Siewert Type Research Articles

ODP159 A Rare Case of Pembrolizumab Induced Diabetic Ketoacidosis

Abstract Introduction Immune checkpoint inhibitors (ICI), such as Pembrolizumab, have demonstrated excellent clinical outcomes in numerous solid organ malignancies. However, this new drug comes with unpredictable adverse reactions which are still under review in the medical literature. We are showcasing a cancer patient treated with an ICI and presenting to the hospital in diabetic ketoacidosis (DKA), despite no significant history of a formal diagnosis of Diabetes Mellitus. Case description The patient is a 69 year old male who presented to the hospital with generalized weakness. His past medical history was significant but not limited to, Hypothyroidism, Tobacco use disorder, Stage IV Siewert type 2 gastroesophageal junction adenocarcinoma (cT4N2M1, HER2/FGFR negative, PD-L1 positive) after completion of one year of chemotherapy. He was now undergoing immunotherapy with Pembrolizumab, with his first dose three weeks ago. Reviews of systems including fever, abdominal pain, nausea, vomiting, polyuria, polydipsia were negative. Vital signs were grossly normal. He gave no personal or family history of diabetes. On admission venous blood gas demonstrated a high anion gap metabolic acidosis (pH 7. 096, Blood glucose 762 mg/dL, Anion Gap 29 mmol/L, bicarbonate 9 mmol/L, Plasma osmolality 337 mOsm/kg). Serum Lipase was 23 U/L. HbA1c was found to be 5.9%. Urinalysis was significant for glucose >500 mg/dl and >80 mg/dl of ketones. The physical exam was only remarkable for dry mucous membranes. Given the presentation and lab findings, he was subsequently diagnosed with DKA. The patient was treated with standard guideline therapy for DKA including bolus fluids, maintenance fluids and intravenous (IV) Insulin. The Anion gap closed and glucose decreased to under 200. He was transitioned to a subcutaneous insulin regimen, and discharged on the same. Discussion Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced DKA. In the acute care setting, an autoimmune workup was not done in our patient. A meta analysis review of 71 such cases from 56 publications showed the average HbA1c concentration was 7.84% + 1. 0% at presentation. The A1c finding of 5.9%, defined at pre-diabetes, in represents an outlier. Another meta-analysis of such patients demonstrated DKA as the first sign of diabetes in 30 out of 35. The pathophysiology of this side effect of ICI's remains unknown, however several mouse studies have shown PD-1/PD L1 blockade precipitating diabetes in prediabetic non-obese mice. Anti -PD-1 drugs might have the same effect, and the reduction of PD-1 might activate autoreactive T cells, resulting in an autoimmune response against pancreatic islet cells. As the use of immunotherapy is expected to increase, it is essential that clinicians become aware of DKA as a rare and life threatening side effects of immunotherapy and that blood glucose monitoring is strongly considered as a method of prevention. Presentation: No date and time listed

Impact of examined lymph node number on accurate nodal staging and long-term survival of resected Siewert type II-III adenocarcinoma of the esophagogastric junction: A large population-based study.

We aimed to investigate the association between the number of examined lymph nodes (ELNs) and accurate nodal staging and long-term survival in Siewert type II-III Adenocarcinoma of the Esophagogastric Junction (AEG) by using large population-based databases and determined the optimal ELN number threshold. Data on Stage I-III Siewert type II-III AEG patients from 2010 to 2014 respectively from the United States (US) SEER database and a Chinese large medical center institutional registry were analyzed for correlation between the ELN number and stage migration (node negative-to-positive) and overall survival (OS) by using multivariable-adjusted logistic and Cox regression models, respectively. The series of odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural breakpoints were determined by Chow test. The selected optimal cut point was then validated with the 2015 to 2016 SEER database. Both the US cohort(n=1387) and China cohort(n=981) showed significantly increases from node-negative to node-positive disease (ORtheUS1.032,95%CI 1.017-1.046;ORChina1.034,95%CI 1.002-1.065) and enhancements in overall survival (HRtheUS0.970,95%CI 0.961-0.979;HRChina0.960,95%CI 0.940-0.980) with the increasing ELN number after controlling for confounders. Associations for both stage migration and overall survival were still significant in most subgroups' stratification. Cut point analysis showed a threshold ELN number of 18, which was validated both in the cohorts where it originated and in an independent SEER data cohort(n=379). More ELNs are associated with accurate nodal staging(negative-to-positive) as well as higher overall survival in resected Siewert types II-III AEG, We recommend 18 ELNs as the optimal cut point for the quality assessment of postoperative lymph node examination or prognostic stratification in clinical practice.

Comparison of short-term surgical outcomes between complete mesenteric resection and traditional transhiatal laparoscopic surgery for Siewert type II/III esophagogastric junction adenocarcinoma.

