A Combination of Robotic Approach and ERAS Pathway Optimizes Outcomes and Cost for Pancreatoduodenectomy.

OBJECTIVE: To determine the impact of enhanced recovery after surgery (ERAS) pathway implementation on outcomes, and cost of robotic and open pancreatoduodenectomy. BACKGROUND: ERAS pathways have shown benefit in open pancreatoduodenectomy (OPD). The impact of ERAS on robotic pancreatoduodenectomy (RPD) is unknown. METHODS: Retrospective review of consecutive RPD and OPDs in the pre-ERAS (July, 2014-July, 2015) and ERAS (July, 2015-July, 2016) period. Univariate and multivariate logistic regression was used to determine impact of ERAS and operative approach alone, or in combination (pre-ERAS + OPD, pre-ERAS + RPD, ERAS + OPD, ERAS + RPD) on length of hospital stay (LOS) and overall cost. RESULTS: In all, 254 consecutive pancreatoduodenectomies (RPD 62%, OPD 38%) were analyzed (median age 67, 47% female). ERAS patients had shorter LOS (6 vs 8 days; P = 0.004) and decreased overall cost (USD 20,362 vs 24,277; P = 0.001) compared with non-ERAS patients, whereas RPD was associated with decreased LOS (7 vs 8 days; P = 0.0001) and similar cost compared with OPD. On multivariable analysis (MVA), RPD was predictive of shorter LOS [odds ratio (OR) 0.33, confidence interval (CI) 0.16-0.67, P = 0.002), whereas ERAS was protective against high cost (OR 0.57, CI 0.33-0.97, P = 0.037). On MVA, when combining operative approach with ERAS pathway use, a combined ERAS + RPD approach was associated with reduced LOS and optimal cost compared with other combinations (pre-ERAS + OPD, pre-ERAS + RPD, ERAS + OPD). CONCLUSION: ERAS implementation is independently associated with cost savings for pancreatoduodenectomy. A combination of ERAS and robotic approach synergistically decreases hospital stay and overall cost compared with other strategies.

Ketorolac use may increase risk of postoperative pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Ketorolac (Toradol), a commonly used nonselective nonsteroidal anti-inflammatory drug (NSAID) in the postoperative period, has been associated with increased risk of anastomotic leak after colon resection. The effect of postoperative NSAID and ketorolac use on postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is unknown. METHODS: Retrospective review of consecutive PDs at a high-volume pancreas center from 2012 to 2015. POPF was identified and graded using International Study Group on Pancreatic Fistula criteria. Demographics, operative variables and 30-d postoperative NSAID use, dosage, and timing (early = postoperative day [POD] 0-5, late > POD 5) were collected. Univariate and multivariate logistic regressions were used to identify predictors of POPF. RESULTS: Four hundred twenty-three PDs were analyzed (mean age 66 y, 47% female), and 60% received NSAIDs postoperatively. Ketorolac (median POD 0-5 cumulative dose = 90 mg, interquartile range 60-165) was used in 35.7% (n = 151). POPF occurred in 90 patients (21.3%). Early (POD 0-5) ketorolac use was associated with increased POPF, especially grade A (odds ratio [OR] 2.16, P = 0.036). Each 25 mg incremental increase in ketorolac use was associated with a 10% increase in the incidence of POPF (OR 1.10, P = 0.021), whereas a cumulative dose of >150 mg was associated with a 44% increased risk of POPF (OR 1.44, 95% confidence interval 1.03-2.01, P = 0.035). A multivariate regression model identified estimated blood loss, soft gland, pancreatic duct diameter, body mass index, and cumulative ketorolac dose >150 mg as independent predictors of POPF (P < 0.0001, pseudo R2 = 0.149). CONCLUSIONS: Increasing doses of ketorolac in the early postoperative period are associated with increased risk of POPF, whereas a cumulative dose of >150 mg is an independent predictor of POPF after PD.

Analysis of Perioperative Chemotherapy in Resected Pancreatic Cancer: Identifying the Number and Sequence of Chemotherapy Cycles Needed to Optimize Survival.

