Small noncoding RNAs and sperm nuclear basic proteins reflect the environmental impact on germ cells.

BACKGROUND: Molecular techniques can complement conventional spermiogram analyses to provide new information on the fertilizing potential of spermatozoa and to identify early alterations due to environmental pollution. METHODS: Here, we present a multilevel molecular profiling by small RNA sequencing and sperm nuclear basic protein analysis of male germ cells from 33 healthy young subjects residing in low and high-polluted areas. RESULTS: Although sperm motility and sperm concentration were comparable between samples from the two sites, those from the high-pollution area had a higher concentration of immature/immune cells, a lower protamine/histone ratio, a reduced ability of sperm nuclear basic proteins to protect DNA from oxidative damage, and an altered copper/zinc ratio in sperm. Sperm levels of 32 microRNAs involved in intraflagellar transport, oxidative stress response, and spermatogenesis were different between the two areas. In parallel, a decrease of Piwi-interacting RNA levels was observed in samples from the high-polluted area. CONCLUSIONS: This comprehensive analysis provides new insights into pollution-driven epigenetic alterations in sperm not detectable by spermiogram.

Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.

BACKGROUND: Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy. STUDY DESIGN: Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared. RESULTS: A total of 1469 patients were selected for inclusion in the study. After 1:1 propensity score matching, a total of 580 patients were matched and included in the final analysis, 290 in each group, RG vs OG. RG had longer operation time (210 vs 330 min, p < 0.0001), reduced intraoperative blood loss (155 vs 119.7 ml, p < 0.0001), time to liquid diet (4.4 vs 3 days, p < 0.0001) and to peristalsis (2.4 vs 2 days, p < 0.0001), and length of postoperative stay (11 vs 8 days, p < 0.0001). Morbidity rate was higher in OG (24.1% vs 16.2%, p = 0.017). CONCLUSION: RG significantly expedites recovery and reduces the risk of complications compared to OG. However, long-term survival is similar.

Impacts of Environmental Pollution on Brain Tumorigenesis.

Pollutants consist of several components, known as direct or indirect mutagens, that can be associated with the risk of tumorigenesis. The increased incidence of brain tumors, observed more frequently in industrialized countries, has generated a deeper interest in examining different pollutants that could be found in food, air, or water supply. These compounds, due to their chemical nature, alter the activity of biological molecules naturally found in the body. The bioaccumulation leads to harmful effects for humans, increasing the risk of the onset of several pathologies, including cancer. Environmental components often combine with other risk factors, such as the individual genetic component, which increases the chance of developing cancer. The objective of this review is to discuss the impact of environmental carcinogens on modulating the risk of brain tumorigenesis, focusing our attention on certain categories of pollutants and their sources.

Impact of Hydrophobic Chains in Five-Coordinate Glucoconjugate Pt(II) Anticancer Agents.

This study describes new platinum(II) cationic five-coordinate complexes (1-R,R') of the formula [PtR(NHC)(dmphen)(ethene)]CF3SO3 (dmphen = 2,9-dimethyl-1,10-phenanthroline), containing in their axial positions an alkyl group R (methyl or octyl) and an imidazole-based NHC-carbene ligand with a substituent R' of variable length (methyl or octyl) on one nitrogen atom. The Pt-carbene bond is stable both in DMSO and in aqueous solvents. In DMSO, a gradual substitution of dmphen and ethene is observed, with the formation of a square planar solvated species. Octanol/water partitioning studies have revealed the order of hydrophobicity of the complexes (1-Oct,Me > 1-Oct,Oct > 1-Me,Oct > 1-Me,Me). Their biological activity was investigated against two pairs of cancer and non-cancer cell lines. The tested drugs were internalized in cancer cells and able to activate the apoptotic pathway. The reactivity of 1-Me,Me with DNA and protein model systems was also studied using UV-vis absorption spectroscopy, fluorescence, and X-ray crystallography. The compound binds DNA and interacts in various ways with the model protein lysozyme. Remarkably, structural data revealed that the complex can bind lysozyme via non-covalent interactions, retaining its five-coordinate geometry.

Robotic Treatment for Large Duodenal Gastrointestinal Stromal Tumor.

