Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

A long-term follow-up study of minimally invasive Ivor Lewis esophagectomy with linear stapled anastomosis.

BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly performed to expect lower complication rate compared to open esophagectomy. Studies of minimally invasive Ivor Lewis esophagectomy (MIILE) with circular staplers have reported better outcomes compared to MIE with cervical anastomosis, but frequent anastomotic complications have also been reported. MIILE with linear staplers is a promising alternative, but the long-term functional and oncological outcomes are uncertain. METHODS: To evaluate the functional and oncological outcomes of MIILE with linear stapled anastomosis, a retrospective cohort study was performed in 104 patients who underwent MIILE with linear stapled anastomosis for esophageal malignant tumors. The primary endpoints were the overall complication and anastomotic leak rates. The secondary endpoints were late complications, overall and disease-free survival, and nutritional status at 6 and 12 months after MIILE. RESULTS: Anastomotic leak occurred in 4 patients (3.8%). The short-term complication rate of grade IIIb or higher was 6.7%. During a median 57-month follow-up period, anastomotic stricture occurred in one patient, 7 required hiatal hernia repair, and 2 underwent conduit revision surgery. The 5-year overall survival and disease-free survival rates were 69.3% and 59.5%, respectively. Status of reflux esophagitis at the time of most recent evaluation was grade N/A/B/C/D in 52/10/10/13/8 among 93 patients who had follow-up endoscopy. The mean body weight loss at 6 and 12 months after MIILE was 11.3 and 11.8% with maintenance of the serum albumin level. CONCLUSIONS: MIILE with linear stapled anastomosis is a safe procedure with a low anastomotic complication rate and favorable long-term functional and survival outcomes.

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.

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.

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.

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.

Clinical advantages of robotic gastrectomy for clinical stage I/II gastric cancer: a multi-institutional prospective single-arm study.

BACKGROUND: Robotic gastrectomy (RG) for gastric cancer (GC) has been increasingly performed for a decade; however, evidence for its use as a standard treatment has not yet been established. The present study aimed to determine the safety, feasibility, and effectiveness of RG for GC. METHODS: This multi-institutional, single-arm prospective study, which included 330 patients from 15 institutions, was designed to compare morbidity rate of RG with that of a historical control (conventional laparoscopic gastrectomy, LG). This trial was approved for Advanced Medical Technology ("Senshiniryo") B. The included patients were operable patients with cStage I/II GC. The primary endpoint was morbidity (Clavien-Dindo Grade ≥ IIIa). The specific hypothesis was that RG could reduce the morbidity rate to less than half of that with LG (6.4%). A sample size of 330 was considered sufficient (one-sided alpha 0.05, power 80%). RESULTS: Among the 330 study patients, the protocol treatment was suspended in 4 patients. Thus, 326 patients fully enrolled and completed the study. The median patient age and BMI were 66 years and 22.4 kg/m2, respectively. Distal gastrectomy was performed in 253 (77.6%) patients. The median operative time and estimated blood loss were 313 min and 20 mL, respectively. No 30-day mortality was seen, and morbidity showed a significant reduction to 2.45% with RG (p = 0.0018). CONCLUSIONS: RG for cStage I/II GC is safe and feasible. It may be effective in reducing morbidity with LG.

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.

Proposal for a Safe and Functional Pancreaticojejunostomy Technique from a Histopathological Perspective.

BACKGROUND: To prevent leakage of pancreatic juice from the main pancreatic duct (MPD), complete external drainage appears to be the most effective technique. However, because this requires a pancreatic stent tube to be ligated with MPD, duct-to-mucosa pancreaticojejunostomy (PJ) is difficult. From our histopathological examination, a large amount of pancreatic juice is drained from the ducts other than MPD. This study aimed to evaluate our new conceptual technique of PJ after pancreaticoduodenectomy (PD). METHODS: We considered it important to drain pancreatic juice from the branch pancreatic ducts to the intestinal tract and to perform duct-to-mucosa PJ, while pancreatic juice from MPD is completely drained out of the body. We designed a technique that could simultaneously achieve these points. In our technique, which is based on conventional "two-row" anastomosis, a stent tube is fixed with MPD and its surrounding tissue by purse-string suture at the cut surface of the pancreas, and duct-to-mucosa PJ is concomitantly performed. RESULTS: Of 45 patients undergoing PD, 12 of soft pancreas underwent surgery with this technique. According to the classification of the International Study Group on Pancreatic Fistula, a Grade A PF was observed in four patients, whereas no patient had a Grade B or C PF. CONCLUSIONS: We propose our anastomotic technique that could simultaneously prevent PF and keep the pancreatic duct patent.

Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle.

Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia.

PTEN loss is associated with a poor response to trastuzumab in HER2-overexpressing gastroesophageal adenocarcinoma.