PURPOSE: Receipt of 6 cycles of adjuvant chemotherapy (AC) is standard of care in pancreatic cancer (PC). Neoadjuvant chemotherapy (NAC) is increasingly utilized; however, optimal number of cycles needed alone or in combination with AC remains unknown. We sought to determine the optimal number and sequence of perioperative chemotherapy cycles in PC. METHODS: Single institutional review of all resected PCs from 2008 to 2015. The impact of cumulative number of chemotherapy cycles received (0, 1-5, and ≥6 cycles) and their sequence (NAC, AC, or NAC + AC) on overall survival was evaluated Cox-proportional hazard modeling, using 6 cycles of AC as reference. RESULTS: A total of 522 patients were analyzed. Based on sample size distribution, four combinations were evaluated: 0 cycles = 12.1%, 1-5 cycles of combined NAC + AC = 29%, 6 cycles of AC = 25%, and ≥6 cycles of combined NAC + AC = 34%, with corresponding survival. 13.1, 18.5, 37, and 36.8 months. On MVA (P < 0.0001), tumor stage [hazard ratio (HR) 1.35], LNR (HR 4.3), and R1 margins (HR 1.77) were associated with increased hazard of death. Compared with 6 cycles AC, receipt of 0 cycles [HR 3.57, confidence interval (CI) 2.47-5.18] or 1-5 cycles in any combination (HR 2.37, CI 1.73-3.23) was associated with increased hazard of death, whereas receipt of ≥6 cycles in any sequence was associated with optimal and comparable survival (HR 1.07, CI 0.78-1.47). CONCLUSIONS: Receipt of 6 or more perioperative cycles of chemotherapy either as combined neoadjuvant and adjuvant or adjuvant alone may be associated with optimal and comparable survival in resected PC.

Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?

BACKGROUND: Locally advanced unresectable pancreatic cancer (LAPC) historically portends a poor prognosis. FOLFIRINOX and gemcitabine/nab-paclitaxel have proven effective in the metastatic setting. We sought to evaluate the outcomes of these regimens compared with older regimens in LAPC. METHODS: A retrospective, single institutional review of all consecutive LAPC treated with "new" (FOLFIRINOX and/or gemcitabine/nab-paclitaxel) and "old" (gemcitabine or 5-FU) chemotherapy from 2010 to 2014 was performed. Univariate and multivariate predictors of resection and survival were determined. RESULTS: A total of 92 patients (new chemotherapy = 61, old chemotherapy = 31) were analyzed, of which 19 (21%) underwent eventual resection (median overall survival [OS] = 32 vs. 14.3 months for unresected patients, P = 0.0002). For the overall cohort, resection (hazard ratio [HR] 0.261, P = 0.014), radiation therapy (HR 0.458, P = 0.004), number of lines of chemotherapy (HR 0.486, P = 0.012), and new chemotherapy (HR 0.593 vs. old regimens, P = 0.065) were independent predictors of OS on multivariate analyses (MVA). On MVA, predictors of eventual resection were head and neck tumors (OR 0.307, P = 0.033) or SMA involvement (OR 0.285, P = 0.023). In nonresected patients (73), MVA showed treatment with new chemotherapy (HR 0.452, P = 0.006), radiation (HR 0.459, P = 0.006), and number of lines of CT (HR 0.705, P = 0.013) to be predictors of survival. CONCLUSIONS: In LAPC, use of FOLFIRNOX and/or gemcitabine/nab-paclitaxel is associated with improved survival compared with older chemotherapy regimens, regardless of eventual resection. Tumor location and relationship to certain vasculature are important determinants of resection in this cohort.

Hepatic Arterial Infusion in Combination with Modern Systemic Chemotherapy is Associated with Improved Survival Compared with Modern Systemic Chemotherapy Alone in Patients with Isolated Unresectable Colorectal Liver Metastases: A Case-Control Study.

