Age-related remodelling of oesophageal epithelia by mutated cancer drivers.

Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which-depending on lifestyle risks-may affect cancer development.

Anterior versus posterior mediastinal reconstruction after esophagectomy in esophageal cancer patients: a systematic review and meta-analysis.

PURPOSE: Esophagectomy is the primary surgical treatment for esophageal cancer, although other treatment approaches are often incorporated, including preoperative chemotherapy and chemoradiotherapy. The two major routes of esophageal reconstruction after esophagectomy are the anterior mediastinal (retrosternal, heterotopic) and posterior mediastinal (prevertebral, orthotopic) routes. However, which of these two routes of reconstruction is the most appropriate remains controversial. This systematic review aimed to compare the efficacy and safety of anterior mediastinal reconstruction with those of posterior mediastinal reconstruction after esophagectomy in esophageal cancer. METHODS: In January 2022, a literature search of the CENTRAL, MEDLINE, and EMBASE databases was conducted to identify all published and unpublished randomized controlled trials, regardless of language. Eight studies were included for quantitative synthesis. RESULTS: Postoperative death (9/129 and 4/125, risk ratio [RR]: 2.07, 95% confidence interval [CI]: 0.65-6.64) and incidence of anastomotic leak (24/208 and 26/208, RR: 0.95, 95% CI: 0.56-1.62) were not significantly different between the two mediastinal reconstructions. We could not perform a meta-analysis for quality of life, loss of body weight, or postoperative hospital stay due to data limitations. CONCLUSION: Overall, there was low-quality evidence to suggest that the outcomes of the anterior and posterior mediastinal routes of reconstruction are not significantly different in patients with esophageal cancer.

Impact of the coronavirus disease 2019 pandemic on gastric and colorectal cancer surgeries: a multicenter epidemiologic study from the Kinki region of Japan.

The coronavirus disease 2019 pandemic affected cancer surgeries and advanced cancer diagnoses; however, the trends in patient characteristics in medical institutions during this time, and the surgical approaches used are unclear. We investigated the impact of the pandemic on gastric and colorectal cancer surgeries in the Kinki region of Japan. We grouped 1688 gastric and 3493 colorectal cancer surgeries into three periods: "pre-pandemic" (April 2019-March 2020), "pandemic 1" (April 2020-March 2021), and "pandemic 2" (April 2021-September 2021), to investigate changes in the number of surgeries, patient characteristics, surgical approaches, and cancer progression after surgery. Gastric and colorectal cancer surgeries decreased from the pre-pandemic levels, by 20% and 4%, respectively, in pandemic 1, and by 31% and 19%, respectively, in pandemic 2. This decrease had not recovered to pre-pandemic levels by September, 2021. Patient characteristics, surgical approaches, and cancer progression of gastric and colorectal surgeries did not change remarkably as a result of the coronavirus disease 2019 pandemic.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Prophylactic supraclavicular lymph node dissection for esophageal squamous cell carcinoma: a systematic review and meta-analysis.

The supraclavicular lymph nodes (SCLNs) have been regarded as regional nodes for esophageal squamous cell carcinoma (ESCC) in Japan and eastern Asian countries, whereas their involvement has been regarded as distant metastasis in Western countries. The importance of thorough dissection of the lymphatic chain along the recurrent laryngeal nerve, including the cervical paraesophageal nodes, has become well understood; therefore, the contemporary clinical question is whether prophylactic SCLN dissection (SLND) in addition to cervical paraesophageal node dissection is beneficial for patients with ESCC. We analyzed studies comparing esophagectomy with SLND vs. esophagectomy without SLND, in both of which cervical paraesophageal node dissection had been completed, based on a comprehensive literature search of the PubMed, Scopus, and Cochrane databases. Our meta-analysis focused on two long-term outcomes: 3-year and 5-year overall survival (OS) rates; and three short-term outcomes: pneumonia, recurrent nerve palsy, and anastomotic leakage. Four studies, with a collective total of 1584 patients were included in the review. No significant differences were found between esophagectomy with SLND vs. esophagectomy without SLND in the meta-analysis of both long-term (3-year and 5-year OS; risk ratio 1.09, 95% CI 0.94-1.26, P = 0.28, and risk ratio 1.14, 95% CI 0.96-1.35, P = 0.15, respectively) and short-term outcomes. Based on our analysis, no clear data support prophylactic SLND on the cervical paraesophageal node dissection.

Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC. METHODS: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m2) on days 1-4 and cisplatin (70 mg/m2) on day 1 every 4 weeks with concurrent radiation (60 Gy). RESULTS: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm. CONCLUSIONS: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

Safety assessment of robotic gastrectomy and analysis of surgical learning process: a multicenter cohort study.

BACKGROUND: The safety of robotic gastrectomy (RG) for gastric cancer in daily clinical settings and the process by which surgeons are introduced and taught RG remain unclear. This study aimed to evaluate the safety of RG in daily clinical practice and assess the learning process in surgeons introduced to RG. METHODS: Patients who underwent RG for gastric cancer at Kyoto University and 12 affiliated hospitals across Japan from January 2017 to October 2019 were included. Any morbidity with a Clavien-Dindo classification grade of II or higher was evaluated. Moreover, the influence of the surgeon's accumulated RG experience on surgical outcomes and surgeon-reported postoperative fatigue were assessed. RESULTS: A total of 336 patients were included in this study. No conversion to open or laparoscopic surgery and no in-hospital mortality were observed. Overall, 50 (14.9%) patients developed morbidity. During the study period, 14 surgeons were introduced to robotic procedures. The initial five cases had surprisingly lower incidence of morbidity compared to the following cases (odds ratio 0.29), although their operative time was longer (+ 74.2 min) and surgeon's fatigue scores were higher (+ 18.4 out of 100 in visual analog scale). CONCLUSIONS: RG was safely performed in actual clinical settings. Although the initial case series had longer operative time and promoted greater levels of surgeon fatigue compared to subsequent cases, our results suggested that RG had been introduced safely.

A long-term follow-up study of minimally invasive Ivor Lewis esophagectomy with linear stapled anastomosis.

BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly performed to expect lower complication rate compared to open esophagectomy. Studies of minimally invasive Ivor Lewis esophagectomy (MIILE) with circular staplers have reported better outcomes compared to MIE with cervical anastomosis, but frequent anastomotic complications have also been reported. MIILE with linear staplers is a promising alternative, but the long-term functional and oncological outcomes are uncertain. METHODS: To evaluate the functional and oncological outcomes of MIILE with linear stapled anastomosis, a retrospective cohort study was performed in 104 patients who underwent MIILE with linear stapled anastomosis for esophageal malignant tumors. The primary endpoints were the overall complication and anastomotic leak rates. The secondary endpoints were late complications, overall and disease-free survival, and nutritional status at 6 and 12 months after MIILE. RESULTS: Anastomotic leak occurred in 4 patients (3.8%). The short-term complication rate of grade IIIb or higher was 6.7%. During a median 57-month follow-up period, anastomotic stricture occurred in one patient, 7 required hiatal hernia repair, and 2 underwent conduit revision surgery. The 5-year overall survival and disease-free survival rates were 69.3% and 59.5%, respectively. Status of reflux esophagitis at the time of most recent evaluation was grade N/A/B/C/D in 52/10/10/13/8 among 93 patients who had follow-up endoscopy. The mean body weight loss at 6 and 12 months after MIILE was 11.3 and 11.8% with maintenance of the serum albumin level. CONCLUSIONS: MIILE with linear stapled anastomosis is a safe procedure with a low anastomotic complication rate and favorable long-term functional and survival outcomes.

Chronological Changes in Skeletal Muscle Mass Two Years after Minimally Invasive Esophagectomy: A Prospective Cohort Study.

BACKGROUND: Preoperative loss of skeletal muscle mass, defined as sarcopenia, has been reported to be associated with higher incidence of complications following esophagectomy in patients with esophageal cancer. Although skeletal muscle loss promotes disability and reduced quality of life (QOL), only a few studies have focused on changes in skeletal muscle mass after surgery. This prospective cohort study aimed to evaluate the chronological changes in skeletal muscle mass after minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer scheduled to undergo MIE at our institution were prospectively registered. Skeletal muscle mass was evaluated before and 2, 6, 12, and 24 months after surgery. The effects of preoperative sarcopenia on surgical outcomes and chronological changes in skeletal muscle mass were evaluated. RESULTS: Among the 71 eligible preoperative patients, 29 (40.8%) were diagnosed with sarcopenia. Patients with sarcopenia had significantly higher incidences of total (79.3% vs 52.4%, p = 0.026) and gastrointestinal (37.9% vs 11.9%, p = 0.019) complications and a significantly longer length of hospital stay (31 vs 23 days, p = 0.005) than those without sarcopenia. The median skeletal muscle mass index (kg/m2) was 7.09 before surgery, which decreased to 6.46 two months after surgery (- 7.2%, P < 0.01). Thereafter, values of 6.90, 6.86, and 7.06 were reported at 6, 12, and 24 months after surgery, respectively. CONCLUSION: Patients with preoperative sarcopenia developed more postoperative complications than those without it. Additionally, patients experienced a decrease in skeletal muscle mass during the early postoperative period following MIE. Further research on perioperative countermeasures to prevent skeletal muscle loss during the early postoperative period and to prevent postoperative complications is necessary for patients undergoing MIE.

