Faculty Bibliography

BACKGROUND:Pancreatic surgery is still a challenge even in high-volume centers. Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study we compared Robotic Distal Pancreatectomy (RDP) versus open (ODP) in terms of CR-POPF development, and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS:We collected data from five high volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long-term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA score, BMI, final pathology and TNM VIII ed. RESULTS:246 patients who underwent 82 RDP and 164 ODP were included. No differences were found in the incidence of CR-POPF. In the PDAC group median DFS and OS were 10.8 months and 14.8 months in the ODP group, and 10.4 months and 15 months in the RDP group, respectively. CONCLUSIONS:RDP is a safe surgical strategy for PDAC and incidence of CR-POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high volume and proficient centers.

OBJECTIVES/OBJECTIVE:Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs. MATERIALS AND METHODS/METHODS:We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival. RESULTS:We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. <50), unmarried (OR: 1.56; 95% CI: 1.02-2.38), and less likely to be diagnosed after 2010 (OR: 0.09; 95% CI: 0.06-0.15). OS for G3 NET (median, 36 mo; 95% CI: 13-92) fell between OS for NEC (median, 7 mo; 95% CI: 6-8), and G1-2 NET (median not reached, >120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs. <50), unmarried patients (HR: 1.40; 95% CI: 1.17-1.68), and those with HG features (HR: 3.97; 95% CI: 3.15-4.99) had worse survival. CONCLUSIONS:We defined a subset of G3 NETs that are HG and well differentiated, more common in older, unmarried patients, with a prognosis between that of NEC and G1-2 NETs. Our analysis adds the first national registry study in support of a new classification of nonpancreatic HG and well-differentiated NETs.

BACKGROUND:There is considerable interest in a neoadjuvant approach for resectable pancreatic ductal adenocarcinoma (PDAC). This study evaluated perioperative gemcitabine + erlotinib (G+E) for resectable PDAC. METHODS:A multicenter, cooperative group, single-arm, phase II trial was conducted between April 2009 and November 2013 (ACOSOG Z5041). Patients with biopsy-confirmed PDAC in the pancreatic head without evidence of involvement of major mesenteric vessels (resectable) were eligible. Patients (n = 123) received an 8-week cycle of G+E before and after surgery. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included toxicity, response, resection rate, and time to progression. Resectability was assessed retrospectively by central review. The study closed early due to slow accrual, and no formal hypothesis testing was performed. RESULTS:Overall, 114 patients were eligible, consented, and initiated protocol treatment. By central radiologic review, 97 (85%) of the 114 patients met the protocol-defined resectability criteria. Grade 3+ toxicity was reported in 60% and 79% of patients during the neoadjuvant phase and overall, respectively. Twenty-two of 114 (19%) patients did not proceed to surgery; 83 patients (73%) were successfully resected. R0 and R1 margins were obtained in 67 (81%) and 16 (19%) resected patients, respectively, and 54 patients completed postoperative G+E (65%). The 2-year OS rate for the entire cohort (n = 114) was 40% (95% confidence interval [CI] 31-50), with a median OS of 21.3 months (95% CI 17.2-25.9). The 2-year OS rate for resected patients (n = 83) was 52% (95% CI 41-63), with a median OS of 25.4 months (95% CI 21.8-29.6). CONCLUSIONS:For resectable PDAC, perioperative G+E is feasible. Further evaluation of neoadjuvant strategies in resectable PDAC is warranted with more active systemic regimens.

