ASO Practice Guidelines Series: Management of Resectable, Borderline Resectable, and Locally Advanced Pancreas Cancer.

Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma.

Contemporary Outcomes of Grade-C Postoperative Pancreatic Fistula in a Nationwide Database.

INTRODUCTION: Grade-C postoperative pancreatic fistulas (POPFs) are dreaded complications following pancreaticoduodenectomy. The aim of this study was to quantify the incidence and risk factors associated with grade C POPF in a national database. METHODS: The National Surgical Quality Improvement Program targeted user files were queried for patients who underwent elective pancreaticoduodenectomy (2014-2020). Outcomes were compared between clinically relevant (CR) grade B POPF and grade C POPF. RESULTS: Twenty-six thousand five hundred fifty-two patients were included, of which 90.1% (n = 23,714) had No CR POPF, 8.7% (n = 2287) suffered grade B POPF, and 1.2% (n = 327) suffered grade C POPF. There was no change in the rate Grade-C fistula overtime (m = 0.06, P = 0.63), while the rate of Grade-B fistula significantly increased (m = +1.40, P < 0.01). Fistula Risk Scores were similar between grade B and C POPFs (high risk: 34.9% versus 31.2%, P = 0.21). Associated morbidity was increased with grade C POPF, including delayed gastric emptying, organ space infections, wound dehiscence, respiratory complications, renal complications, myocardial infarction, and bleeding. On multivariate logistic regression, diabetes mellitus (odds ratio: 1.41 95% confidence interval: 1.06-1.87, P = 0.02) was associated with grade C POPF. CONCLUSIONS: This study represents the largest contemporary series evaluating grade C POPFs. Of those suffering CR POPF, the presence of diabetes mellitus was associated with grade C POPF. While modern management has led to grade C POPF in 1% of cases, they remain associated with alarmingly high morbidity and mortality, requiring further mitigation strategies to improve outcomes.

Defining the operative time threshold for safety in patients undergoing robotic pancreaticoduodenectomy.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is a safe and efficacious procedure in appropriately selected patients, though frequently with increased operative times compared to open pancreaticoduodenectomy (OPD). METHODS: From 2014 to 2019, patients who underwent elective, low-risk, RPDs and OPDs in the NSQIP database were isolated. The operative time threshold (OTT) for safety in RPD patients was estimated by identifying the operative time at which complication rates for RPD patients exceeded the complication rate of the benchmark OPD control. RESULTS: Of 6270 patients identified, 939 (15%) underwent RPD and 5331 (85%) underwent OPD. The incidence of major morbidity or mortality for the OPD cohort was 35.1%. The OTT was identified as 7.7 h. Patients whose RPDs were above the OTT experienced a higher incidence of major morbidity (42.5% vs. 35.0%, p < 0.01) and 30-day mortality (2.7% vs. 1.2%, p = 0.03) than the OPD cohort. Preoperative obstructive jaundice (OR: 1.47, [95% CI: 1.08-2.01]) and pancreatic duct size <3 mm (OR: 2.44, [95% CI: 1.47-4.06]) and 3-6 mm (OR: 2.15, [95% CI: 1.31-3.52]) were risk factors for prolonged RPDs on multivariable regression. CONCLUSION: The operative time threshold for safety, identified at 7.7 h, should be used to improve patient selection for RPDs and as a competency-based quality benchmark.

Robotic-Assisted Minimally Invasive Esophagectomy: Postoperative Outcomes in a Nationwide Cohort.

INTRODUCTION: Robotic-assisted minimally invasive esophagectomy (RAMIE) in clinical trials has demonstrated improved outcomes compared to open esophagectomy (OE). However, outcomes after national implementation remain unknown. The aim of this study was to evaluate postoperative outcomes after RAMIE. METHODS: Patients who underwent elective esophagectomy between 2016 and 2020 were identified from the American College of Surgeons-- National Surgical Quality Improvement Program esophageal targeted participant user files and categorized by operative approach, with patients who underwent hybrid procedures excluded. Outcomes were compared between OE and minimally invasive esophagectomy (MIE)/RAMIE, with subset analyses by minimally invasive operative approach. Primary outcomes included pulmonary complications, anastomotic leak requiring reintervention, all-cause morbidity, and 30-d mortality. RESULTS: In total 2786 patients were included, of which 58.3% underwent OE, 33.2% underwent MIE, and 8.4% underwent RAMIE. In the entire cohort, Ivor Lewis esophagectomy was the most common technique (64.6%), followed by transhiatal (22.0%), and a McKeown technique (13.4%). Comparing OE and MIE/RAMIE, pulmonary complications (21.5% versus 16.1%, P < 0.01) and all-cause morbidity (40.9% versus 32.3%, P < 0.01) were both reduced in the MIE/RAMIE group. When directly comparing MIE to RAMIE, there was no difference in the rate of pulmonary complications, anastomotic leak, all-cause morbidity, and mortality. However, RAMIE was associated with decreased all-cause morbidity compared to OE (40.9% versus 33.3%, P = 0.03). CONCLUSIONS: RAMIE was associated with decreased morbidity compared to OE, with similar outcomes to MIE. The national adoption of RAMIE in this select cohort appears safe.