Mesenteric closure after laparoscopic total gastrectomy with Roux-en-Y reconstruction is effective for prevention of internal hernia: a multicenter retrospective study.

BACKGROUND: Internal hernia (IH) is one of the critical complications after gastrectomy with Roux-en-Y reconstruction, which can be prevented by closing mesenteric defects. However, only few studies have investigated the incidence of IH after laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction for gastric cancer till date. This study aimed to assess the efficacy of defect closure for the prevention of IH after LTG. METHODS: This multicenter, retrospective cohort study collected data from 714 gastric cancer patients who underwent LTG with Rou-en-Y reconstruction between 2010 and 2016 in 13 hospitals. We evaluated the incidence of postoperative IH by comparing closure and non-closure groups of Petersen's defect, jejunojejunostomy mesenteric defect, and transverse mesenteric defect. RESULTS: The closure group for Petersen's defect included 609 cases, while the non-closure group included 105 cases. The incidence of postoperative IH in the closure group for Petersen's defect was significantly lower than it was in the non-closure group (0.5% vs. 4.8%, p < 0.001). The closure group for jejunojejunostomy mesenteric defect included 641 cases, while the non-closure group included 73 cases. The incidence of postoperative IH in the closure group of jejunojejunostomy mesenteric defect was significantly lower than that in the non-closure group (0.8% vs. 4.1%, p = 0.004). Out of 714 patients, 41 underwent retro-colic reconstruction. No patients in the transverse mesenteric defect group developed IH. CONCLUSION: Mesenteric defect closure after LTG with Roux-en-Y reconstruction may reduce postoperative IH incidence. Endoscopic surgeons should take great care to prevent IH by closing mesenteric defects.

Lower Incidence of Postoperative Pulmonary Complications Following Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: Propensity Score-Matched Comparison to Conventional Minimally Invasive Esophagectomy.

BACKGROUND: Whether robot-assisted minimally invasive surgery (RAMIE) is more beneficial than conventional minimally invasive surgery (MIE) remains unclear. METHODS: In total, 165 consecutive patients with esophageal carcinoma who underwent esophagectomy between January 2015 and April 2020 were retrospectively assessed. A 1:1 propensity score matching analysis was performed to compare the short-term outcomes between RAMIE and conventional MIE. RESULTS: After matching, 45 patients were included in the RAMIE and conventional MIE groups. RAMIE had a significantly longer total operative time (708 vs. 612 min, P < 0.001) and thoracic operative time (348 vs. 285 min, P < 0.001) than conventional MIE. However, there were no significant differences in terms of oncological outcomes, such as R0 resection rate and number of resected lymph nodes. The overall postoperative morbidity (Clavien-Dindo [C-D] grade II or higher) rate of RAMIE and conventional MIE were 51% and 73% (P = 0.03), respectively, and the severe postoperative morbidity (C-D grade III or higher) rates were 11% and 29% (P = 0.04), respectively. The incidence rate of recurrent laryngeal nerve palsy was halved in RAMIE (7%) compared with conventional MIE (20%) (P = 0.06). Finally, the pulmonary complication rate (18%) was significantly lower in patients who underwent RAMIE than in those who underwent conventional MIE (44%) (P = 0.006). CONCLUSIONS: RAMIE was safe and feasible, even during the early period of its application at a specialized center. Moreover, it may be a promising alternative to conventional MIE, with better short-term outcomes, including significantly lower incidence of pulmonary complications.

Long-Term Outcomes of Laparoscopic Radical Gastrectomy for Highly Advanced Gastric Cancer: Final Report of a Prospective Phase II Trial (KUGC04).