Introduction: The decision of admitting a stable patient to the ICU after major operation currently relies on clinical judgment and local hospital policies. We programmed an artificial intelligence (AI) to determine the appropriate level of care after major operation and compared its performance with clinician's judgement.
Method(s): ICU admission was deemed "appropriate" when at least 1 of 15 criteria (eg re-intubation, prolonged hypotension, new-onset arrhythmia) was observed. Using Institutional data (512 patients, 87 clinical variables), we programmed an AI to predict when ICU admission would have been appropriate. We prospectively evaluated whether surgeon, anesthesiologist, intensivist, or AI was the most accurate predictor in determining appropriateness of ICU admissions across 50 patients undergoing major surgery (general, vascular, urological). Accuracy of predictions was compared using receiver operating characteristic curve analysis.
Result(s): ICU care was appropriate (at least 1 of 15 objective criteria met) in 9 of 50 patients. Artificial intelligence correctly triaged to the appropriate level of care 82% of patients (surgeon 70%, anesthesiologist 58%, intensivist 64%). Receiver operating characteristic curve analysis revealed that AI's triage was the most accurate (area under the curve [AUC] 0.82), followed by anesthesiologist's (AUC 0.70), intensivist's (AUC 0.69), and surgeon's (AUC 0.60). Overall, clinicians leaned toward over-triaging patients to the ICU (Table).
Conclusion(s): Our study provides the first evidence that AI can have a role in supporting clinical decisions on postoperative triage. In the future, more sophisticated platforms can become integrated in daily clinical practice. [Figure presented]
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BACKGROUND & AIMS/OBJECTIVE:In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US. METHODS:We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% Caucasian) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999 through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined. RESULTS:The mean size of gastric adenocarcinomas was 23.0±16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively. CONCLUSION/CONCLUSIONS:The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases.

Background: Prior data from Asian countries showed comparable outcomes of endoscopic submucosal dissection (ESD)vs surgery in patients with early gastric cancer (EGC)meeting standard and expanded criteria. Data from comparative studies using strict criteria in North American population are lacking.
Method(s): We conducted a multicenter retrospective study from 16 North American centers. All patient underwent ESD and/or gastrectomy for EGC between 12/2004 and 2/2018, with follow-up until 10/2018. Patients who did not meet either standard or expanded criteria, those with evidence of lymph node or distant metastasis at time of diagnosis, those without curative resection, and those with follow-up time of less than 6 months were excluded. Primary outcomes were overall survival (OS), cancer-specific survival (CSS)and recurrence-free survival (RFS). Kaplan-Meier using log-rank analysis was used to compare outcomes between ESD and surgery groups. Factors associated with outcomes were analyzed using Cox hazards regression and linear regression analyses.
Result(s): There were 393 patients with EGC who underwent ESD or gastrectomy from 14 US and 2 Canadian centers. Of these, 318 patients were excluded due to unfulfilled standard or expanded criteria (n=254), evidence of lymph node metastasis (n=1), no data on lymphovascular invasion (n=1), non-R0 resection (n=17)and follow-up time of less than 6 months (n=45). A total of 75 patients were analyzed (38 treated with ESD and 37 treated with surgery). Patients treated with surgery had a higher proportion of pedunculated lesions (P=0.02), undifferentiated tumors (P =0.01), EGCs fulfilling expanded criteria (P <0.0001)and longer follow-up time (P=0.0004)(Table 1). OS (P= 1.00), CSS (P=1.00)and RFS (P=1.00)were not statistically different between ESD vs surgery groups. There was no subsequent nodal or distant metastasis in either group. A single patient in the surgery group died of an etiology not related to gastric cancer at 7.9 years after gastrectomy. There were no deaths in the ESD group. One patient with moderately differentiated adenocarcinoma in the gastric antrum, treated with curative ESD, developed a gastric cardiac neuroendocrine tumor at 7.2 years (Table 2). The metachronous lesion was treated with a repeat curative endoscopic resection. There was no demographic, procedural or histological factor associated with OS, CSS or RFS.
Conclusion(s): The standard and expanded criteria for gastric ESD are clinically applicable to a North American population. ESD provides comparable oncologic outcomes and is thus an alternative treatment option to surgery. Recurrence after ESD is uncommon, and can be managed successfully using follow-up and repeat endoscopic treatment. [Figure presented][Figure presented]
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INTRODUCTION/BACKGROUND:Innovative strategies to reduce costs while maintaining patient satisfaction and improving delivery of care are greatly needed in the setting of rapidly rising health care expenditure. Intensive care units (ICUs) represent a significant proportion of health care costs due to their high resources utilization. Currently, the decision to admit a patient to the ICU lacks standardization because of the lack of evidence-based admission criteria. The objective of our research is to develop a prediction model that can help the physician in the clinical decision-making of postoperative triage. MATERIALS AND METHODS/METHODS:Our group identified a list of index events that commonly grants admission to the ICU independently of the hospital system. We analyzed correlation among 200 quantitative and semiquantitative variables for each patient in the study using a decision tree modeling (DTM). In addition, we validated the DTM against explanatory models, such as bivariate analysis, multiple logistic regression, and least absolute shrinkage and selection operator. RESULTS:Unlike explanatory modeling, DTM has several unique strengths: tree models are easy to interpret, the analysis can examine hundreds of variables at once, and offer insight into variable relative importance. In a retrospective analysis, we found that DTM was more accurate at predicting need for intensive care compared with current clinical practice. DISCUSSION/CONCLUSIONS:DTM and predictive modeling may enhance postoperative triage decision-making. Future areas of research include larger retrospective analyses and prospective observational studies that can lead to an improved clinical practice and better resources utilization.

