The use of indocyanine green (ICYG) angiography intraoperatively to evaluate gastric conduit perfusion during esophagectomy: does it impact surgical decision-making?

BACKGROUND: Ischemia is known to be a major contributor for anastomotic leaks and indocyanine green (ICYG) fluorescence angiography has been utilized to assess perfusion. Experienced esophageal surgeons have clinically assessed the gastric conduit with acceptable outcomes for years. We sought to examine the impact of ICYG in a surgeon's decision-making during esophagectomy. METHODS: We queried a prospectively maintained database to identify patients who underwent robotic esophagectomy. Time to initial perfusion, time to maximum perfusion, and residual ischemia were measured and used as a guide to resection of residual stomach. During esophagectomy the surgeon identified the anticipated line of ischemic demarcation (LOD) prior to ICYG injection. The distance between the surgeon's LOD and ICYG LOD was measured. RESULTS: We identified 312 patients who underwent robotic esophagectomy, 251 without ICYG and 61 with ICGY. There were no differences in age, sex, race, body mass index, histology, stage, or neoadjuvant therapy use between groups. The incidence of anastomotic leak did not differ between groups (non-ICYG, 5.2% vs. ICYG, 6.6%), p = 0.67. The initial perfusion time was ≥ 10 s and max perfusion was > 25 s in all the patients in the ICYG that developed anastomotic leaks. All patients were noted to have at least 1 cm of residual gastric ischemia. Fifteen patients underwent independent surgeon evaluation of the ischemic LOD prior to ICYG. Differential distances were noted in 12 (80%) patients with a mean distance between surgical line of demarcation and ICYG LOD of 0.77 cm. CONCLUSION: While the implementation of ICYG during esophagectomy demonstrates no significant improvements in anastomotic leak rates compared to historical controls, surgeon's decision-making is impacted in 80% of cases resulting in additional resection of the gastric conduit. Elevated times to initial perfusion and maximum perfusion were associated with increased gastric ischemia and anastomotic leaks.

Comparative outcomes of laparoscopic and robotic approaches to gastrectomy: a National Cancer Database study.

BACKGROUND: Gastric cancer is associated with significant mortality worldwide. Radical gastrectomy with lymphadenectomy is considered the only curative option. Traditionally, these operations are associated with significant morbidity. Laparoscopic gastrectomy (LG) and more recently robotic gastrectomy (RG) techniques have been developed to potentially decrease the perioperative morbidity. We sought to compare oncologic outcomes with laparoscopic and robotic techniques for gastrectomy. METHODS: Utilizing the National Cancer Database we identified patients who underwent gastrectomy for adenocarcinoma. Patients were stratified by open, robotic or laparoscopic surgical technique. Open gastrectomy patients were excluded. RESULTS: We identified 1,301 patients who underwent RG and 4,892 LG with median ages of 65 (20-90) and 66 (18-90) respectively, p = 0.02. The mean number of positive lymph nodes were higher in the LG 2.2 ± 4.4 vs RG 1.9 ± 3.8, p = 0.01. The R0 resections were higher in the RG at 94.5% vs 91.9% in LG, p = 0.001. Conversions to open were 7.1% in the RG and 16% in the LG group, p < 0.001. The median length of hospitalization was 8 (6-11) in both groups. There was no difference in the 30-day readmission (p = 0.65), 30-day mortality (p = 0.85) and 90-day mortality (p = 0.34) between groups. The median and overall 5-year survival was 71.3 mo and 56% in the RG and 66.1 mo and 52% in the LG, p = 0.03. Multivariate analysis revealed that age, Charlson-Deyo comorbidity scores, location of gastric cancer, histology grade, pathologic T-stage, pathologic N-stage, surgical margins, and facility volume were all predictors of survival. CONCLUSIONS: Robotic and laparoscopic techniques are both acceptable approaches to gastrectomy. However, conversions to open are higher and R0 resections rates are lower in the laparoscopic group. Additionally, a survival benefit is demonstrated in those undergoing robotic gastrectomy.

Adjuvant therapy for margin positive pancreatic cancer: A propensity score matched analysis.