To explore the effectiveness and safety of laparoscopic transhiatal complete mesenteric resection (CME) surgery compared with those of the traditional laparoscopic transhiatal approach in the treatment of Siewert II/III adenocarcinoma of the esophagogastric junction (AEG). Ninety-nine patients with Siewert type II/III AEG were enrolled and divided into two groups: the laparoscopic CME transhiatal approach (CEM-TH, n = 61) group and traditional laparoscopic transhiatal (TH, n = 38) group. Intraoperative and postoperative clinical data of both groups were analyzed. The laparoscopic trasihiatal surgery was technically successful in all patients. The surgical time, intraoperative bleeding, and hospital stay were all significantly (P < 0.05) reduced in the CME-TH group compared with those in the TH group. The levels of white blood cells on postoperative day (POD) 1 and 5, postoperative CRP on POD 3 and 5, and postoperative PCT were significantly (P < 0.05) lower while lymph nodes were harvested significantly (P < 0.05) more in the CME-TH group than in the TH group. Complications were not significantly (P > 0.05) different between two groups. No death occurred within 90days. The CME theory could be safely and effectively applied laparoscopically to treat patients with Siewert II/III AEG. Mesogastrium and lower mesoesophagus can be completely resected together with the tumor, lymph nodes, adipose tissue, and blood vessels as an "intact package," leading to better short-term outcomes.

Adenocarcinoma of the Esophagogastric Junction:Classification and Surgical Treatment Strategy

Despite substantial declines in gastric cancer incidence, the incidence of adenocarcinoma of the esophagogastricjunction (AEG) has been rising remarkably worldwide and is drawing considerable attention as well as concern.However, the optimal extent of esophagogastric resection for this tumor entity, especially Siewert type II tumorslocated at the true cardia, remains highly controversial. Given the uncertainty about the optimal extent of prophylactic lymph node dissection, both subtotal esophagectomy and extended total gastrectomy have been advocatedfor this tumor entity. A recent Japanese questionnaire-based national retrospective study showed that completenodal clearance along the distal portion of the stomach offered marginal survival benefits for patients with AEGless than 4 cm in diameter. A prospective nationwide multicenter study accurately identified the distribution oflymph node metastases from advanced AEG, suggesting that it is not recommended to completely dissect lymphnode stations along the distal portion of the stomach. Total gastrectomy might be employed less frequently andconsequently replaced by subtotal esophagectomy or extended proximal gastrectomy in clinical practice.

Modified mattress inversion suturing with double barbed sutures used for totally laparoscopic esophagojejunostomy overlap anastomosis after radical total gastrectomy

Objective: To explore the advantages and safety of a modified mattress inversion suturing using double barbed sutures compared with the traditional overlap method in totally laparoscopic esophagojejunostomy overlap anastomosis. Methods: A retrospective cohort study was conducted. The inclusion criteria were as follows: (1) patients were aged 18 - 80 years old; (2) adenocarcinoma was preoperatively confirmed by pathological analysis; (3) patients had undergone a complete laparoscopic radical total gastrectomy; (4) patients had undergone esophagojejunostomy using the overlap method; (5) patients received a grade of I-III on the American Society of Anesthesiologists physical status classification system; (6) patients' complete follow-up data had been collected. Patients with a history of other malignant tumors, multi-origin tumors, emergency surgery, non-R0 radical resection or distant metastasis were excluded. The clinical data of 89 gastric cancer patients who underwent total laparoscopic radical total gastrectomy in the Department of Gastrointestinal Surgery in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2020 were collected. These patients were grouped according to the esophagojejunostomy method used. Of 89 patients, 32 received modified mattress inversion suturing with double barbed sutures to close the common opening of esophagojejunostomy (the modified anastomosis group), while 57 received traditional overlap anastomosis in which the common opening was closed by barbed suture (the traditional anastomosis group). The operation conditions (incision length, conversion to laparotomy, duration of esophagojejunostomy) and postoperative recovery (time to commencement of a liquid diet, duration of postoperative hospital stay, anastomotic leakage, anastomotic stenosis, and anastomotic bleeding) were compared between the two groups. Results: There was no significant difference in the baseline data of the two groups for any parameter (all P>0.05). All patients received complete laparoscopic radical gastrectomy without conversion to laparotomy. There were no significant differences in the length of the median incision, the proportion of food intake on the first day after surgery, or in the incidence of anastomotic complications such as anastomotic leakage, anastomotic stenosis, and anastomotic bleeding between the two groups (P>0.05). Compared with the traditional anastomosis group, patients in the modified anastomosis group had shorter anastomosis time [26 (19-62) minutes vs. 36 (20-50) minutes, Z=-2.546, P=0.011] and postoperative hospital stay [7 (6-12) days vs. 9 (7-42) days, Z=-4.202, P<0.001]. The differences were statistically significant (all P<0.05). In a subgroup analysis of tumor TNM stage III, Siewert type II and neoadjuvant chemotherapy patients, there was no significant difference in the incidence of anastomotic complications between the modified group and the traditional group. However, the postoperative hospital stay duration in the modified anastomosis group was less than in the traditional anastomosis group. The duration of anastomosis in Siewert type II patients was also shorter in the modified anastomosis group than in the traditional anastomosis group [26 (19-62) minutes vs. 38 (21-50) minutes, Z=-2.105, P=0.035], and the difference was statistically significant (all P<0.05). Conclusion: Complete laparoscopic esophagojejunostomy using modified mattress inversion suturing with double barbed sutures is a safe and feasible anastomosis method to close the common opening of esophagojejunostomy, with shorter operation time, faster postoperative recovery and shorter hospital stay than the traditional method.