General Surgery Residency Virtual Recruitment During the Pandemic: An Analysis of Applicant Surveys.

INTRODUCTION: The COVID-19 pandemic forced a sudden change from in-person to virtual interviews for the general surgery residency match. General surgery programs and applicants adopted multiple strategies to best mimic in-person recruitment. The purpose of this study was to evaluate applicant opinions of the virtual recruitment format. MATERIALS AND METHODS: Postinterview survey responses for applicants interviewing at a single general surgery residency program in the 2020-2021 and 2021-2022 cycles were evaluated. All interviewed applicants were sent an anonymous survey assessing the virtual interview structure, their impression of the program, and their opinions on recruitment in the future. RESULTS: The response rate was 31.2% (n = 60). Most (88.4%) respondents reported a more favorable view of the program after a virtual interview. Factors that were most likely to create a favorable impression were residents (89.6%) and culture (81.0%). 50.8% of applicants favored virtual-only interviews. The majority of applicants (60.3%), however, preferred the virtual interview remain a component of the application process, 34.4% recommended that virtual interviews be used as an initial screen before in-person invites, while 19.0% suggested applicants should interview in-person or virtually without penalty. 62.1% favored capping the number of interviews offered by programs and accepted by applicants. CONCLUSIONS: The virtual interview format for general surgery residency allows applicants to effectively evaluate a residency program. Applicants are in favor of a combination of virtual and in-person interviews in the future. Innovation in the recruitment process, including limiting the number of applications and incorporating virtual events, is supported by applicants.

Feeding Jejunostomy Tube in Patients Undergoing Esophagectomy: Utilization and Outcomes in a Nationwide Cohort.

BACKGROUND: Feeding jejunostomy (JT) tubes are often utilized as an adjunct to optimize nutrition for successful esophagectomy; however, their utility has come into question. The aim of this study was to evaluate utilization and outcomes associated with JTs in a nationwide cohort of patients undergoing esophagectomy. METHODS: The NSQIP database was queried for patients who underwent elective esophagectomy. JT utilization was assessed between 2010 and 2019. Post-operative outcomes were compared between those with and without a JT on patients with esophagectomy-specific outcomes (2016-2019), with results validated using a propensity score-matched (PSM) analysis based on key clinicopathologic factors, including tumor stage. RESULTS: Of the 10,117 patients who underwent elective esophagectomy over the past decade, 53.0% had a JT placed concurrently and 47.0% did not. Utilization of JTs decreased over time, accounting for 60.0% of cases in 2010 compared to 41.7% in 2019 (m = - 2.14 95%CI: [- 1.49]-[- 2.80], p < 0.01). Patients who underwent JT had more composite wound complications (17.0% vs. 14.1%, p = 0.02) and a higher rate of all-cause morbidity (40.4% vs. 35.5%, p = 0.01). Following PSM, 1007 pairs were identified. Analysis of perioperative outcomes demonstrated a higher rate of superficial skin infections (6.1% vs. 3.5%, p = 0.01) in the JT group. However, length of stay, reoperation, readmission, anastomotic leak, composite wound complications, all-cause morbidity, and mortality rates were similar between groups. CONCLUSIONS: Among patients undergoing elective esophagectomy, feeding jejunostomy tubes were utilized less frequently over the past decade. Similar perioperative outcomes among matched patients support the safety of esophagectomy without an adjunct feeding jejunostomy tube.

The Kidney Transplant Equity Index: Improving Racial and Ethnic Minority Access to Transplantation.

OBJECTIVES: To develop a scalable metric which quantifies kidney transplant (KT) centers' performance providing equitable access to KT for minority patients, based on the individualized prelisting prevalence of end-stage renal disease (ESRD). BACKGROUND: Racial and ethnic disparities for access to transplant in patients with ESRD are well described; however, variation in care among KT centers remains unknown. Furthermore, no mechanism exists that quantifies how well a KT center provides equitable access to KT for minority patients with ESRD. METHODS: From 2013 to 2018, custom datasets from the United States Renal Data System and United Network for Organ Sharing were merged to calculate the Kidney Transplant Equity Index (KTEI), defined as the number of minority patients transplanted at a center relative to the prevalence of minority patients with ESRD in each center's health service area. Markers of socioeconomic status and recipient outcomes were compared between high and low KTEI centers. RESULTS: A total of 249 transplant centers performed 111,959 KTs relative to 475,914 nontransplanted patients with ESRD. High KTEI centers performed more KTs for Black (105.5 vs 24, P <0.001), Hispanic (55.5 vs 7, P <0.001), and American Indian (1.0 vs 0.0, P <0.001) patients than low KTEI centers. In addition, high KTEI centers transplanted more patients with higher unemployment (52 vs 44, P <0.001), worse social deprivation (53 vs 46, P <0.001), and lower educational attainment (52 vs 43, P <0.001). While providing increased access to transplant for minority and low socioeconomic status populations, high KTEI centers had improved patient survival (hazard ratio: 0.86, 95% confidence interval: 0.77-0.95). CONCLUSIONS: The KTEI is the first metric to quantify minority access to KT incorporating the prelisting ESRD prevalence individualized to transplant centers. KTEIs uncover significant national variation in transplant practices and identify highly equitable centers. This novel metric should be used to disseminate best practices for minority and low socioeconomic patients with ESRD.