BACKGROUND: This is the final report evaluating the long-term outcomes of a single-arm phase II clinical trial that demonstrated the short-term efficacy of laparoscopic gastrectomy (LG) for highly advanced gastric cancer (AGC) [KUGC04]. PATIENTS AND METHODS: Seventy-three patients with histologically confirmed gastric adenocarcinoma and diagnosed with clinical stage II or higher, who potentially underwent curative resection between August 2009 and November 2014, were prospectively enrolled. Long-term outcomes with 5-year progression-free survival (PFS) and 5-year overall survival (OS) were evaluated according to clinical or pathological stages. Recurrence and progression patterns were also investigated. These outcomes were compared with those of previous reports to assess the applicability of LG for highly advanced gastric cancer (HAGC). RESULTS: The median observation period of all surviving patients was 75.1 months. The 5-year PFS and 5-year OS of all patients was 47.4% and 54.4%, respectively. Clinical stage-specific 5-year PFS and 5-year OS was 75.0, 69.1, 53.9, 39.4, 40.0 and 9.1, and 75.0, 68.8, 61.5, 45.0, 60.0 and 27.3, respectively, in stages IIA, IIB, IIIA, IIIB, IIIC, and IV, respectively. Pathological stage-specific 5-year PFS and 5-year OS, including ypStage with preoperative chemotherapy, was 100, 80.0, 100, 62.5, 80.0, 51.3, 16.7, 22.2 and 12.5, and 100, 80.0, 100, 75.0, 80.0, 64.2, 25.0, 33.3 and 12.5, respectively, in stage X (no residual tumor with preoperative chemotherapy), IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV, respectively. Recurrence or progression was observed in 30 patients (41.1%). CONCLUSION: LG for HAGC performed by experienced surgeons is safe and oncologically acceptable.

Educational application of intraoperative records from an energy device in laparoscopic gastrectomy: a preliminary report.

PURPOSE: Video review is a reliable method for surgical education in laparoscopic gastrectomy (LG), but more objective methods are still needed. The purpose of this study was to determine whether the energy device records reflected surgical competency, and thereby may improve surgical education. METHODS: A total of 16 patients who underwent LG for gastric cancer using the Thunderbeat® device were preliminarily retrospectively analyzed. This device has the function of 'intelligent tissue monitoring' (ITM), a safety assist system stopping energy output, and can record ITM detections and firing time during surgery. The number of ITM detections and firings, and the total firing time during gastrocolic ligament dissection and infrapyloric dissection were compared between trainees (n = 9 by 5 surgeons) and experts (n = 7 by 5 surgeons). The non-edited videos (n = 16) were scored, and the correlations between the scores and the records were then analyzed. RESULTS: Significantly more ITM detections, firings, and a longer total firing time were observed in trainees than in experts. The number of ITM detections and firing had negative correlations with the scores of the operation speed, the use of the non-dominant hand, and the use of an energy device. CONCLUSIONS: Our preliminary study suggested that the above described energy device records reflected surgical competency, and thereby may improve surgical education.

[One-stage Radical Surgery for Aortoesophageal Fistula after Graft Replacement of Descending Aorta].

A 31-year-old woman was referred to our institution because of aortoesophageal fistula (AEF) six months after the descending aortic replacement for acute aortic dissection. We operated one-stage repair of the AEF. Thoracoscopic esophagectomy was firstly performed in prone position from right thoracic cavity, and then the esophagus was reconstructed with gastric conduit via posterior mediastinal route with omental flap. Secondly, graft replacement of the descending aorta using lateral oblique straight incision was performed and the graft was covered with omental flap simultaneously. The postoperative course was uneventful, and she started oral intake on the 13th day after surgery. Although the one-stage surgery for the AEF is highly invasive, it could be a good option for selected cases.

Simple technique of azygos arch division and retraction for minimally invasive esophagectomy.

The azygos arch is usually divided during esophagectomy. To achieve thorough lymphadenectomy up to upper mediastinum, many surgeons prefer to retract the distal stump of the azygos arch by pulling out the thread which ligates the stump to the skin through the dorsal side of the intercostal space. However, the access to the dorsal chest wall near vertebrae for percutaneous puncture is difficult during robot-assisted minimally invasive esophagectomy in the prone position. This paper reports a new simple method of azygos arch division and retraction using a polymer locking ligation system Hem-o-lok (Teleflex, Morrisville, NC, USA) and a barbed suture device. This technique can be easily performed completely as a robotic procedure without extra puncture, and it is also applicable for conventional thoracoscopic procedures with the potential benefits of less trauma and bleeding.

