscopic group. Conclusion Although this retrospective study has limitations, we can conclude that laparoscopic surgery for transverse and descending colon cancer is oncologically safe and yields better short-term results than open surgery.

Background To investigate the efficacy of amino acid administration via peripheral veins in addition to conventional enteral feeding following esophagectomy. Materials and methods Retrospective analysis of data pertaining to 33 patients with esophageal cancer who underwent radical esophagectomy and satisfied the required nutrition control. Patients were divided into the amino acid group (n = 17) and control group (n = 16). Primary outcomes were albumin (Alb) and prealbumin (PreAlb) levels, urinary 3-methylhistidine/creatinine (3-MeHis/Cre) ratios, nitrogen balance, and weight; postoperative complications were noted as secondary outcomes. Results Alb levels were significantly higher in the amino acid group on postoperative day (POD)-14 (3.4 ± 0.3 vs. 3.1 ± 0.4 mg/dL in the control group, p = 0.018) and at 1 month after surgery (3.8 ± 0.4 vs. 3.5 ± 0.3 mg/dL, p = 0.045). No significant differences were observed in PreAlb and urinary 3-MeHis/Cre rates between the treatment groups. Body weights at 3 months postoperatively were decreased by 6% and 3% in the control and amino acid groups, respectively. Conclusion Peripheral venous administration of amino acids soon after surgical stress is an effective method for nutritional control., Highlights • Radical resection for esophageal cancer is a highly invasive procedure. • Enteral feeding has been used in postoperative period for esophagectomy. • Peripheral vein infusion of amino acids is effective for post esophagectomy.

Besides antibiotic prophylaxis, antiseptic skin preparation is an important measure to prevent surgical site infection (SSI). No reports have detailed the relationship between SSI and umbilical microflora following laparoscopic colorectal cancer with a transumbilical longitudinal incision. Risk factors and the rate of SSI were investigated in 453 patients who underwent laparoscopic colorectal resection over a 3-year period. Microbiological samples were collected from the umbilicus and SSI areas. After laparoscopic procedure, we observed SSIs in approximately 5% of cases, with superficial SSI in 15 (3.3%) patients and organ/space SSIs 7 (1.5%). In univariate analysis, preoperative albumin (Alb) value and anastomosis of enterocolostomy were significantly associated with superficial SSI development. Also, age, blood loss, stoma, tumor site (rectum), and Hartmann/abdominal perineal resection (APR) were significant risk factors for organ/space SSI. In multivariate analysis, the preoperative Alb value was the most significant factor associated with a predisposition to superficial SSI. The bacteria detected in SSI were mostly different from those at wound closure. Antibiotic-resistant bacteria were included in organ/space SSI all cases. SSI development with laparoscopic surgery reportedly occurs in about 3–15% cases. The SSI rate in this study and other reports was comparable. Using small transumbilical longitudinal incision in laparoscopic colorectal surgery is less likely to cause SSI when sufficient control measures are enacted, even though the umbilicus contains resident bacteria in abundance.

Background: Previous studies have shown that enteral nutrition (EN) helps reduce severe postoperative complications after esophagectomy. However, the incidence of jejunostomy-related complications is approximately 30%. We evaluated the operative outcomes in patients who did not receive EN via feeding jejunostomy after esophagectomy. Methods: We retrospectively reviewed 76 consecutive patients with esophageal cancer who received radical esophagectomy. Operative outcomes were compared between 33 patients who received postoperative EN via feeding jejunostomy (group A; from May 2014 to September 2015) and 43 patients who did not receive EN via feeding jejunostomy (group B; from September 2015 to December 2017). Results: The American Society of Anesthesiologists performance status score of the patients in group B was significantly higher than that of patients in group A (P=0.002). The postoperative morbidity rate was comparable between the two groups (group A, 30.3% vs . group B, 44.2%, P=0.217). No significant between-group differences were observed in the incidence of infectious complications, postoperative hospital stay, readmission within 30 days after discharge, or pneumonia after discharge within 6 months. The incidence of bowel obstruction was significantly higher in group A than in group B (group A, 9.1% vs . group B, 0%, P=0.044). Two patients in group B required nutritional support via total parenteral nutrition due to bilateral vocal cord palsy or pneumonia. Conclusions: Jejunostomy-related bowel obstruction in the patients with feeding jejunostomy was significantly higher than that in the patients without jejunostomy. There was no increase in postoperative complications (including pneumonia) in the patients who did not receive EN via feeding jejunostomy. Our results suggest that routine feeding jejunostomy may not be necessary for all patients undergoing esophagectomy.

Background Anastomotic leakage during laparoscopic low anterior resection (Lap-LAR) for rectal cancer remains challenging for colorectal surgeons. Firing linear staplers multiple times has been reported as a risk factor for iatrogenic anastomotic leakage. Our institute usually performs rectal transection using 2 planned stapler fires followed by anastomosis with the double-stapling technique. Methods Between November 2009 and September 2016, a total of 272 consecutive patients underwent Lap-LAR with double-stapling anastomosis for rectal cancer. We inserted a linear 45-mm stapler cartridge from a port in the lower right quadrant of the abdomen. The first transection was made up to three-quarters of the rectal wall, and the remaining rectum was completely resected using a second stapler. During this procedure, the intersection of the 2 staple lines, which might otherwise cause anastomotic leakage, was located in the center of the stump of the distal rectum, so the intersection at the rectal stump was able to be easily removed using a circular stapler. Results None of our patients were converted to open surgery. Among the 272 Lap-LAR procedures for which use of 2 stapler fires was planned, 3 fires occurred in error only once (0.4%). Rectovaginal fistula and anastomotic leakage occurred in 1 patient (0.4%) and 9 patients (3.3%), respectively, and 49 (18.0%) patients required protective diverting stoma. Conclusion Rectal transection with 2 planned stapler fires appears safe, practical, and straightforward to standardize, and reduces the need for multiple linear fires and the incidence of anastomotic leakage.