BACKGROUND: Duodenal gastrointestinal stromal tumors (D-GISTs) represent a rare entity.1 Surgery is the primary treatment choice for localized or potentially resectable D-GISTs. The main principle is the complete excision of the lesion with microscopically negative margins, without performing lymph node dissection.2 Nevertheless, the best surgical choice is still controversial since the strategy depends not only on the tumor size but also on its anatomic location.3,4 As a result, surgical management ranges from a major resection such as pancreaticoduodenectomy to more conservative procedures.5-8 This video presents a duodenal sparing robotic resection of a large GIST of the second-third duodenal portion. METHODS: A 49-year-old healthy female complained episodes of melena. Endoscopy with endoscopic ultrasound identified a 6-cm lesion of the second-third portion of the duodenum with recent bleeding, arising from muscolaris propria. A computed tomography scan confirmed a large mass suspected to be a GIST without metastases or involvement of the ampulla of Vater. On the basis of these findings, after a multidisciplinary consultation, she was offered robotic surgery with a radical intent. RESULTS: A duodenal-sparing da Vinci®Si™ resection with robot-sewn primary duodenal closure was performed. After an uneventful postoperative course, the patient was discharged on post-operative day 7. Final pathology revealed a high-grade risk D-GIST with free margins: adjuvant Imatinib was recommended.9 At 4 years follow-up, no recurrence has been detected. CONCLUSIONS: A robotic approach might be considered in cases of large D-GISTs amenable to a conservative R0 surgery. This system provides several technical advantages that facilitate otherwise complex resection and reconstruction.10.

Correction to: Robotic Versus Laparoscopic Right Colectomy with Complete Mesocolic Excision for the Treatment of Colon Cancer: Perioperative Outcomes and 5-Year Survival in a Consecutive Series of 202 Patients.

Dario Ribero's affiliation is corrected as reflected here.

Robotic Versus Laparoscopic Right Colectomy with Complete Mesocolic Excision for the Treatment of Colon Cancer: Perioperative Outcomes and 5-Year Survival in a Consecutive Series of 202 Patients.

BACKGROUND: During the past decade, the concept of complete mesocolic excision (CME) has emerged as a possible strategy to minimize recurrence for right colon cancers. The purpose of this study was to compare robotic versus laparoscopic CME in performing right colectomy for cancer. METHODS: Pertinent data of all patients who underwent robotic or laparoscopic right colectomy with CME using a Pfannenstiel incision and intracorporeal anastomosis performed between October 2005 and November 2015 were entered in a prospectively maintained database. RESULTS: A total of 202 patients underwent robotic (n = 101) or laparoscopic (n = 101) right colectomy within the study period. Patient characteristics were equivalent between groups. The robotic group showed a statistically significant reduction in conversion rate (0% vs. 6.9%, p = 0.01) but a longer operative time (279 min vs. 236 min, p < 0.001) compared with the laparoscopic group. There were no other differences in perioperative clinical or pathological outcomes. Five-years overall survival was 77 versus 73 months for the robotic versus laparoscopic groups (p = 0.64). The disease-free survival (DFS) rates were 85% and 83% for the robotic versus laparoscopic groups (p = 0.58). Among UICC stage III patients, there was a slight but not significant difference in 5-year DFS for the robotic group (81 vs. 68 months; p = 0.122). CONCLUSIONS: Both approaches for right colectomy with CME were safe and feasible and resulted in excellent survival. Robotic assistance was beneficial for performing intracorporeal anastomosis and dissection as evidenced by the lower conversion rates. Further robotic experience may shorten the operative time.

Robotic Right Colectomy with Modified Complete Mesocolic Excision: Long-Term Oncologic Outcomes.

