The diagnosis of pancreatic mucinous cystic neoplasm and associated adenocarcinoma in males: An eight‐institution study of 349 patients over 15 years

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137278/1/jso24582_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137278/2/jso24582.pd

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study

Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN

Molecular Determinants of Substrate Specificity in Plant 5′-Methylthioadenosine Nucleosidases

5′-Methylthioadenosine (MTA)/S-adenosylhomocysteine (SAH) nucleosidase (MTAN) is essential for cellular metabolism and development in many bacterial species. While the enzyme is found in plants, plant MTANs appear to select for MTA preferentially, with little or no affinity for SAH. To understand what determines substrate specificity in this enzyme, MTAN homologues from Arabidopsis thaliana (AtMTAN1 and AtMTAN2, which are referred to as AtMTN1 and AtMTN2 in the plant literature) have been characterized kinetically. While both homologues hydrolyze MTA with comparable kinetic parameters, only AtMTAN2 shows activity towards SAH. AtMTAN2 also has higher catalytic activity towards other substrate analogues with longer 5′-substituents. The structures of apo AtMTAN1 and its complexes with the substrate- and transition-state-analogues, 5′-methylthiotubercidin and formycin A, respectively, have been determined at 2.0–1.8 Å resolution. A homology model of AtMTAN2 was generated using the AtMTAN1 structures. Comparison of the AtMTAN1 and AtMTAN2 structures reveals that only three residues in the active site differ between the two enzymes. Our analysis suggests that two of these residues, Leu181/Met168 and Phe148/Leu135 in AtMTAN1/AtMTAN2, likely account for the divergence in specificity of the enzymes. Comparison of the AtMTAN1 and available Escherichia coli MTAN (EcMTAN) structures suggests that a combination of differences in the 5′-alkylthio binding region and reduced conformational flexibility in the AtMTAN1 active site likely contribute to its reduced efficiency in binding substrate analogues with longer 5′-substituents. In addition, in contrast to EcMTAN, the active site of AtMTAN1 remains solvated in its ligand-bound forms. As the apparent pKa of an amino acid depends on its local environment, the putative catalytic acid Asp225 in AtMTAN1 may not be protonated at physiological pH and this suggests the transition state of AtMTAN1, like human MTA phosphorylase and Streptococcus pneumoniae MTAN, may be different from that found in EcMTAN

Does Intentional Support of Degree Programs in General Surgery Residency Affect Research Productivity or Pursuit of Academic Surgery? A Multi-Institutional Study

To determine whether pursuit of an advanced degree during dedicated research time (DRT) in a general surgery residency training program impacts a resident's research productivity. A retrospective, multi-institutional cohort study. General surgery residency programs that were approved to graduate more than 5 categorical residents per year and that offered at least 1 year of DRT were contacted for participation in the study. A total of 10 general surgery residency programs agreed to participate in the study. Residents who started their residency between 2000 and 2012 and spent at least one full year in DRT (n = 511) were included. Those who completed an advanced degree were compared on the following parameters to those who did not complete one: total number of papers, first-author papers, the Journal Citation Reports impact factors of publication (2018, or most recent), and first position after residency or fellowship training. During DRT, 87 (17%) residents obtained an advanced degree. The most common degree obtained was a Master of Public Health (MPH, n = 42 (48.8%)). Residents who did not obtain an advanced degree during DRT published fewer papers (median 8, [interquartile range 4-12]) than those who obtained a degree (9, [6-17]) (p = 0.002). They also published fewer first author papers (3, [2-6]) vs (5, [2-9]) (p = 0.002) than those who obtained a degree. Resident impact factor (RIF) was calculated using Journal Citation Reports impact factor and author position. Those who did not earn an advanced degree had a lower RIF (adjusted RIF, 84 ± 4 vs 134 ± 5, p < 0.001) compared to those who did. There was no association between obtaining a degree and pursuit of academic surgery (p = 0.13) Pursuit of an advanced degree during DRT is associated with increased research productivity but is not associated with pursuit of an academic career

Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer

BACKGROUND: While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC). METHODS: Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age. RESULTS: The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p 64 0.05). The cure fraction for patients with a CA 19.9 &lt; 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 65 50 who also had lymph node metastasis. CONCLUSIONS: Examining an "all comer" cohort, &lt;15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship

The Hand-Assisted Laparoscopic Approach to Resection of Pancreatic Mucinous Cystic Neoplasms: An Underused Technique?

