Open left diaphragm method enables safe surgery with a good visual field in a laparoscopic transhiatal approach for esophagogastric junction adenocarcinoma laparoscopic transhiatal reconstruction via an open left diaphragm method.

BACKGROUND: Despite being oncologically acceptable for esophagogastric junction adenocarcinoma with an esophageal invasion length of 3-4 cm, the transhiatal approach has not yet become a standard method given the difficulty of reconstruction in a narrow space and the risk of severe anastomotic leakage. This study aimed to clarify the safety and feasibility of the open left diaphragm method during the transhiatal approach for esophagogastric junction adenocarcinoma. METHODS: This retrospective study compared the clinical outcomes of patients who underwent proximal or total gastrectomy with lower esophagectomy for Siewert type II/III adenocarcinomas with esophageal invasion via the laparoscopic transhiatal approach with or without the open left diaphragm method from April 2013 to December 2021. RESULTS: Overall, 42 and 13 patients did and did not undergo surgery with the open left diaphragm method, respectively. The median operative time was only slightly shorter in the open left diaphragm group than in the non-open left diaphragm group (369 vs. 482 min; P = 0.07). Grade ≥ II postoperative respiratory complications were significantly less common in the open left diaphragm group than in the non-open left diaphragm group (17% vs. 46%, P = 0.03). Neither group had grade ≥ IV anastomotic leakage, and two cases of anastomotic leakage requiring reoperation were drained using the left diaphragmatic release technique. CONCLUSIONS: Transhiatal lower esophagectomy with gastrectomy using the open left diaphragm method is safe, highlighting its advantages for Siewert type II/III esophagogastric junction adenocarcinoma with an esophageal invasion length of ≤ 4 cm.

Minimally invasive elective gastrectomy after preoperative chemotherapy in a patient with frailty who presented with locally far advanced-stage gastric cancer: a case report.

BACKGROUND: Herein, we report a case of gastric antrum cancer with multiple invasions to other organs that was completely cured with laparoscopic distal gastrectomy after preoperative chemotherapy in a patient with poor general condition. CASE PRESENTATION: An 80-year-old male patient was diagnosed with anemia during follow-up for cerebral lacunar infarction at another hospital. He was diagnosed with advanced-stage gastric antrum cancer and was referred to our hospital. On esophagogastroduodenoscopy, type 2 advanced-stage gastric cancer was detected at the greater curvature of the antrum, and the biopsy results revealed tubular adenocarcinoma. Contrast-enhanced computed tomography scan revealed multiple invasions to other organs, thick gastric wall with contrast effect, and superior mesenteric vein tumor thrombus. However, there was no evidence of distant metastasis on positron emission tomography/computed tomography scan. The clinical diagnosis was stage IVA gastric cancer. Pancreatoduodenectomy with portal vein resection could be important at this point. However, preoperative chemotherapy with S-1 and oxaliplatin was administered instead of performing extended surgery because the patient had poor general condition (performance status score of 3). The patient received three cycles of preoperative chemotherapy at the hospital along with rehabilitation and nutritional management with oral nutritional supplements. After treatment, the performance status score of the patient improved from 3 to 1. Furthermore, in terms of clinical therapeutic effect, the patient achieved partial response. Hence, laparoscopic distal gastrectomy with D2 lymph node dissection and partial transverse colectomy was performed. After surgery, the patient was admitted for oral intake on postoperative day 6 and was discharged on postoperative day 21. Based on the histopathological examination, gastric cancer had disappeared, and there were no evident malignant findings. Therefore, gastric cancer was classified as grade 3 according to the histological treatment efficacy criteria. The patient did not present with recurrence at 2 years after surgery. CONCLUSIONS: By actively administering preoperative chemotherapy, minimally invasive radical surgery with maximum preservation of the surrounding organs can be performed for locally far advanced-stage gastric cancer in older patients with poor general condition.

Clinical significance of the maximum standardized uptake value on positron emission tomography to predict treatment response and outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

PURPOSES: The association between the reduction rate of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) during neoadjuvant chemoradiotherapy (NACRT) and the prognosis in patients with locally advanced rectal cancer is unknown. METHODS: We retrospectively analyzed 62 patients with locally advanced rectal cancer who underwent curative surgery after NACRT at Kobe University between 2008 and 2021. The SUVmax reduction rate was calculated from preoperative and postoperative PET scans, and its association with the prognosis was investigated. RESULTS: The cutoff value for SUVmax reduction rate was 61.5%. Twenty patients had an SUVmax reduction rate > 61.5% (SUV responder group) and 38 patients had an SUVmax reduction rate ≤ 61.5% (SUV nonresponder group). Regarding pathological outcomes, the rate of a good histological response was significantly higher in the SUV responder group than in the SUV nonresponder group (80.0% vs. 21.1%, p < 0.001). Both the overall (OS) and relapse-free survival (RFS) rates were significantly better in the SUV responder group than in the SUV nonresponder group (OS, p = 0.035; RFS, p = 0.019). In the SUV responder group, only 1 case of recurrence was observed, with a median follow-up period of 56 months. CONCLUSION: The rate of SUVmax reduction during NACRT might predict the long-term prognosis of patients with locally advanced rectal cancer.

