Relevance of Subcarinal Lymph Node Dissection for Gastroesophageal Junction Adenocarcinoma.

INTRODUCTION: Reported rates of subcarinal lymph node (LN) metastases for esophageal carcinoma vary from 20% to 25% and the relevance of subcarinal lymph node dissection (LND) for gastroesophageal junction (GEJ) adenocarcinoma is poorly defined. This study aimed to evaluate rates of subcarinal LN metastasis in GEJ carcinoma and determine their prognostic significance. METHODS: Patients with GEJ adenocarcinoma undergoing robotic minimally invasive esophagectomy from 2019 to 2021 were retrospectively assessed within a prospectively maintained database. Baseline characteristics and outcomes were examined with attention to subcarinal LND and LN metastases. RESULTS: Among 53 consecutive patients, the median age was 62, 83.0% were male, and all had Siewert type I/II tumors (49.1% and 50.9%, respectively). Most patients (79.2%) received neoadjuvant therapy. Three patients had subcarinal LN metastases (5.7%) and all had Siewert type I tumors. Two had clinical evidence of LN metastases preoperatively and all three additionally had non-subcarinal nodal disease. A greater proportion of patients with subcarinal LN disease had more advanced (T3) tumors compared to patients without subcarinal metastases (100.0% versus 26.0%; P = 0.025). No patient with subcarinal nodal metastases remained disease free at 3 y after surgery. CONCLUSIONS: In this consecutive series of patients with GEJ adenocarcinoma undergoing minimally invasive esophagectomy, subcarinal LN metastases were found only in patients with type I tumors and were noted in just 5.7% of patients, which is lower than historical controls. Subcarinal nodal disease was associated with more advanced primary tumors. Further study is warranted to determine the relevance of routine subcarinal LND, especially for type 2 tumors.

Acute gastric conduit dilation after minimally invasive esophagectomy: a 10-year experience.

Despite decreasing overall morbidity with minimally invasive esophagectomy (MIE), conduit functional outcomes related to delayed emptying remain challenging, especially in the immediate postoperative setting. Yet, this problem has not been described well in the literature. Utilizing a single institutional prospective database, 254 patients who underwent MIEs between 2012 and 2020 were identified. Gastric conduit dilation was defined as a conduit occupying >40% of the hemithorax on the postoperative chest X-ray. Sixty-seven patients (26.4%) demonstrated acute conduit dilation. There was a higher incidence of conduit dilation in the patients who underwent Ivor Lewis esophagectomy compared to those with a neck anastomosis (67.2% vs. 47.1%; P = 0.03). Patients with dilated conduits required more esophagogastroduodenoscopies (EGD) (P < 0.001), conduit-related reoperations within 180 days (P < 0.001), and 90-day readmissions (P = 0.01). Furthermore, in 37 patients (25.5%) undergoing Ivor Lewis esophagectomy, we returned to the abdomen after intrathoracic anastomosis to reduce redundant conduit and pexy the conduit to the crura. While conduit dilation rates were similar, those who had intraabdominal gastropexy required EGD significantly less and trended toward a lower incidence of conduit-related reoperations (5.6% vs. 2.7%). Multivariable analysis also demonstrated that conduit dilation was an independent predictor for delayed gastric conduit emptying symptoms, EGD within 90 days, conduit-related reoperation within 180 days, and 30-day as well as 90-day readmission. Patients undergoing MIE with acute gastric conduit dilation require more endoscopic interventions and reoperations.

Robotic versus thoraco-laparoscopic minimally invasive Ivor Lewis esophagectomy, a matched-pair single-center cohort analysis.