BACKGROUND: Adjuvant chemotherapy or chemoradiation is often recommended for resected pancreatic adenocarcinoma. We sought to examine the impact of these therapies on R1 resected pancreatic cancer. METHODS: Utilizing the National Cancer Database we identified patients who underwent pancreatic resection for adenocarcinoma. Patients were stratified by resection status and adjuvant therapy. RESULTS: We identified 28,440 patients who underwent pancreatic resection. Patients with tumor size >2 cm were more likely to undergo R1 resections, p < 0.001. Adjuvant therapy improved survival in all patients with median and 5-year survival: adjuvant chemotherapy (21.7 months, 17.45%), chemoradiation (23.3 months, 20.9%) vs no adjuvant therapy (19.5 months, 19.1%), p < 0.001. In the R1 resection cohort survival was also improved with adjuvant therapy with chemoradiation demonstrating the most significant improvement: adjuvant chemotherapy (15.9 months, 6.5%), chemoradiation (18.7 months, 11.2%) vs no adjuvant therapy (12.5 months, 8.7%), p < 0.001. Chemoradiation but not adjuvant chemotherapy improved survival in the R1 node negative, p < 0.004, and node positive, p < 0.001. Adjuvant chemotherapy benefited survival in R1 node positive patients, p < 0.001. CONCLUSIONS: Patients with pancreatic cancer who undergo R1 resection have significant improvement in survival when treated with adjuvant chemoradiation and adjuvant chemotherapy. However, benefits were greater in those receiving adjuvant chemoradiation.

Comparative outcomes of transthoracic versus transhiatal esophagectomy.

BACKGROUND: Surgical resection has become a mainstay of therapy for locally advanced esophageal cancer and can increase survival significantly. With the advancement of minimally invasive surgery, there is still debate on the best approach for esophagectomy. We report a modern analysis of outcomes with transthoracic versus transhiatal esophagectomy. METHODS: A prospectively managed esophagectomy database was queried for patients undergoing transthoracic or transhiatal esophagectomy between 1996 and 2016. Continuous variables were compared using the Kruskal-Wallis or the analysis of variance tests as appropriate. Pearson χ2 test was used to compare categorical variables. All statistical tests were 2-sided and an α (type I) error < .05 was considered statistically significant. RESULTS: A total of 846 patients underwent esophagectomy with a median age of 66 (28-86) years. There was no difference in estimated blood loss for transthoracic and transhiatal, but mean operating room times were longer for transthoracic versus transhiatal (P < .001), and the number of retrieved lymph nodes was higher for transthoracic versus transhiatal (P < .002). Postoperative complications occurred in 207 (29%) transthoracic patients vs 59 (44.7%) transhiatal patients, (P < .001). The most common complications in transthoracic versus transhiatal techniques, respectively, were anastomotic leaks: 4.3% vs 9.8%; (P = .01), anastomotic stricture 7% vs 26.5%; (P < .001), and pneumonia 12.6% vs 22.7%; (P < .002). Median survival significantly improved in patients undergoing transthoracic (62 months) vs transhiatal (39 months) P = .03. CONCLUSION: We found that a transthoracic approach was associated with lower pneumonias, anastomotic leaks, wound infections, and strictures, with an improvement in nodal harvest. Survival was also significantly improved in patients who underwent transthoracic esophagectomy.

Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future.

A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing.

Comparative outcomes of minimally invasive and robotic-assisted esophagectomy.

OBJECTIVE: Minimally invasive esophagectomy (MIE) has demonstrated superior outcomes compared to open approaches. The myriad of techniques has precluded the recommendation of a standard approach. The addition of robotics to esophageal resection has potential benefits. We sought to examine the outcomes with MIE to include robotics. METHODS: Utilizing a prospective esophagectomy database, we identified patients who underwent (MIE) Ivor Lewis via thoracoscopic/laparoscopic (TL), transhiatal (TH), or robotic-assisted Ivor Lewis (RAIL). Patient demographics, tumor characteristics, and complications were analyzed via ANOVA, χ2, and Fisher exact where appropriate. RESULTS: We identified 302 patients who underwent MIE: TL 95 (31.5%), TH 63 (20.8%), and RAIL 144 (47.7%) with a mean age of 65 ± 9.6. The length of operation was longer in the RAIL: TL (299 ± 87), TH (231 ± 65), RAIL (409 ± 104 min), p < 0.001. However, the EBL was lower in the patients undergoing transthoracic approaches (RAIL + TL): TL (189 ± 188 ml), TH (242 ± 380 ml), RAIL (155 ± 107 ml), p = 0.03. Conversion to open was also lower in these patients: TL 7 (7.4%), TH 8 (12.7%), RAIL 0, p < 0.001. The R0 resection rate and lymph node (LN) harvest also favored the RAIL cohort: TL 86 (93.5%), TH 60 (96.8%), and RAIL 144 (100%), p = 0.01; LN: TL 14 ± 7, TH 9 ± 6, and RAIL 20 ± 9, p < 0.001. The overall morbidity was lower in MIE patients that underwent a transthoracic approach vs. transhiatal: TL 29 (30.5%), TH 39 (61.9%), RAIL 34 (23.6%), p < 0.001. CONCLUSIONS: Patients undergoing MIE via thoracoscopic/laparoscopic and robotic transthoracic approaches demonstrated lower EBL, morbidity, and conversion to open compared to the transhiatal approach. Additionally the oncologic outcomes measured by R0 resections and LN harvest also favored the patients who underwent a transthoracic approach.