The number of resected lymph nodes from the upper mediastinal area predicts long-term outcomes of esophageal squamous cell carcinoma after minimally invasive esophagectomy.

BACKGROUND: The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, the resected LN counts from areas that affect long-term outcomes remain unclear. METHODS: This study included 406 patients who underwent minimally invasive esophagectomies (MIEs) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis of the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18, respectively, in patients with upper and middle thoracic (Ut/Mt) ESCC and 7, 6, 5, and 24, respectively, in patients with lower thoracic (Lt) ESCC. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, LN metastasis, and the resected LN count from the UM area were independent risk factors for overall survival [hazard ratio (HR), 7.04; 95% confidence interval (CI) 4.47-11.1; HR, 4.01; 95% CI 1.96-8.21; HR, 2.18; 95% CI 1.24-3.82, respectively]. In patients with Lt ESCC, tumor invasion depth, LN metastasis, and pulmonary complications were independent risk factors for overall survival (HR, 4.23; 95% CI 2.14-8.35; HR, 3.83; 95% CI 1.75-8.38; HR, 2.80; 95% CI 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. CONCLUSION: The number of resected LNs from the UM area influenced the survival outcomes of patients with Ut/Mt ESCC after MIE.

Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

Significance of Preoperative Tooth Loss in Patients Who Underwent Gastrectomy for Gastric Cancer.

Background/Aim: The relationship between gastric cancer and oral health has been reported in several studies. This study aimed to determine the relationship between the postoperative prognosis of gastric cancer and oral health using preoperative tooth loss as a simple index. Patients and Methods: We conducted a single-center retrospective cohort study. Patients were divided into two groups according to the number of tooth losses. The survival curve was constructed using the Kaplan-Meier method. We also performed univariate and multivariate analyses of overall survival based on Cox proportional hazard regression to determine prognostic factors. Results: A total of 191 patients were divided into two groups: those with seven or more tooth losses and those with less than seven tooth losses. The three-year overall survival rate was 71.5% in the group with seven or more tooth losses and 87.0% in the group with less than seven tooth losses. The group with seven or more tooth losses had a significantly lower overall survival rate compared to the group with less than seven tooth losses (p=0.0014). However, in multivariate analysis, tooth loss was not identified as an independent prognostic factor whereas age, clinical T stage, CEA level, and serum albumin level were independent poor prognostic factors. Conclusion: Preoperative tooth loss was not a prognostic factor for gastric cancer after gastrectomy, but tooth loss may be a simple and useful method for evaluating frailty in patients.

Impact of Tumor Size on Survival Outcome in Esophageal Squamous Cell Carcinoma After Esophagectomy Following Neoadjuvant Chemotherapy.

BACKGROUND: Large tumor size is a prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the effect of tumor size on outcomes following neoadjuvant chemotherapy (NAC) has not been evaluated. This study aimed to assess the influence of tumor size on prognosis of patients undergoing esophagectomy after NAC. PATIENTS AND METHODS: This study was made up of 272 patients who underwent esophagectomy after NAC at Kobe University Hospital. We evaluated the pathological tumor size and determined the cutoff level for tumor size using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The patients were categorized into two groups: patients with tumor sizes ≥ 36 mm and < 36 mm. Deep pathological tumor invasion and worse histological response to NAC were associated with tumor size ≥ 36 mm. In patients with pT0-1, pT2, and pT4 ESCC, no significant differences in overall survival (OS) rates were observed between the two groups. In patients with pT3, OS of the tumor size ≥ 36 mm group was significantly worse than that of the tumor size < 36 mm group (p < 0.0001). Multivariate analysis in pT3 patients revealed tumor size ≥ 36 mm was an independent risk factor for OS. The 5-year OS rate was 10% in patients with tumor size ≥ 36 mm pT3 ESCC with pathological lymph node metastasis (p < 0.0001). CONCLUSIONS: Tumor size ≥ 36 mm is an independent risk factor for poorer survival in pT3 patients. Furthermore, tumor size ≥ 36 mm with pathological lymph node metastasis in pT3 patients was associated with very poor survival.

Effectiveness of long-term tube feeding intervention in preventing skeletal muscle loss after minimally invasive esophagectomy.

