Molecular and clinicopathological features of KIT/PDGFRA wild-type gastrointestinal stromal tumors.

Approximately 10% of gastrointestinal stromal tumors (GISTs) harbor reportedly no KIT and PDGFRA mutations (wild-type GISTs). The clinicopathological features and oncologic outcomes of wild-type GISTs based on molecular profiles are unknown. We recruited 35 wild-type GIST patients from the two registry studies of high-risk GISTs between 2012 and 2015 and primary GISTs between 2003 and 2014. Molecular profiling of wild-type GISTs was performed by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tumor samples. Among 35 wild-type GISTs, targeted NGS analysis detected NF1, SDH, or BRAF mutation: 16 NF1-GISTs with various NF1 mutations, 12 SDH-GISTs (4 with SDHA mutations, 4 with SDHB mutations, and 4 with SDHB-negative staining), and 5 BRAF-GISTs with the V600E mutation. Two GISTs showed no mutations based on our targeted NGS analysis. Additional gene mutations were infrequent in primary wild-type GISTs and found in TP53, CREBBP, CDKN2A, and CHEK2. Most NF1-GISTs were located in the small intestine (N = 12; 75%) and showed spindle cell features (N = 15; 94%) and multiple tumors (N = 6, 38%) with modest proliferation activities. In contrast, SDH-GISTs were predominantly found in the stomach (N = 11; 92%), exhibiting epithelioid cell (N = 6; 50%) and multiple (N = 6, 50%) features. The overall survival of patients with SDH-GISTs appeared to be better than that of BRAF-GISTs (p = 0.0107) or NF1-GISTs (p = 0.0754), respectively. In conclusion, major molecular changes in wild-type GISTs include NF1, SDH, and BRAF. NF1-GISTs involved multifocal spindle cell tumors in the small intestine. SDH-GISTs occurred in young patients and were multifocal in the stomach and clinically indolent.

Impact of the coronavirus disease 2019 pandemic on gastric and colorectal cancer surgeries: a multicenter epidemiologic study from the Kinki region of Japan.

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Robotic gastrectomy for gastric cancer: systematic review and future directions.

BACKGROUND: Robotic gastrectomy (RG) using the da Vinci Surgical System for gastric cancer was approved for national medical insurance coverage in Japan in April 2018, and its number has been rapidly increasing since then. AIM: We reviewed and compared current evidence on RG and conventional laparoscopic gastrectomy (LG) to identify the differences in surgical outcomes. METHODS: Three independent reviewers systematically reviewed the data collected from a comprehensive literature search by an independent organization, focusing on the following nine endpoints: mortality, morbidity, operative time, estimated blood loss volume, length of postoperative hospital stay, long-term oncologic outcome, quality of life, learning curve, and cost. RESULTS: Compared to LG, RG has lower intraoperative blood loss volume, shorter length of hospital stay, and shorter learning curve, but both procedures have similar mortality. Contrarily, its disadvantages include longer procedural time and higher costs. Although the morbidity rate and long-term outcomes are almost comparable, RG showed superior potentials. Currently, the outcomes of RG are considered comparable to or better than LG. CONCLUSION: RG might be applicable to all gastric cancer patients who fulfill the indication of LG at institutions that meet specific criteria and are approved to claim the National Health Insurance costs for the use of the surgical robot in Japan.

Three-year outcomes of robotic gastrectomy versus laparoscopic gastrectomy for the treatment of clinical stage I/II gastric cancer: a multi-institutional retrospective comparative study.

