Metformin suppresses esophageal cancer progression through the radiation­induced cellular senescence of cancer­associated fibroblasts.

Senescent cells are known to secrete proteins, including inflammatory cytokines and damage­associated molecular patterns. This phenomenon is known as the senescence­associated secretory phenotype (SASP). SASP in cancer stromal fibroblasts is involved in cancer growth and progression. Conversely, metformin, an antidiabetic drug, has been reported to inhibit SASP induction by inhibiting the activation of NF­κB, a regulator of SASP. To date, at least to the best of our knowledge, there have been no reports regarding cellular senescence in fibroblasts and tumor progression via the SASP­mediated paracrine pathway. The present study thus aimed to elucidate the induction mechanisms of SASP in radiation­induced fibroblasts and to determine its effects on cancer progression via the paracrine pathway. Furthermore, the present study aimed to determine whether controlling SASP using metformin suppresses cancer progression. A well­differentiated esophageal cancer cell line established by the authors' department and fibroblasts isolated and cultured from the non­cancerous esophageal mucosa of resected esophageal cancer cases were used for the experiments. Fibroblasts were irradiated with 8 Gy radiation, and the changes in the expression of the senescence markers, SA­ß­gal, p21, p16 and NF­κB were evaluated using immunofluorescent staining and western blot analysis in the presence or absence of metformin treatment. The culture supernatants of irradiated fibroblasts treated with metformin and those treated without metformin were collected and added to the cancer cells to evaluate their proliferative, invasive and migratory abilities. Vimentin and E­cadherin expression levels were also evaluated using immunofluorescent staining and western blot analysis. The expression levels of p16, p21 and NF­κB in irradiated fibroblasts were attenuated by treatment with metformin. Supernatants collected from irradiated fibroblasts exhibited the proliferative activity of esophageal cancer cells, and the promotion of migratory and invasion abilities, which may be due to epithelial­mesenchymal transition and changes in cell morphology. These reactions were confirmed to be suppressed by the addition of the supernatant of cultured fibroblasts pre­treated with metformin. On the whole, the present study demonstrates that fibroblasts in the cancer stroma may be involved in tumor progression through cellular senescence.

Noninferiority of additional gastrectomy after endoscopic submucosal dissection compared with surgery alone on long-term prognosis: a propensity score matching analysis.

BACKGROUND: Patients in whom endoscopic submucosal dissection (ESD) has resulted in noncurative resection need further surgical treatment. However, the oncologic outcome of additional gastrectomy after ESD compared with surgery alone remains unclear. METHODS: The clinical data of 778 patients who underwent gastrectomy for early gastric cancer (EGC) from January 2008 to December 2019 in Ishikawa Prefectural Central Hospital were retrospectively analyzed. Of these 778 patients, 187 underwent additional gastrectomy after ESD [ESD (+) group] and 591 underwent surgery alone [ESD (-) group]. We compared the overall survival and disease-free survival between the ESD (+) and ESD (-) groups, using propensity score matching (PSM) to adjust for baseline characteristics. We also assessed early postoperative outcomes. RESULTS: After PSM based on sex (male or female), age, tumor diameter, tumor gross type, and operative procedure, each group comprised 144 patients with no significant differences in clinical background characteristics. After matching, the 5-year overall survival rate in the ESD (+) and ESD (-) group was 90.9% and 87.8%, respectively, with no significant difference (P = .470). In addition, there was no significant difference in the disease-free survival rate (97.6% vs 95.8%, respectively; P = .504). The postoperative complication rate was similar in both groups. CONCLUSION: Additional gastrectomy for patients in whom ESD resulted in noncurative resection did not adversely affect the long-term prognosis. Additional gastrectomy after ESD is oncologically acceptable for EGC.

Usefulness of Perioperative Nutritional Therapy with the Glutamine/Arginine/Calcium ß-Hydroxy-ß-Methylbutyrate Product in Esophageal Cancer Surgery: A Single-Center Retrospective Study.