OBJECTIVE:The purpose of this study was to assess the use of apparent diffusion coefficient (ADC) during DWI for predicting complete pathologic response of rectal cancer after neoadjuvant therapy. MATERIALS AND METHODS/METHODS:A systematic review of available literature was conducted to retrieve studies focused on the identification of complete pathologic response of locally advanced rectal cancer after neoadjuvant chemoradiation, through the assessment of ADC evaluated before, after, or both before and after treatment, as well as in terms of the difference between pretreatment and posttreatment ADC. Pooled mean pretreatment ADC, posttreatment ADC, and Δ-ADC (calculated as posttreatment ADC minus pretreatment ADC divided by pretreatment ADC and multiplied by 100) in complete responders versus incomplete responders were calculated. For each parameter, we also pooled sensitivity and specificity and calculated the area under the summary ROC curve. RESULTS:/s, in complete and incomplete responders, respectively (p = 0.00001). The Δ-ADC percentages were also significantly higher in complete responders than in incomplete responders (59.7% vs 29.7%, respectively, p = 0.016). Pooled sensitivity, specificity, and AUC were 0.743, 0.755, and 0.841 for pretreatment ADC; 0.800, 0.737, and 0.782 for posttreatment ADC; and 0.832, 0.806, and 0.895 for Δ-ADC. CONCLUSION/CONCLUSIONS:Use of ADC during DWI is a promising technique for assessment of results of neoadjuvant treatment of rectal cancer.

Background/UNASSIGNED:Half of patients with pancreatic adenocarcinoma (PC) present with regionally advanced disease. This includes borderline resectable and locally advanced unresectable tumors as defined by current NCCN guidelines for resectability. Chemoradiation (CH-RT) is used in this setting in attempt to control local disease, and possibly downstage to resectable disease. We report a phase I/II trial of a combination of 5FU/Oxaliplatin with concurrent radiation in patients presenting with borderline resectable and locally advanced unresectable pancreatic cancer. Methods/UNASSIGNED:. Concurrent radiation therapy consisted of 4,500 cGy in 25 fractions (180 cGy/fx/d) followed by a comedown to the tumor and margins for an additional 540 cGy ×3 (total dose 5,040 cGy in 28 fractions). Following completion of CH-RT, patients deemed resectable underwent surgery; those who remained unresectable for cure but did not progress (SD, stable disease) received mFOLFOX6 ×6 cycles. Survival was calculated using Kaplan-Meier analysis. End-points of the phase II portion were resectability and overall survival. Results/UNASSIGNED:) was well tolerated and it was used as the recommended phase II dose. An additional 7 patients were treated in the phase II portion, 5 of whom completed CH-RT; the remaining 2 patients did not complete treatment because of grade 3 toxicities. Overall, 4/24 did not complete CH-RT. Grade 4 toxicities related to initial CH-RT were observed during phase I (n=2, pulmonary embolism and lymphopenia) and phase II (n=3, fatigue, leukopenia and thrombocytopenia). Following restaging after completion of CH-RT, 4 patients had progressed (PD); 9 patients had SD and received additional chemotherapy with mFOLFOX6 (one of them had a dramatic response after two cycles and underwent curative resection); the remaining 7 patients (29.2%) were noted to have a response and were explored: 2 had PD, 4 had SD, still unresectable, and 1 patient was resected for cure with negative margins. Overall 2 patients (8.3%) in the study received curative resection following neoadjuvant therapy. Median overall survival for the entire study population was 11.4 months. Overall survival for the two resected patients was 41.7 and 21.6 months. Conclusions/UNASSIGNED:Combined modality treatment for borderline resectable and locally advanced unresectable pancreatic cancer with oxaliplatin, 5FU and radiation was reasonably well tolerated. The majority of patients remained unresectable. Survival data with this regimen were comparable to others for locally advanced pancreas cancer, suggesting the need for more novel approaches.