Comparison of the survival outcomes between retrocolic and antecolic Roux-en-Y reconstruction after gastrectomy for gastric cancer.

Background: There are two methods of Roux-en-Y (RY) reconstruction after gastrectomy: the antecolic route (ACR) and retrocolic route (RCR). There is no evidence to support that the ACR achieves comparable long-term survival. Methods: This was a multi-center historical cohort study. Patients diagnosed with clinical T3/4a and any N stage who underwent open gastrectomy and R0 resection for gastric adenocarcinoma between January 2006 and December 2012 were enrolled. The primary outcome was the hazard ratio of ACR for overall survival, with adjustment for confounding factors by propensity score matching, and a Cox proportional hazards model. Results: A total of 1758 eligible patients were identified from the database. After matching, 410 patients in the ACR and RCR groups were included in the final analysis. The adjusted hazard ratio (95% CI) for ACR was 1.148 (0.870-1.492). The five-year survival rates in the ACR and RCR groups were 74.3% (69.5-78.4) and 77.3% (72.3-81.2), respectively. The short-term surgical outcomes of the two groups did not differ to a statistically significant extent. Conclusion: The route used to lift the jejunum in RY reconstruction did not affect the incidence of long-term survival or postoperative complications. The ACR and RCR are both acceptable options for RY reconstruction during gastric cancer surgery.

Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer.

BACKGROUND: We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). METHODS: A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. RESULTS: Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). CONCLUSIONS: Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

BACKGROUND: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). METHODS: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. RESULTS: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. CONCLUSION: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Comparing the outcomes of laparoscopic proximal and laparoscopic total gastrectomy: A retrospective analysis of a single center in Japan.

INTRODUCTION: Despite the increasing performance of laparoscopic proximal gastrectomy (LPG) for proximal gastric cancer and esophagogastric junction cancer, the benefit of LPG over laparoscopic total gastrectomy (LTG) remains to be established. Therefore, this study was conducted to compare postoperative outcomes between LPG and LTG. METHODS: Data from 141 patients who underwent LPG or LTG for gastric neoplasm with curative intent between 2016 and 2022 were retrospectively reviewed. Clinicopathological findings, body weight changes, and serological nutritional markers during the postoperative course were evaluated. RESULTS: LPG and LTG were performed in 78 patients and 63 patients, respectively. Patients' characteristics did not differ; however, tumor stages in patients who underwent LTG were more advanced than those who underwent LPG. The mean (± standard deviation) weight loss rate after 1 year was -13.5 (±6.9)% and -18.7 (±6.6)% for LPG and LTG, respectively (p < .01). LTG (OR: 3.326, p < .01), pT disease (OR: 3.000, p = .01), pN disease (OR: 2.708, p = .02), and postoperative chemotherapy (OR: 2.488, p = .05) were correlated with severe weight loss (16% or more) 1 year after surgery, then multivariate analysis identified LTG as an independent factor (p = .01). The mean (± standard deviation) serum total protein level of LPG was significantly higher than that of LTG at 3 months (6.8 ± 0.5 vs. 6.6 ± 0.4 g/dL, p = .02) and 1 year (6.9 ± 0.4 vs. 6.7 ± 0.5 g/dL, p = .01) postoperatively. No difference was observed in postoperative serum hemoglobin and albumin levels. CONCLUSION: LPG more improved postoperative weight loss than LTG.

Solitary choroidal metastasis of distal cholangiocarcinoma: A case report.

Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal cholangiocarcinoma, which was successfully managed using stereotactic radiotherapy (SRT). A 67-year-old Japanese man underwent pancreaticoduodenectomy for distal cholangiocarcinoma. The pathological stage was T2N0M0 stage IIA, according to the Union for International Cancer Control 8th edition. After surgery, the patient received adjuvant chemotherapy with oral TS-1® for 1 month. A total of 2 months after surgery, the patient was readmitted to hospital due to decreased visual acuity. Fundoscopy revealed a macular hole in the right eye that accounted for the decreased visual acuity. Additionally, Goldmann three-mirror contact lens examination revealed a 4-mm choroidal mass with a yellowish color situated at a considerable distance from the optic nerve. Magnetic resonance imaging revealed an enhanced choroidal mass. Based on the findings of ophthalmologic examinations and the patient's history of cholangiocarcinoma, they were diagnosed with choroidal metastasis from distal cholangiocarcinoma. SRT was administered at a total dose of 40 Gy divided into 8 Gy fractions. A total of 1 year after SRT, the patient achieved complete remission without decreased visual acuity. The patient remains alive and in good health without recurrence, 4 years after the diagnosis of choroidal metastasis. To the best of our knowledge, this is the second reported case of intraocular metastasis from cholangiocarcinoma. In conclusion, SRT may provide an opportunity to control metastatic choroidal carcinoma without decreasing visual acuity.