A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino-acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium ß-hydroxy-ß-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥ III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight were significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p < 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino-acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

Neutral selection and clonal expansion during the development of colon cancer metastasis.

Intratumor heterogeneity has been shown to play a role in the malignant progression of cancer. Although clonal evolution in primary cancer has been well studied, that in metastatic tumorigenesis is not fully understood. In this study, we established human colon cancer-derived organoids and investigated clonal dynamics during liver metastasis development by tracking barcode-labelled subclones. Long-term subclone co-cultures showed clonal drift, with a single subclone becoming dominant in the cell population. Interestingly, the selected subclones were not always the same, suggesting that clonal selection was not based on cell intrinsic properties. Furthermore, liver tumors developed by co-transplantation of organoid subclones into the immunodeficient mouse spleen showed a progressive drastic reduction in clonal diversity, and only one or two subclones predominated in the majority of large metastatic tumors. Importantly, selections were not limited to particular subclones but appeared to be random. A trend towards a reduction in clonal diversity was also found in liver metastases of multiple color-labeled organoids of mouse intestinal tumors. Based on these results, we propose a novel mechanism of metastasis development, i.e. a subclone population of the disseminated tumor cells in the liver is selected by neutral selection during colonization and constitutes large metastatic tumors.

Initial 12 Cases of Robot-Assisted Gastrectomy for Gastric Cancer Using the Hinotori Surgical Robot System: Tips for the Efficient Introduction of a New Surgical Robot.

Introduction: The use of robotic platform for gastrectomy for gastric cancer is rapidly increasing. This study aimed to describe the perioperative outcomes of 12 patients who underwent robotic gastrectomy for gastric cancer using the hinotori™ surgical robot system (hinotori), a novel robot-assisted surgical platform, and compare the outcomes with the existing system, the da Vinci® Surgical System (DVSS). Methods: This study included 12 consecutive patients with gastric cancer who underwent robotic gastrectomy for gastric cancer using the hinotori between March 2023 and September 2023 at our institution. The comprehensive perioperative outcomes of these patients were retrospectively analyzed and compared to 11 patients who underwent robotic gastrectomy using the DVSS during the same period. Results: The median age and body mass index were 71 years (range: 56-86) and 22.7 kg/m2 (range: 16.1-26.7). Distal and total gastrectomy were performed in 8 and 4 patients, respectively. The median console time and operation times were 187 (range: 112-270) and 252 minutes (range: 173-339), respectively. The median blood loss was 3 mL (range: 2-5). No intra- or postoperative complications were observed. There were no significant differences in perioperative outcomes between the hinotori and the DVSS. Conclusions: Robotic gastrectomy for gastric cancer using the hinotori is a feasible procedure and achieved perioperative outcomes similar to that using the DVSS. Clinical Trial Registration number: 114167-1.

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%.

[Three Cases of Preoperative Chemotherapy(FOLFOXIRI plus Bevacizumab)for Locally Advanced Colorectal Cancer with Urinary Bladder Invasion].

Radical cystectomy for locally advanced colorectal cancer with urinary bladder invasion significantly reduces the quality of life in exchange for a cure. We performed preoperative chemotherapy with FOLFOXIRI plus bevacizumab for 3 patients with locally advanced colorectal cancer with urinary bladder invasion to avoid radical cystectomy and to achieve local control for urinary bladder preservation. Grade 3 neutropenia was observed in 2 patients as an adverse reaction to the preoperative chemotherapy, but all 3 patients showed good tumor regression. All 3 patients underwent laparoscopic high anterior rectal resection and partial cystectomy, and all were able to undergo R0 resections with urinary bladder preservation. One patient had anastomotic leakage as a postoperative complication. One patient had local recurrence in the urinary bladder, and 2 had recurrence with peritoneal dissemination during their postoperative courses. Preoperative chemotherapy(FOLFOXIRI plus bevacizumab)for locally advanced colorectal cancer with urinary bladder invasion is considered to be a useful treatment option because of its potential for tumor shrinkage and bladder preservation.