587. ROLE OF THORACOSCOPIC HAND-SEWN ESOPHAGO-GASTRIC ANASTOMOSIS IN 2-STAGE TOTALLY MINIMALLY INVASIVE ESOPHAGECTOMY. REPORT OF 200 CONSECUTIVE CASES

Abstract Esophagectomy is the mainstay of treatment of esophageal and gastro-esophageal junction cancer. Minimally invasive esophagectomy has been introduced in the 2000s in an effort to reduce post-operative pulmonary and cardiac complications. 2-stage totally minimally invasive esophagectomy combines laparoscopic abdominal phase followed by thoracoscopic thoracic phase. The rate limiting step of the procedure is the construction of esophago-gastric anastomosis. We aim to present our technique and results on hand-sewn thoracoscopic esophago-gastric anastomosis in prone position. This is prospective analysis of consecutive patients that underwent 2-stage totally minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers. All operations were identical in terms of patient positioning, lymphadenectomy and type of anastomosis formed. Study included adult patients with no upper age limit (&amp;gt;18 years); all hybrid esophagectomies, esophagectomies for malignancy and emergency operations were excluded from the study. The anastomosis was manually facilitated thoracoscopic in prone position, in 2-layers, using barbed sutures. Primary endpoints were anastomotic leakage and anastomotic stricture rate. Secondary endpoints were 30- and 90-day mortality rates. During a 5-years-period, n=200 consecutive patients underwent 2-stage totally minimally invasive esophagectomy for cancer. Most patients were males. Median age was 65.5 years. Median operative time was 280 minutes while median suturing time for the anastomosis was 50 minutes. Anastomosis was thoracoscopic, hand-sewn constructed in prone position in all cases. There was no conversion to open. Anastomotic leak complicated n=5 patients (2.5%); n=4 were type I anastomotic leaks and n=1 was type I, which was treated with chest drainage. Anastomotic stricture was presented in n=13 patients (6.5%). 30-day mortality rate was 1% and 90-day mortality rate was 2.5%. Formation of the esophago-gastric anastomosis is one of the most challenging aspects during 2-stage totally minimally invasive esophagectomy. Most surgeons prefer the construction using circular or linear staplers. Our anastomotic technique, present a safe and effective anastomosis, with favorable clinical outcomes. It can be reproduced and established in the hand of experts, offering all the advantages of manual anastomosis and reduction of devastating post-operative anastomotic leakage, which still complicates stapled constructed anastomosis with significant incidence.

256. LOCAL CONTROL OF HEPATIC/PULMONARY OLIGOMETASTASIS IS EFFECTIVE IN EGJ ADENOCARCINOMA

Abstract This study investigated the clinicopathological features of distant metastasis of esophagogastric junction (EGJ) adenocarcinoma. Survival benefit of local management was also examined in the patients with hepatic or pulmonary oligometastasis. Among a total of 449 cases of Siewert type I-II surgically resected EGJ adenocarcinoma (2005–2020), 166 cases with distant metastasis were eligible. Examining 22 cases with liver metastasis alone who treated in our hospital, liver-resected cases (N = 13) experienced better outcomes (mOS; 48 M for resection, vs. 8.1 M for those without resection, P = 0.0002). More favorable outcome was observed in the patients with 1–3 nodules (N = 11, P = 0.0023). Regarding lung metastasis alone, systemic chemotherapy was applied to bilateral multiple nodules, otherwise, local control including resection or stereotactic irradiation was selected. The mOS in the patients who underwent local control was significantly longer than that of chemotherapy (44 M for resection vs. 17 M for chemotherapy, P = 0.035). Tumor location or histological type of the primary tumor was associated with organ sites of distant metastasis. Local management conferred survival benefit in the patients with oligometastasis in liver or lung alone.

