Gasdermin D represses inflammation-induced colon cancer development by regulating apoptosis.

Chronic inflammation is widely recognized as a major risk factor for cancer formation, but the underlying mechanisms are poorly understood. Recently, it was shown that Gasdermin D (GSDMD) protein drives pyroptotic cell death in macrophages on cleavage by inflammatory caspases. Even though the Gsdmd gene is specifically expressed in the intestinal epithelium, the role of Gsdmd in the intestinal tissues remains poorly characterized. In this study, we examined the biological role of Gsdmd in colorectal cancer (CRC) development, employing an azoxymethane/dextran sulfate sodium carcinogenesis model. Results show that GSDMD deficiency enhances CRC development, probably due to decreased apoptosis caused by downregulation of interferon-gamma (IFNγ)-signal transducer and activator 1 (STAT1) signaling. Furthermore, we show that GSDMD protein is diminished in human colorectal cancer, indicating involvement of GSDMD in repression of CRC development in humans. Our findings provide a new insight into functions of Gsdmd/GSDMD in colonic inflammation and human CRC development.

Double stapling technique versus hemi-double stapling technique for esophagojejunostomy with OrVil™ after laparoscopic total gastrectomy: a single-blind, randomized clinical trial.

BACKGROUND: The transorally inserted anvil (OrVil™) is frequently selected for esophagojejunostomy after laparoscopic total gastrectomy (LTG) because of its versatility. During anastomosis with OrVil™, the double stapling technique (DST) or hemi-double stapling technique (HDST) can be selected by overlapping the linear stapler and the circular stapler. However, no studies have reported the differences between the methods and their clinical significance. METHODS: A randomized controlled clinical trial with a parallel assignment and single-blind outcomes assessment analysis was conducted. Patients with gastric cancer eligible for LTG who met the selection criteria were randomized. Preoperative characteristics and perioperative and postoperative outcomes were compared between the DST and HDST. The primary endpoint was an anastomosis-related complication, and the secondary endpoints were perioperative outcomes and postoperative complications, excluding anastomosis-related complications. RESULTS: Thirty patients with gastric cancer were eligible and randomized. LTG and esophagojejunostomy were successfully performed in all patients, without conversion to laparotomy. Preoperative characteristics, excluding preoperative chemotherapy, were not significantly different between the two groups. One anastomotic leakage of Clavien-Dindo classification grade ≥ IIIa was observed in the DST, although no significant difference was found between the two groups (6.6% vs. 0%, P = 0.30). In the HDST, one case of anastomotic stricture required endoscopic balloon dilation. No significant differences were found in operative time, whereas the anastomosis time was significantly shorter in the HDST than in the DST (47.5 ± 15.8 vs. 38.2 ± 8.8 min, P = 0.028). Except for anastomosis-related complications, postoperative complications (P = 0.282) and postoperative hospital stay for the DST and HDST were not significantly different. CONCLUSIONS: No superiority was found between the DST and HDST with OrVil™ in esophagojejunostomy of LTG for gastric cancer with respect to postoperative complications, whereas the HDST may be preferable in terms of the simplicity of the surgical technique.

Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence.

BACKGROUND: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence. METHODS: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence. RESULTS: Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, ß-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified ß-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001). CONCLUSIONS: The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. ß-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.

Survival Outcomes of Two Phase 2 Studies of Adjuvant Chemotherapy with S-1 Plus Oxaliplatin or Capecitabine Plus Oxaliplatin for Patients with Gastric Cancer After D2 Gastrectomy.

BACKGROUND: Two phase 2 trials of oxaliplatin-containing adjuvant therapy for patients with gastric cancer (GC) after D2 gastrectomy were conducted in Japan. The SOXaGC trial evaluated the tolerability and safety of adjuvant therapy with S-1 plus oxaliplatin (SOX), whereas the J-CLASSIC trial evaluated the feasibility of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX). Because both were studies that did not evaluate survival results as study end points, the authors evaluated the survival outcomes for the patients in the two trials. METHODS: All 62 and 100 patients in the full analysis set of the SOXaGC and J-CLASSIC trials, respectively, were included in the current study. Their information about survival outcome was collected. The primary end point was relapse-free survival (RFS), and the secondary end point was overall survival (OS). RESULTS: For the pathologic stage (pStage 2) patients treated with CAPOX, the 3-year RFS rate was 87.8% and the 3-year OS rate was 92.7%. For the pStage 3 patients treated with SOX and CAPOX, the 3-year RFS rates were respectively 70.9% and 67.8% (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.50-1.72), whereas the 3-year OS rates were respectively 75.7% and 79.3% (HR, 1.10; 95% CI, 0.54-2.26). Subgroup analysis showed significant interactions between the treatment (SOX vs. CAPOX) and both sex (male vs. female; P = 0.024) and histologic type (diffuse vs. other, P = 0.069). CONCLUSIONS: This exploratory analysis demonstrated that SOX and CAPOX are suggested to have similar efficacy for pStage 3 GC patients after D2 gastrectomy. Differences in the treatment effect according to sex and histologic type warrant further evaluation.

Technique and outcome of percutaneous endoscopic transgastric jejunostomy for continuous infusion of levodopa-carbidopa intestinal gel for treatment of Parkinson's disease.

Objective: A new method of drug delivery via the small bowel, continuous infusion of levodopa-carbidopa intestinal gel (LCIG), for patients with advanced Parkinson's disease (PD) has been developed and shown to improve patients' quality of life. Levodopa is infused directly and continuously into the proximal jejunum via a percutaneous endoscopic transgastric jejunostomy (PEG-J) tube that is connected to a portable infusion pump. The aim of this study was to evaluate the safety and outcomes of our PEG-J technique performed in advance of LCIG therapy in patients with advanced PD. Material and methods: We reviewed the cases of 37 patients who underwent PEG-J for LCIG therapy at our hospital between November 2016 and May 2018. Pull-through percutaneous endoscopic gastrostomy (PEG) and gastropexy were performed in all patients. The J-tube was inserted through the PEG tube and placed beyond the ligament of Treitz endoscopically under fluoroscopic guidance. After two weeks, the gastropexy sutures were removed. Results: PEG-J with placement of the tube beyond the ligament of Treitz was successful in all 37 patients. Median procedure time was 26.4 min. Median hospital stay after the procedure was 16 days. Median follow-up with the PEG-J tube in place was 11 months. There were five procedure-related complications (13.5%) and 13 device-related complications (35.1%). There was no death related to the procedure. Conclusions: Our PEG-J technique can be performed safely in patients with advanced PD, and favorable outcomes have been achieved to date.

[A Case of Advanced Gastric Cancer with Pathological Complete Response after Chemotherapy(S-1/Cisplatin)].

A 68-year-old female patient presented with advanced gastric cancer and multiple hepatic tumors. Upper GI endoscopy showed a type 3 lesion in the posterior wall of the gastric body. Abdominal computed tomography revealed multiple liver metastases, and staging laparoscopy identified peritoneal dissemination. She was diagnosed with clinical Stage Ⅳ gastric cancer(cT3N2M1H1). She received 3 courses of combined chemotherapy containing S-1 and cisplatin. The therapeutic response was PR. We performed total gastrectomy with D2 lymph node dissection and splenectomy. Histopathological examination revealed no residual cancer cells, indicating pCR. She continued S-1 adjuvant chemotherapy and has remained free from recurrence for 18 months.

Augmented rectangle technique for Billroth I anastomosis in totally laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Billroth I reconstruction is a means of anastomosis that is widely performed after surgical resection for distal gastric cancer. Interest has grown in totally laparoscopic gastrectomy, and several methods for totally laparoscopic performance of Billroth I reconstruction have been reported. However, the methods are cumbersome, and postoperative complications such as twisting at the site of anastomosis and obstruction due to stenosis have arisen. We developed an augmented rectangle technique (ART) by which the anastomosis is created laparoscopically with the use of three automatic endoscopic linear staplers, and the resulting anastomotic opening is wide and less likely to become twisted or stenosed. The technical details of our ART-based Billroth I anastomosis are presented herein along with results of the procedure to date. METHODS: The technique was applied in 160 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer between December 2013 and August 2017. Clinicopathological data, surgical data, and postoperative outcomes were analyzed. RESULTS: During surgery, there were no troubles associated with gastrointestinal reconstruction and there was no transition to laparotomy. There were no postoperative complications, including suture failure and stenosis, associated with the gastrointestinal reconstruction, and the average postoperative hospital stay was 12 days. CONCLUSION: Totally laparoscopic ART-based Billroth I reconstruction is both feasible and safe. We expect this technique to contribute to the spread of safe totally laparoscopic surgery for gastric cancer.

Triple-stapled quadrilateral anastomosis: a new technique for creation of an esophagogastric anastomosis.

BACKGROUND: Esophagogastric anastomosis performed after esophagectomy is technically complex and often the source of postoperative complications. The best technique for this anastomosis remains a matter of debate. We describe a new all-stapled side-to-side anastomosis, which we refer to as triple-stapled quadrilateral anastomosis (TRIQ), that can be performed after minimally invasive surgery, and we report results of a retrospective evaluation of postoperative outcomes among the 60 patients in whom this anastomosis has been performed thus far. METHODS: The anastomosis is created by apposition of the posterior walls of the esophagus and stomach. A linear stapler is applied to create a V-shaped posterior anastomotic wall. The anterior wall is closed in a gentle chevron-like shape with the use of 2 separate linear staplers, resulting in a wide quadrilateral anastomosis. The anastomosis is then wrapped with a greater omentum flap. RESULTS: The patient group comprised 48 men and 12 women with a mean age of 67.8 years. Neoadjuvant chemotherapy was performed in 43 of these patients. Neither the thoracoscopic or laparoscopic procedure was converted to open surgery in any patient. The median operation time was 474 min (range 680-320 min). The intraoperative blood loss volume was 104.4 mL (range 240-30 mL). There were no anastomosis-related complications above Clavien-Dindo grade II. CONCLUSIONS: TRIQ can be performed easily and safely, and good short-term outcome can be expected.

Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study.

BACKGROUND: Adjuvant chemotherapy with XELOX (capecitabine plus oxaliplatin) has been shown to be beneficial following resection of gastric cancer in South Korean, Chinese, and Taiwanese patients. This phase II study (J-CLASSIC-PII) was undertaken to evaluate the feasibility of XELOX in Japanese patients with resected gastric cancer. METHODS: Patients with stage II or III gastric cancer who underwent curative D2 gastrectomy received adjuvant XELOX (eight 3-week cycles of oral capecitabine, 1000 mg/m2 twice daily on days 1-14, plus intravenous oxaliplatin 130 mg/m2 on day 1). The primary endpoint was dose intensity. Secondary endpoints were safety, proportion of patients completing treatment, and 1-year disease-free survival (DFS) rate. RESULTS: One hundred patients were enrolled, 76 of whom completed the study as planned. The mean dose intensity was 67.2 % (95 % CI, 61.9-72.5 %) for capecitabine and 73.4 % (95 % CI, 68.4-78.4 %) for oxaliplatin, which were higher than the predefined age-adjusted threshold values of 63.4 % and 69.4 %, respectively, and the study therefore met its primary endpoint. The 1-year DFS rate was 86 % (95 % CI, 77-91 %). No new safety signals were identified. CONCLUSIONS: The feasibility of adjuvant XELOX in Japanese patients with resected gastric cancer is similar to that observed in South Korean, Chinese, and Taiwanese patients in the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study. Based on findings from this study and the CLASSIC study, the XELOX regimen can be considered an adjuvant treatment option for Japanese gastric cancer patients who have undergone curative resection.

Preoperative Chronic Inflammation Is a Risk Factor for Postoperative Complications Independent of Body Composition in Gastric Cancer Patients Undergoing Radical Gastrectomy.

The purpose of this study was to investigate the association between preoperative inflammation and postoperative complications in gastric cancer patients having elective gastrectomy. Participants in this study were those who underwent radical gastrectomy between April 2008 and June 2018 and were diagnosed with stage I-III primary gastric cancer. Preoperative CRP values were used to divide the patients into two groups: the inflammation group comprised individuals having a CRP level of ≥0.5 mg/dL; the other was the non-inflammation group. The primary outcome was overall complications of Clavien-Dindo grade II or higher after surgery. Using propensity score matching to adjust for background, we compared the postoperative outcomes of the groups and conducted a multivariate analysis to identify risk variables for complications. Of 951 patients, 852 (89.6%) were in the non-inflammation group and 99 (10.4%) were in the inflammation group. After matching, both groups included 99 patients, and no significant differences in patient characteristics were observed between both groups. The inflammation group had a significantly greater total number of postoperative complications (p = 0.019). The multivariate analysis revealed that a preoperative CRP level of ≥0.5 mg/dL was an independent risk factor for total postoperative complications in all patients (odds ratio: 2.310, 95% confidence interval: 1.430-3.730, p < 0.001). In conclusion, in patients undergoing curative resection for gastric cancer, preoperative inflammation has been found to be an independent risk factor for overall complications after surgery. Patients with chronic inflammation require preoperative treatment to reduce inflammation because chronic inflammation is the greatest risk factor for postoperative complications.

Impact of Perioperative Immunonutrition on Postoperative Outcomes in Patients with Upper Gastrointestinal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is no consensus on the efficacy of perioperative immunonutrition in patients with upper gastrointestinal (GI) cancer surgery. We clarified the impact of perioperative immunonutrition on postoperative outcomes in patients with upper GI cancers. We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981-2022 using search terms related to immunonutrition and upper GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy, including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. After screening, 23 studies were included in the qualitative synthesis and in the quantitative synthesis. The meta-analysis showed that immunonutrition reduced infectious complications (relative risk ratio: 0.72; 95% confidence interval: 0.57-0.92; certainty of evidence: Moderate) compared with standard nutritional therapy. In conclusion, nutritional intervention with perioperative immunonutrition in patients with upper GI cancers significantly reduced infectious complications. The effect of immunonutrition for upper GI cancers in reducing the risk of infectious complications was about 30%.

NTRK2 expression in gastrointestinal stromal tumors with a special emphasis on the clinicopathological and prognostic impacts.

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.

Oncologic outcomes of laparoscopy-assisted distal gastrectomy for gastric cancer.

BACKGROUND: In both advanced and early gastric cancer with preoperatively suspected lymph node metastasis, extended lymph node dissection is needed to achieve R0. Since extended lymph node dissection is difficult to perform laparoscopically, few reports have reported long-term outcomes in large numbers of patients. The purpose of this study was to investigate oncologic outcomes after laparoscopy-assisted distal gastrectomy (LADG) with extended lymph node dissection. METHODS: Between April 2004 and March 2010, LADG with extended lymph node dissection was performed at our hospital for 880 patients diagnosed with T1N0-1 or T2N0 (N is classified by Japanese topographic classification) gastric cancer in the lower or middle body of the stomach. D2 lymph node dissection was performed for stage IB (T1N1, T2N0) cancers. Modified D2 lymph node dissection was performed for stage IA (T1N0). Overall survival (OS), disease-free survival (DFS), and form of tumor recurrence at 4 years were investigated retrospectively. RESULTS: Median follow-up was 42 months. The 4-year OS was 98.2 % for all patients. By stage, OS/DFS were 99.0/99.0 % in stage IA patients, 95.9/95.9 % in stage IB, 92.6/92.0 % in stage IIA, and 90.0/92.9 % in stage IIB. A total of 11 patients died, including 4 deaths from recurrence (liver metastasis, n = 1; peritoneal dissemination, n = 2; distant lymph node and bone metastases, n = 1). There is 1 patient is alive with recurrence (liver). Mean time until recurrence was 14 months. CONCLUSIONS: Oncologic outcomes were good in patients with T1N0-1 and T2N0 gastric cancer who underwent LADG with extended lymph node dissection. This approach appears effective for treating T1N0-1 and T2N0 gastric cancer.

A prospective feasibility and safety study of laparoscopy-assisted distal gastrectomy for clinical stage I gastric cancer initiated by surgeons with much experience of open gastrectomy and laparoscopic surgery.

BACKGROUND: The aim of this prospective study was to evaluate the feasibility and safety of laparoscopy-assisted distal gastrectomy (LADG) initiated by surgeons with much experience of open gastrectomy and laparoscopic surgery. METHODS: Three surgeons who each had experience with more than 300 cases of open gastrectomy, more than 100 cases of laparoscopic cholecystectomy, more than 5 cases of laparoscopic colectomy, and more than 5 cases of laparoscopic partial gastrectomy were nominated as LADG operators. All three operators received training for LADG with study materials including videotapes, a box simulator, and an animal laboratory, with lectures and assistance from LADG instructors who each had experience of more than 50 LADG operations. Then the nominated LADG operators performed LADG with the instructors, in which their skills were evaluated and certified. Thereafter, they performed LADG without assistance from the instructors. The target of this study was clinical stage I gastric cancer that was resectable by distal gastrectomy. D1 + alpha, D1 + beta, or D2 dissection was performed laparoscopically. Basically reconstruction was done extracorporeally with a Billroth-I gastroduodenostomy. An extramural review board checked the surgical quality of the operations performed by the three surgeons. The primary endpoint was morbidity and mortality. RESULTS: A total of 193 patients were enrolled in this study between August 2004 and July 2009. The median blood loss was 35 ml and the median operation time was 250 min. Conversion to open surgery was seen in 6 patients; 4 due to bleeding and 2 due to advanced disease. Overall morbidity was 1.6 %, including grade 2 anastomotic leakage in 0.5 % and grade 2 pancreatic fistula in 0.5 %. No mortality was observed. The number of cases required until the LADG operators acted as LADG surgeons without an instructor was 3 for each of the three surgeons. When comparing the data between that in the training period (n = 9) and the operators' data (n = 174), the median operation time was significantly longer in the training period (355 min) than in the latter period (247.5 min) (p = 0.015). Median blood loss was also greater in the training period (150 ml) than the latter period (32.5 ml), but the difference did not reach statistical significance (p = 0.084). During the training period, no patient developed any complications of ≥ grade 2. CONCLUSION: These results suggested that LADG could be initiated and performed feasibly and safely if surgeons with much experience of open gastrectomy and laparoscopic surgery received adequate training for LADG.

A splenic volume increase due to preoperative chemotherapy may impair the long-term outcome after hepatectomy in patients with initially non-optimally resectable colorectal cancer liver metastases.

BACKGROUND/AIMS: In patients with colorectal cancer liver metastases (CRCLM), chemotherapy-associated hepatotoxicity (CAH) has been shown to be associated with splenomegaly. The aim of the present study was to investigate whether a higher splenic volume increase (SVI) after preoperative chemotherapy was associated with a worse long-term outcome after hepatectomy in patients with CRCLM. METHODOLOGY: Between 2007 and 2012, there were 36 patients who received preoperative chemotherapy based on a diagnosis of initially non-optimally resectable synchronous CRCLM. The splenic volume was measured by CT-volumetry before preoperative chemotherapy and 12 weeks after the start of the chemotherapy. Long-term outcome was analyzed in these patients. RESULTS: The overall survival was significantly shorter in the SVI ≥30% group than in the SVI <30% group (3-year survival = 52% vs. 28%, p <0.05). The disease-free survival was also significantly shorter in the SVI ≥30% group than in the SVI <30% group (Median = 11 vs. 6 months, p <0.05). The survival after recurrence was significantly shorter in the SVI ≥30% group than in the SVI <30% group (Median = 12.0 vs. 18 months, p<0.05). CONCLUSIONS: In patients with non-optimally resectable CRCLM, the SVI during the first 12 weeks of preoperative chemotherapy may be a significant predictor of the long-term survival after hepatectomy.

Internal hernia through the foramen of Winslow: the "narrowed portal vein" sign on abdominal CT.

We report a case of ileal internal hernia through the foramen of Winslow into the lesser sac. Preoperative computed tomography (CT) demonstrated that the herniated ileum, which showed a closed-loop obstruction, was located behind the portal vein, and the vein was subsequently compressed and narrowed by the herniated ileum. We found that similar cases in the literature of Winslow's foramen hernias that caused portal vein compression; however, portal vein narrowing has not been described as a characteristic CT finding. The narrowed portal vein sign could be useful in diagnosing the hernia through the foramen of Winslow.

Association of GLIM Defined Malnutrition According to Preoperative Chronic Inflammation with Long-Term Prognosis after Gastrectomy in Patients with Advanced Gastric Cancer.

This study aimed to investigate the association of malnutrition, defined by the Global Leadership Initiative on Malnutrition (GLIM) according to preoperative chronic inflammation with long-term prognosis after gastrectomy in patients with advanced gastric cancer. We included patients with primary stage I-III gastric cancer who underwent gastrectomy between April 2008 and June 2018. Patients were categorized as normal, moderate malnutrition, and severe malnutrition. Preoperative chronic inflammation was defined as a C-reactive protein level of >0.5 mg/dL. The primary endpoint was overall survival (OS), compared between the inflammation and non-inflammation groups. Among the 457 patients, 74 (16.2%) and 383 (83.8%) were included in the inflammation and non-inflammation groups, respectively. The prevalence of malnutrition was similar in both groups (p = 0.208). Multivariate analyses for OS showed that moderate malnutrition (hazard ratios: 1.749, 95% concordance interval: 1.037-2.949, p = 0.036) and severe malnutrition (hazard ratios: 1.971, 95% CI: 1.130-3.439, p = 0.017) were poor prognostic factors in the non-inflammation group, but malnutrition was not a prognostic factor in the inflammation group. In conclusion, preoperative malnutrition was a poor prognostic factor in patients without inflammation, but it was not a prognostic factor in patients with inflammation.

Impact of Sex-Specific Preoperative Fat Mass Assessment on Long-Term Prognosis after Gastrectomy for Gastric Cancer.

We investigated the impact of the difference in fat distribution between men and women on long-term prognosis after gastrectomy in patients with advanced gastric cancer. Patients with advanced gastric cancer deeper than p-T2 who underwent gastrectomy between April 2008 and June 2018 were included. Visceral fat mass index (VFI) and subcutaneous fat mass index (SFI) were calculated by dividing the cross-sectional area at the umbilical level by the height squared. The medians of VFI and SFI by sex were defined as cut-off values, below which values were defined as low VFI and low SFI. Of the 485 patients, 323 (66.6%) were men and 162 (33.4%) were women. Men with a low VFI had a significantly worse overall survival (OS) (p = 0.004) and women with a low SFI had a significantly worse OS (p = 0.007). Patients with a low VFI and low SFI had the worst prognosis. Multivariate analysis showed that a low VFI was an independent poor prognostic factor in men, while a low SFI was an independent poor prognostic factor in women. In conclusion, a low visceral fat mass in men and a low subcutaneous fat mass in women were independent poor prognostic factors after radical gastrectomy for advanced gastric cancer.

Current status of the association between malnutrition defined by the GLIM criteria and postoperative outcomes in gastrointestinal surgery for cancer: a narrative review.

In 2018, the Global Leadership Initiative on Malnutrition consortium published global consensus diagnostic criteria for malnutrition and highlighted the association between malnutrition and poor postoperative outcomes in patients with gastrointestinal cancer. The aforementioned criteria consist of phenotypic and etiologic criteria to diagnose malnutrition in individuals who undergo conventional screening to determine the at-risk population. Recent studies have reported the usefulness of prediction of postoperative outcomes using body mass index, weight loss, and reduced muscle mass as phenotypic criteria. Reduced muscle mass is an essential diagnostic criterion for sarcopenia, which is associated with poor outcomes in patients with cancer. The Global Leadership Initiative on Malnutrition criteria define reduced muscle mass as undernutrition. Malnutrition diagnosed based on the Global Leadership Initiative on Malnutrition criteria is an important risk factor for postoperative complications and also an independent poor prognostic factor for long-term outcomes; greater severity of malnutrition is associated with poorer outcomes. The current Global Leadership Initiative on Malnutrition criteria for malnutrition accurately predict outcomes, including postoperative complications and long-term prognosis; however, a revision may be warranted to ensure consistency with the diagnostic criteria for sarcopenia. Patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition criteria should be targeted for nutritional intervention. Further accumulation of evidence is necessary to conclusively establish the role of nutritional interventions in patients with malnutrition to improve postoperative complications and long-term outcomes.

Impact of malnutrition as defined by the GLIM criteria on treatment outcomes in patients with cancer: A systematic review and meta-analysis.

BACKGROUND & AIMS: Malnutrition has been reported to lead to poor postoperative outcomes. The Global Leadership Initiative on Malnutrition (GLIM) criteria were published in 2019 as a global consensus on the criteria for diagnosing malnutrition. However, the relationship between GLIM-defined malnutrition and treatment outcomes in patients with cancer has not been fully investigated. Therefore, this study aimed to clarify the impact of GLIM-defined malnutrition on the treatment outcomes of patients with cancer. METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the World Health Organization International Clinical Trials Platform Search Portal, and ClinicalTrials.gov and identified observational studies published from inception to January 17, 2022. We conducted a systematic review and random-effects meta-analysis studies that included patients with cancer aged >18 years who received any kind of treatment and whose nutritional status was assessed using GLIM criteria. We independently assessed the risk of bias and quality of evidence using Quality In Prognosis Studies and Grading of Recommendations, Assessment, Development, and Evaluation approach. The primary outcomes were overall survival (OS) and postoperative complications. Hazard ratios and 95% confidence intervals (CIs) for OS and relative risk ratios and 95% CIs for postoperative complications were pooled. The protocol was published by PROSPERO (CRD42022304004). RESULTS: Of 67 studies after screening, ten studies (n = 11,700) reported the impact of GLIM-defined malnutrition on postoperative outcomes. Compared with no malnutrition, GLIM-defined malnutrition may worsen OS (hazard ratio, 1.56; 95% CI, 1.38-1.75; I2 = 37%) and increase postoperative complications (relative risk ratio, 1.82; 95% CI, 1.28-2.60; I2 = 87%). The risk of bias in each study was either moderate or high. The certainty of the evidence was low because of publication bias and a moderate or high risk of bias. CONCLUSIONS: GLIM-defined malnutrition may worsen OS and increase the risk of postoperative complications in patients with cancer undergoing treatment. Further studies are needed to confirm these findings and mitigate this risk.