Impact of Arteriosclerosis on Reconstruction-related Complications After Esophagectomy and Usefulness of Tailor-made Reconstruction Technique.

BACKGROUND/AIM: Anastomotic leakage is one of the most common and serious postoperative complications following esophagectomy. This study analyzed the effect of risk factors, such as the degree of arteriosclerosis, comorbidities, and patient characteristics on the incidence of reconstruction-related complications including anastomotic leakage. Furthermore, the usefulness of tailor-made reconstruction methods was clarified using wide gastric conduit. PATIENTS AND METHODS: Patients who underwent esophagectomy with a gastric conduit for esophageal cancer between 2011 and 2018 were enrolled. In the initial group that underwent esophagectomy between August 2011 and February 2016, gastrointestinal reconstruction was performed using a narrow gastric conduit. In the latter group, reconstruction using subtotal gastric conduit was selected for high-risk patients between March 2016 and March 2018. Postoperative complications including reconstruction-related complications were assessed. RESULTS: The occurrence of anastomotic leakage was significantly associated with the patient's risk in the initial group. The rates of anastomotic leakage and reconstruction-related complications were significantly lower in the latter group than in the initial group (3.2% vs. 23.0%, p=0.001; 27.0% vs. 44.3%, p=0.044). The incidence of all complications was significantly lower in the latter group than in the initial group (28.6% vs. 59.0%, p=0.001). The change in bodyweight loss one year after the operation was significantly lower in the latter group than in the initial group (p=0.042). CONCLUSION: Tailor-made reconstruction using wide gastric conduit for high-risk cases of esophageal cancer could reduce the occurrence of anastomotic leakage and promote a better quality of life after surgery.

Thoracoscopic endoscopic cooperative surgery for gastric tube cancer after esophagectomy: a case report.

The incidence of gastric tube cancer (GTC) is increasing due to the improved prognosis of patients after esophagectomy for esophageal cancer. Total resection of the gastric tube is expected to be curative for patients with GTC. However, several studies have reported that this procedure is associated with high mortality and morbidity rates. We here present a case of GTC without lymph node metastasis in a patient who underwent partial resection of a gastric tube via thoracoscopic-endoscopic cooperative surgery. No postoperative complications or recurrence was observed. This procedure is a favorable and minimally invasive procedure for GTC without lymph node metastasis.

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.

Chemoprevention of esophageal adenocarcinoma in a rat surgical model by a cysteinyl leukotriene receptor­1 antagonist.

Reflux of gastroduodenal contents into the esophagus leads to the development of esophagitis and inflammation-associated pathologies, such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The role of the lipoxygenase (LOX) pathway in carcinogenesis has been recently reported; however, its involvement in esophageal carcinogenesis remains unclear. To address this, the present study investigated the potential of pranlukast, a cysteinyl leukotriene receptor-1 antagonist, to suppress the progression of BE and EAC in a rat duodenogastroesophageal reflux (DGER) model. Male Wistar rats that underwent DGER were divided into two groups. One group was fed commercial chow (control group), and the other was fed experimental chow containing pranlukast (pranlukast group). The rats were sacrificed at 10, 20, 30 and 40 weeks after surgery, and their esophagi were examined. Expression levels of 5-LOX, CD68, IL-8, VEGF and Ki-67 were investigated using immunohistochemistry, and apoptosis was analyzed using the TUNEL method. In the pranlukast group, esophagitis was milder, and the incidence of BE and EAC was significantly lower (P<0.05) compared with that in the control group at 40 weeks after surgery. The number of cells positive for IL-8 and VEGF were significantly lower in the pranlukast group compared with the control group. Proliferative activity was also lower in the pranlukast group compared with the control group (P<0.05). Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF.

Multidisciplinary treatment of advanced cervical esophageal adenocarcinoma derived from a gastric inlet patch: A case report.