596. MINIMALLY INVASIVE ESOPHAGECTOMY FOR ESOPHAGEAL AND GASTRO-ESOPHAGEAL JUNCTION TUMORS. A SINGLE CENTER EXPERIENCE

Abstract Esophagectomy carries high rates of post-operative morbidity and mortality. Minimally invasive esophagectomy was introduced more than 20 years ago offering all the advantages of minimally invasive surgery and significantly reducing post-operative pulmonary and cardiac complications associated with open esophagectomy. Clinical and oncological outcomes are vastly improved standardizing this approach as inferior in the hand of experts. Herein, we aim to present our results of minimally invasive esophagectomy for esophageal and gastro-esophageal junction cancer. This is prospective analysis of consecutive patients that underwent 2-stage minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers. Operations included hybrid 2-stage esophagectomy (laparoscopic/open thoracotomic or open laparotomy/thoracoscopy) and 2-stage totally minimally invasive esophagectomy (laparoscopic/thoracoscopic). Study included adult patients with no upper age limit (&amp;gt;18 years). All esophagectomies for benign disease, as well as emergency operations were excluded from the study. Primary endpoints were 30- and 90-day mortality rate, anastomotic leak, anastomotic stricture, pulmonary complications, and length of hospital stay. Secondary endpoints were overall survival and progression-free survival rates respectively. During an 8-year-period, n=350 consecutive patients underwent 2-stage minimally invasive esophagectomy for cancer. Our team has a cumulative experience of more than 300 open-esophagectomies. Since September 1st, 2013, hybrid 2-stage esophagectomy program was initiated. On September 1st, 2016, the program offered 2-stage totally minimally invasive esophagectomy in-all comers. Most patients were males. Anastomotic leak complicated 5.1% of the patients; 10% of the patients presented anastomotic stricture post-operatively, while pulmonary and cardiac complications reached up to 25 and 12% respectively. Medial LOS was 8 days. Median follow-up was 60 months. OS survival rate was 53 months and PFS was 48 months. Advances in minimally invasive surgery can benefit all patients with esophageal and gastro-esophageal junction tumors. Hybrid and totally minimally invasive 2-stage esophagectomy are well established approaches, with safe and feasible profile in tertiary cancer centers. They can lead to significantly improved clinical and oncological outcomes comparing to open esophagectomy and its complications burden.

594. TOTALLY MINIMALLY INVASIVE 2-STAGE ESOPHAGECTOMY VERSUS HYBRID 2-STAGE ESOPHAGECTOMY. A SINGLE CENTER EXPERIENCE

Abstract Totally minimally invasive 2-stage esophagectomy (TMIE) eliminates the thoracotomy associated with hybrid 2-stage minimally invasive esophagectomy (hybrid-MIE). This has an important role in minimizing post-operative respiratory complications. There is ongoing growing evidence in published literature of improved clinical and oncological outcomes in totally MIE comparing to hybrid MIE, due to enhanced optics and extend of lymphadenectomy as well as to shorter length of hospital stay and surgical trauma associated to thoracoscopy. This is a retrospective analysis of consecutive patients that underwent 2-stage minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers. TMIE combines a laparoscopic and thoracoscopic approach while hybrid-MIE includes laparoscopic open thoracotomic phase. Study included adult patients with no upper age limit (&amp;gt;18 years). All esophagectomies for benign disease, as well as emergency operations were excluded from the study. Primary endpoints were 30- and 90-day mortality rate, anastomotic leak, anastomotic stricture, pulmonary complications, and length of hospital stay. Secondary endpoints were overall survival and progression-free survival rates respectively. During an 8-year-period, 150 patients underwent hybrid-MIE, while 200 underwent TMIE. Operative-time was shorter in the hybrid-MIE group (320 vs 280 min). Anastomotic leak was significantly reduced in the TMIE group comparing to the hybrid-MIE group (2.5% vs 9.5%). Respiratory complications were reduced in the TMIE group (10 vs 25%). Median LOS was similar (7 vs 7.5 days). Median number of resected-lymph nodes was increased in the TMIE group (28 vs 35 lymph nodes). OS survival rate was 60 versus 51 months and PFS was 52 vs 43 months in the TMIE and hybrid-MIE groups respectively. In general, TMIE was associated with moderately lower morbidity compared to hybrid-MIE, but randomized controlled evidence is lacking. The higher anastomotic leakage rate, higher rate of pulmonary complications and lower lymph node count that was found after hybrid-MIE in comparative analysis, indicate that TMIE can significantly improve clinical outcomes of patients undergoing esophagectomy. The findings of this study should be considered carefully by surgeons when moving from hybrid-MIE to TMIE.