BACKGROUND: Oncological benefits of robotic gastrectomy (RG) remain unclear. We aimed to determine and compare the 3-year outcomes of RG and laparoscopic gastrectomy (LG) for the treatment of gastric cancer. METHODS: This was a multi-institutional retrospective study of patients who prospectively underwent RG in a previous study (UMIN000015388) and historical controls who underwent LG. Operable patients with cStage I/II primary gastric cancer were enrolled. The inverse probability of treatment weighting method based on propensity scores was used to balance patient demographic factors and surgeon volume between the RG and LG groups. The primary outcome measure was the 3-year overall survival rate (3yOS). RESULTS: Of the 1,127 patients in the previous study, 326 and 752 patients in the RG and LG groups, respectively, completed the study. The standardized difference of all confounding factors was reduced to 0.09 or less after weighting. In the weighted population, 3yOS was 96.3% and 89.6% in the RG and LG groups, respectively (hazard ratio [HR] 0.34 [0.15, 0.76]; p = 0.009), whereas there was no difference in 3-year recurrence-free survival rate (3yRFS) between the two groups (HR 0.58 [0.32, 1.05]; p = 0.073). Sub-analyses showed that RG improved 3yOS (HR 0.05 [0.01, 0.38]; p = 0.004) and 3yRFS (HR 0.05 [0.01, 0.34]; p = 0.003) in patients with pStage IA disease. Recurrence rates and patterns were similar between the RG and LG groups. RG did not improve the morbidity rate, however, it attenuated some of the adverse events, including anastomotic leakage and intra-abdominal abscess. RG improved estimated blood loss and duration of postoperative hospitalization. CONCLUSION: This study showed surgical and oncological safety of RG for cStage I/II gastric cancer considering the 3-year outcomes, compared with those of LG.

Safety assessment of robotic gastrectomy and analysis of surgical learning process: a multicenter cohort study.

BACKGROUND: The safety of robotic gastrectomy (RG) for gastric cancer in daily clinical settings and the process by which surgeons are introduced and taught RG remain unclear. This study aimed to evaluate the safety of RG in daily clinical practice and assess the learning process in surgeons introduced to RG. METHODS: Patients who underwent RG for gastric cancer at Kyoto University and 12 affiliated hospitals across Japan from January 2017 to October 2019 were included. Any morbidity with a Clavien-Dindo classification grade of II or higher was evaluated. Moreover, the influence of the surgeon's accumulated RG experience on surgical outcomes and surgeon-reported postoperative fatigue were assessed. RESULTS: A total of 336 patients were included in this study. No conversion to open or laparoscopic surgery and no in-hospital mortality were observed. Overall, 50 (14.9%) patients developed morbidity. During the study period, 14 surgeons were introduced to robotic procedures. The initial five cases had surprisingly lower incidence of morbidity compared to the following cases (odds ratio 0.29), although their operative time was longer (+ 74.2 min) and surgeon's fatigue scores were higher (+ 18.4 out of 100 in visual analog scale). CONCLUSIONS: RG was safely performed in actual clinical settings. Although the initial case series had longer operative time and promoted greater levels of surgeon fatigue compared to subsequent cases, our results suggested that RG had been introduced safely.

Chronological Changes in Skeletal Muscle Mass Two Years after Minimally Invasive Esophagectomy: A Prospective Cohort Study.

BACKGROUND: Preoperative loss of skeletal muscle mass, defined as sarcopenia, has been reported to be associated with higher incidence of complications following esophagectomy in patients with esophageal cancer. Although skeletal muscle loss promotes disability and reduced quality of life (QOL), only a few studies have focused on changes in skeletal muscle mass after surgery. This prospective cohort study aimed to evaluate the chronological changes in skeletal muscle mass after minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer scheduled to undergo MIE at our institution were prospectively registered. Skeletal muscle mass was evaluated before and 2, 6, 12, and 24 months after surgery. The effects of preoperative sarcopenia on surgical outcomes and chronological changes in skeletal muscle mass were evaluated. RESULTS: Among the 71 eligible preoperative patients, 29 (40.8%) were diagnosed with sarcopenia. Patients with sarcopenia had significantly higher incidences of total (79.3% vs 52.4%, p = 0.026) and gastrointestinal (37.9% vs 11.9%, p = 0.019) complications and a significantly longer length of hospital stay (31 vs 23 days, p = 0.005) than those without sarcopenia. The median skeletal muscle mass index (kg/m2) was 7.09 before surgery, which decreased to 6.46 two months after surgery (- 7.2%, P < 0.01). Thereafter, values of 6.90, 6.86, and 7.06 were reported at 6, 12, and 24 months after surgery, respectively. CONCLUSION: Patients with preoperative sarcopenia developed more postoperative complications than those without it. Additionally, patients experienced a decrease in skeletal muscle mass during the early postoperative period following MIE. Further research on perioperative countermeasures to prevent skeletal muscle loss during the early postoperative period and to prevent postoperative complications is necessary for patients undergoing MIE.

Mesenteric closure after laparoscopic total gastrectomy with Roux-en-Y reconstruction is effective for prevention of internal hernia: a multicenter retrospective study.