Minimally invasive esophagectomy (MIE) is becoming more widespread with a documented improvement in postoperative morbidity based on level I evidence. However, there is a lack of consensus regarding the optimal MIE approach, conventional thoracoscopy/laparoscopy vs robotics as well as the ideal anastomotic technique. All patients who underwent MIE via an Ivor Lewis approach with a side-to-side stapled anastomosis were included. The thoracoscopy-laparoscopy (TL) group was compared to the robotic group with respect to perioperative outcomes using the entire cohorts and after 1:1 propensity score matching. Comparisons were made using the Mann-Whitney U and Fisher's exact tests. Between July 2013 and November 2020, 72 TL and 67 robotic Ivor Lewis MIE were performed. After comparing the two unadjusted cohorts and 51 propensity matched pairs, there was a decrease in Clavien-Dindo Grade 2 or above complications in the robotic vs TL group (59.7% vs 41.8% [P = 0.042], (62.7% vs 39.2% [P = 0.029]), respectively. In both analyses, there was a reduction in hospital length of stay (median of 8 vs 7 days, P < 0.001) and a trend toward less anastomotic leaks in the robotic group (Unadjusted: 12.5 vs 3% [P = 0.057], Propensity-matched analysis: 13.7% vs 3.9% [P = 0.16]), respectively. A clinically significant decrease in overall morbidity, cardiac complications and hospital length of stay was observed in the robotic Ivor Lewis cohort when compared with the TL group at a high volume MIE program. Side-to-side stapled thoracic anastomoses utilizing a robotic platform provides the best outcomes in this single institution experience.

Robotic Enucleation of a Large Gastroesophageal Junction Leiomyoma.

In this multimedia article, we demonstrate transabdominal robotic enucleation of a large, multilobulated leiomyoma at the gastroesophageal junction (GEJ). The robotic platform provides stereoscopic visualization and wristed motion, which improved ease of an organ-sparing resection in a challenging anatomic location. Alternative minimally invasive approaches to tumors in this location have been reported including endoscopic, endoscopic with laparoscopic assistance, laparoscopic, and thoracoscopic approaches, with choice of approach dependent upon the location and configuration of the tumor Milito et al. in J Gastrointest Surg 24:499-504, 2020;Li et al. in Dis Esophagus. 22:185-189, 2009;Armstrong et al. in Am Surg. 79:968-972, 2013;Kent et al. in J Thorac Cardiovasc Surg. 134:176-181, 2007.

Technique for Robotic Transhiatal Esophagectomy.

Minimally invasive esophagectomy is increasing performed for cancers of the esophagus and gastroesophageal junction. This video demonstrates the setup and key steps for a robotic transhiatal esophagectomy with a cervical anastomosis.

Risk-stratified analysis of pasireotide for patients undergoing pancreatectomy.

BACKGROUND AND OBJECTIVES: Pasireotide was shown in a randomized trial to decrease the rate of postoperative pancreatic fistula (POPF). However, retrospective series from other centers have failed to confirm these results. METHODS: Patients who underwent pancreatoduodenectomy or distal pancreatectomy between January 2014 and February 2019 were included. Patients treated after November 2016 routinely received pasireotide and were compared to a retrospective cohort. Multivariate analysis was performed for the outcome of clinically relevant POPF (CR-POPF), with stratification by fistula risk score (FRS). RESULTS: Ninety-nine of 300 patients received pasireotide. The distribution of high, intermediate, low, and negligible risk patients by FRS was comparable (P = .487). There were similar rates of CR-POPF (19.2% pasireotide vs 14.9% control, P = .347) and percutaneous drainage (12.1% vs 10.0%, P = .567), with greater median number of drain days in the pasireotide group (6 vs 4 days, P < .001). Multivariate modeling for CR-POPF showed no correlation with operation or pasireotide use. Adjustment with propensity weighted models for high (OR, 1.02, 95% CI, 0.45-2.29) and intermediate (OR, 1.02, CI, 0.57-1.81) risk groups showed no correlation of pasireotide with reduction in CR-POPF. CONCLUSIONS: Pasireotide administration after pancreatectomy was not associated with a decrease in CR-POPF, even when patients were stratified by FRS.

Laparoscopic proximal gastrectomy for gastric neoplasms.