455. ESOPHAGOGASTRIC JUNCTION CANCER: A DIFFICULT BORDER: A WORLDWIDE SURVEY ON ONCOLOGICAL AND SURGICAL APPROACH

Abstract The incidence of esophagogastric junctional adenocarcinoma (EGJ) has been steadily increasing over the last 30 years, especially in Western countries. Surgical and oncological treatment of these malignancies are still debated, in particular in case of true junctional cancer (Siewert type II tumors). The aim of the study is to compare different approaches to EGJ cancers in high volume centers around the world. We administered a survey to 39 international opinion leaders, working in high volume centers, with a minimum of 50 gastrectomies and 20 esophagectomies performed as first operator. The survey was structured in the form of clinical case scenarios, created to focus on different peculiar issues in the management of Siewert type II tumors. The main fields of investigation were the oncological approach of these malignancies (i.e. choice and type of neoadjuvant treatment) and the preferred surgical strategy. Our first finding was that almost 80% of responders would choose a neoadjuvant treatment even in cT2N0 patients, fearing probably the low accuracy of the clinical staging. Secondly, 60% of surgeons would prefer chemotherapy over chemoradiotherapy in locally advanced Siewert II tumors, regardless of histological subtype and nodal diffusion. As for the surgical strategy, we reported a strong preference (75% of responders) for two-field esophagectomy, over three-field esophagectomy (11%) and total extended gastrectomy (14%). However, in case of signet-ring cell carcinoma, up to 20% of surgeons would prefer an extended total gastrectomy, to avoid a distal positive margin. Our survey confirms that the management of Siewert type II tumors is greatly debated, even among experts of the field, and it needs to be tailored on the patient and tumor characteristics. Even so, we observed a trend towards the choice of chemo over chemoradiotherapy for any histological subtype. When operating on Siewert type II tumors, a thoracic approach is considered necessary by most of responders.

Effect of splenic hilar lymphadenectomy on locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction with a tumor diameter ≥4 cm: a five-year survival analysis

Objective: To examine the long term outcome of splenic hilar lymphadenectomy (SHL) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) with a tumor diameter ≥4 cm. Methods: A total of 489 locally advanced Siewert type Ⅱ and Ⅲ AEG patients with a tumor diameter ≥4 cm who underwent radical resection from January 2010 to April 2016 were included. There were 383 males and 106 females. There were 225 patients aged≥65 years and 264 patients aged <65 years. SHL was conducted in 270 patients(SHL group). Wilcoxon rank-sum test or χ2 test were conducted for inter-group comparison. Cox proportional hazard regression was used to analyze the long term outcome of SHL and the prognosis factors of overall survival. Kaplan-Meier curve was drawn finally. The results of survival analysis were verified by Log-rank test. Results: Followed-up to April 2021,the median follow-up time was 78.0 months (range: 74.0 to 85.0 months), the follow-up rate was 95.5%(467/489). The splenic hilar lymphnode metastasis rate of the SHL group was 12.6% (34/270). Younger patients (<65 years old), less complications, higher proportion of patients received adjuvant chemotherapy were demonstrated in the SHL group (χ2: 5.644 to 6.744, all P<0.05). Multivariate analysis showed that SHL was the independent prognosis factor of overall survival for patients with Siewert type Ⅱ and Ⅲ AEG and a tumor diameter≥4 cm (HR=0.68, 95%CI: 0.52 to 0.88, P=0.004) along with preoperative CA19-9, pathological T stage, pathological N stage, adjuvant chemotherapy and postoperative complication. Further subgroup analysis demonstrated that the SHL group had better 5-year overall survival than non-SHL group (62.4% vs. 39.2%, χ2=17.983, P=0.006) in Siewert type Ⅲ AEG rather than in Siewert type Ⅱ AEG(57.3% vs. 53.7%, χ2=3.031, P=0.805). Conclusion: In experienced center, splenic hilar lymphadenectomy can improve the prognosis of Siewert type Ⅲ AEG with a tumor diameter ≥4 cm.

Efficacy of the No. 10 lymphadenectomy with spleen preservation on patients with gastric cancer and/or esophagogastric junction adenocarcinoma who underwent total gastrectomy: a systematic review and meta-analysis.

BackgroundSurgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy.MethodsThe PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ2) and I2 tests.ResultsEight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62–0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58–0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75–1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61–0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60–0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56–0.76, P<0.00001) years compared with those in the non-No. 10 LND group.DiscussionEvidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected.

The impact of different comprehensive treatment models on patients with adenocarcinoma of esophagogastric junction based on propensity score matching: a single center cohort study