A gastric inlet patch (GIP) is an ectopic gastric mucosal lesion usually arising at the cervical esophagus that may rarely cause esophageal adenocarcinoma (EAC). To the best of our knowledge, this is the first case of a GIP-derived EAC that was successfully treated using a multidisciplinary treatment approach. A 64-year-old man was referred to the Department of Gastrointestinal Surgery, Kanazawa University Hospital (Kanazawa, Japan) for surgical treatment of refractory recurrent cervical EAC derived from GIP who had previously been treated with induction chemotherapy, definitive chemoradiotherapy and photodynamic therapy (PDT). Esophagogastroduodenoscopy revealed a stenotic tumor at the GIP site in the cervical esophagus and submucosal tumors with suspected multiple intramural metastases in the anal side of the thoracic esophagus. The patient underwent robot-assisted thoracoscopic esophagectomy with laryngopharyngectomy and cervical lymphadenectomy as radical salvage surgery 4 months after the last PDT procedure. After postoperative adjuvant chemotherapy using oral administration of tegafur/gimeracil/oteracil (oral 5-fluorouracil prodrug) for 1 year; at present, the patient is alive without recurrence 3 years after the operation.

Long­term survival prognosis of function­preserving curative gastrectomy for early gastric cancer.

Segmental gastrectomy, mini-distal gastrectomy and local resection of the stomach are function-preserving curative gastrectomies (FPGs), which are used to treat gastric cancer in specialized centers. These surgical options are less invasive and can alleviate postgastrectomy symptoms more than standard gastrectomy; however, their association with prognosis remains to be fully elucidated. The present study aimed to compare the survival prognosis of patients diagnosed as node-negative by sentinel node biopsy (SNB) treated via FPG with reduced lymph node dissection with that of patients who underwent guideline gastrectomy (GL). This retrospective study was conducted between April 1999 and March 2016. The inclusion criteria were a diagnosis of gastric cancer type 0, of ≤5 cm, located in L or M areas, and pT1N0. Patients who underwent distal gastrectomy and pylorus-preserving gastrectomy were included as controls in the GL group. Among the 146 and 300 patients in the FPG and GL groups, respectively, only 1 patient in the GL group experienced recurrence. The overall survival (OS) of the FPG group was 96.6% at 5 years and 92.5% at 10 years, which was significantly higher than that of the GL group (P<0.05). In addition, the cumulative incidence of non-cancer-related deaths, especially pulmonary diseases, was lower in the FPG group than that in the GL group (P<0.05). Notably, the OS and non-cancer death rate in the FPG group remained significantly better after propensity score-matching analysis. In conclusion, for early gastric cancer located in M or L areas, patients treated via FPG guided by SNB have a better prognosis and fewer deaths caused by respiratory disease than those treated via GL. The present clinical trial was registered under the following trial registration numbers: UMIN000010154 (2013/3/4), UMIN000023828 (2016/8/29), jRCTs041180006 (2018/10/9).

An international Delphi consensus for surgical quality assessment of lymphadenectomy and anastomosis in minimally invasive total gastrectomy for gastric cancer.

BACKGROUND: Minimally invasive total gastrectomy (MITG) is a mainstay for curative treatment of patients with gastric cancer. To define and standardize optimal surgical techniques and further improve clinical outcomes through the enhanced MITG surgical quality, there must be consensus on the key technical steps of lymphadenectomy and anastomosis creation, which is currently lacking. This study aimed to determine an expert consensus from an international panel regarding the technical aspects of the performance of MITG for oncological indications using the Delphi method. METHODS: A 100-point scoping survey was created based on the deconstruction of MITG into its key technical steps through local and international expert opinion and literature evidence. An international expert panel comprising upper gastrointestinal and general surgeons participated in multiple rounds of a Delphi consensus. The panelists voted on the issues concerning importance, difficulty, or agreement using an online questionnaire. A priori consensus standard was set at > 80% for agreement to a statement. Internal consistency and reliability were evaluated using Cronbach's α. RESULTS: Thirty expert upper gastrointestinal and general surgeons participated in three online Delphi rounds, generating a final consensus of 41 statements regarding MITG for gastric cancer. The consensus was gained from 22, 12, and 7 questions from Delphi rounds 1, 2, and 3, which were rephrased into the 41 statetments respectively. For lymphadenectomy and aspects of anastomosis creation, Cronbach's α for round 1 was 0.896 and 0.886, and for round 2 was 0.848 and 0.779, regarding difficulty or importance. CONCLUSIONS: The Delphi consensus defined 41 steps as crucial for performing a high-quality MITG for oncological indications based on the standards of an international panel. The results of this consensus provide a platform for creating and validating surgical quality assessment tools designed to improve clinical outcomes and standardize surgical quality in MITG.