BACKGROUND: Internal hernia (IH) is one of the critical complications after gastrectomy with Roux-en-Y reconstruction, which can be prevented by closing mesenteric defects. However, only few studies have investigated the incidence of IH after laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction for gastric cancer till date. This study aimed to assess the efficacy of defect closure for the prevention of IH after LTG. METHODS: This multicenter, retrospective cohort study collected data from 714 gastric cancer patients who underwent LTG with Rou-en-Y reconstruction between 2010 and 2016 in 13 hospitals. We evaluated the incidence of postoperative IH by comparing closure and non-closure groups of Petersen's defect, jejunojejunostomy mesenteric defect, and transverse mesenteric defect. RESULTS: The closure group for Petersen's defect included 609 cases, while the non-closure group included 105 cases. The incidence of postoperative IH in the closure group for Petersen's defect was significantly lower than it was in the non-closure group (0.5% vs. 4.8%, p < 0.001). The closure group for jejunojejunostomy mesenteric defect included 641 cases, while the non-closure group included 73 cases. The incidence of postoperative IH in the closure group of jejunojejunostomy mesenteric defect was significantly lower than that in the non-closure group (0.8% vs. 4.1%, p = 0.004). Out of 714 patients, 41 underwent retro-colic reconstruction. No patients in the transverse mesenteric defect group developed IH. CONCLUSION: Mesenteric defect closure after LTG with Roux-en-Y reconstruction may reduce postoperative IH incidence. Endoscopic surgeons should take great care to prevent IH by closing mesenteric defects.

Lower Incidence of Postoperative Pulmonary Complications Following Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: Propensity Score-Matched Comparison to Conventional Minimally Invasive Esophagectomy.

BACKGROUND: Whether robot-assisted minimally invasive surgery (RAMIE) is more beneficial than conventional minimally invasive surgery (MIE) remains unclear. METHODS: In total, 165 consecutive patients with esophageal carcinoma who underwent esophagectomy between January 2015 and April 2020 were retrospectively assessed. A 1:1 propensity score matching analysis was performed to compare the short-term outcomes between RAMIE and conventional MIE. RESULTS: After matching, 45 patients were included in the RAMIE and conventional MIE groups. RAMIE had a significantly longer total operative time (708 vs. 612 min, P < 0.001) and thoracic operative time (348 vs. 285 min, P < 0.001) than conventional MIE. However, there were no significant differences in terms of oncological outcomes, such as R0 resection rate and number of resected lymph nodes. The overall postoperative morbidity (Clavien-Dindo [C-D] grade II or higher) rate of RAMIE and conventional MIE were 51% and 73% (P = 0.03), respectively, and the severe postoperative morbidity (C-D grade III or higher) rates were 11% and 29% (P = 0.04), respectively. The incidence rate of recurrent laryngeal nerve palsy was halved in RAMIE (7%) compared with conventional MIE (20%) (P = 0.06). Finally, the pulmonary complication rate (18%) was significantly lower in patients who underwent RAMIE than in those who underwent conventional MIE (44%) (P = 0.006). CONCLUSIONS: RAMIE was safe and feasible, even during the early period of its application at a specialized center. Moreover, it may be a promising alternative to conventional MIE, with better short-term outcomes, including significantly lower incidence of pulmonary complications.

Long-Term Outcomes of Laparoscopic Radical Gastrectomy for Highly Advanced Gastric Cancer: Final Report of a Prospective Phase II Trial (KUGC04).

BACKGROUND: This is the final report evaluating the long-term outcomes of a single-arm phase II clinical trial that demonstrated the short-term efficacy of laparoscopic gastrectomy (LG) for highly advanced gastric cancer (AGC) [KUGC04]. PATIENTS AND METHODS: Seventy-three patients with histologically confirmed gastric adenocarcinoma and diagnosed with clinical stage II or higher, who potentially underwent curative resection between August 2009 and November 2014, were prospectively enrolled. Long-term outcomes with 5-year progression-free survival (PFS) and 5-year overall survival (OS) were evaluated according to clinical or pathological stages. Recurrence and progression patterns were also investigated. These outcomes were compared with those of previous reports to assess the applicability of LG for highly advanced gastric cancer (HAGC). RESULTS: The median observation period of all surviving patients was 75.1 months. The 5-year PFS and 5-year OS of all patients was 47.4% and 54.4%, respectively. Clinical stage-specific 5-year PFS and 5-year OS was 75.0, 69.1, 53.9, 39.4, 40.0 and 9.1, and 75.0, 68.8, 61.5, 45.0, 60.0 and 27.3, respectively, in stages IIA, IIB, IIIA, IIIB, IIIC, and IV, respectively. Pathological stage-specific 5-year PFS and 5-year OS, including ypStage with preoperative chemotherapy, was 100, 80.0, 100, 62.5, 80.0, 51.3, 16.7, 22.2 and 12.5, and 100, 80.0, 100, 75.0, 80.0, 64.2, 25.0, 33.3 and 12.5, respectively, in stage X (no residual tumor with preoperative chemotherapy), IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV, respectively. Recurrence or progression was observed in 30 patients (41.1%). CONCLUSION: LG for HAGC performed by experienced surgeons is safe and oncologically acceptable.