BACKGROUND: For cancers of the distal gastroesophageal junction or the proximal stomach, proximal gastrectomy can be performed. It is associated with several perioperative benefits compared with total gastrectomy. The use of laparoscopic proximal gastrectomy (LPG) has become an increasingly popular approach for select tumors. METHODS: We describe our method of LPG, including the preoperative work-up, illustrated depictions of the key steps of the surgery, and our postoperative pathway. RESULTS: A total of 6 patients underwent LPG between July, 2013 to June, 2017. Five patients had early-stage adenocarcinoma, and 1 patient had a gastrointestinal stromal tumor. The median age of the cohort was 70, and each patient had significant comorbidities. Conversion to open was required for 1 patient. All patients had negative final margins and an adequate lymph node dissection (median number of nodes examined was 15, range 12-22). The median postoperative length of stay was 7 days (range 4-7). Two patients developed anastomotic strictures requiring intervention, and 1 patient experienced significant reflux. At a median follow-up of 11 months, there was 1 recurrence. Three patients were alive without evidence of disease, and 2 patients died from other causes. CONCLUSIONS: For carefully selected patients, LPG is a safe and reasonable alternative to total gastrectomy, which is associated with similar oncologic outcomes and low morbidity.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

BACKGROUND: Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. METHODS: Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. RESULTS: 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). CONCLUSION: Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS.

Minimally Invasive Esophagectomy Utilizing a Stapled Side-to-Side Anastomosis is Safe in the Western Patient Population.

BACKGROUND: There has been an increased utilization of minimally invasive esophagectomy (MIE) in an effort to reduce morbidity, decrease length of stay, and improve quality of life. However, there are limited large series of patients undergoing MIE from the United States and no standardized approach. We reviewed our experience with MIE utilizing a stapled side-to-side anastomosis during a 7.5-year period. STUDY DESIGN: A retrospective review of prospectively maintained databases for patients undergoing planned esophagectomy were reviewed from 2007 to 2015. Esophagogastric anastomoses were performed via a 6-cm linear stapled side-to-side method. Demographics, comorbidities, surgical approach, pathology data, and postoperative morbidities were recorded and reviewed. RESULTS: A MIE was attempted in 303 of 315 (96 %) patients, and a total minimally invasive approach was completed in 293 of 315 (93 %) patients. Location of anastomosis was predominantly in the neck, with 244 patients (77.5 %) undergoing a total minimally invasive McKeown approach (n = 231). A total, minimally invasive Ivor-Lewis was completed in 60 patients (19.1 %). Anastomotic leak was identified in 24 patients (7.6 %). Rates of anastomotic leak were 4.4 % for Ivor-Lewis and 8.5 % for McKeown resection. Median length of stay was 8 days, and in-hospital mortality occurred in only three patients (n = 1 %). Ninety-day follow-up demonstrated a 4.1 % stricture rate requiring dilatation. CONCLUSIONS: In the Western patient population, MIE utilizing a 6-cm stapled side-to-side anastomosis is associated with low rates of anastomotic leak, stricture, and mortality.

Total laparoscopic resection for advanced gastric cancer is safe and feasible in the Western population.

BACKGROUND: There is debate surrounding the use of laparoscopic resection for advanced gastric cancer in the Western population. Here we aim to assess the feasibility and short-term outcomes of laparoscopic gastrectomy in consecutive patients in a Western population. METHODS: From 2012 to 2014, retrospective review of 28 patients with clinically staged advanced gastric cancer (≥T3 or ≥N1) treated with laparoscopic resection. RESULTS: Sixty-one percentage of patients were male. Median age was 67 years (range 35-86). Median BMI was 26.5 (range 19.4-46.1). Resection types were proximal (n = 2), distal (n = 14), and total (n = 12). Twenty-six (93 %) patients underwent D2 lymphadenectomy. Four patients underwent conversion to open. Median blood loss was 125 mL (range 30-300). Median LOS was 7 days (range 4-16). Of postoperative complications, five were minor: arrhythmia (n = 1), surgical site infection (n = 3), in-hospital fall (n = 1); and four were major (intra-abdominal abscess, stricture, PE, and anastomotic bleed). T stages were Tx (n = 1), T2 (n = 3), T3 (n = 18), and T4 (n = 6). N stages were N0 (n = 4), N1 (n = 8), N2 (n = 1), and N3 (n = 15). Median tumor size was 5.8 cm (range 0-9.5). Median lymph node yield was 22 (range 6-53). All margins were negative. Median follow-up was 12.8 months (range 2-27). Six patients have died of progressive disease. CONCLUSION: Following total laparoscopic resection for advanced gastric cancer, oncologic endpoints, postoperative course, and early cancer-specific follow-up are excellent. The results demonstrated here support the routine use of these techniques in the Western patient population.