BACKGROUND: In the era of effective modern systemic chemotherapy (CT), the role of hepatic arterial infusion of fluoxuridine (HAI-FUDR) in the treatment of isolated unresectable colorectal liver metastasis (IU-CRCLM) remains controversial. This study aimed to compare the overall survival (OS) of HAI-FUDR in combination with modern systemic CT versus modern systemic CT alone in patients with IU-CRCLM. METHODS: This was a case-control study of IU-CRCLM patients who underwent HAI + modern systemic CT or modern systemic CT alone. Modern systemic CT was defined as the use of multidrug regimens containing oxaliplatin and/or irinotecan ± biologics. RESULTS: Overall, 86 patients met the inclusion criteria (n = 40 for the HAI + CT group, and n = 46 for the CT-alone group). Both groups were similar in demographics, primary and stage IV tumor characteristics, and treatment-related variables (carcinoembryonic antigen, use of biologic agents, total number of lines of systemic CT administered) (all p > 0.05). Additionally, both groups were comparable with respect to liver tumor burden [median number of lesions (13.5 vs. 15), percentage of liver tumor replacement (37.5 vs. 40 %), and size of largest lesion] (all p > 0.05). Median OS in the HAI + CT group was 32.8 months compared with 15.3 months in the CT-alone group (p < 0.0001). Multivariate analysis revealed HAI + CT (hazard ratio 0.4, 95 % confidence interval 0.21-0.72; p = 0.003), Eastern Cooperative Oncology Group status, and receipt of increasing number of lines of systemic CT to be independent predictors of survival. CONCLUSIONS: In this case-control study of patients with IU-CRCLM, HAI in combination with CT was associated with improved OS when compared with modern systemic CT alone.

Robotic approach mitigates perioperative morbidity in obese patients following pancreaticoduodenectomy.

INTRODUCTION: The aim was to evaluate the impact of obesity on perioperative outcomes in patients undergoing robotic pancreaticoduodenectomy (RPD) compared to open pancreaticoduodenectomy (OPD). METHODS: A retrospective review of all pancreaticoduodenectomies from 9/2011 to 4/2015 was performed. Obesity was defined as body mass index (BMI) > 30 kg/m2. RESULTS: Of 474 pancreaticoduodenectomies performed: RPD = 213 (45%) and OPD = 261 (55%). A total of 145 (31%) patients were obese (70 RPD, 75 OPD). Obese patients had increased EBL (p = 0.03), pancreatic fistula (B&C; p = 0.077), and wound infection (p = 0.068) compared to the non-obese. For obese patients, RPD had decreased OR time (p = 0.0003), EBL (p < 0.001), and wound infection (p = 0.001) with no difference in Clavien ≥3 complications, margins, LOS or 30-day mortality compared with OPD. In multivariate analysis, obesity was the strongest predictor of Clavien ≥3 (OR 1.6; p = 0.041) and wound infection if BMI > 35 (OR 2.6; p = 0.03). The robotic approach was protective of Clavien ≥3 (OR 0.6; p = 0.03) on univariate analysis and wound infection (OR 0.3; p < 0.001) and grade B/C pancreatic fistula (OR 0.34; p < 0.001) on multivariate analysis. CONCLUSIONS: Obese patients are at risk for increased postoperative complications regardless of approach. However, the robotic approach mitigates some of the increased complication rate, while preserving other perioperative outcomes.

Grading of Surgeon Technical Performance Predicts Postoperative Pancreatic Fistula for Pancreaticoduodenectomy Independent of Patient-related Variables.

OBJECTIVE: To evaluate and quantify surgical skill by grading surgical performance of the pancreaticojejunostomy from robotic pancreaticoduodenectomies (RPDs). We hypothesized that video grading of surgical performance would contribute to estimating risk of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. BACKGROUND: POPF majorly contributes to pancreaticoduodenectomy morbidity. Risk scores [Fistula Risk Score (FRS) and Braga] derived from patient variables are validated for predicting POPF. Birkmeyer et al showed assessment of surgical proficiency is an important component of outcomes. METHODS: POPF was diagnosed using International Study Group definition. Technical performance of robotic pancreaticojejunostomy video was graded by 2 blinded surgeons using: (1) pancreaticojejunostomy step-by-step variables [PJ-specific variables (PJVs); max = 115]; and (2) the Objective Structured Assessment of Technical Skills (OSATS) score. RESULTS: One hundred thirty-three pancreaticojejunostomies were analyzed. POPF was 18%. Higher FRS (P = 0.011) and Braga (P = 0.041) scores predicted POPF. Graders' subjective prediction did not correlate with FRS/Braga scores. Grader 1 scores (P = 0.043), but not grader 2 (P = 0.44), predicted POPF. PJV scores >105 were predictive of POPF (P = 0.039). Scoring only PJV duct-to-mucosa stitches (max = 50) was highly predictive of POPF (P = 0.0053). Higher OSATS scores were associated with a decreased rate of POPF (P = 0.022). On multivariate analysis, adding technical scoring to statistically significant patient variables (ie, gland texture) improves the model and can independently predict POPF. The strongest predictive model for POPF consisted of soft gland (odds ratio = 18.28, 95% confidence interval = 2.19-152.57) and low OSATS (odds ratio = 0.82, 95% confidence interval = 0.70-0.96). OSATS, modeled with FRS or Braga scores, independently predicted POPF. CONCLUSIONS: This is the first study to demonstrate that technical scoring of a surgeon's performance independently predicts patient outcomes in pancreatic surgery. Future studies should consider how to validate and incorporate technical metrics.

A Multi-institutional Comparison of Perioperative Outcomes of Robotic and Open Pancreaticoduodenectomy.

OBJECTIVES: Limited data exist comparing robotic and open approaches to pancreaticoduodenectomy (PD). We performed a multicenter comparison of perioperative outcomes of robotic PD (RPD) and open PD (OPD). METHODS: Perioperative data for patients who underwent postlearning curve PD at 8 centers (8/2011-1/2015) were assessed. Univariate analyses of clinicopathologic and treatment factors were performed, and multivariable models were constructed to determine associations of operative approach (RPD or OPD) with perioperative outcomes. RESULTS: Of the 1028 patients, 211 (20.5%) underwent RPD (4.7% conversions) and 817 (79.5%) underwent OPD. As compared with OPD, RPD patients had higher body mass index, rates of prior abdominal surgery, and softer pancreatic remnants, whereas OPD patients had a higher percentage of pancreatic ductal adenocarcinoma cases, and greater proportion of nondilated (<3 mm) pancreatic ducts. On multivariable analysis, as compared with OPD, RPD was associated with longer operative times [mean difference = 75.4 minutes, 95% confidence interval (CI) 17.5-133.3, P = 0.01], reduced blood loss (mean difference = -181 mL, 95% CI -355-(-7.7), P = 0.04) and reductions in major complications (odds ratio = 0.64, 95% CI 0.47-0.85, P = 0.003). No associations were demonstrated between operative approach and 90-day mortality, clinically relevant postoperative pancreatic fistula and wound infection, length of stay, or 90-day readmission. In the subset of 522 (51%) pancreatic ductal adenocarcinomas, operative approach was not a significant independent predictor of margin status or suboptimal lymphadenectomy (<12 lymph nodes harvested). CONCLUSIONS: Postlearning curve RPD can be performed with similar perioperative outcomes achieved with OPD. Further studies of cost, quality of life, and long-term oncologic outcomes are needed.

Deviations from Expected Treatment of Pancreatic Cancer in Octogenarians: Analysis of Patient and Surgeon Factors.

BACKGROUND: Morbidity and mortality of pancreatectomy has improved and chemotherapeutic options for pancreatic cancer (PC) are growing, yet there is reluctance to treat octogenarians. This study examined the reasons for failure to treat and analyzes outcomes in octogenarians with PC. METHODS: Retrospective chart review 2005-2013. Demographics, tumor characteristics, treatment, reason for lack of treatment, Charlson comorbidity index (CCI), and survival were analyzed. Expected treatment for early-stage patients (I/II) included surgery ± chemotherapy ± radiation. Expected treatment for advanced stage patients (III/IV) was chemotherapy. RESULTS: A total of 431 octogenarians were analyzed. Mean age was 84.0 ± 3.4, 59.6 % female, and 44.1 % received no treatment. Patients with operable tumors (I = 31 [7.2 %]/II = 214 [49.7 %]) had surgery 39.2 % of the time. Age was a predictor of not receiving surgery (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.70-0.86; p = 0.0001), whereas CCI was not. The most common reason for no surgery was contraindication despite similar CCI. Median overall survival for early-stage patients was better in the surgical group (15.8 vs. 5.5 months) than nonsurgical group (p < 0.0001). Advanced patients (III = 54 [12.5 %]/IV = 132 [30.6 %]) had similarly low treatment rates (n = 65 [34.9 %]). Survival for advanced disease was best for treated patients (6.9 vs. 1.8 months; p < 0.0001). CCI did not differ between those receiving chemotherapy and not, although age was significantly different (p < 0.0001). CONCLUSIONS: There is significant deviation from expected treatment for octogenarians with PC. While no correlation existed between CCI and treatment, age correlated with therapy for nearly all stages. Chronological age, not comorbidity, may drive recommendation for treatment in elderly patients.

A policy of omitting an intensive care unit stay after robotic pancreaticoduodenectomy is safe and cost-effective.

BACKGROUND: Immediate postoperative admission to the intensive care unit (ICU) after pancreaticoduodenectomy (PD) is still a standard practice at many institutions. Our aim was to examine whether omission of an immediate postoperative ICU admission would be safe and result in improved outcomes and cost after robotic pancreaticoduodenectomy (RPD). METHODS: In December 2014, a non-ICU admission policy was implemented for patients undergoing RPD. Before this date, all RPDs were routinely admitted to the ICU on post operative day = 0. Using a prospective database, outcomes of the patients in the no-ICU cohort were compared with those of the patients routinely admitted to the ICU before implementation of this policy. RESULTS: The ICU (n = 49) and no-ICU cohorts (n = 47) were comparable in age, gender, body mass index, Charlson comorbidity index and American Society of Anesthesiologists scores, receipt of neoadjuvant therapy, operative time, estimated blood loss, tumor size, and pathologic diagnosis (all P values = NS). Clavien complications, pancreatic leak, reoperation, readmission, and mortality were similar between both the groups (all P values = NS). Hospital length of stay (LOS) was shorter for the no-ICU group (median 6.8 versus 7.7 d, P = 0.01). This reduced LOS and omission of routine postoperative ICU admission translated into a cost reduction from $23,933 (interquartile range $19,833-$28,991) in the ICU group to $19,516 (interquartile range $17,046-$23,893) in the no-ICU group, P = 0.004. The reduction in LOS and cost remained significant after adjusting for all related demographics and perioperative characteristics. CONCLUSIONS: A standard policy of omitting a postoperative ICU admission on post operative day 0 after RPD is safe and can result in reduced LOS and overall savings in total hospital cost.

A pancreatic cancer multidisciplinary clinic: insights and outcomes.

BACKGROUND: The purpose of this study was to evaluate the impact of a multidisciplinary clinic (MDC) on the treatment of pancreatic ductal adenocarcinoma. We hypothesized that an MDC would improve trial participation, multimodality therapy, neoadjuvant therapy, time to treatment, and survival. MATERIALS AND METHODS: Pancreatic ductal adenocarcinoma cancer registry patients from 2008-2012 were analyzed. Outcomes of patients evaluated at the MDC were compared with patients not evaluated at the MDC (non-MDC). RESULTS: A total of 1408 patients were identified, 557 (40%) MDC and 851 (60%) non-MDC. MDC were more likely to be an earlier stage than non-MDC (P = 0.0005): I - 4% versus 4%, II - 54% versus 43%, III - 11% versus 9%, and IV - 32% versus 44%. MDC were younger than non-MDC (68 versus 70; P = 0.005); however, younger (<75) and older (≥75) patients were more likely to receive treatment in MDC than non-MDC. MDC were more likely to participate in trials than non-MDC (28% versus 14%; P < 0.0001). MDC were more likely to receive treatment than non-MDC (90% versus 71%; P < 0.0001). MDC were more likely to receive two (38% versus 24%; P < 0.0001) or three (12% versus 9%; P = 0.02) therapies than non-MDC. No difference in time to first treatment in MDC than non-MDC (0.95 versus 0.92 mo; P = 0.69). After adjusting for age, stage, and therapy, there was a trend; however, no statistical difference in disease-free survival (hazard ratio [HR] of non-MDC versus MDC 0.80; 95% confidence interval [95% CI] 0.61-1.05; P = 0.11), time to recurrence (HR of non-MDC versus MDC 0.69; 95% CI 0.45-1.04; P = 0.07), or overall survival (HR of non-MDC versus MDC 0.81; 95% CI, 0.62-1.07; P = 0.13). CONCLUSIONS: Patients evaluated in an MDC were more likely to receive any treatment, receive multimodality therapy, neoadjuvant therapy, and participate in a clinical trial.

Robotic assisted placement of hepatic artery infusion pump is a safe and feasible approach.

BACKGROUND: Hepatic artery infusion (HAI) chemotherapy can be combined with systemic chemotherapy for the treatment of isolated unresectable colorectal liver metastases (IU-CRLM) and intrahepatic cholangiocarcinoma (U-ICC). However, HAI pump placement requires a major laparotomy that may be associated with morbidity. We hypothesized that the computer-assisted robotic platform would be well suited for this procedure and report the first single institutional case series of robotic assisted HAI pump placement for primary and secondary malignancies of the liver. METHODS: A retrospective review of patients who underwent robotic assisted HAI pump placement from January 2008 to January 2016. Peri-operative outcomes were evaluated. RESULTS: A total of 24 consecutive patients underwent robotic assisted HAI pump placement. Median age was 61 years and 50% were females. Main indications were colorectal cancer = 17 (71%) and intrahepatic cholangiocarcinoma = 4 (17%). The majority (87.5%) of patients had bilobar disease with a median of 6 liver lesions. Concurrent procedures including ablation +/- resection and colectomies were performed in 58% of the patients. Median operative time was 282 min, with median blood loss of 100 ml and length of stay 6 days. Conversion to open was required in one (4%) case. Grade 3 or higher complications were seen in 13% of cases and pump related complications were seen in 21% of patients. All except one HAI pumps could be used for pump chemotherapy. CUSUM analysis of operative time indicated a learning curve of eight cases. CONCLUSION: Robotic assisted placement of HAI pump placement is safe, feasible, and obviates the need for major laparotomy. J. Surg. Oncol. 2016;114:342-347. © 2016 Wiley Periodicals, Inc.

The indolent nature of pulmonary metastases from ductal adenocarcinoma of the pancreas.

BACKGROUND AND OBJECTIVES: The natural history of pulmonary metastases from pancreatic ductal adenocarcinoma (PDAC) is not well studied. Limited evidence suggests patients with isolated pulmonary metastases from PDAC follow a more benign clinical course than those with other sites of metastases. METHODS: We performed a retrospective review of all patients with pulmonary metastases from PDAC from 2000 to 2010 and analyzed survival utilizing the Kaplan-Meier method based upon location of first metastasis (lung first, intra-abdominal first, or synchronous intra-abdominal and lung metastases). RESULTS: Median survival among subjects with lung as the only site of metastases was significantly longer than those with other metastatic patterns. In subjects that had undergone resection of their PDAC, survival in those with lung as a first site of recurrence remained significantly longer than those with abdominal first or synchronous intra-abdominal and lung recurrence. Among resected patients that developed lung only recurrence, survival was significantly prolonged (67.5 months) in those who underwent surgical resection/stereotactic radiosurgery compared to chemotherapy (33.8 months) or observation (29.9 months) for treatment of lung recurrence. CONCLUSION: Patients with isolated pulmonary recurrence from PDAC may realize a survival benefit from surgical intervention or stereotactic radiosurgery compared to chemotherapy or observation for treatment of lung recurrence.

Robotic pancreaticoduodenectomy in the presence of aberrant or anomalous hepatic arterial anatomy: safety and oncologic outcomes.

BACKGROUND: Hepatic arterial anomalies (HAAs) are not infrequently encountered during pancreatic resections. In view of the current emergence of the robotic platform as a safe alternative to open surgery in experienced centres, this study sought to determine the implications of HAAs on the safety and oncologic outcomes of robotic pancreaticoduodenectomy (RPD). METHODS: A prospectively maintained database of patients with HAAs who underwent RPD (RPD + HAA) at a single institution between 2008 and 2013 was retrospectively reviewed. Demographic information and perioperative outcomes of RPD were compared for patients with and without HAAs. RESULTS: A total of 142 patients underwent RPD; 112 (78.9%) did not have and 30 (21.1%) did have HAAs. The majority (90.0%) of RPDs in patients with HAAs were performed for malignant indications and all aberrant vessels were preserved without conversion to laparotomy. There were no statistically significant differences between RPD patients with and without HAAs with respect to preoperative demographics, tumour characteristics, operative metrics (operative time, estimated blood loss, conversion) and postoperative outcomes, including complications, length of stay and readmissions. Negative margin (R0) rates were similar in both groups. CONCLUSIONS: Robot-assisted pancreaticoduodenectomy is safe and feasible in patients with HAAs and has outcomes similar to those in patients with normal arterial anatomy.

Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma.

BACKGROUND: Baseline carbohydrate antigen 19-9 (CA 19-9) is a useful prognostic marker in pancreatic ductal adenocarcinoma (PDA); however, data on the significance of a change in CA 19-9 following neoadjuvant therapy are lacking. METHODS: All patients receiving neoadjuvant therapy for PDA from July 2010 to February 2013 were retrospectively reviewed. Resection rate, R0 resection rate, need for venous resection, and overall survival were correlated to CA 19-9 response. Fisher's exact test, Kaplan-Meier survival analysis, and multivariate analysis using Cox regression were used. RESULTS: A total of 78 patients were studied (21 patients with resectable disease, 40 borderline resectable, and 17 with locally advanced disease). A variety of chemotherapies ± radiation were utilized during the study period. Overall, 56 patients (72 %) had a decrease in CA 19-9 of >50 % with neoadjuvant treatment. In borderline resectable patients, CA 19-9 response of >50 % predicted R0 resection (odds ratio 4.2; p = 0.05). In borderline resectable patients who had an increase in CA 19-9, none of five (0 %) underwent R0 resection compared with 80 % of the remaining cohort (p = 0.001). The complete pathologic response rate was 29 % in patients who had a CA 19-9 response of >90 % versus 0 % in the remaining patients (p < 0.001). A CA 19-9 response of >50 % resulted in improved overall survival (28.0 vs. 11.1 months; p < 0.0001) and was an independent predictor of survival (hazard ratio 0.26; 95 % CI 0.13-0.55; p < 0.0001). CONCLUSIONS: CA 19-9 response to neoadjuvant therapy is associated with R0 resection rate, histopathologic response, and survival. Incorporation of this easily obtainable biomarker into future clinical trials may facilitate more rapid evaluation of novel regimens.

Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer.

BACKGROUND: Trials examining FOLFIRINOX in metastatic pancreatic cancer demonstrate higher response rates compared to gemcitabine-based regimens. There is currently limited experience with neoadjuvant FOLFIRINOX in pancreatic cancer. METHODS: Retrospective review of outcomes of patients with borderline resectable or locally unresectable pancreatic cancer who were recommended to undergo neoadjuvant treatment with FOLFIRINOX. RESULTS: FOLFIRINOX was recommended for 25 patients with pancreatic cancer, 13 (52%) unresectable and 12 (48%) borderline resectable. Four patients (16%) refused treatment or were lost to follow-up. Twenty-one patients (84%) were treated with a median of 4.7 cycles. Six patients (29%) required dose reductions secondary to toxicity. Two patients (9%) were unable to tolerate treatment and three patients (14%) had disease progression on treatment. Seven patients (33%) underwent surgical resection following treatment with FOLFIRINOX alone, 2 (10%) of which were initially unresectable. Two patients underwent resection following FOLFIRINOX + stereotactic body radiation therapy (SBRT). The R0 resection rate for patients treated with FOLFIRINOX ± SBRT was 33% (55% borderline resectable, 10% unresectable). A total of five patients (24%) demonstrated a significant pathologic response. CONCLUSIONS: FOLFIRINOX is a biologically active regimen in borderline resectable and locally unresectable pancreatic cancer with encouraging R0 resection and pathologic response rates.

Factors associated with prolonged hospitalization in patients undergoing pancreatoduodenectomy.

BACKGROUND: Complex surgeries such as a pancreatoduodenectomy (PD) traditionally have long hospital stays (LOS). METHODS: Patients who underwent elective PD at our institution from 8/2011-6/2015 were retrospectively examined. Interquartile ranges were calculated from LOS. Patient were compared between the highest quartile and the remainder of the cohort. RESULTS: 492 patients had a median LOS of 9 days, with 106 (22%) admitted for >14 days. Characteristics associated with prolong hospitalization include age (p = 0.004) and preoperative albumin <3.5 (p = 0.007). Significant intra-operative measures associated with prolonged LOS were blood loss (EBL, p = 0.004) and increased operative time (p = 0.008). Any complication extended hospitalizations (p < 0.001). Patients in the top quartile were less likely to be discharged home (p < 0.0001) and more likely to be readmitted (p < 0.0001). CONCLUSION: Older patients with hypoalbuminemia are at higher risk of prolonged LOS following PD as well as high EBL, operative time, and surgical complications. Focused efforts to counsel and optimize patients pre-operatively and minimize intra-operative complications may shorten hospital stays.

Performing the Difficult Cholecystectomy Using Combined Endoscopic and Robotic Techniques: How I Do It.

Laparoscopic cholecystectomy is the standard of care for cholelithiasis as well as cholecystitis. However, in the setting of Mirizzi syndrome or gangrenous cholecystitis where the critical view cannot be ascertained, subtotal cholecystectomy may be necessary. Using the robot-assisted approach, difficult cholecystectomies can be performed upfront without need for partial cholecystectomy. Even in the setting of Mirizzi syndrome where severe scarring and fibrosis are evident, definitive cholecystectomy and takedown of the cholechystocholedochal fistula can be performed in a safe and feasible fashion following successful endoscopic common bile duct stent placement. The purposes of this report are to review the history of Mirizzi syndrome as well as its traditional and novel treatment techniques and highlight technical pearls of the robotic approach to this diagnosis.

Disturbances of the Perioperative Microbiome Across Multiple Body Sites in Patients Undergoing Pancreaticoduodenectomy.

OBJECTIVE: The goals of this study were to characterize bacterial communities within fecal samples, pancreatic fluid, bile, and jejunal contents from patients undergoing pancreaticoduodenectomy (PD) and to identify associations between microbiome profiles and clinical variables. METHODS: Fluid was collected from the pancreas, common bile duct, and proximal jejunum from 50 PD patients. Postoperative fecal samples were also collected. The microbial burden within samples was quantified with droplet digital polymerase chain reaction. Bacterial 16S ribosomal RNA gene sequences were amplified, sequenced, and analyzed. Data from fecal samples were compared with publicly available data obtained from volunteers. RESULTS: Droplet digital polymerase chain reaction confirmed the presence of bacteria in all sample types, including pancreatic fluid. Relative to samples from the American Gut Project, fecal samples from PD patients were enriched with Klebsiella and Bacteroides and were depleted of anaerobic taxa (eg, Roseburia and Faecalibacterium). Similar patterns were observed within PD pancreas, bile, and jejunal samples. Postoperative fecal samples from patients with a pancreatic fistula contained increased abundance of Klebsiella and decreased abundance of commensal anaerobes, for example, Ruminococcus. CONCLUSIONS: This study confirms the presence of altered bacterial populations within samples from PD patients. Future research must validate these findings and may evaluate targeted microbiome modifications to improve outcomes in PD patients.

Primary Tumor Resection Following Favorable Response to Systemic Chemotherapy in Stage IV Pancreatic Adenocarcinoma with Synchronous Metastases: a Bi-institutional Analysis.

INTRODUCTION: Patients with metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone, and the role of surgery in these patients remains unknown. METHODS: A bi-institutional retrospective review was performed for patients with metastatic pancreatic adenocarcinoma who underwent resection of the primary tumor from 2008 to 2013. The primary outcome measured was postoperative overall survival. Secondary outcomes included postoperative disease-free survival and overall survival from the time of diagnosis. RESULTS: Twenty-three patients were identified who met the study criteria with a median follow-up of 30 months. Metastatic sites included the liver (n = 16), the lung (n = 6), and the peritoneum (n = 2). Chemotherapy included FOLFIRINOX (n = 14) and gemcitabine-based regimens (n = 9), with a median of 9 cycles (range 2-31) prior to surgical treatment. Median time from diagnosis to surgery was 9.7 months (IQR 5.8-12.8). Median overall survival (OS) from surgery, disease-free survival, and OS from diagnosis were 18.2 months (95 % CI 11.8-35.5), 8.6 months (95 % CI 5.2-16.8), and 34.1 months (95 % CI 22.5-46.2), respectively. The 1- and 3-year OS from surgery were 72.7 % (95 % CI 49.1-86.7) and 21.5 % (95 % CI 4.3-47.2), respectively. CONCLUSION: Resection of the primary tumor in patients with metastatic pancreatic adenocarcinoma may be considered in highly selected patients with favorable imaging and CA 19-9 response following chemotherapy at high-volume centers providing multidisciplinary care. These patients should be enrolled in prospective clinical trials or institutional registries to better quantify the potential benefits of such a strategy.