Educational application of intraoperative records from an energy device in laparoscopic gastrectomy: a preliminary report.

PURPOSE: Video review is a reliable method for surgical education in laparoscopic gastrectomy (LG), but more objective methods are still needed. The purpose of this study was to determine whether the energy device records reflected surgical competency, and thereby may improve surgical education. METHODS: A total of 16 patients who underwent LG for gastric cancer using the Thunderbeat® device were preliminarily retrospectively analyzed. This device has the function of 'intelligent tissue monitoring' (ITM), a safety assist system stopping energy output, and can record ITM detections and firing time during surgery. The number of ITM detections and firings, and the total firing time during gastrocolic ligament dissection and infrapyloric dissection were compared between trainees (n = 9 by 5 surgeons) and experts (n = 7 by 5 surgeons). The non-edited videos (n = 16) were scored, and the correlations between the scores and the records were then analyzed. RESULTS: Significantly more ITM detections, firings, and a longer total firing time were observed in trainees than in experts. The number of ITM detections and firing had negative correlations with the scores of the operation speed, the use of the non-dominant hand, and the use of an energy device. CONCLUSIONS: Our preliminary study suggested that the above described energy device records reflected surgical competency, and thereby may improve surgical education.

Simple technique of azygos arch division and retraction for minimally invasive esophagectomy.

The azygos arch is usually divided during esophagectomy. To achieve thorough lymphadenectomy up to upper mediastinum, many surgeons prefer to retract the distal stump of the azygos arch by pulling out the thread which ligates the stump to the skin through the dorsal side of the intercostal space. However, the access to the dorsal chest wall near vertebrae for percutaneous puncture is difficult during robot-assisted minimally invasive esophagectomy in the prone position. This paper reports a new simple method of azygos arch division and retraction using a polymer locking ligation system Hem-o-lok (Teleflex, Morrisville, NC, USA) and a barbed suture device. This technique can be easily performed completely as a robotic procedure without extra puncture, and it is also applicable for conventional thoracoscopic procedures with the potential benefits of less trauma and bleeding.

Mesenteric excision of upper esophagus: a concept for rational anatomical lymphadenectomy of the recurrent laryngeal nodes in thoracoscopic esophagectomy.

BACKGROUND: The recurrent laryngeal nerve (RLN) lymph nodes are among the most frequently involved lymph nodes in esophageal cancer. Surgical removal of these lymph nodes is considered beneficial for postoperative prognosis, especially in patients with squamous cell carcinoma. Unfortunately, the precise surgical anatomy of the upper mediastinum is not well understood and no distinct high-resolution images are currently available. METHODS: In this article, we provide a simple intuitive concept of upper mediastinal surgical anatomy that could facilitate rational anatomical lymphadenectomy of the RLN lymph nodes. The essential concept of this mesenteric excision is to mobilize mesoesophagus including RLN in an en bloc fashion and to save RLN laterally by incising visceral sheath. This is applicable identically to both right and left upper mediastinum. RESULTS: Between January 2009 and December 2017, thoracoscopic esophagectomy with upper mediastinal lymphadenectomy for primary esophageal cancer was performed in 189 patients. Median thoracoscopic procedure time was 297 (range 205-568) min and median intraoperative blood loss was 70 ml (range unmeasurable up to 2545 ml). Median number of harvested upper mediastinal lymph nodes was 12. Postoperative complication of Clavien-Dindo classification grade III or higher events was observed in 14% of patients. RLN palsy of grade II or higher occurred in 20 patients (11%). CONCLUSION: The mesoesophagus in the upper mediastinum is an anatomical unit surrounded by fibrous connective tissue containing the esophagus, trachea, tracheoesophageal vessels, lymphatic tissue, and RLNs. Thus, mesenteric excision of esophagus is defined to resect this area by sparing trachea and RLNs for rational anatomical lymphadenectomy. We believe that this concept makes upper mediastinal lymphadenectomy safer and more appropriate.