Pancreatic cancer metastatic to a limited number of lymph nodes has no impact on outcome.

BACKGROUND: The purpose of this study was to determine the association of the extent of metastatic lymph node involvement with survival in pancreatic cancer. METHODS: This is a retrospective review of a prospectively maintained database of patients who underwent resection for pancreatic adenocarcinoma, 1999-2011. RESULTS: 165 patients were identified and divided into 3 groups based on the number of positive lymph nodes - 0 (group A), 1-2 (B), >3 (C). Each group had 55 patients. Those in group C were more likely to have a higher T stage, poorly differentiated grade, lymphovascular invasion (LVI), higher mean intraoperative blood loss, positive margins, tumor location involving the uncinate process, and a higher likelihood of undergoing a pancreaticoduodenectomy. Median overall survival (OS) for group A, B and C was 25.5 months (mo), 21 mo and 12.3 mo, respectively (p < 0.001). No survival difference was noted for survival between groups A and B (p = 0.86). The ratio of involved lymph nodes <0.2 was predictive of improved survival (p < 0.001). CONCLUSIONS: Resected pancreatic cancer patients with only 1-2 positive lymph nodes or less than 20% involvement have a similar prognosis to patients without nodal disease. Current staging should consider stratification based on the extent of nodal involvement.

Molecular Targets in Biliary Carcinogenesis and Implications for Therapy.

UNLABELLED: Biliary tract cancers (BTCs) encompass a group of invasive carcinomas, including cholangiocarcinoma (intrahepatic, perihilar, or extrahepatic), and gallbladder carcinoma. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. The latest recommendation is to treat advanced or metastatic disease with gemcitabine and cisplatin, although chemotherapy has recorded modest survival benefits. Comprehension of the molecular basis of biliary carcinogenesis has resulted in experimental trials of targeted therapies in BTCs, with promising results. This review addresses the emerging role of targeted therapy in the treatment of BTCs. Findings from preclinical studies were reviewed and correlated with the outcomes of clinical trials that were undertaken to translate the laboratory discoveries. IMPLICATIONS FOR PRACTICE: Biliary tract cancers are rare. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. Median overall and progression-free survival are 12 and 8 months, respectively. Because chemotherapy has recorded modest survival benefits, targeted therapies are being explored for personalized treatment of these cancers. A comprehensive review of targeted therapies in biliary tract cancers was undertaken to present emerging evidence from laboratory and/or molecular studies as they translate to clinical trials and outcomes. The latest evidence on this topic is presented to clinicians and practitioners to guide decisions on treatment of this disease.

Minimally Invasive Esophagectomy with Cervical Anastomosis.

This video demonstrates our technique for a minimally invasive esophagectomy with side-to-side stapled cervical esophagogastric anastomosis. This technique is routinely utilized in most patients undergoing esophagectomy for esophageal or gastroesophageal junction malignancy, excluding type III gastroesophageal junction tumors. Absolute contraindications include significant tumor involvement of the fundus which may necessitate an intrathoracic anastomosis. Relative contraindications include poor pulmonary function or prior extensive surgical history that may either preclude surgery altogether or prevent the ability of the conduit from reaching the cervical region, or could preclude utilization of a minimally invasive approach. We have not found large body habitus to be an absolute contraindication for this approach. The technique involves thoracoscopic mobilization of the esophagus, laparoscopic dissection of the stomach and creation of gastric conduit, and creation of a 6 cm side-to-side stapled cervical esophagogastric anastomosis. The pylorus is treated with a botox injection; routine pyloroplasty is not performed. In our experience, this technique is safe, oncologically appropriate, and provides excellent functional results.