Successful treatment of nonocclusive mesenteric ischemia in a reconstructed jejunum after esophagectomy and remnant gastric tube resection: a case report.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI), an ischemic bowel disease without a disruption of the mesenteric blood flow or strangulation of the mesentery or intestine, may cause a lethal clinical course. We report a very rare case of jejunal necrosis caused by NOMI in the pedicled mesentery of the reconstructed jejunum after remnant gastric tube resection for heterochronous gastric tube cancer after esophagectomy. CASE PRESENTATION: An 80-year-old man visited our department with chief complaints of fever and appetite loss after 4 months from gastric tube resection and digestive reconstruction with pedicled jejunum. Contrast-enhanced computed tomography (CT) revealed impaired blood flow without torsion of the mesentery, severe wall thickness, and micro-penetration in the reconstructed jejunum and combined pyothorax in the right thoracic cavity. Esophagogastroduodenoscopy demonstrated extensive mucosal necrosis confined to the jejunum, which was elevated in the thoracic cavity. The jejunal necrosis due to NOMI occurring in the reconstructed jejunum was suspected, and lifesaving small bowel resection with right thoracotomy was considered necessary. However, radical operation with right thoracotomy was considered to be excessively invasive and not valid due to the patient's poor physical status, advanced age, and presence of left adrenal metastasis from the remnant gastric cancer. Therefore, we selected the conservative treatment with fasting, transnasal drainage, and administration of antibiotics due to the patient's intention. CT-guided right thoracic drainage for the intrathoracic abscess was needed 10 days after starting treatment and the inflammatory response rapidly improved. Follow-up CT and esophagogastroduodenoscopy revealed the improvement in the ischemic changes in jejunal mucosa without perforation. Intake was initiated at 20 days after symptom onset, and the patient was discharged at 40 hospital days without any complications and sequelae. CONCLUSIONS: To the best of our knowledge, this is the first case of NOMI occurring in the reconstructed jejunum after remnant gastric tube resection that was successfully treated with a conservative treatment. For NOMI, it is important to make appropriate diagnosis based on imaging findings and perform proper assessment of the patient's condition. Conservative treatments may be also useful depending on the patient's condition.

Impact of preoperative docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy on degree of malignant esophageal stenosis.

BACKGROUND: Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis. METHODS: Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment by fluoroscopy, and compared the differences before and after chemotherapy. In addition, we evaluated the dysphagia score (Mellow-Pinkas scoring system) as the evaluation of patients' symptoms. The antitumor effects of chemotherapy were also investigated. RESULTS: A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P = 0.038). Dysphagia score after chemotherapy significantly improved in the DCF group compared to the FP group (P = 0.007). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group. CONCLUSION: DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis.

Analysis of factors associated with operative difficulty in thoracoscopic esophageal cancer surgery in the left-decubitus position: a single-center retrospective study.