BACKGROUND: Although trastuzumab improves the outcome of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing gastric or gastroesophageal junction adenocarcinoma (collectively referred to as "gastroesophageal adenocarcinoma"; GEA), no clinical response is observed in a substantial population of patients. A predictive biomarker of trastuzumab response is required. The aim of this study was to evaluate whether the hyperactivation of the downstream phosphatidylinositol 3-kinase pathway, due to phosphatase and tensin homolog (PTEN) loss or PIK3CA mutations, could provide trastuzumab resistance in GEA. METHODS: Expression of HER2 and PTEN, and PIK3CA gene mutations were screened in 264 surgically resected GEA specimens. The effects of PTEN knockdown on the response to trastuzumab on cell viability, HER2 downstream signaling, apoptosis, and cell cycle were evaluated in HER2-overexpressing NCI-N87 gastric adenocarcinoma and OE19 esophageal adenocarcinoma cell lines. Inhibition of xenograft tumor growth by trastuzumab was investigated in OE19 cells with or without PTEN knockdown. The PTEN expression and objective response were analyzed in 23 GEA patients who received trastuzumab-based therapy. RESULTS: PTEN loss was identified in 34.5 % of HER2-overexpressing GEA patients, whereas PIK3CA mutations were rare (5.6 %). Trastuzumab-mediated growth suppression, apoptosis, and G1 cell cycle arrest were inhibited by PTEN knockdown through Akt activation in NCI-N87 and OE19 cells. PTEN knockdown impaired the antiproliferative effect of trastuzumab in OE19 xenograft models. A clinical response was observed in 50 % of PTEN-positive tumors (9 of 18) but in no tumors with PTEN loss (none of 5). CONCLUSIONS: PTEN loss was frequently found in HER2-overexpressing tumors, and was associated with a poor response to trastuzumab-based therapy in patients with GEA.

Superiority of laparoscopic proximal gastrectomy with hand-sewn esophagogastrostomy over total gastrectomy in improving postoperative body weight loss and quality of life.

BACKGROUND: Proximal gastrectomy is not widely performed because the procedure is complicated, particularly under laparoscopy. We developed a simple laparoscopic technique of hand-sewn esophagogastrostomy with an anti-reflux mechanism. This study aimed to evaluate and compare the postoperative body weight loss (BWL) and quality of life (QOL) following laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG) in patients with upper gastric cancer. METHODS: We retrospectively analyzed patients with stage I upper gastric cancer undergoing LPG or LTG at Kyoto University Hospital between March 2006 and June 2014. The main outcome measures were the % BWL 1 year after gastrectomy, postoperative anastomotic stricture, and reflux esophagitis. Additionally, patient-reported outcomes were evaluated using the Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 in patients presenting at the outpatient clinic and exhibiting no recurrence. RESULTS: A total of 62 patients were included in this study (LTG, n = 42 vs. LPG, n = 20). The % BWL at 12 months in the LPG group was less than that in the LTG group (-16.3 vs. -10.7%). Multivariate analysis revealed that LPG was associated with less BWL (P = 0.003). Anastomotic stricture occurred more frequently in the LPG group than in the LTG group (0 vs. 25%). One patient in each group exhibited grade B severity of reflux esophagitis (based on the Los Angeles classification). In the questionnaire survey, LPG was better than LTG in terms of diarrhea and dissatisfaction with symptoms. In terms of reflux symptoms, patients in the LPG group experienced less acid and bile regurgitation symptoms compared with those in the LTG group. CONCLUSIONS: LPG with hand-sewn esophagogastrostomy results in less postoperative BWL and better QOL than LTG despite higher rates of anastomotic stricture.

Staging laparoscopy for advanced gastric cancer: significance of preoperative clinicopathological factors.

PURPOSE: Although the use of staging laparoscopy (SL) for detecting peritoneal metastasis (P) and determining peritoneal lavage cytology (CY) is widespread in advanced gastric cancer, an indication for SL based on preoperative clinicopathological factors is controversial. METHODS: From May 2006 to September 2015, 120 patients with advanced gastric cancer with primary tumors ≥5 cm and/or with bulky regional lymph nodes (bulky N) underwent SL for assessment of P/CY status. Clinicopathological factors were analyzed retrospectively to determine their influence on peritoneal spread (P1 and/or CY1). An additional analysis of 379 consecutive patients with clinically T2 or deeper gastric cancer in the same time period was carried out to confirm the SL results. RESULTS: Peritoneal spread was confirmed by SL in 54 cases (45%). The presence of type-4 tumors (n = 38, p < 0.0001) and diffuse-type tumors (n = 85, p = 0.04) correlated significantly with peritoneal spread. These two factors were also correlated significantly with increased peritoneal spread in a subgroup analysis among patients with tumors with bulky N (n = 44). The additional analysis of 379 patients showed results consistent with the SL results. The frequency of peritoneal spread was 78% among type-4 tumors, 47% among diffuse-type tumors ≥5 cm, and 38% among diffuse-type tumors with bulky N, whereas among intestinal-type tumors, it was 18% in tumors ≥5 cm and 13% among tumors with bulky N. CONCLUSIONS: Among tumors ≥5 cm or with bulky N, type-4 tumors and diffuse-type tumors had a high potential for peritoneal spread and patients with such tumors were considered more suitable candidates for SL.

Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303).

BACKGROUND: The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. METHODS: One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. RESULTS: The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). CONCLUSIONS: Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. CLINICAL TRIAL INFORMATION: UMIN000000861.

Feasibility of Laparoscopic Radical Gastrectomy for Gastric Cancer of Clinical Stage II or Higher: Early Outcomes in a Phase II Study (KUGC04).

PURPOSE: A phase II study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) for gastric cancer of clinical stage II or higher. METHODS: The eligibility criteria were gastric cancer of clinical stage II or higher that was amenable to potentially curative resection. Patients with prior chemotherapy, tumors requiring total gastrectomy (TG), tumors that invaded adjacent organs, and patients with bulky lymph node metastasis were included. The primary endpoint was incidence of postoperative complications of grade II or higher in the Clavien-Dindo classification. The sample size was determined to be 73, based on an expected rate of complications of 19 % and a threshold of 30 %. Gastrectomy was performed by expert surgeons who were certified by the Japan Society for Endoscopic Surgery. RESULTS: A total of 73 patients were enrolled; 54 patients (74 %) had clinical T stage T4a/T4b, and 47 patients (64 %) were administered preoperative chemotherapy. The type of surgery was distal gastrectomy in 41 patients and TG in 31 patients. Dissection of D2 or more was performed in 62 patients (85 %). Of the 25 patients who underwent D2/D2+ TG, 15 underwent splenectomy or pancreaticosplenectomy. R0 resection was performed in 64 patients (88 %). The median number of resected lymph nodes was 56, and postoperative complications occurred in 15 patients (20.5 %), which was significantly lower than the threshold value (p = 0.039). One in-hospital death occurred (1.4 %). CONCLUSION: LG for gastric cancer of clinical stage II or higher can be safely performed by experienced surgeons.

Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy.

BACKGROUND: The critical risk factors for surgical site infection (SSI) after laparoscopic total gastrectomy (LTG) remain unclear. We analyzed the association between body composition and SSI after LTG. METHODS: We performed a retrospective study of patients with gastric cancer who underwent LTG between March 2006 and October 2014 at Kyoto University Hospital, Japan. Visceral fat area and skeletal muscle mass were assessed from preoperative computed tomography scans to define sarcopenia and obesity. Patients were classified into one of four body composition categories according to the presence or absence of sarcopenia or obesity. The incidence of SSI was compared between the four body composition categories. RESULTS: Of the 157 eligible patients, 45 (24 %) fulfilled the criteria for sarcopenic obesity, 28 (18 %) for nonsarcopenic obesity, 52 (33 %) for sarcopenic nonobesity, and 32 (20 %) for nonsarcopenic nonobesity. Thirty-two patients developed SSI (overall incidence rate, 20 %). The incidence of SSI in each body composition category was 33, 25, 13, and 9 %, respectively (P = 0.03). Multivariate logistic regression analysis showed that only sarcopenic obesity was associated with an increased incidence of SSI (odds ratio 4.59, 95 % confidence interval 1.18-17.78, P = 0.028). CONCLUSIONS: Sarcopenic obesity is an independent risk factor for the development of SSI after LTG.

Sarcopenia as a predictor of pulmonary complications after esophagectomy for thoracic esophageal cancer.

BACKGROUND AND OBJECTIVES: Sarcopenia or loss of skeletal muscle mass has been identified as a poor prognostic factor for a wide variety of diseases and conditions. We investigated whether preoperative sarcopenia is associated with postoperative complications in patients undergoing esophagectomy for thoracic esophageal cancer. METHODS: We retrospectively reviewed the medical records of consecutive patients with thoracic esophageal cancer who underwent esophagectomy between September 2005 and July 2014 at Kyoto University Hospital. Skeletal muscle mass was assessed using preoperative computed tomographic scans by measuring the cross-sectional muscle area at the third lumbar vertebral level. RESULTS: Among the 199 eligible patients, 149 (75%) were classified as having sarcopenia. There was no difference in the incidence of overall complications between the groups (risk ratio [RR]: 1.10, 95% confidence interval [CI]: 0.80-1.53, P = 0.54). However, pulmonary complications were significantly more frequent in the sarcopenia group than in the nonsarcopenia group (RR: 2.63, 95% CI: 1.20-5.77, P = 0.007). Multivariate analyses demonstrated that sarcopenia was associated with a high adjusted risk of one or more pulmonary complications (odds ratio: 2.96, 95% CI: 1.14-7.69, P = 0.026). CONCLUSIONS: Sarcopenia independently predicts pulmonary complications after esophagectomy for thoracic esophageal cancer. J. Surg. Oncol. 2016;113:678-684. © 2016 Wiley Periodicals, Inc.