Neoadjuvant therapy and pancreatic cancer: a national cancer database analysis.

BACKGROUND: We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent or multiagent chemotherapy, and neoadjuvant chemoradiation (NCRT) on survival in pancreatic cancer. METHODS: Utilizing the National Cancer Database, we identified patients who underwent pancreatic resection for adenocarcinoma (2006 to 2013). Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. RESULTS: We identified 26,563 patients who underwent pancreatic resection: UFS =23,877, NCRT =1,482, and NCT =1,204. Multiagent chemotherapy was utilized in 77% of NCT and 42% of NCRT. There was improved R0 resections associated with neoadjuvant therapy compared to UFS, however, there was no difference between NCT and NCRT. In addition, the was improved R0 with MA-NCT (P<0.001) but not for single agent NCT (P=0.26). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001), and 23.6, 23.9, 31.6, 25.9, and 26.6 months in R0 patients (P=0.03), respectively. There was no difference in OS in patients with R1/2 resection. MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. CONCLUSIONS: There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy.

Clinical fate of T0N1 esophageal cancer: results from the National Cancer Database.

The long-term survival for patients with locally advanced esophageal cancer (EC) remains poor despite improvements in multi-modality care. Neoadjuvant chemoradiation (NCR) followed by surgical resection remains pivotal in the management of patients with EC. However, the outcome of patients whose primary tumor exhibits a complete response with residual regional nodal disease (T0N1) remains unclear as well as the role for adjuvant therapy.Utilizing the National Cancer Database we identified patients with EC who underwent NCR followed by esophagectomy who had subsequent pathology of T0N1. Baseline univariate comparisons of patient characteristics were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests as appropriate. Pearson's Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and α (type I) error <0.05 was considered statistically significant.We identified 7,116 patients diagnosed with EC; 6,235 (87.6%) adenocarcinoma (AC), 881 (12.4%) squamous cell carcinoma (SCC) with a median age of 62 [21-88] years. There were 6,031 (84.8%) males and 1,085 (15.2%) females. R0 resections were achieved in 6,668 (93.7%) patients and this correlated to improved median survival 39.5 (R0) and 20.1 (R1) months respectively, P<0.001. The median nodes harvested were 13 [0-83] with a mean positive LN's of 1.4±2.9. Pathologic complete response (pCR) was achieved in 1,334 (18.7%), partial response (pPR) 2,812 (39.5%) and non-response (pNR) 2,970 (41.7%). There were 230 (3.2%) patients deemed as pathologic T0N1. The median survival of patients with pCR was 61.7 months compared to 32.1 months in the T0N1 patients P<0.001. T0N1 patients did not demonstrate an improved survival over T1/2 patients who had a median survival of 30.5 months, P=0.79. However, T0N1 did reveal an improved survival over T3/4 patients who had a median survival of 24.6 months, P=0.02. Adjuvant chemotherapy in T0N1 did not provide a benefit in survival, median survival adjuvant versus no adjuvant 30.8 vs. 32.1 months respectively, P=0.08. Multivariate analysis in T0N1 patients demonstrated only number of LN's positive, and histology SCC vs. ACC as predictive of survival, HR, 1.22, 95% CI: 1.10-1.36, P<0.001; HR, 0.43, 95% CI: 0.24-0.75, P=0.003, respectively.Patients with EC who exhibit a pathologic T0N1 after NCR have oncologic fates similar to node positive patients. Patients with pCR of the primary tumor and regional lymph nodes continue to demonstrate significant survival benefits over all remaining pathologic cohorts.

Anastomotic leak and neoadjuvant chemoradiotherapy in esophageal cancer.

BACKGROUND: Anastomotic leaks (AL) cause significant morbidity after esophagectomy. Most patients receive neoadjuvant chemoradiation (NCR) prior to esophagectomy which has been associated with increase perioperative complications and mortality. We report on a comparison of AL rates in upfront surgical (UFS) and NCR patients. METHODS: An esophagectomy database was queried for UFS and NCR patients treated between 1996 and 2015. Predictors of AL rate were identified using univariate and multivariate (MVA) analysis and propensity score matching (PSM). RESULTS: We identified 820 patients (UFS, 288; NCR, 532). Overall AL rate was 5.4%. Decreased AL rate was observed in NCR patients on MVA (8.0% vs. 4.1%; P=0.02) but no difference was seen after PSM (7.7% vs. 4.2%; P=0.14). MVA of factors associated with decreased AL in UFS patients included distal esophageal tumors and body mass index (BMI) >25. Age, gender, year of surgery, histology, anastomotic location, and diabetes were not prognostic. Before PSM, MVA of NCR patients of factors associated with decreased AL revealed that only thoracic anastomosis was prognostic. However, this was not observed after PSM. MVA of factors associated with decreased AL in all patients revealed thoracic anastomosis, NCR, and BMI 25-30. After PSM, only distal esophageal tumors and thoracic anastomosis were prognostic for decreased AL. CONCLUSIONS: There is no difference in the AL rate between UFS and NCR patients. Decreased AL rate was observed in patients with distal esophageal tumors and thoracic anastomosis.