Mesenteric excision of upper esophagus: a concept for rational anatomical lymphadenectomy of the recurrent laryngeal nodes in thoracoscopic esophagectomy.

BACKGROUND: The recurrent laryngeal nerve (RLN) lymph nodes are among the most frequently involved lymph nodes in esophageal cancer. Surgical removal of these lymph nodes is considered beneficial for postoperative prognosis, especially in patients with squamous cell carcinoma. Unfortunately, the precise surgical anatomy of the upper mediastinum is not well understood and no distinct high-resolution images are currently available. METHODS: In this article, we provide a simple intuitive concept of upper mediastinal surgical anatomy that could facilitate rational anatomical lymphadenectomy of the RLN lymph nodes. The essential concept of this mesenteric excision is to mobilize mesoesophagus including RLN in an en bloc fashion and to save RLN laterally by incising visceral sheath. This is applicable identically to both right and left upper mediastinum. RESULTS: Between January 2009 and December 2017, thoracoscopic esophagectomy with upper mediastinal lymphadenectomy for primary esophageal cancer was performed in 189 patients. Median thoracoscopic procedure time was 297 (range 205-568) min and median intraoperative blood loss was 70 ml (range unmeasurable up to 2545 ml). Median number of harvested upper mediastinal lymph nodes was 12. Postoperative complication of Clavien-Dindo classification grade III or higher events was observed in 14% of patients. RLN palsy of grade II or higher occurred in 20 patients (11%). CONCLUSION: The mesoesophagus in the upper mediastinum is an anatomical unit surrounded by fibrous connective tissue containing the esophagus, trachea, tracheoesophageal vessels, lymphatic tissue, and RLNs. Thus, mesenteric excision of esophagus is defined to resect this area by sparing trachea and RLNs for rational anatomical lymphadenectomy. We believe that this concept makes upper mediastinal lymphadenectomy safer and more appropriate.

Linear or circular stapler? A propensity score-matched, multicenter analysis of intracorporeal esophagojejunostomy following totally laparoscopic total gastrectomy.

BACKGROUND: Presently, there is no consensus as to what procedure of intracorporeal esophagojejunostomy (EJS) in totally laparoscopic total gastrectomy (TLTG) is best to reduce postoperative complications. The aim of this study was to demonstrate the superiority of linear stapled reconstruction in terms of anastomotic-related complications for EJS in TLTG. METHODS: We collected data on 829 consecutive gastric cancer patients who underwent TLTG reconstructed by the Roux-en-Y method with radical lymphadenectomy between January 2010 and December 2016 in 13 hospitals. The patients were divided into two groups according to reconstruction method and matched by propensity score. Postoperative EJS-related complications were compared between the linear stapler (LS) and the circular stapler (CS) groups. RESULTS: After matching, data from 196 patients in each group were analyzed. The overall incidence of EJS-related complications was significantly lower in the LS group than in the CS group (4.1% vs. 11.7%, p = 0.008). The incidence of EJS anastomotic stenosis during the first year after surgery was significantly lower in the LS group than in the CS group (1.5% vs. 7.1%, p = 0.011). The incidence of EJS bleeding did not differ significantly between the groups, although no bleeding was observed in the LS group (0% vs. 2.0%, p = 0.123). The incidence of EJS leakage did not differ significantly between the groups (2.6% vs. 3.6%, p = 0.771). CONCLUSION: The use of linear stapled reconstruction is safer than the use of circular stapled reconstruction for intracorporeal EJS in TLTG because of its lower risks of stenosis.

A Phase 2 Study of Induction Chemotherapy Using Docetaxel, Cisplatin, and S-1 for Gastric Cancer with Peritoneal Metastasis (KUGC06).