Linear or circular stapler? A propensity score-matched, multicenter analysis of intracorporeal esophagojejunostomy following totally laparoscopic total gastrectomy.

BACKGROUND: Presently, there is no consensus as to what procedure of intracorporeal esophagojejunostomy (EJS) in totally laparoscopic total gastrectomy (TLTG) is best to reduce postoperative complications. The aim of this study was to demonstrate the superiority of linear stapled reconstruction in terms of anastomotic-related complications for EJS in TLTG. METHODS: We collected data on 829 consecutive gastric cancer patients who underwent TLTG reconstructed by the Roux-en-Y method with radical lymphadenectomy between January 2010 and December 2016 in 13 hospitals. The patients were divided into two groups according to reconstruction method and matched by propensity score. Postoperative EJS-related complications were compared between the linear stapler (LS) and the circular stapler (CS) groups. RESULTS: After matching, data from 196 patients in each group were analyzed. The overall incidence of EJS-related complications was significantly lower in the LS group than in the CS group (4.1% vs. 11.7%, p = 0.008). The incidence of EJS anastomotic stenosis during the first year after surgery was significantly lower in the LS group than in the CS group (1.5% vs. 7.1%, p = 0.011). The incidence of EJS bleeding did not differ significantly between the groups, although no bleeding was observed in the LS group (0% vs. 2.0%, p = 0.123). The incidence of EJS leakage did not differ significantly between the groups (2.6% vs. 3.6%, p = 0.771). CONCLUSION: The use of linear stapled reconstruction is safer than the use of circular stapled reconstruction for intracorporeal EJS in TLTG because of its lower risks of stenosis.

CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer.

Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.).

A Phase 2 Study of Induction Chemotherapy Using Docetaxel, Cisplatin, and S-1 for Gastric Cancer with Peritoneal Metastasis (KUGC06).

BACKGROUND: The authors previously showed the significant efficacy of S-1 plus cisplatin for gastric cancer with limited peritoneal metastasis. They conducted a phase 2 study to evaluate the safety and efficacy of induction chemotherapy using a docetaxel, cisplatin, and S-1 (DCS) triplet regimen to treat gastric cancer with peritoneal metastasis. METHODS: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology but no other distant metastases and capability of oral administration. The patients received three 28-day cycles of DCS (60 mg/m2 of cisplatin, 40 mg/m2 of docetaxel on day 1, and 80 mg/m2 of S-1 from day 1 to day 14), then underwent D2 gastrectomy if R0 was possible. The primary end point was the R0 resection rate. The sample size was determined to have 80% power for detecting a 20% improvement in the R0 resection rate over a 45% baseline for a one-tailed alpha of 0.1. RESULTS: Among 30 enrolled patients, 24 completed three cycles of DCS. The most frequent grade 3 or 4 toxicity was neutropenia (60%). A complete response of peritoneal metastasis was observed in 16 patients, and 14 patients achieved R0 resection (47%; 95% confidence interval 28-66%). When the extent of peritoneal metastasis was classified as P0CY1, P1, P2, and P3 according to the Japanese classification, the R0 resection rates were respectively 63%, 60%, 46% and 0%. CONCLUSIONS: Induction chemotherapy with DCS is safe and can achieve R0 resection for some patients with limited peritoneal metastasis or positive peritoneal cytology. The efficacy, however, appears similar to that of S-1 plus cisplatin.

Revisiting the infracardiac bursa using multimodal methods: topographic anatomy for surgery of the esophagogastric junction.

In embryology, the infracardiac bursa (ICB) is a well-known derivative separated from the omental bursa. During surgeries around the esophagogastric junction (EGJ), surgeons often encounter a closed space considered to be equivalent to the ICB, but the macroscopic anatomy in adults is hardly known. This study aimed to revisit the ICB using multimodal methods to show its development from the embryonic to adult stage and clarify its persistence and topographic anatomy. Histological sections of 79 embryos from Carnegie stage (CS) 16 to 23 and magnetic resonance (MR) images of 39 fetuses were examined to study the embryological development of the ICB. Horizontal sections around the EGJ obtained from three adult cadavers were examined to determine the topographic anatomy and histology of the ICB. Further, 32 laparoscopic surgical videos before (n = 16) and after (n = 16) the start of this study were reviewed to confirm its remaining rate and topographic anatomy in surgery. The ICB was formed in 1 out of 10 CS17 samples, and in 8 out of 10 CS18 samples. Further, it was observed in all CS19-23 except one CS23 sample and in 25 (64%) out of 39 fetus samples. Three-dimensional reconstructed MR images of fetuses revealed that the ICB was located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. In one adult cadaver, the caudal end of the ICB arose from the level of the esophageal hiatus and the cranial end reached up to the level of the pericardium. The inner surface cells of the space consisted of the mesothelium. In laparoscopic surgery, the ICB was identified in only 11 (69%) out of 16 surgeries before. However, subsequently we were able to identify the ICB reproducibly in 15 (94%) out of 16 surgeries. Thus, the ICB is the structure commonly remaining in almost all adults as a closed space located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. It may be available as a useful landmark in surgery of the EGJ.

Feasibility of robotic radical gastrectomy using a monopolar device for gastric cancer.

PURPOSES: Laparoscopic gastrectomy using ultrasonic devices occasionally causes postoperative pancreatic fistula. Robotic gastrectomy using monopolar scissors may reduce intraoperative injury to the pancreas. We evaluated the safety and feasibility of robotic gastrectomy. METHODS: A multicenter prospective study was conducted to evaluate the surgical outcomes of robotic gastrectomy. The primary endpoints were the incidence of intraoperative and postoperative complications and operative mortality. RESULTS: A total of 115 patients were enrolled. The clinical T stages were T1 in 68 patients and T2 or higher in 47 patients. The types of surgery included distal gastrectomy (n = 72), total gastrectomy (n = 39), and proximal gastrectomy (n = 4). Two patients developed intraoperative complications (1.7%), but no cases required conversion to open surgery. The amylase concentration in drainage fluid was higher in cases with pancreatic compression, especially in those with compression for longer than 20 min. Postoperative complications of Clavien-Dindo grade ≥ II occurred in 11 patients (9.6%). There was no mortality. A multivariate analysis indicated that a high body mass index and pancreatic compression by an assistant for longer than 20 min were independent risk factors for postoperative complications (P = 0.029 and P = 0.010). CONCLUSIONS: Robotic gastrectomy using monopolar scissors is safe and feasible. Robotic dissection without compression of the pancreas may reduce postoperative complications.

Optimal Cutoff Values of Skeletal Muscle Index to Define Sarcopenia for Prediction of Survival in Patients with Advanced Gastric Cancer.

BACKGROUND: Sarcopenia, characterized by loss of skeletal muscle mass, is recognized as a prognostic factor in patients with gastric cancer. However, wide variability exists in the cutoff values of muscle mass for defining sarcopenia across previous studies, and the best cutoff values to predict survival remain unknown. This study aimed to determine the optimal cutoff values for sarcopenia to predict survival in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with clinical stage II/III gastric cancer who underwent gastrectomy at Kyoto University Hospital were included in the study. The cross-sectional area of skeletal muscle at the third lumbar vertebra level was measured using preoperative computed tomography scan. The skeletal muscle index (SMI) was calculated by dividing the area by height in meters squared. Five sex-specific cutoffs of SMI, which were significantly associated with prognosis in patients with gastric and nongastric cancers, were examined as a threshold to define sarcopenia. RESULTS: In the 177 eligible patients, the five cutoffs of SMI resulted in an incidence of sarcopenia between 6 (3%) and 114 (64%). The 5-year overall survival was 48% in patients with sarcopenia based on the cutoffs reported by Martin et al., compared with 68% in those without sarcopenia (p = 0.013). A multivariate regression model demonstrated that sarcopenia based on the cutoffs was significantly associated with overall survival (hazard ratio 2.00, 95% confidence interval 1.24-3.24, p = 0.005). CONCLUSIONS: The cutoff values reported by Martin et al. were optimal to predict survival in patients with advanced gastric cancer.