Objective: To compare the prognostic influence and postoperative pathology of different comprehensive treatment models for adenocarcinoma of esophagogastric junction. Methods: Between January 2012 and December 2017, a total of 219 patients with adenocarcinoma of esophagogastric junction underwent surgery in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute and were enrolled in this study. The clinicopathological data of these patients were collected. The patients were categorized into 3 groups according to different treatment models: surgery-first group, neoadjuvant chemotherapy (NAC) group and neoadjuvant chemoradiotherapy (nCRT) group. A trimatch propensity score analysis was applied to control potential confounders among the three groups by using R language software. A total of 7 covariates including gender, age, comorbidity, body mass index, clinical T stage, clinical N stage and Siewert type were included, and the caliper value was taken as 0.2. After matching, a total of 87 patients were included for analysis with 27 patients for each group. There were 82 males and 5 females, with a median age of 63 years (range: 38 to 76 years). The effect of preoperative treatment on postoperative tumor pathology among the three different comprehensive treatment models was explored by χ2 test, ANOVA or Wilcoxon rank sum test. Mann-Whitney U test or χ2 test were used to undergo pairwise comparisons. Kaplan-Meier method and Log-rank test were used to analyze the overall survival and progression-free survival. Results: The proportion of vascular embolism in the surgery-first group was 72.4% (21/29), which was significantly higher than NAC group (37.9% (11/29), χ2=6.971, P=0.008) and nCRT group (6.9% (2/29), χ2=26.696, P<0.01). The proportions of pathological T3-4 stage in nCRT group and NAC group were 55.2% (16/29) and 62.1% (18/29), respectively, which were significantly lower than the surgery-first group (93.1% (27/29), χ2=10.881, P=0.001; χ2=8.031, P=0.005). Compared with the NAC group (55.2% (16/29), χ2=6.740, P=0.009) and nCRT group (31.0% (9/29), χ2=18.196, P<0.01), the proportion of lymph node positivity 86.2% (25/29) were significantly higher in the surgery-first group. The 5-year overall survival rates were 62.1%, 68.6% and 41.4% for the surgery-first group, NAC group and nCRT group, respectively (χ2=4.976, P=0.083). The 5-year progression-free survival rates were 61.7%, 65.1% and 41.1% for the surgery-first group, NAC group and nCRT group, respectively. The differences in overall survival (χ2=4.976, P=0.083) and progression-free survival (χ2=4.332, P=0.115) among the three groups were nonsignificant. Conclusions: Postoperative pathology is significantly different among the three groups. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy could decrease the proportions of vascular embolism, pathological T3-4 stage and lymph node positivity to achieve local tumor control. The prognosis of overall survival and progression-free survival are not significantly different among the three groups.

Whether the infracardiac bursa protect right pleura during laparoscopic radical operation of Siewert type II adenocarcinoma of esophagogastric junction?

BackgroundTransthoracic single-port assisted laparoscopic five-step maneuver inferior mediastinal lymphadenectomy for Siewert type II adenocarcinoma of esophagogastric junction (AEG) has superiority in lower mediastinal lymph nodes dissection and digestive tract reconstruction. However, the right pleura was probably ruptured in this surgical technique. The aim of this study was to explore whether the infracardiac bursa (ICB) exposed could protect right pleura.MethodsWe retrospectively collected and evaluated the clinical and pathological data of patients who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymphadenectomy for Siewert II AEG at Guangdong Provincial Hospital of Chinese Medicine between May 2017 and February 2022.ResultsA total of 49 patients were eligible, including 31 patients in ICB exposed group (group A) and 18 patients in ICB unexposed group (group B). There were no statistically significant differences in baseline characteristics between the two groups. 4 patients (12.9%) had right pleura rupture in group A, while 14 patients (77.8%) in group B, and the difference was statistically significant (p < 0.001). Compared with group B, the extubation time of endotracheal intubation (10.0 (6.0 ~ 12.0) vs. 13.0 (8.0 ~ 15.0) min, p = 0.003) and thoracic drainage tube stay (6.0 (5.0 ~ 7.0) vs. 8.0 (6.0 ~ 10.5) days, p = 0.041) were significantly shorted in the group A. The drainage volume of thorax (351.61 ± 125.00 vs. 418.61 ± 207.86 mL, p = 0.146) was non-significant less and the rate of complications (3.2% vs. 11.1%, p = 0.074) was non-significant lower in group A compared with group B. The postoperative hospital stay (9.0 (8.0,13.0) vs. 9.0 (8.0,12.0) days, p = 0.983) were similar in two groups. No serious adverse event occurred in any patient.ConclusionsThe ICB exposed could protect the right pleura and may promote postoperative recovery, which may be used as an anatomical marker in inferior mediastinal lymphadenectomy.

Adjuvant chemoradiotherapy vs adjuvant chemotherapy in locally advanced Siewert type II/III adenocarcinoma of gastroesophageal junction after D2/R0 resection.

BACKGROUNDFor Siewert type II/III adenocarcinoma of gastroesophageal junction (AGE), the efficacy of adjuvant chemoradiotherapy (CRT) after D2/R0 resection remains uncertain.AIMTo determine whether CRT was superior to chemotherapy (CT) alone after D2/R0 resection for locally advanced Siewert type II/III AGE.METHODSWe identified 316 locally advanced Siewert type II/III AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018. 57 patients received adjuvant CRT and 259 patients received adjuvant CT. We followed patients for overall survival (OS), relapse-free survival, and recurrence pattern.RESULTSFive-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9% (P = 0.010). Five-year OS rates of the CRT group and the CT group for Siewert type III AGE patients were 65.7% and 43.9% (P = 0.006). Among the 195 patients whose recurrence information could be obtained, 18 cases (34.6%) and 61 cases (42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively. The local and regional recurrence rates in the CRT group were lower than that in the CT group (22.2% vs 24.6%, 27.8% vs 39.3%). Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type III AGE.CONCLUSIONFor locally advanced Siewert type III AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.