Gastrointestinal stromal tumors (GISTs) at uncommon locations: a large population based analysis.

INTRODUCTION: Sparse information is available about GISTs in uncommon locations. Our large database analysis aims to determine the characteristics of GISTs in the esophagus, colon and rectum and compare to gastric GISTs. METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried from 1990 to 2009 using CS SCHEMA v0203. Characteristics of each location were compared to gastric GISTs. RESULTS: 4411 GIST (29 esophageal, 2658 stomach, 1463 small intestine, 126 colonic, and 135 rectal) from 1990 to 2009 were identified. Univariate and multivariate predictors of worse disease specific survival in both the entire cohort and surgical resection group include older age, male gender, tumor size > 5 cm, no surgical intervention and anatomical location. Although less likely to undergo surgical resection, esophageal GIST (all patients and resected) had a comparable survival to gastric GIST. A higher proportion of colonic GISTs presented with distant disease and had a worse disease specific survival when compared to rectal GISTs. CONCLUSION: Our results show a rising incidence in GISTs and highlight the characteristics of GISTs based on anatomical location. In addition, this is the first study to demonstrate that colonic GISTs behave differently when compared to rectal GISTs and warrants further prospective evaluation.

Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS expression as independent biomarker for survival.

Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results to other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human GEP-NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT-PCR was used to validate these findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6% and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression in GEP-NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis and distant metastasis (p < 0.05). Patients with TS-positive NETs had markedly worse outcomes than TS-negative NETs as shown by univariate (p < 0.001) and multivariate (p = 0.01) survival analyses. Expression of p18 predicted survival in TS-positive patients that received chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent prognostic biomarker for GEP-NETs. The strong association of increased TS expression with aggressive disease and early death supports the role of TS as a cancer promoting agent in these tumors.

Transhiatal versus transthoracic esophagectomy for esophageal cancer: a 2005-2011 NSQIP comparison of modern multicenter results.

BACKGROUND: The surgical approach to esophageal cancer continues to be controversial. A transthoracic approach is often advocated for better oncologic staging and improved survival. A transhiatal approach is often preferred due to a perceived decreased operative morbidity and mortality. METHODS: Using the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) participant-use file, patients were identified who underwent either a transhiatal or transthoracic esophagectomy for cancer at participating hospitals from 2005 to 2011. Demographic, clinical, intra-operative variables, and 30-day morbidity and mortality were collected. RESULTS: Of the 1,428 patients that had esophagectomy, 750 (52.5%) had a transhiatal (TH) resection and 678 (47.5%) had a transthoracic (TT) resection. The transhiatal group was older (66 vs. 63 years, P = 0.003) with a lower ASA class (2.84 vs. 2.91, P = 0.025). Operative time was greater in the TT group (364 vs. 298 min, P < 0.001). There was no significant difference in 30 day overall mortality (TH = 2.9%, TT = 4.7%, P = 0.095) however a trend favored the TH group. Serious morbidity remains clinically significant in both groups (TH = 39.6%, TT = 43.5%, P = 0.146). The TH group had a significantly higher superficial wound infection rate (11.6% vs. 6.2%, P < 0.001) while the TT group required more perioperative blood transfusions (12.5% vs. 8.9%, P = 0.032) and returns to operating room (14.5% vs. 10.9%, P = 0.046). CONCLUSION: Serious morbidity continues to be high for both types of esophagectomy. There needs to be continued efforts to diminish these complications.

Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer.

BACKGROUND: Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium. METHODS: From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed. RESULTS: We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation. CONCLUSIONS: ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins.