Thoracic Duct Visualization in Esophageal Resection: A Pilot Trial.

INTRODUCTION: Inadvertent thoracic duct injury is common during esophagectomy and may result in postoperative chylothorax. This study's objective was to investigate utility of patent blue injection as a modality for intraoperative thoracic duct visualization. METHODS: A prospective, single-arm, interventional study of patients undergoing minimally invasive esophagectomy was performed. Patients were injected with patent blue dye into both groins prior to thoracic stage of surgery and assessed for duct visualization. Control group was formed by propensity score matching using retrospectively collected data regarding patients who underwent esophagectomy. RESULTS: A total of 25 patients were included in analysis, compared to a control of 50 patients after matching. Thoracic duct was visualized in 60% of patients in the study group (15/25 patients). Significant differences were found between study and control groups (p < 0.05) with regards to median operative time (422 vs. 285 min, respectively), overall complications (16 vs. 34%, respectively), and median postoperative length of stay (13.5 vs. 10 days, respectively). There was a difference in rate of chyle leak between study and control groups; however, this was not significant (0 vs. 12%, respectively, p = 0.17). CONCLUSION: Patent blue injection represents a simple method for thoracic duct visualization during minimally invasive esophagectomy which may improve surgical outcomes.

Implementing the first program of minimally invasive esophagectomy for cancer in Israel: shifting the paradigm in a high-volume center - a cohort study.

BACKGROUND: Esophagectomy is associated with significant perioperative morbidity. Limited data are available on the process of implementation of minimally invasive techniques in esophagectomy and related outcomes. The authors sought to describe implementation processes and outcomes following the implementation of the first minimally invasive esophagectomy (MIE) program at a high-volume center in Israel under the mentorship of American early adopters. METHODS: Patients who underwent esophagectomy for esophageal carcinoma 2011-2022 were included. Early and late cohorts were created for learning curve analysis. Secondary analysis included patients who underwent open esophagectomy 1997-2011. RESULTS: Overall, 300 patients underwent MIE: three-field MIE (3F-MIE) was performed in 242 (80.7%) patients, two-field MIE (2F-MIE) in 58 (19.3%) patients. Following program implementation in 2012, the number of MIE performed increased during the first 3 years ( n =33, 86.8% in 2015). Among 3F-MIE patients, a higher number of retrieved lymph nodes was reported during later cases (median, IQR1-3 17, 12-23 vs. 12, 8-12, P <0.001) while surgeries required a longer time (median, IQR1-3 300 min, 261-355 vs. 262.5, 239-300, P <0.001). Among 2F-MIE patients, the late cohort had lower rates of prolonged ICU admissions than earlier counterparts ( n =2, 6.9% vs. n =9, 31%, P =0.041), overall and severe 30-day complications ( n =12, 41.4% vs. n =23, 79.3%, P <0.001 and n =7, 24.1% vs. n =23, 79.3%, P =0.003). CONCLUSIONS: MIE was safely implemented. Nodal yield was higher among MIE patients than open esophagectomy. During the study years, open approach was gradually abandoned in favor of 3F-MIE procedures, while 2F-MIE increased over the course of the last years.

Gastrectomy for Distal Gastric Cancer: Transitioning from an Open to a Minimally Invasive Surgical Practice. A Single Surgeon Experience.

BACKGROUND: Surgical resection is the only curative option for gastric carcinoma (GC). Minimally invasive techniques are gaining popularity. OBJECTIVES: To present a single-surgeon's experience in transitioning from an open to a minimally invasive approach, focusing on surgical and oncological outcomes. METHODS: We conducted a retrospective analysis including distal gastrectomy patients 2012-2020 operated by a single surgeon. Two cohorts were compared: open (ODG) and laparoscopic distal gastrectomy (LDG). RESULTS: Overall, 173 patients were referred for gastrectomy during the study years. We excluded 80 patients because they presented with non-GC tumors, underwent proximal or total gastrectomy, or underwent palliative surgery. Neoadjuvant treatment was administered to 62 patients (33.3%). Billroth 1 was the preferred method of reconstruction (n=77, 82.8%), followed by Roux-en-Y (n=12, 13%). Fifty-one patients (54.8%) underwent LDG, 42 (45.2%) underwent ODG. The LDG group had significantly shorter lengths of stay (6 days, interquartile range [IQR] 1-3 5-8 vs. 5 days, IQR 1-3 4-6, P = 0.001, respectively), earlier return to oral feeding (1 day, IQR 1-3 1-3 vs. 2 days, IQR 1-3 1-3.2, P < 0.001), and earlier removal of drains (4 days, IQR 1-3 3-5.2 vs. 5 days, IQR 1-3 3.5-6.7, P < 0.001). Overall lymph node yield was 30 (IQR 1-3 24-39) and was similar among groups (P = 0.647). CONCLUSIONS: Laparoscopic techniques for resection of distal GC are feasible and safe, leading to good perioperative outcomes and adequate lymph node yield.

Predicting Factors for a Favorable Pathologic Response to Neoadjuvant Therapy in Esophageal Cancer.

BACKGROUND: Favorable pathologic response(FPR) is a significant predictor for improved survival following Neoadjuvant therapy(NAT) in esophageal and gastroesophageal cancer(GEJ). Preoperative prediction of FPR could modify treatment plans. No reliable method for predicting FPR exists. We sought to identify preoperative predicting factors for FPR. MATERIALS AND METHODS: Retrospective analysis of patients with esophageal and GEJ cancer who underwent esophagectomy following (NAT). Univariate and multivariate analysis was used to identify preoperative predicting factors for FPR. A comparison of Tumor Regression Grade(TRG) was used to assess treatment response on overall survival(OS). RESULTS: Out of 121 patients, 82(67.8%) had neoadjuvant chemoradiation. FPR was observed in 60(49.6%). Female sex, Radiation therapy(RT), squamous cell carcinoma(SCC), lack of signet ring feature, and FDG avidity posttreatment were associated with FPR on univariate analysis. RT and SCC were associated with FPR (OR=3.9 and 4.0, respectively) on multivariate analysis. OS was lower among patients who did not achieve FPR to NAT(P=0.027). CONCLUSIONS: FPR is a predictor of improved OS. SCC and radiation therapy-based protocol were identified as major prediction factors of FPR in patients with esophageal and GEJ cancers.

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study.

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen. Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD). Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)]. Conclusions: Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.

Signet Ring Cell Features are Associated with Poor Response to Neoadjuvant Treatment and Dismal Survival in Patients with High-Grade Esophageal Adenocarcinoma.

BACKGROUND: While the prognosis of patients with locoregional esophageal adenocarcinoma (EAC) has improved in the neoadjuvant treatment (NAT) era, high-grade histology (G3) is still associated with a limited treatment response. We sought to investigate oncologic outcomes in patients after esophagectomy for G3 EAC and to identify predictors of poor survival among these patients. METHODS: Patients with EAC who underwent resection with curative intent in 2011-2018 were divided by histologic grade (G3, G1/2) and compared for overall survival (OS). Cox regression was performed to analyze the response to NAT and the predictive role of signet ring cell (SRC) features. RESULTS: The cohort included 163 patients, 94 (57.7%) with G3 histology. NAT was administered to 69 (73.4%) patients. Following resection, OS in the G3 EAC group was 30 months (95% confidence interval [CI] 23.9-36.1). On univariate analysis, G3 disease (p = 0.050) and SRC features (p = 0.019) predicted low OS. Median survival in the G3 EAC group was worse in patients with SRC histology (18 months, 95% CI 8.6-27.4) than those without (30 months, 95% CI 23.8-36.1; p = 0.041). No patients with SRC histology were alive at 5 years of follow-up. Among all patients administered NAT, 88.2% of those with SRC showed minimal or no pathologic response and only 27.8% were downstaged. CONCLUSIONS: High-grade histology was found in most patients with EAC and predicted poor survival and treatment response. SRC features in patients with G3 disease were associated with lower OS. The benefit of NAT for G3 EAC in patients with SRC histology appears limited.

Abdominal Surgery in Patients with a Ventricular Assist Device: A Single Center Experience in Israel.

BACKGROUND: Left ventricular assist devices (LVADs) are used more commonly in patients with advanced-stage heart failure. Some of these patients may require elective or urgent abdominal surgical procedures. OBJECTIVES: To determine the outcomes of the management of LVAD-supported patients who underwent elective and urgent abdominal surgical procedures in our institution. METHODS: A retrospective review was conducted on 93 patients who underwent LVAD implantation between August 2008 and January 2017. All abdominal surgeries in these patients were studied, and their impact on postoperative morbidity and mortality Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patientswas evaluated. RESULTS: Ten patients underwent abdominal surgical procedures. Of these procedures, five were emergent and five were elective. The elective cases included one bariatric surgery for morbid obesity, one hiatal hernia repair, two cholecystectomies, and one small bowel resection for a carcinoid tumor. The emergency cases included suspected ischemic colitis, right colectomy for bleeding adenocarcinoma, laparotomy due to intraabdominal bleeding, open cholecystectomy for gangrenous cholecystitis, and laparotomy for sternal and abdominal wall infection. All patients undergoing elective procedures survived. Of the five patients who underwent emergency surgery, three died (60%, P = 0.16) and one presented with major morbidity. One of the two survivors required reintervention. In total, 12 interventions were performed on this group of patients. CONCLUSIONS: It is safe to perform elective abdominal procedures for LVAD-supported patients. The prognosis of these patients undergoing emergency surgery is poor and has high mortality and morbidity rates.

The addition of cetuximab to preoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is associated with high rate of long term survival: Mature results from a prospective phase Ib/II trial.