Selection of Digestive Tract Reconstruction After Partial Gastric Sparing Surgery in Patients With Adenocarcinoma of the Esophagogastric Junction of cT2-T3 Stage.

ObjectiveTo investigate the appropriate reconstruction method of the digestive tract after partial gastric sparing surgery for adenocarcinoma of the esophagogastric junction of stage cT2-T3.MethodsA retrospective analysis of the clinical data of patients with adenocarcinoma of the esophagogastric junction from January 2015 to January 2019 in the General Surgery Department of Zhengzhou University Affiliated Tumor Hospital was performed. Patients with intraoperative double tract anastomosis composed the double tract reconstruction (DTR) group, and patients with intraoperative oesophagogastrostomy with a narrow gastric conduit group composed the oesophagogastrostomy by a narrow gastric conduit (ENGC) group. We analysed and compared the short-term postoperative complications and long-term postoperative nutritional status of the two groups of patients.ResultThere were no statistically significant differences between the two groups of patients in terms of age, sex, preoperative haemoglobin level, albumin level, cT, cN, neoadjuvant therapy or not, pathological type and Siewert type. In terms of BMI and body weight, the ENGC group was higher than the DTR group, but the difference was not statistically significant (p = 0.099, p = 0.201). There was no significant difference between the two groups of patients in terms of upper resection margin, operation time, blood loss, tumor diameter, pT, pN and postoperative hospital stay. The gastric resection volume of the DTR group was much larger than that of the ENGC group, and there was a significant difference between the two (p = 0.000). The length of the lower resection margin of the DTR group was also significantly greater than that of the ENGC group (p = 0.000). In terms of surgical approach, the proportion of the DTR group with the abdominal approach was significantly higher than that of the ENGC group, and the difference between the two was statistically significant (p = 0.003). The postoperative exhaust time in the ENGC group was significantly shorter than that in the DTR group (p = 0.013). However, there was no statistically significant difference between the two groups in terms of anastomotic leakage, anastomotic bleeding, intestinal obstruction, abdominal infection, pneumonia, pancreatic leakage, lymphatic leakage,death within 30 days after surgery, or overall complications. In terms of anastomotic stenosis, the incidence in the ENGC group was higher than in the DTR group, and the difference was statistically significant (p = 0.001). There was no significant difference in oral PPI, haemoglobin or albumin levels in patients at 3 months, 6 months, or 12 months after surgery. Comparing reflux/heartburn symptoms at 3 months and 6 months after surgery, we found no statistically significant difference between the two, while in terms of reflux/heartburn symptoms at 12 months after surgery, the findings of the ENGC group were higher than those of the DTR group, and the difference was statistically significant (p = 0.045). In terms of poor swallowing, the ENGC group was always higher than the DTR group, and the difference between the two groups was statistically significant (p < 0.05). There was no statistically significant difference in body weight between the two groups at 3 months or 6 months after surgery. At 12 months after surgery, the body weight of the patients in ENGC group was significantly higher than that in the DTR group, and the difference between the two groups was statistically significant (p = 0.039).ConclusionsFor patients with cT2-T3 stage oesophagogastric junction adenocarcinoma with tumours less than 4 cm in diameter, ENGC anastomosis is recommended for patients with a high tumour upper boundary, with obesity, short mesentery, or disordered vascular arch, and for routine patients, DTR anastomosis is recommended.

Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients

BackgroundThis study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA.MethodsA total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan–Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA.ResultsThere were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages.ConclusionThoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Diverse contributions of the visceral fat area to the etiology of two distinct subtypes of esophago-gastric junctional adenocarcinoma

Background There are two distinct etiologies of esophago-gastric junctional adenocarcinomas (EGJACs): one associated with extensive gastric mucosal atrophy (GA), resembling non-cardiac gastric cancers; and the other related to gastro-esophageal reflux disease, resembling esophageal adenocarcinoma. In this study, we investigated the associations between the visceral fat area (VFA) and EGJACs separately in the two subtypes of EGJACs, depending on the extent of background GA. Methods Sixty-four consecutive patients with EGJACs (Siewert type 2) were enrolled from a population-based database in Akita Prefecture, Japan, between 2014 and 2019. Two age- and sex-matched healthy controls were randomly assigned to each EGJAC case. The extents of GA were evaluated endoscopically, and the VFA values were measured based on computed tomography images. Logistic regression analyses were performed to investigate the associations between EGJACs and the VFA. Results Study subjects were classified into 2 subgroups depending on the extent of endoscopic GA: 29 (45.3%) without and 35 (54.7%) with extensive GA. Multivariable regression analyses revealed that a VFA of ≥100 cm2 was significantly associated with EGJACs in subjects without extensive GA [odds ratio (95% confidence interval): 2.65 (1.08–6.54)], while there was no such association in subjects with extensive GA [odds ratio (95% confidence interval): 1.52 (0.60–3.83)]. Conclusions The contribution of the VFA to the etiology of EGJACs seems to differ depending on the extent of background GA, with the VFA more prominently associated with EGJACs in subjects without extensive GA than in those with it, providing further rationale concerning the heterogeneous nature of EGJAC etiology.

Surgical Strategies for Siewert Type II Esophagogastric Junction Carcinomas: A Randomized Controlled Trial.

AimTo determine the ideal surgical approach for Siewert type II EGJ carcinomas.MethodsWe conducted the randomized controlled trial (RCT) at Shanxi Cancer Hospital from January 2014 to August 2016. A total of 105 patients with T1-4N1-3M0 Siewert type II EGJ carcinomas were initially recruited. The final follow-up was up to June 30, 2019. Patients were randomized to undergo either a proximal gastrectomy plus jejunal interposition (PG+JI), proximal gastrectomy plus esophagogastrostomy (PG+EG), or total gastrectomy plus Roux-en-Y esophagojejunostomy (TG+RY). The primary endpoint was postoperative complications. Secondary endpoints were 5-year survival and recovery indexes.ResultsAmong 105 patients, 100 patients (95.2%; mean age, 56.2 years) with tumors <3cm in size underwent surgery: PG+JI (n=33) vs. PG+EG (n=33) and TG+RY (n=34); 91 patients completed the study. Among the groups, the PG+JI group had the longest reconstruction time: 34.11 ± 6.10 min vs. 21.97 ± 3.30 min (PG+EG) vs. 30.56 ± 4.26 min (TG+RY); p<0.001. There was no postoperative mortality. In the per-protocol analysis, the PG+JI group showed a decreased tendency in complication rate: 6.9% vs. 23.3% (PG+EG) vs. 18.8% (TG+RY), but there was no significant difference. For recovery indexes, the TG+RY group had the lowest values of the amount of single meal, weight loss, hemoglobin, albumin, pepsin, and gastrin among the three groups. There was no significant difference among the three groups in 5-year survival.ConclusionsProximal gastrectomy is preferable for T1-4N1-3M0 Siewert type II EGJ carcinomas with tumors <3cm in size because of its better nutrition status under similar postoperative complication to total gastrectomy. Jejunal interposition can be recommended as a optional reconstruction approach after proximal gastrectomy.Clinical Trial Registrationhttps://www.chictr.org.cn/, identifier ChiCTR-IIR-16007733.

Nomograms for Predicting Disease-Free Survival in Patients With Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction Receiving Neoadjuvant Therapy and Radical Surgery.

ObjectiveThis study aimed to develop prognostic prediction models for patients with Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG) who received neoadjuvant therapy (neoadjuvant chemoradiotherapy or neoadjuvant chemotherapy) and radical surgery. A baseline nomogram and a post-operative nomogram were constructed before neoadjuvant therapy and after surgery. The predictive performance of the constructed nomograms was internally validated and compared to the TNM staging system.Materials and MethodsA total of 245 patients diagnosed with Siewert type II/III AEG and treated with neoadjuvant therapy followed by radical surgery at The Fourth Hospital of Hebei Medical University between January 2011 and December 2017 were enrolled. The variables before neoadjuvant therapy were defined as baseline factors, while the variables of baseline factors along with the variables of treatment and postoperative pathology were defined as post-operative factors. To construct the corresponding nomograms, independent predictors of baseline and post-operative factors were identified. The C-index and a time-dependent receiver operating characteristic curve were used to evaluate the model’s discrimination ability. The calibration ability of the model was determined by comparing the probability of predicted free-recurrence to the actual free-recurrence. Decision curve analysis (DCA) was used to determine the clinical usefulness of the nomogram.ResultsAmong the baseline factors, age, cT stage, cN stage, Borrmann type, and staging laparoscopy were independent prognostic predictors. In contrast, among the post-operative factors, age, cN stage, staging laparoscopy, ypT stage, clinical response, number of positive lymph nodes, number of negative lymph nodes, laurén classification, and lymphatic, or perineural invasion (VELPI) were independent prognostic predictors. The two nomograms were constructed using the independent predictors of prognosis. The C-indexes for the baseline and post-operative nomograms were 0.690 (95% CI, 0.644-0.736) and 0.817 (95% CI, 0.782-0.853), respectively. The AUCs of the baseline nomogram at 3 and 5 years were both greater than cTNM (73.1 vs 58.8, 76.1 vs 55.7). Similarly, the AUCs of the post-operative nomogram were both greater than ypTNM (85.2 vs 69.1, 88.2 vs 71.3) at 3 and 5 years. The calibration curves indicated that both models had a high degree of calibration ability. By comparing the DCA at 3 and 5 years, we determined that the two nomograms constructed had better clinical utility than the TNM staging system.ConclusionsThe constructed nomograms have a more accurate predictive ability than the eighth edition TNM staging system, which can be useful for treatment selection and follow-up monitoring of patients.