Real-world management and outcomes of older patients with locally advanced esophageal squamous cell carcinoma: a multicenter retrospective study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. METHODS: We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0-1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. RESULTS: The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22-2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10-11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10-3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57-1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02-3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58-2.22; P = 0.717). CONCLUSIONS: NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.

Predictive significance of surgery-induced lymphopenia on the survival after curative resection for locally advanced gastric cancer: a retrospective cohort analysis.

BACKGROUND: Following the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome. METHODS: Database entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as < 1000/µL. RESULTS: The ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p < 0.001) and a low post-ALC (p < 0.001) were both correlated with a poor relapse-free survival (RFS). A multivariate analysis of RFS identified a low post-ALC (hazard ratio 1.875, 95% CI 1.156-3.402, p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p < 0.001), stage II (p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373-3.769, p = 0.01). CONCLUSIONS: A decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer. HIGHLIGHTS: Postoperative lymphopenia was a poor prognostic factor for gastric cancer.

Ulcer Scarring in the Gastric Conduit Is a Risk Factor for Anastomotic Leakage After Esophagectomy for Esophageal Cancer.

BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL. METHODS: Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively. RESULTS: AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004). CONCLUSIONS: Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.

Conversion surgery for stage IV gastric cancer: a multicenter retrospective study.

BACKGROUND: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC. METHODS: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis. RESULTS: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011). CONCLUSIONS: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.

Simple modifications of conventional esophagogastrostomy after proximal gastrectomy adequately reduces the postoperative reflux esophagitis: a retrospective analysis of posterolateral fundoplication.

PURPOSE: While proximal gastrectomy is being performed increasingly frequently for the treatment of gastric cancer, a standard reconstruction method to obtain optimal postoperative quality of life (QOL) still remains to be established. We modified the original esophagogastrostomy technique by introducing an additional posterolateral fundoplication (PLF) technique to minimize the risk of reflux esophagitis in patients undergoing proximal gastrectomy. The aim of this study was to clarify the clinical benefit of PLF. METHODS: A retrospective analysis of the database was conducted to evaluate the effects of PLF. The data were compared between 44 patients in whom PLF was performed (PLF group) and 17 patients in whom conventional esophagogastrostomy without PLF was performed (C group). A number of incidence of postoperative reflux esophagitis and symptoms were assessed by findings of endoscopic examination and the PGSAS-45 questionnaire, respectively. RESULTS: The incidence of grade B or worse esophagitis after surgery was significantly lower in the PLF group than in the C group (0% vs. 58.8%, P < 0.01). The score for the esophageal reflux subscale, as the main outcome measure of PGSAS-45, was significantly better in the PLF group (PLF: 1.5 vs C: 2.4, P < 0.01). Cohen's d value was 1.75, which suggested a rather large effect size. Postoperative benign anastomotic stricture was encountered in 10 cases (22.7%) of the PLF group and 4 cases (23.5%) of the C group, all of whom were successfully treated by brief endoscopic mechanical dilatation. CONCLUSION: PLF is an expedient procedure for reconstruction after proximal gastrectomy.

Intracorporeal hand-sewn anastomosis following pylorus-preserving gastrectomy: surgical technique and short-term surgical outcome.

BACKGROUND: Although several procedures for mechanical anastomosis have recently been reported, intracorporeal manually hand-sewn anastomosis for totally laparoscopic pylorus-preserving gastrectomy (TLPPG) is considered technically difficult. Here, we report a new technique for laparoscopic reconstruction using hand-sewn sutures. METHODS: Together with a proper lymphadenectomy, the stomach was detached and resected using separate two-layer incisions, similar to the original laparotomy method. An approximately 5-cm antral cuff was left in place. The essential concept of this new method was to align the anastomotic site by rotating each clamped gastric stump. This allowed us to perform a secure, hand-sewn, two-layer anastomosis successfully. The short-term surgical outcome after TLPPG was retrospectively compared with that for patients who underwent a conventional laparoscopy-assisted procedure (LAPPG). RESULTS: Of the 20 consecutive patients who underwent pylorus-preserving gastrectomy in our department between 2014 and 2021, the first 8 patients and the subsequent 12 patients underwent LAPPG and TLPPG, respectively. The operation time was significantly longer in the TLPPG group (median, 302 vs. 269 min). The morbidity was comparable (8.3% in TLPPG vs. 12.5% in LAPPG). Postoperative delayed gastric emptying was only observed in one patient in the LAPPG group. TLPPG reduced the cost of the operation by reducing the number of linear stapler cartridges required. CONCLUSION: A purely hand-sewn gastrogastrostomy is safe, feasible, and cost-effective, and it omits the need for a mini-laparotomy in the upper abdomen.