PURPOSE: Esophageal cancer is a lethal tumor typically treated by neoadjuvant chemotherapy and surgery. For patients undergoing esophagectomy, postoperative enteral nutrition is important in preventing complications. Sarcopenia is associated with poor postoperative outcomes in esophageal cancer. In this study, we evaluated the benefits of tube feeding intervention and compared its short- and long-term outcomes in patients who underwent esophagectomy. METHODS: Propensity score matching was performed in 303 patients who underwent esophagectomy at Kobe University Hospital between 2010 and 2020. Patients were divided into feeding and nonfeeding jejunostomy tube groups (n = 70 each). The feeding jejunostomy tube group was further divided into long-term (≥ 60 days) and short-term (< 60 days) subgroups. The groups were then retrospectively compared regarding postoperative albumin levels, body weight, and psoas muscle area and volume. RESULTS: In the long-term feeding jejunostomy tube group, anastomotic leakage (p = 0.013) and left laryngeal nerve palsy (p = 0.004) occurred frequently. There were no significant between-group differences in postoperative albumin levels, body weight, or psoas muscle area. However, significant psoas muscle volume recovery was confirmed in the long-term jejunostomy tube group at 6 months postoperatively (p = 0.041). CONCLUSIONS: Tube feeding intervention after minimally invasive esophagectomy may attenuate skeletal muscle mass loss and help prevent sarcopenia.

Alb-dNLR Score as a Novel Prognostic Marker for Patients With Locally Advanced Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy.

BACKGROUND/AIM: The albumin and derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score, which combines an inflammation index with a nutritional index, has recently been reported as a useful prognostic marker in various cancers. However, evaluation of the usefulness of Alb-dNLR score in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NACRT) has not been reported yet. PATIENTS AND METHODS: This retrospective study included 69 patients with LARC undergoing NACRT followed by surgery between November 2005 and July 2020. The cutoff value of the Alb-dNLR score for relapse-free survival (RFS) was determined using a receiver operating characteristic curve. Patients were divided into high and low Alb-dNLR-score groups and analyzed for RFS and overall survival (OS). RESULTS: A total of 10 patients had high Alb-dNLR scores, and 59 had low Alb-dNLR scores. The high Alb-dNLR-score group had significantly higher rates of open surgery (70.0% vs. 28.8%; p<0.026), greater intraoperative blood loss (2,009 g vs. 421 g; p<0.001), and longer postoperative hospital stays (70 days vs. 42 days, p=0.012) than those of the low-Alb-dNLR-score group. The high Alb-dNLR-score group further demonstrated significantly worse RFS and OS than the low Alb-dNLR-score group (both p<0.001). Multivariate analysis identified the Alb-dNLR score as the most independent prognostic factor for RFS (hazard ratio=5.27; 95% confidence interval=2.09-13.27; p<0.001). CONCLUSION: The Alb-dNLR score is a valuable prognostic marker for predicting the oncological outcomes in patients with LARC undergoing NACRT.

[Analysis of Nuclear ß-Catenin before Starting Treatment Could Potentially Predict the Therapeutic Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer].

Although a therapeutic response to neoadjuvant chemoradiotherapy(NACRT)is important to improve oncological outcomes after surgery in patients with locally advanced rectal cancer, there is no reliable predictor for this. The Wnt/ß-catenin signal is known to be crucial for the tumorigenesis of colorectal cancer. This study aimed to investigate the association between Wnt/ß-catenin signal activation and the response to NACRT in patients with locally advanced rectal cancer. We analyzed the expression of nuclear and membranous ß-catenin in biopsy samples obtained from 60 patients who underwent curative surgery following NACRT. We found that patients with low nuclear ß-catenin expression had a higher rate of good histological responses compared to those with high nuclear ß-catenin expression. Additionally, patients with low nuclear/high membranous ß-catenin expression tended to have better relapse-free survival. The activation of the Wnt/ß- catenin signal pathway, represented by nuclear ß-catenin accumulation, was significantly associated with a poor response to NACRT in patients with rectal cancer. The analysis of nuclear ß-catenin accumulation before starting treatment could potentially predict the therapeutic response to NACRT.

[Significance of Preoperative Adjuvant Therapy and Subsequent Selective Inguinal Lymph Node Dissection for Rectal or Anal Canal Adenocarcinoma with Inguinal Lymph Node Metastases].

Adenocarcinoma of the rectum and anal canal with inguinal lymph node metastasis(ILNM)is rare and the prognosis is generally poor. The aim of this study was to clarify the clinical significance of selective inguinal lymph node dissection and total mesorectal excision after preoperative therapy for adenocarcinoma of the rectum and anorectal canal with clinically suspected ILNM. Of the 15 patients, 11 received preoperative chemoradiotherapy, 3 received chemotherapy, and 1 received chemotherapy after chemoradiotherapy. 14 patients received preoperative therapy followed by FDG-PET scans were performed in 14 patients after preoperative treatment. 5 patients had negative FDG accumulation in inguinal lymph nodes on FDG-PET scans, and postoperative pathological diagnosis was also negative for metastasis in the inguinal lymph nodes. Of the 9 patients with positive FDG accumulation, 4 had pathologically positive inguinal lymph nodes, 7 had postoperative inguinal seroma, the 5-year survival rate was 77.5%, and the 5-year recurrence-free survival rate was 64.2%. No patient had a recurrence in the inguinal region. Patients with adenocarcinoma of the rectum and anal canal with clinical ILNM had good long-term survival after radical resection with preoperative therapy.