Esophagectomy from then to now.

We have come a long way from the onset of surgery for esophageal cancer. Surgical resection is pivotal for the long-term survival in patients with locally advanced esophageal cancer. Moreover, advancements in post-operative care and surgical techniques have contributed to reductions in morbidity. More recently minimally invasive esophagectomy has been increasingly used in patients undergoing esophageal cancer resection. Potential advantages of MIE include: the decreased pulmonary complications, lower post-operative wound infection, decreased post-operative pain, and decreased length of hospitalization. The application of robotics to esophageal surgery is becoming more widespread. Robotic esophageal surgery has potential advantages over the known limitations of laparoscopic and thoracoscopic approaches to esophagectomy while adhering to the benefits of the minimally invasive approach. This paper is a review of the evolution from open esophagectomy to the most recent robotic approach.

Correlation of tumor size and survival in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NT) for resectable pancreatic adenocarcinoma (PAC) continues to be debated. We sought to establish the relationship between pancreatic tumor size, neoadjuvant chemotherapy (NCT), neoadjuvant chemoradiation (NCRT), and definitive surgery (DS) on survival. METHODS: Utilizing the National Cancer Database we identified patients with PAC who underwent NT and DS. Patient characteristics and survival were compared with Mann-Whitney U, Pearson's Chi-square, and the Kaplan-Meier method. Multivariable analysis (MVA) was developed to identify predictors of survival. All tests were two-sided and α <0.05 was significant. RESULTS: We identified 11,707 patients: 9,722 patients with tumors >2 cm and 1,985 with tumors ≤2 cm. There were 523 patients treated with NCT, 559 treated with NCRT, and 10,625 DS. Patients with tumors >2 cm were more likely to have higher T-stage, P<0.001, positive lymph nodes, P<0.001, poor histologic grade, P<0.001, and R1 resections, P<0.001. The median survival for patients with tumors ≤2 cm was 30.6 months compared to 20.5 months for those whose tumors were >2 cm, P<0.001. In the >2 cm groups the median survival for NCT, NCRT, and DS was 22.9, 25.8 and 21.3 months, P=0.01. MVA revealed that age, Charlson/Deyo score, N-stage, grade, tumor size >2 cm, R0 resection, and NT were predictors of survival. Ninety-day mortality was worse in both the NCT and NCRT compared to DS, P<0.001. CONCLUSIONS: The size of pancreatic cancer correlates to pathologic stage and overall survival. Tumors >2 and <2 cm benefited from a NT. However, the 90-operative mortality was significantly worse in those patients receiving NT.

Outcomes associated with robotic approach to pancreatic resections.

Minimally invasive techniques have improved post-operative outcomes, however, the majority of pancreatic surgery, known for its complexity, is still performed via open approaches. The development of robotics has improved dexterity which may allow for application in more complex surgeries. We queried a prospectively maintained robotic database to identify patients who underwent robotic pancreatic resection by a single surgeon between 2012 and 2016. Patient demographics and operative outcomes were compared using Mann-Whitney U, Kruskal Wallis and Pearson's Chi-square test as appropriate. We identified 119 patients; 65 Whipples [Robotic Whipple (RW)], 43 distal pancreatectomies, 4 total pancreatectomies, 6 pancreatic enucleations, and 1 robotic cyst gastrostomy with a median age of 71 [24-91], median body mass index (BMI) of 27.6 (16.8-40.2), and American society of anesthesiologists (ASA) of 3. The median estimated blood loss (EBL) was 125 [25-800] and loss of heterozygosity (LOH) 6 [1-34]. Mean operative time for RW decreased after 15 cases (578 vs. 457 minutes, P<0.004). Conversions to open occurred in 5 (4.2%) patients. In total of 117 (98.3%) patients underwent R0 resections and the median lymph node (LN) harvest was 16 [0-37]. The 30 and 90 days mortality was 1 (0.8%). Major complications (Clavien-Dindo grade 3-5) were seen in 16 (13.4%) cases (20.3%) but decreased steadily as volume increased (case 30). Pancreatic leaks occurred in 14 (11.8%): A, 8 (6.7%); B, 4 (3.4%); and C, 2 (1.7%). Robotic assisted approaches to pancreatic resections is feasible. However, it takes approximately 15 cases before a decrease in operative time and 30 cases before major complications are decreased. These trends in complications are associated with surgeon experience and volume are critical to consider in robotic pancreatic surgery.