BACKGROUND: A modified complete mesocolic excision (mCME) technique for the treatment of right-sided colon cancer recently was shown by Hohenberger and colleagues to provide impressive long-term oncologic outcomes. This report aims to describe the authors' experience with robotic right colectomy using mCME. The safety, feasibility, and efficacy of this procedure are measured by complications, conversion rates, and 4-year oncologic outcomes. METHODS: A retrospective study analyzed 100 consecutive patients who underwent robotic right colectomy with mCME and intracorporeal anastomosis at the authors' institution between November 2005 and November 2013. Intra- and postoperative clinical outcomes, pathologic data, and survival were analyzed. RESULTS: Robotic right colectomy with mCME was successfully performed for all the patients. No conversions or intraoperative complications occurred. The major complication rate (Dindo 3 or 4) was 4 %. During a median follow-up period of 48.5 months (range 24-114 months), the survival rates were 94.5 % for disease-specific survival, 91.4 % for disease-free survival, and 90.3 % for overall survival. CONCLUSIONS: The authors' experience confirms the feasibility and safety of mCME for the treatment of right-sided colon cancer. This technique provided satisfying short-term outcomes with promising 4-year oncologic results. However, the real benefits of the CME technique should be evaluated further by well-conducted randomized studies before its adoption in routine practice is recommended.

Molecular and toxicological mechanisms behind the effects of chromium (VI) on the male reproductive system of Mytilus galloprovincialis: First evidence for poly-ADP-ribosylation of protamine-like II.

Studies on the molecular mechanisms of heavy metal toxicity in invertebrate reproduction are limited. Given that PARP-catalysed ADP-ribosylation is also involved in counteracting heavy metal toxicity and maintaining genomic integrity, and that PARylation is implicated in chromatin remodelling but its role in sperm chromatin remains to be elucidated, we investigated the effects of chromium(VI) at 1, 10 and 100 nM on the reproductive health of Mytilus galloprovincialis. The damage to the gonads was assessed by morphological analyses and the damage indices PARP and É£H2A.X were measured. Changes in the binding of protamine-like (PL) to DNA and the possibility of poly(ADP-ribosyl)ation of PL proteins were also investigated. Gonadal chromium accumulation and morphological damage were found, especially when the mussels were exposed to the highest dose of chromium(VI). In addition, the maximum expression of gonadal É£H2A.X and PARP were obtained at 100 and 10 nM Cr(VI), respectively. Interestingly, for the first time in all exposed conditions, poly(ADP)-ribosylation was detected on PL-II, which, together with PL-III and PL-IV, are the major nuclear basic proteins of Mytilus galloprovincialis sperm chromatin. Since PL-II is involved in the final high level of sperm chromatin compaction, this post-translational modification altered the binding of the PL protein to DNA, favouring the action of micrococcal nuclease on sperm chromatin. This study provides new insights into the effects of chromium(VI) on Mytilus galloprovincialis reproductive system and proposes a molecular mechanism hypothesis describing the toxic effects of this metal on PL-DNA binding, sperm chromatin and gonads.

Application of fluorescence in robotic general surgery: review of the literature and state of the art.

The initial use of the indocyanine green fluorescence imaging system was for sentinel lymph node biopsy in patients with breast or colorectal cancer. Since then, application of this method has received wide acceptance in various fields of surgical oncology, and it has become a valid diagnostic tool for guiding cancer treatment. It has also been employed in numerous conventional surgical procedures with much success and benefit to the patient. The advent of minimally invasive surgery brought with it a new use for fluorescence in helping to improve the safety of these procedures, particularly for single-site procedures. In 2010, a near-infrared camera was integrated into the da Vinci Si System, creating a combination of technical and minimally invasive advantages that have been embraced by several experienced surgeons. The use of fluorescence, although useful, is considered challenging. Only a few studies are currently available on the use of fluorescence in robotic general surgery, whereas many articles have focused on its application in open and laparoscopic surgery. Many of these reports describe promising and satisfactory results, although with some shortcomings. The purpose of this article is to review the current status of the use of fluorescence in general surgery and particularly its role in robotic surgery. We also review potential uses in the future.

Robot-assisted esophagectomy with robot-sewn intrathoracic anastomosis (Ivor Lewis): surgical technique and early results.