AIM: This phase IB/II study evaluated the safety and efficacy of the addition of cetuximab to standard preoperative chemoradiotherapy (CRT) in locally advanced esophageal cancer (LAEC). METHODS: Patients (pts) with resectable LAEC (T2-3N0-1M0, T1-3N1M0 or T1-3N0-1M1A) received an induction cycle of cisplatin 100 mg/m2, day 1, and 5-fluorouracil (5-FU) 1000 mg/m2/day, days 1-5, followed 4 weeks later by radiotherapy, 50.4 Gy, given with 2 cycles of cisplatin 75 mg/m2 and escalating doses of 5-FU, days 1-4 and 29-32. Pts received 10 weekly infusions of cetuximab, 250 mg/m2, with a loading dose, 400 mg/m2. Surgery was planned 6-8 weeks after CRT. RESULTS: 64 pts were treated and 60 completed CRT. Median age was 65 years and 66% were males. Adenocarcinoma/squamous ratio was 61%/39%. Tumors were advanced: 95% T3 and 67% N1. Grade ≥3 toxicities occurred in 72%, with two (3%) toxic deaths. The 5-FU maximal tolerated dose (MTD) was 1000 mg/m2/day. Clinical complete response rate was 33%. Of the 55 operated pts, R0 resection was achieved in 51 (93%) and pathological complete response (pCR) in 18 (33%), with 8 (14%) postoperative deaths. The 5-year survival rate for all pts was 38%. Pts with squamous histology had higher pCR (55% vs 20%, p = 0.015), local control (96% vs. 74%, p < 0.001) and 5-year survival (58% vs 25%, p = 0.011) rates. CONCLUSIONS: This study suggests that the addition of cetuximab to standard preoperative CRT is feasible. R0, pCR and local control rates are encouraging. Pts with squamous cell tumors benefited more from the addition of cetuximab.

Esophageal Cancer in Israel has Unique Clinico-Pathological Features: A Retrospective Study.

Introduction: Data regarding esophageal cancer (EC) in Israel are limited. The aim of this study was hence to characterize this entity in the Israeli population and to compare it to the literature. Patients/Methods: This is a retrospective study of all consecutive EC patients treated at our institution between 1997-2013. Data were retrieved from patients' medical files. Results: Two hundred patients were included. The median age at diagnosis was 70.5 years; 63.5% were males; 63% were Ashkenazi Jews, 29% were Sephardic Jews, and 0.5% were Arabs. Squamous cell carcinoma (SCC) was predominant: 52% versus 45.5% with adenocarcinoma (ADC). SCC was common even in the distal esophagus (45%). The overall 5-year survival rate was 25.5%. A temporal trend (2006-2013 vs 1997-2005) shows a decline in the proportion of SCC (47% vs 63%, p=0.061) and a rise in ADC (50% vs 33%, p=0.041), with a parallel decrease in patients' age (median: 68.5 vs 73 years, p=0.014). In the later period, patients received more treatment for localized and metastatic disease, with a trend for improved median survival (20.1 vs 14.9 months, p=0.658). Ashkenazi Jews were diagnosed at an older age than Sephardic Jews (median: 73 vs. 65 years, p=0.001), had a higher rate of family history of GI cancer (34% vs. 17%, p=0.026) and a higher rate of cardiovascular co-morbidity (41% vs. 24%, p=0.041). Conclusion: EC in Israel represents an intermediate entity between the Western and the endemic subtypes, showing some unique features. These included delayed reversal of the SCC/ADC ratio, commonness of SCC in the distal esophagus, prevalence of other malignancies and predominance of Ashkenazi ethnicity. The reason for these findings is unclear and its further evaluation is warranted.

Gastrointestinal Stromal Tumor of Stomach: A Gentle Enemy of the Surgeon. Our Experience in Confronting the Disease.

BACKGROUND: Surgical resection is considered to be the best treatment for gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the gastrointestinal tract. Tumor size, mitotic rate, and anatomic locations are directly related to the potential malignancy, surgical approach, oncological treatment, and recurrence rate. MATERIALS AND METHODS: This was a retrospective study of 40 patients who underwent surgical resection of histologically or immunohistochemistry-proven GIST of the stomach at the Rabin and Kaplan Medical Center between 2004 and 2013. Tumor size, location, margin status, pathologic characteristics, surgical approach, surgical outcome, and long-term follow-up were analyzed from hospital records. RESULTS: The most common presentation was upper gastrointestinal bleeding (40%), although 30% of cases were asymptomatic. A laparoscopic approach was the preferred technique whenever feasible; 85% of tumors were localized in the proximal stomach, with a median size of 5.6 cm. Most of the resected tumors revealed a low mitotic rate and thus had low-moderate risks of malignancy. All tumors were completely resected with free surgical margins. The median follow-up period was 40 months with 93% disease-free survival. CONCLUSIONS: Gastric GIST is a snake in the grass and its diagnosis is often incidental to endoscopy and computed tomographic scan. The most important technical point is to avoid tumor rupture during removal.