Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi-institutional analysis.

BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.

The prognostic role of aspartate transaminase to platelet ratio index on outcomes after nonemergent major hepatectomy.

INTRODUCTION: Noninvasive screening methods to identify patients preoperatively with abnormal liver texture remain limited. Aspartate transaminase to platelet ratio index has been validated to predict fibrosis in patients with hepatitis C; however, its use as a predictor of postoperative outcomes in patients without viral hepatitis remains unknown. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program dataset to identify patients who underwent a major hepatectomy between 2014 and 2021. We excluded patients who underwent emergent operations, patients with viral hepatitis, and patients with ascites. Aspartate transaminase to platelet ratio index was calculated using the following equation: (aspartate transaminase/40)/(platelet count) × 100. An aspartate transaminase to platelet ratio index ≥0.7 was used to identify patients with significant fibrosis. Univariable analysis was performed to identify factors associated with aspartate transaminase to platelet ratio index ≥0.7, perioperative transfusion, serious morbidity, overall morbidity, and 30-day mortality. Multivariable logistic regression analysis was performed to identify adjusted predictors of these outcomes. RESULTS: Of the 8,933 patients who met inclusion criteria, 1,170 (13.1%) patients had an aspartate transaminase to platelet ratio index ≥0.7. A perioperative blood transfusion was administered to 2,497 (28.0%). The number of patients who experienced overall morbidity, serious morbidity, and mortality were 3,195 (35.8%), 2,665 (29.8%), and 238 (2.7%), respectively. Aspartate transaminase to platelet ratio index ≥0.7 was an independent predictor of transfusion (odds ratio: 1.51 [1.32-1.72], P < .001), overall morbidity (1.16 [1.01-1.33], P = .032), and mortality (1.56 [1.12-2.13], P = .006). Transfusion was an independent predictor of overall morbidity (2.50 [2.26-2.76], P < .001), serious morbidity (2.51 [2.26-2.79], P < .001), and mortality (3.28 [2.49-4.33], P < .001). CONCLUSION: An aspartate transaminase to platelet ratio index ≥0.7 is associated with perioperative transfusion, overall morbidity, and 30-day mortality. The aspartate transaminase to platelet ratio index may serve as a noninvasive tool to risk stratify patients before elective major hepatectomy.

"The Prognostic Role of Aspartate Transaminase to Platelet Ratio Index (APRI) on Outcomes Following Non-emergent Minor Hepatectomy".

INTRODUCTION: Fibrosis and cirrhosis are associated with worse outcomes after hepatectomy. Aspartate transaminase to platelet ratio index (APRI) is associated with fibrosis and cirrhosis in hepatitis C patients. However, APRI has not been studied to predict outcomes after hepatectomy in patients without viral hepatitis. METHODS: We reviewed the ACS-NSQIP dataset to identify patients who underwent a minor hepatectomy between 2014 and 2021. We excluded patients with viral hepatitis or ascites as well as patients who underwent emergent operations or biliary reconstruction. APRI was calculated using the following equation: (AST/40)/(platelet count) × 100. APRI ≥0.7 was used to identify significant fibrosis. Univariable analysis was performed to identify factors associated with APRI ≥0.7, transfusion, serious morbidity, overall morbidity, and 30-day mortality. Multivariable logistic regression was performed to identify adjusted predictors of these outcomes. RESULTS: Of the 18,069 patients who met inclusion criteria, 1630 (9.0%) patients had an APRI ≥0.7. A perioperative blood transfusion was administered to 2139 (11.8%). Overall morbidity, serious morbidity, and mortality were experienced by 3162 (17.5%), 2475 (13.7%), and 131 (.7%) patients, respectively. APRI ≥0.7 was an independent predictor of transfusion (adjusted OR: 1.48 [1.26-1.74], P < .001), overall morbidity (1.17 [1.02-1.33], P = .022), and mortality (1.97 [1.22-3.06], P = .004). Transfusion was an independent predictor of overall morbidity (3.31 [2.99-3.65], P < .001), serious morbidity (3.70 [3.33-4.11], P < .001), and mortality (5.73 [4.01-8.14], P < .001). CONCLUSIONS: APRI ≥0.7 is associated with perioperative transfusion, overall morbidity, and 30-day mortality. APRI may serve as a noninvasive tool to risk stratify patients prior to elective minor hepatectomy.

The Kidney Transplant: Maintaining Excellent Outcomes While Increasing Skills Acquisition.