Esophagectomy is the selected treatment for nonmetastatic esophageal and esophagogastric junction cancer, although high perioperative morbidity and mortality incur. Robot-assisted minimally invasive esophagectomy (RAMIE) effectively reduces cardiopulmonary complications compared to open esophagectomy and offers a technical advantage, especially for lymph node dissection and intrathoracic anastomosis. This article aims at describing our initial experience of Ivor Lewis RAMIE, focusing on the technique's main steps and robotic-sewn esophagogastrostomy. Prospectively collected data from all consecutive patients who underwent Ivor Lewis RAMIE for cancer was reviewed. Reconstruction was performed with a gastric conduit pull-up and a robotic-sewn intrathoracic anastomosis. Intraoperative and postoperative complications were recorded as prescribed by the Esophagectomy Complications Consensus Group (ECCG). Thirty patients underwent Ivor Lewis RAMIE with complete mediastinal lymph node dissection and robot-sewn anastomosis. No intraoperative complications nor conversion occurred. Pulmonary complications totaled 26.7%. Anastomotic leakage (ECCG, type III) and conduit necrosis (ECCG, type III) both occurred in one patient (3.3%). Chylothorax appeared in 2 patients (6.7%) (ECCG, Type IIA). Anastomotic stricture, successfully treated with endoscopic dilatations, occurred in 8 cases (26.7%). Median overall postoperative stay was 11 days (range, 6-51 days). 30 day and 90 day mortality was 0%. R0 resection was performed in 96.7% of patients with a median number of 47 retrieved lymph nodes. RAMIE with robot-sewn intrathoracic anastomosis appears to be feasible, safe and effective, with favorable perioperative results. Nevertheless, further high-quality studies are needed to define the best anastomotic technique for Ivor Lewis RAMIE.

The MIS-COVID-AGICT Study: Trend of Minimally Invasive Surgery for Gastrointestinal Cancer Treatment During the First Waves of the COVID-19 Pandemic in Italy. Subgroup Analysis from the COVID-AGICT Study: COVID-19 and Advanced Gastrointestinal Cancer Surgical Treatment.

Background: A preliminary analysis from the COVID-Advanced Gastrointestinal Cancer Surgical Treatment (AGICT) study showed that the rate of minimally invasive surgery (MIS) for elective and urgent procedures did not decrease during the pandemic year. In this article, we aimed to perform a subgroup analysis using data from the COVID-AGICT study to evaluate the trend of MIS during the COVID-19 pandemic period in Italy. Methods: This study was conducted collecting data of MIS patients from the COVID-AGICT database. The primary endpoint was to demonstrate whether the SARS-CoV-2 pandemic scenario reduced MIS for elective treatment of gastrointestinal cancer (GIC) in Italy in 2020. The secondary endpoint was to evaluate the impact of the pandemic period on perioperative outcomes in the MIS group. Results: In the pandemic year, 62% of patients underwent surgery with a minimally invasive approach, compared to 63% in 2019 (P = .23). In 2020, the proportion of patients undergoing elective MIS decreased compared to the previous year (80% versus 82%, P = .04), and the rate of urgent MIS did not differ between the 2 years (31% and 33% in 2019 and 2020 - P = .66). Colorectal cancer was less likely to be treated with MIS approach during 2020 (78% versus 75%, P < .001). Conversely, the rate of MIS pancreatic resection was higher in 2020 (28% versus 22%, P < .002). Conversion to an open approach was lower in 2020 (7.2% versus 9.2% - P = .01). Major postoperative complications were similar in both years (11% versus 11%, P = .9). Conclusion: In conclusion, although MIS for elective treatment of GIC in Italy was reduced during the COVID-19 pandemic period, our study revealed that the overall proportion of MIS (elective and urgent) and postoperative outcomes were comparable to the prepandemic period. ClinicalTrial.gov (NCT04686747).

The COVID - AGICT study: COVID-19 and advanced gastro-intestinal cancer surgical treatment. A multicentric Italian study on the SARS-CoV-2 pandemic impact on gastro-intestinal cancers surgical treatment during the 2020. Analysis of perioperative and short-term oncological outcomes.

BACKGROUND: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic. METHOD: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined. RESULTS: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001). CONCLUSIONS: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.

Laparoscopic versus open colorectal resections in patients with symptomatic stage IV colorectal cancer.