BACKGROUND: The authors previously showed the significant efficacy of S-1 plus cisplatin for gastric cancer with limited peritoneal metastasis. They conducted a phase 2 study to evaluate the safety and efficacy of induction chemotherapy using a docetaxel, cisplatin, and S-1 (DCS) triplet regimen to treat gastric cancer with peritoneal metastasis. METHODS: The key eligibility criteria were gastric cancer with peritoneal metastasis or positive peritoneal cytology but no other distant metastases and capability of oral administration. The patients received three 28-day cycles of DCS (60 mg/m2 of cisplatin, 40 mg/m2 of docetaxel on day 1, and 80 mg/m2 of S-1 from day 1 to day 14), then underwent D2 gastrectomy if R0 was possible. The primary end point was the R0 resection rate. The sample size was determined to have 80% power for detecting a 20% improvement in the R0 resection rate over a 45% baseline for a one-tailed alpha of 0.1. RESULTS: Among 30 enrolled patients, 24 completed three cycles of DCS. The most frequent grade 3 or 4 toxicity was neutropenia (60%). A complete response of peritoneal metastasis was observed in 16 patients, and 14 patients achieved R0 resection (47%; 95% confidence interval 28-66%). When the extent of peritoneal metastasis was classified as P0CY1, P1, P2, and P3 according to the Japanese classification, the R0 resection rates were respectively 63%, 60%, 46% and 0%. CONCLUSIONS: Induction chemotherapy with DCS is safe and can achieve R0 resection for some patients with limited peritoneal metastasis or positive peritoneal cytology. The efficacy, however, appears similar to that of S-1 plus cisplatin.

Revisiting the infracardiac bursa using multimodal methods: topographic anatomy for surgery of the esophagogastric junction.

In embryology, the infracardiac bursa (ICB) is a well-known derivative separated from the omental bursa. During surgeries around the esophagogastric junction (EGJ), surgeons often encounter a closed space considered to be equivalent to the ICB, but the macroscopic anatomy in adults is hardly known. This study aimed to revisit the ICB using multimodal methods to show its development from the embryonic to adult stage and clarify its persistence and topographic anatomy. Histological sections of 79 embryos from Carnegie stage (CS) 16 to 23 and magnetic resonance (MR) images of 39 fetuses were examined to study the embryological development of the ICB. Horizontal sections around the EGJ obtained from three adult cadavers were examined to determine the topographic anatomy and histology of the ICB. Further, 32 laparoscopic surgical videos before (n = 16) and after (n = 16) the start of this study were reviewed to confirm its remaining rate and topographic anatomy in surgery. The ICB was formed in 1 out of 10 CS17 samples, and in 8 out of 10 CS18 samples. Further, it was observed in all CS19-23 except one CS23 sample and in 25 (64%) out of 39 fetus samples. Three-dimensional reconstructed MR images of fetuses revealed that the ICB was located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. In one adult cadaver, the caudal end of the ICB arose from the level of the esophageal hiatus and the cranial end reached up to the level of the pericardium. The inner surface cells of the space consisted of the mesothelium. In laparoscopic surgery, the ICB was identified in only 11 (69%) out of 16 surgeries before. However, subsequently we were able to identify the ICB reproducibly in 15 (94%) out of 16 surgeries. Thus, the ICB is the structure commonly remaining in almost all adults as a closed space located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. It may be available as a useful landmark in surgery of the EGJ.

Intraperitoneal chemotherapy for peritoneal metastases using sustained release formula of cisplatin-incorporated gelatin hydrogel granules.

PURPOSE: We previously reported the effectiveness of gelatin microspheres incorporating cisplatin in a mouse model of peritoneal metastases. In this study, we report our new complete sustained-release formula of gelatin hydrogel granules incorporating cisplatin (GHG-CDDP), which exerted a good anti-tumor effect with less toxicity. METHODS: GHG-CDDP was prepared without organic solvents to enable its future clinical use. The pharmaceutical characterization of GHG-CDDP was performed, and its in vivo degradability was evaluated. The anti-tumor effect was evaluated using a murine peritoneal metastasis model of the human gastric cancer MKN45-Luc cell line. RESULTS: Our new manufacturing process dramatically reduced the initial burst of CDDP release to approximately 2% (wt), while the previous product had a 25-30% initial burst. In intraperitoneal degradation tests, approximately 30% of GHG-CDDP remained in the murine abdominal cavity 7 days after intraperitoneal injection and disappeared within 3 weeks. GHG-CDDP significantly suppressed the in vivo tumor growth (p = 0.02) and prolonged the survival time (p = 0.0012) compared with the control. In contrast, free CDDP did not show a significant therapeutic effect at any dose. Weight loss and hematological toxicity were also significantly ameliorated. CONCLUSIONS: GHG-CDDP is a promising treatment option for peritoneal metastases through the complete sustained-release of CDDP with less systemic toxicity.