OBJECTIVE/BACKGROUND: Kidney transplantation is a complex operation that incorporates multiple fundamental surgical techniques and is an excellent opportunity for surgical skill development during residency training. We hypothesized that increasing resident competency, measured as anastomosis time, could be demonstrated while maintaining high-quality surgical outcomes during the learning process. METHODS: We performed a retrospective cohort study of surgical resident involvement in kidney transplantation and recorded the anastomosis time. The study population comprised adult, single organ kidney transplants (n = 2052) at a large academic transplant center between 2006 and 2019. Descriptive statistics included frequencies, medians, and means. A mixed model of anastomosis time on number of procedures was fitted. Poisson models were fitted with outcomes of the number of patients with delayed graft function and number of patients that underwent reoperation postoperatively, with the exposure being number of kidney transplants performed by resident. RESULTS: Results from the mixed model suggest that as the number of times a resident performs the surgery increases, the time to conduct the operation decreases with statistical significance. The Poisson regression demonstrated no significant relationship between the operative volume of a resident and postoperative complications. CONCLUSION: This study demonstrated statistical evidence that with an increase in the number of renal transplantations performed by a surgical resident, anastomosis time decreased. It also demonstrated no significant relationship between number of kidney transplants performed by a resident and postoperative complications, suggesting that patient outcomes for this operation are not adversely affected by resident involvement.

Accuracy of models to prognosticate survival after surgery for pancreatic cancer in the era of neoadjuvant therapy.

BACKGROUND: Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). METHODS: We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. RESULTS: A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. CONCLUSIONS: Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

Clinical classification of symptomatic heterotopic pancreas of the stomach and duodenum: A case series and systematic literature review.

BACKGROUND: Heterotopic pancreas (HP) is an aberrant anatomic malformation that occurs most commonly in the upper gastrointestinal tract. While the majority of heterotopic pancreatic lesions are asymptomatic, many manifest severe clinical symptoms which require surgical or endoscopic intervention. Understanding of the clinical manifestations and symptoms of HP is limited due to the lack of large volume studies in the literature. The purpose of this study is to review symptomatic cases at a single center and compare these to a systematic review of the literature in order to characterize common clinical manifestations and treatment of this disease. AIM: To classify the common clinical manifestations of heterotopic pancreas. METHODS: A retrospective review was conducted of pathologic samples containing heterotopic pancreas from 2000-2018. Review was limited to HP of the upper gastrointestinal tract due to the frequency of presentation in this location. Symptomatic patients were identified from review of the medical records and clinical symptoms were tabulated. These were compared to a systematic review of the literature utilizing PubMed and Embase searches for papers pertaining to heterotopic pancreas. Publications describing symptomatic presentation of HP were selected for review. Information including demographics, symptoms, presentation and treatment were compiled and analyzed. RESULTS: Twenty-nine patient were identified with HP at a single center, with six of these identified has having clinical symptoms. Clinical manifestations included, gastrointestinal bleeding, gastric ulceration with/without perforation, pancreatitis, and gastric outlet obstruction. Systemic review of the literature yielded 232 publications detailing symptomatic cases with only 20 studies describing ten or more patients. Single and multi-patient studies were combined to form a cohort of 934 symptomatic patients. The majority of patients presented with abdominal pain (67%) combined with one of the following clinical categories: (1) Dyspepsia, (n = 445, 48%); (2) Pancreatitis (n = 260, 28%); (3) Gastrointestinal bleeding (n = 80, 9%); and (4) Gastric outlet obstruction (n = 80, 9%). The majority of cases (n = 832, 90%) underwent surgical or endoscopic resection with 85% reporting resolution or improvement in their symptoms. CONCLUSION: Heterotopic pancreas can cause significant clinical symptoms in the upper gastrointestinal tract. Better understanding and classification of this disease may result in more accurate identification and treatment of this malformation.

Improved outcomes with minimally invasive pancreaticoduodenectomy in patients with dilated pancreatic ducts: a prospective study.