BACKGROUND: The purpose of this study was to evaluate short-term and oncologic outcomes of laparoscopic resection (LR) for patients with symptomatic stage IV colorectal cancer compared with open resection (OR). METHODS: This study is a retrospective analysis of a prospective database. Patients with a minimum follow-up of 12 months after LR or OR for metastatic colorectal cancer were included. All analyses were performed on an "intention-to-treat" basis. RESULTS: A total of 162 consecutive patients submitted to LR and 127 submitted to OR were included. In the LR group, conversion rate was 26.5 %, mostly due to locally advanced disease (88.4 %). A greater risk of conversion was observed among patients with a tumor size greater than 5 cm regardless the tumor site (P = 0.07). Early postoperative outcome was significantly better for LR group, with a shorter hospital stay (P = 0.008), earlier onset of adjuvant treatment, and similar postoperative complications (P = 0.853) and mortality rates (P = 0.958). LR for rectal cancer was associated with a higher morbidity compared with colon cancer (P = 0.058). During a median follow-up time of 72 months, there was no significant difference in overall survival between the two groups (P = 0.622). CONCLUSIONS: LR for symptomatic metastatic CRC is safe and, compared with OR, is associated with a shorter hospital stay and with similar survival rates. Concerns remain about LR of bulky tumors and rectal cancers due to the increased risk of conversion and postoperative complications.

Abdominal wall endometriosis misdiagnosed as a desmoid tumor: A case report.

INTRODUCTION: Abdominal wall masses have different aetiologies. Diagnosis includes desmoid tumors (DTs) and other benign and malignant lesions, among which abdominal wall endometriosis (AWE). Diagnosis is challenging if symptoms are aspecific, and the contribution of imaging may be weak. We present a case of AWE that according to clinical history and imaging was misdiagnosed as DT. PRESENTATION OF CASE: A healthy 35-year-old female presented, 4 years after a cesarean delivery, a rapidly growing painless subumbilical mass within the right rectus abdominis muscle. Ultrasound and magnetic resonance imaging suspected a DT. The patient underwent complete resection of the mass and pathological examination revealed foci of endometriosis in the muscle. Patient's post-operative course was uneventful and at 18-month follow-up, no recurrence has been detected. DISCUSSION: The current case highlights differences in clinical presentation and imaging in case of AWE and DTs, underlining possible pitfalls in diagnosis. In young women with previous gynaecological abdominal surgery, AWE is the most likely disease when a mass in the region of the scar appears. Differential diagnosis is complex and rare entities like DTs should nevertheless be taken into consideration. A complete surgical resection with negative margins is considered the primary treatment for AWE and for selected DTs. Final pathology of the tumor can state the precise diagnosis. CONCLUSION: Since AWE and DTs share similar clinical signs and aspecific imaging exams, both diseases should be considered in case of abdominal wall mass in female patients of childbearing age and history of uterine-related surgery.

Robotic Intraoperative Tracheobronchial Repair during Minimally Invasive 3-Stage Esophagectomy.

Tracheobronchial injury (TBI) is an uncommon but potentially fatal event. Iatrogenic lesions during bronchoscopy, endotracheal intubation, or thoracic surgery are considered the most common causes of TBI. When TBI is detected during surgery, concomitant surgical treatment is recommended. Herein we present a case of successful robotic primary repair of iatrogenic tracheal and left bronchial branch tears during a robot-assisted hybrid 3-stage esophagectomy after neoadjuvant chemoradiotherapy. A robotic approach can facilitate the repair of this injury while reducing both the potential risk of conversion to open surgery and the associated increased risk of postoperative respiratory complications.

Robotic versus laparoscopic right colectomy within a systematic ERAS protocol: a propensity-weighted analysis.

The purpose of this study is to compare the early postoperative and pathological outcomes of robotic right colectomy (RRC) to those of laparoscopic right colectomy (LRC) with intracorporeal anastomosis (IA) within the systematic application of an enhanced recovery after surgery (ERAS) program. A single-institution prospective database of patients who underwent elective RRC or LRC with IA for neoplastic lesions between April 2010 and June 2018 was retrospectively reviewed. The patients' demographic characteristics, and perioperative and pathological outcomes were analyzed. Propensity-weighted analysis was employed to address potential selection biases of treatment allocation. A total of 216 patients (46 RRC, 170 LRC) were included. RRC demonstrated a significantly longer operative time (mean 242.43 min, SD 47.51) compared to LRC (mean 187.60 min, SD 56.60) (p = 0.001), confirmed by the propensity-weighted analysis (Coefficient 50.65; p < 0.001). Conversion rate between the two groups was comparable (p = 0.99). Median length of hospital stay (LOS) was the same in the RRC and the LRC group (4 days, p = 0.35). Readmission rate within 30 days in the RRC and LRC group was 2.2% and 2.4%, respectively (p = 0.99). Overall 30-day morbidity and 30-day mortality was 32.6% versus 27.1% (p = 0.46), and 0% versus 1.2% (p = 0.99) in the robotic and laparoscopic groups, respectively. No difference was found in the number of harvested lymph nodes (p = 0.75). In an ERAS environment, without the bias of mixed techniques of anastomosis, RRC had similar postoperative and pathological outcomes compared to the laparoscopic approach, but was associated with a longer operative time.