BACKGROUND: The degree of difficulty in the overall procedure and forceps handling encountered by surgeons is greatly influenced by the positional relationship of intrathoracic organs in minimally invasive esophagectomy. This study aimed to identify the anatomical factors associated with the difficulty of minimally invasive esophagectomy assessed by intraoperative injuries and postoperative outcomes. METHODS: Minimally invasive esophagectomy in the left-decubitus position was performed in 258 patients. We defined α (mm) as the anteroposterior distance between the front of the vertebral body and aorta, ß (mm) as the distance between the center of the vertebral body and center of the aorta, and γ (degree) as the angle formed at surgeon's right-hand port site by insertion of lines from the front of aorta and from the front of vertebrae in the computed tomography slice at the operator's right-hand forceps hole level. We retrospectively analyzed the correlations among clinico-anatomical factors, surgeon- or assistant-caused intraoperative organ injuries, and postoperative complications. RESULTS: Intraoperative injuries significantly correlated with shorter α (0.2 vs. 3.9), longer ß (33.0 vs. 30.5), smaller γ (3.0 vs. 4.3), R1 resection (18.5% vs. 8.3%), and the presence of intrathoracic adhesion (46% vs. 26%) compared with the non-injured group. Division of the median values into two groups showed that shorter α and smaller γ were significantly associated with organ injury. Longer ß was significantly associated with postoperative tachycardia onset, respiratory complications, and mediastinal recurrence. Furthermore, the occurrence of intraoperative injuries was significantly associated with the onset of postoperative pulmonary complications. CONCLUSIONS: Intrathoracic anatomical features greatly affected the procedural difficulty of minimally invasive esophagectomy, suggesting that preoperative computed tomography simulation and appropriate port settings may improve surgical outcomes.

Impact of laparoscopic gastrectomy on long-term prognosis of patients with primary T3 or more advanced gastric cancer: A propensity score matching analysis.

Background: There is no consensus regarding a better long-term prognosis with laparoscopic gastrectomy than with open surgery in patients with advanced gastric cancer, especially in patients with T3 or more advanced gastric cancer. We investigated the impact of laparoscopic gastrectomy on the long-term prognosis of patients who underwent radical gastrectomy for primary T3 or more advanced gastric cancer. Methods: This single-center, retrospective cohort study included 294 consecutive patients who underwent radical gastrectomy for primary T3 or more advanced gastric cancer from April 2008 through April 2017. We compared overall survival between laparoscopic and open surgery, using propensity score matching to adjust for baseline characteristics. We also investigated prognostic factors for overall survival by a forward stepwise procedure of Cox proportional hazards regression for multivariate analysis. Results: There were 136 (46.3%) and 158 (53.7%) patients in the laparoscopy and open groups, respectively. The median follow-up period was 39 mo. After matching, there were 97 patients in each group, with no significant differences in background characteristics. After matching, the overall survival was significantly worse in the open group than in the laparoscopy group (P < 0.001). Multivariate analyses also showed that open surgery was an independent poor prognostic factor for overall survival (hazard ratio: 2.160, 95% concordance interval: 1.365-3.419, P = 0.001). Conclusion: Overall survival may be better with laparoscopic gastrectomy than with open surgery for patients with primary T3 or more advanced gastric cancer.

Impact of Preoperative Nutritional Assessment on Other-Cause Survival after Gastrectomy in Patients with Gastric Cancer.

This study aimed to clarify the factors associated with death due to other diseases after a gastrectomy for gastric cancer. This retrospective cohort study included consecutive patients who had undergone gastrectomy between April 2008 and June 2018 for primary stage II-III gastric cancer. The primary outcome was other-cause survival. To identify prognostic factors for other-cause survival for univariate analysis, we used a Cox proportional hazard regression model. A total of 512 patients met the inclusion criteria. The average age was 67.93 years, and the average body mass index was 22.75 kg/m2, with 84 (16.4%) being moderately malnourished and 88 (17.2%) being severely malnourished, as defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria. The other-cause survival for the malnourished group was significantly worse than that for the normal group (p < 0.001). The prognosis was worse when the severity of malnutrition was worse (p < 0.001). Multivariate analysis showed that severe malnutrition was significantly independent of prognostic factors for other-cause survival (hazard ratio: 3.310; 95% confidence interval: 1.426-7.682; p = 0.005). Undernutrition, as defined by the GLIM criteria, is useful for the preoperative prediction of death due to other diseases after gastrectomy in patients with advanced gastric cancer.