BACKGROUND: Little is known about what factors predict better outcomes for patients who undergo minimally invasive pancreaticoduodenectomy (MIPD) versus open pancreaticoduodenectomy (OPD). We hypothesized that patients with dilated pancreatic ducts have improved postoperative outcomes with MIPD compared to OPD. METHODS: All patients undergoing pancreaticoduodenectomy were prospectively followed over a time period of 47 months, and perioperative and pathologic covariates and outcomes were compared. Ideal outcome after PD was defined as follows: (1) no complications, (2) postoperative length of stay < 7 days, and (3) negative (R0) margins on pathology. Patients with dilated pancreatic ducts (≥ 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with dilated ducts who underwent OPD and outcomes compared. Likewise, patients with non-dilated pancreatic ducts (< 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with non-dilated ducts who underwent OPD and outcomes were compared. RESULTS: 371 patients underwent PD-74 (19.9%) MIPD and 297 (80.1%) underwent OPD. Overall, patients who underwent MIPD had significantly less intraoperative blood loss. After 1:3 propensity score matching, patients with dilated pancreatic ducts who underwent MIPD (n = 45) had significantly lower overall complication and 90-day readmission rates compared to matched OPD patients (n = 135) with dilated ducts. Patients with dilated duct who underwent MIPD were more likely to have an ideal outcome than patients with OPD (29 vs 15%, p = 0.035). There were no significant differences in postoperative outcomes among propensity score-matched patients with non-dilated pancreatic ducts who underwent MIPD (n = 29) compared to matched patients undergoing OPD (n = 87) with non-dilated ducts. CONCLUSIONS: MIPD is safe with comparable perioperative outcomes to OPD. Patients with pancreatic ducts ≥ 3 mm appear to derive the most benefit from MIPD in terms of fewer complications, lower readmission rates, and higher likelihood of ideal outcome.

Less is more in the difficult gallbladder: recent evolution of subtotal cholecystectomy in a single HPB unit.

INTRODUCTION: Subtotal cholecystectomy (SC) is a technique to manage the difficult gallbladder and avoid hazardous dissection and biliary injury. Until recently it was used infrequently. However, because of reduced exposure to open total cholecystectomy in resident training, we recently adopted subtotal cholecystectomy as the bail-out procedure of choice for resident teaching. This study reports our experience and outcomes with subtotal cholecystectomy in the years immediately preceding adoption and since adoption. METHODS: A retrospective analysis was conducted of patients undergoing SC from July 2010 to June 2019. Outcomes, including bile leak, reoperation and need for additional procedures, were analyzed. Complications were graded by the Modified Accordion Grading Scale (MAGS). RESULTS: 1571 cholecystectomies were performed of which 71 were SC. Subtotal cholecystectomy patients had several indicators of difficulty including prior attempted cholecystectomy and previous cholecystostomy tube insertion. The most common indication for SC was marked inflammation in the hepatocystic triangle (51%). As our experience increased, fewer patients required open conversion to accomplish SC and SC was completed laparoscopically, usually subtotal fenestrating cholecystectomy (SFC). Most patients (85%) had a drain placed and 28% were discharged with a drain. The highest MAGS complication observed was grade 3 (11 patients, 15%). Six patients had a bile leak from the cystic duct resolved by ERCP. At mean follow-up of about 1 year no patient returned with recurrent symptoms. CONCLUSIONS: Subtotal fenestrating cholecystectomy is a useful technique to avoid biliary injury in the difficult gallbladder and can be performed with very satisfactory rates of bile fistula, ERCP, and reoperation.

Does Surgical Margin Impact Recurrence in Noninvasive Intraductal Papillary Mucinous Neoplasms?: A Multi-institutional Study.

OBJECTIVE: The relevance of margin positivity on recurrence after resection of intraductal papillary mucinous neoplasms (IPMNs) is poorly defined and represents one reason controversy remains regarding optimal surveillance recommendations. METHODS: Patients undergoing surgery for noninvasive IPMN at 8 academic medical centers from the Central Pancreas Consortium were analyzed. A positive margin was defined as presence of IPMN or pancreatic intraepithelial neoplasia. RESULTS: Five hundred two patients underwent surgery for IPMN; 330 (66%) did not have invasive cancer on final pathology and form the study cohort. Of these, 20% harbored high grade dysplasia. A positive margin was found in 20% of cases and was associated with multifocal disease (P = 0.02). The majority of positive margins were associated with low grade dysplasia. At a median follow-up of 36 months, 34 (10.3%) patients recurred, with 6.7% developing recurrent cystic disease and 3.6% developing invasive cancer. On multivariate analysis, margin positivity was not associated with recurrence of either IPMN or invasive cancer (P > 0.05). No association between margin status and development of recurrence at the margin was found. Only 6% of recurrences developed at the resection margin and median time to recurrence was 22 months. Of note, 18% of recurrences occurred > 5 years following surgery. CONCLUSION: Margin positivity after resection for noninvasive IPMNs is primarily due to low grade dysplasia and is not associated with developing recurrence in the remnant pancreas or at the resection margin. Long-term surveillance is required for all patients, as a significant number of recurrences developed over 5 years after the index operation.