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors typically of the distal pancreas that harbor malignant potential. Although resection is recommended, data are limited on optimal operative approaches to distal pancreatectomy for MCN. MCN resections (2000–2014; eight institutions) were included. Outcomes of minimally invasive and open MCN resections were compared. A total of 289 patients underwent distal pancreatectomy for MCN: 136(47%) minimally invasive and 153(53%) open. Minimally invasive procedures were associated with smaller MCN size (3.9 vs 6.8 cm; P = 0.001), lower operative blood loss (192 vs 392 mL; P = 0.001), and shorter hospital stay(5 vs 7 days; P = 0.001) compared with open. Despite higher American Society of Anesthesiologists class, hand-assisted (n = 46) had similar advantages as laparoscopic/robotic (n = 76). When comparing hand-assisted to open, although MCN size was slightly smaller (4.1 vs 6.8 cm; P = 0.001), specimen length, operative time, and nodal yield were identical. Similar to laparoscopic/robotic, hand-assisted had lower operative blood loss (161 vs 392 mL; P = 0.001) and shorter hospital stay (5 vs 7 days; P = 0.03) compared with open, without increased complications. Hand-assisted laparoscopic technique is a useful approach for MCN resection because specimen length, lymph node yield, operative time, and complication profiles are similar to open procedures, but it still offers the advantages of a minimally invasive approach. Hand-assisted laparoscopy should be considered as an alternative to open technique or as a successive step before converting from total laparoscopic to open distal pancreatectomy for MCN

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma

Background: The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA. Methods: Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status. Results: Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p&nbsp;&gt;&nbsp;0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5&nbsp;months and 7.9%, respectively, for patients with an R1 resection (p&nbsp;=&nbsp;0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p&nbsp;=&nbsp;0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0\u20131.7; p&nbsp;=&nbsp;0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4\u20132.3; p&nbsp;=&nbsp;0.829). Conclusions: Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA

A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma

Introduction: Although widely used, the 7th edition American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (PHC) may be limited. Disease-specific nomograms have been proposed as a better means to predict long-term survival for individual patients. We sought to externally validate a recently proposed nomogram by Memorial Sloan Kettering Cancer Center (MSKCC) for PHC, as well as identify factors to improve the prediction of prognosis for patients with PHC. Methods: Four hundred seven patients who underwent surgery for PHC between 1988 and 2014 were identified using an international, multi-center database. Standard clinicopathologic and outcome data were collected. The predictive power of the AJCC staging system and nomogram were assessed. Results: Median survival was 24.4&nbsp;months; 3- and 5-year survival was 37.2 and 20.8&nbsp;%, respectively. The AJCC 7th edition staging system (C-index 0.570) and the recently proposed PHC nomogram (C-index 0.587) both performed poorly. A revised nomogram based on age, lymphovascular invasion, perineural invasion, and lymph node metastases performed better (C-index 0.682). The calibration plot of the revised PHC nomogram demonstrated good calibration. Conclusion: The 7th edition AJCC staging system and the MSKCC nomogram had a poor ability to predict long-term survival for individual patients with PHC. A revised nomogram provided more accurate prediction of survival, but will need to be externally validated

Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases

Background: The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. Methods: Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers. Results: In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p <0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%Cl: 0197-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%Cl: 1.09-2.69) were independent poor prognostic factors in the resected cohort. Conclusion: Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resectio