Efficacy and safety of ramucirumab plus paclitaxel therapy for advanced gastric cancer patients treated previously with docetaxel-containing chemotherapy.

BACKGROUND: Ramucirumab (RAM) plus paclitaxel (PTX) therapy has shown promising results as a standard second-line treatment for advanced gastric cancer patients. Recently, combined docetaxel (DOC) plus S-1 (DS) therapy could be regarded as the new standard adjuvant chemotherapy for patients with curatively resected stage III gastric cancer. However, the efficacy and safety of RAM plus PTX therapy in patients treated previously with DOC-containing therapy remains unclear. METHODS: This study assessed the clinical outcomes of RAM plus PTX therapy in advanced gastric cancer patients with or without a previous history of treatment with a DOC-containing regimen. RESULTS: In a series of 107 consecutive patients enrolled for this study, the median PFS and OS were 4.2 and 6.2 months, respectively. Fifty-five patients had a history of prior therapy with DOC and 52 did not. There was no significant difference between with and without DOC groups in the ORR (22.2% vs. 23.5%), PFS (4.2 vs. 5.3 months), or OS (7.2 vs. 6.4 months). In a comparison taking into account the interval from the DOC-containing therapy to the RAM plus PTX therapy, the number of treatment courses was significantly smaller and the PFS significantly shorter in the patient group with an interval of ≤ 6 months (median, 2 vs 4.5 courses, P = 0.033; 3.4 months vs. 5.1 months, P = 0.043). CONCLUSIONS: RAM plus PTX therapy in patients with advanced gastric cancer is effective even in patients who have previously received DOC-containing chemotherapy, especially if the interval is > 6 months.

Clinical Utility of ypTNM Stage Grouping in the 8th Edition of the American Joint Committee on Cancer TNM Staging System for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific 'ypTNM' stage grouping for patients with esophageal cancer. OBJECTIVE: This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). METHODS: We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. RESULTS: Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike's information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. CONCLUSIONS: ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

Incidence of Multiple Metachronous Gastric Cancers After Pyloric-Preserving Gastrectomy.

AIM: Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG. METHODS: The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1-290.7) months. RESULTS: Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611-12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113-7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient. CONCLUSIONS: There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.

[Long-Term Complete Response in Postoperative Multiple Lung and Mediastinal Lymph Node Metastases of Esophageal Cancer Using Systemic Chemotherapy with DCF Treatment - A Case Report].

A 59-year-old man was diagnosed with advanced thoracic esophageal cancer.He underwent neoadjuvant chemotherapy with cisplatin(CDDP), 5-fluorouracil(5-FU)(CF)followed by transthoracic esophagectomy with three-field lymphadenectomy. Histopathological examination revealed that the tumor was poorly differentiated squamous cell carcinoma invading the adventitia with 6 regional lymph node metastases.Four months after surgery, follow-up thoracic computed tomography (CT)showed multiple lung and mediastinal lymph node metastases.The patient's general condition was favorable, and he underwent systemic chemotherapy with docetaxel, CDDP, 5-FU(DCF).After 2 courses of DCF, chest CT revealed that the lung and mediastinal lymph node metastases had markedly decreased in size to the point of being unmeasurable.After receiving additional chemotherapy consisting of 2 courses of DCF and 8 courses of monthly docetaxel, the patient has been followed up without treatment.No tumor re-recurrence has occurred in the 6 years and 8 months since the first recurrence.In cases of recurrent or unresectable esophageal cancer, the rate of clinical response is reported to be higher for DCF than for CF. DCF is a tolerable regimen, even for postoperative patients, provided that monitoring is conducted for severe adverse events. In patients whose general conditions are favorable, DCF should be considered as a treatment option for recurrent esophageal cancer.