Robotic Wedge Resection for Unfavorably Located Gastric Gastrointestinal Stromal Tumors: Perioperative and Long-Term Oncological Outcomes.

Background and Objectives: Robotic wedge resection for gastrointestinal stromal tumors (GISTs) located in the stomach offers remarkable advantages, especially for lesions in unfavorable places. Although promising, long-term oncological results associated with this surgical procedure are poorly represented in literature. We present our experience of robotic wedge resection with gastrotomy for challenging gastric GISTs, in terms of both surgical outcomes and long-term oncological results. Methods: From April 2014 to February 2020, all consecutive patients affected by unfavorably located gastric GISTs (based on the Privette/Al-Thani classification system) underwent robotic wedge resection. Clinicopathological, surgical, and long-term oncological results were retrospectively analyzed. Results: Seventeen patients underwent full-thickness gastric wedge resection with primary robot-sewn closure of the defect. In 64.7% of cases, the lesion was ≥5 cm in diameter. No conversion nor tumor rupture were recorded and complete R0 resection was achieved in all cases. Median hospital stay was 5 days (range 3-18). At a median follow-up of 46 months (range 7-67), the disease-free survival rate and the overall survival rate were 94.1% and 82.3%, respectively. Conclusions: Robotic wedge resection with gastrotomy and robotic-sewn suture is a safe and feasible procedure for GISTs located in unfavorable anatomic positions, without compromising oncological outcomes.

Body composition parameters predict pathological response and outcomes in locally advanced gastric cancer after neoadjuvant treatment: A multicenter, international study.

BACKGROUND: Body composition profiles influence the prognosis of several types of cancer; however, the role of body composition in patients with locally advanced gastric cancer (LAGC) after neoadjuvant treatment (NT) has not been well characterized. PATIENTS AND METHODS: A total of 213 patients with LAGC who underwent gastrectomy after NT at a high-volume institution from southern China were comprehensively evaluated for primary analysis. Additionally, 170 and 77 patients from Western China and Italy, respectively, were reviewed for external validation. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and the subcutaneous as well as the visceral adiposity index were assessed from clinically acquired CT scans at diagnosis and preoperatively. RESULTS: Overall, none of the body composition parameters significantly changed after NT. The pre-NT skeletal muscle radiodensity (SMD) and change in SMI (ΔSMI) were both significantly lower in the patients with poor response (tumor regression <50%; mean SMD: 43.5 vs 46.5, P = 0.003; mean ΔSMI: -1.0 vs 2.2, P < 0.001), and the cutoff values were calculated according to the Youden index as 43.7 and 1.2, respectively. Based on these 2 parameters, a novel model, the Skeletal Muscle Score (SMS), was proposed to predict the pathological response (AUC = 0.764 alone and = 0.822 in combination with the radiological response). Moreover, patients with an SMI loss >1.2 had a significantly prolonged drainage tube removal time (mean: 10.0 vs 8.2, P = 0.003) and postoperative hospital stay (mean: 11.1 vs 9.8, P = 0.048), as well as a significantly higher rate of postoperative complications (30.9% vs 16.7%, P = 0.015). In the multivariate analysis, SMI loss >1.2 independently predicted poor overall survival (HR: 1.677, 95% CI 1.040-2.704, P = 0.034) and recurrence-free survival (HR: 1.924, 95% CI 1.165-3.175, P = 0.011). ΔSMI was also significantly associated with pathological response, surgical outcomes, and survival in the 2 external cohorts (P all < 0.05). CONCLUSIONS: For LAGC, the pre-NT SMD and ΔSMI could accurately predict the pathological response after NT. An SMI loss >1.2 is closely associated with poorer outcomes and may indicate the need more supportive treatment.