A National Assessment of T2 Staging for Intrahepatic Cholangiocarcinoma and the Poor Prognosis Associated with Multifocality.

BACKGROUND: T2 intrahepatic cholangiocarcinoma (ICC) is defined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC. The patients were grouped based on T2 staging, multifocality, and lymph node involvement. RESULTS: The study enrolled and classified 4887 patients into clinical (c) stage groups as follows: 15.2% with solitary T2N0 (sT2N0) tumors, 21.3% with multifocal T2N0 (mT2N0) tumors, and 63.5% with node-positive (TxN1) disease. Patients with (c)sT2N0 tumors had higher rates of surgical resection than those with (c)mT2N0 or (c)TxN1 disease (33.5% vs 19.7% vs 15.0%; p < 0.01). Median overall survival (OS) was better for the patients with (c)sT2N0 tumors than for those with multifocal and node-positive disease (15.4 vs 10.4 vs 10.4 months; p < 0.01). On multivariate analysis, (c)sT2N0 tumors were associated with better OS than (c)mT2N0 tumors [hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.17-1.46; p < 0.01] or (c)TxN1 disease (HR,1.41; 95% CI 1.28-1.56; p < 0.01). In a subset analysis based on pathologic (p) staging of patients who underwent surgical resection with regional lymphadenectomy, multivariate analysis demonstrated that (p)sT2N0 tumors were associated with better OS than (p)mT2N0 tumors (HR,1.40; 95% CI 1.03-1.92; p = 0.03) or (p)TxN1 disease (HR, 2.05; 95% CI 1.62-2.58; p < 0.01). CONCLUSIONS: Multifocal T2N0 ICC is associated with poor OS and has a disparate prognosis compared with solitary T2N0 disease, even among patients who undergo resection. Future staging criteria should account for the poor outcomes associated with multifocal ICC.

Systemic Therapy for Resected Pancreatic Adenocarcinoma: How Much is Enough?

BACKGROUND: Systemic therapy is an essential part of treatment for pancreatic ductal adenocarcinoma (PDAC). However, not all patients receive every cycle of chemotherapy and even if they do, the impact of reduced dose density (DD) on survival is not known. PATIENTS AND METHODS: A single institutional prospective database was queried for patients with PDAC who underwent curative resection between 2009 and 2018. The primary outcome was DD, defined as the percentage of total planned chemotherapy actually received and associated survival. RESULTS: Of the 126 patients included, 38.9% underwent a neoadjuvant approach, which was associated with a greater median number of completed chemotherapy cycles (5 cycles versus 4 cycles, p < 0.01) and a higher median total DD (93.0% versus 65.0%, p < 0.01), compared with an adjuvant treatment approach. In both groups, adjuvant chemotherapy completion rates were low, with only 55 patients completing all adjuvant cycles. After sequential survival analysis, patients who received a DD ≥ 80% had improved median overall survival (OS) (27.1 months versus 18.6 months, p = 0.01), compared with patients who achieved a DD < 80%. On multivariate Cox proportional-hazards modeling, only the presence of lymphovascular invasion (HR: 1.77, 95% CI: 1.04-2.99, p = 0.04) and DD < 80% (HR: 1.91, 95% CI: 1.23-3.00, p = 0.01) were associated with decreased OS. CONCLUSIONS: In this cohort study, patients who received ≥ 80% DD had significantly better OS. DD should be considered an important prognostic metric in pancreatic cancer, and strategies are needed to improve chemotherapy tolerance to improve patient outcomes.

Is There a Benefit to Adjuvant Chemotherapy in Resected, Early Stage Pancreatic Ductal Adenocarcinoma?

BACKGROUND: The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in patients with early stage disease. METHODS: The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC. Exclusion criteria included neoadjuvant therapy, radiation, or those who suffered a 90-day mortality. RESULTS: Of the 1526 patients included in the study, 42.2% received AC and 57.8% underwent surgery alone. Patients who received AC were younger, had fewer comorbidities, and were more likely to have private insurance, compared with those treated with surgery alone. Patients who received AC had longer median overall survival (OS) compared with those who underwent surgery alone (105.7 months vs 72.0 months, p < 0.01). Subset analyses based on individual "good" prognostic features (size ≤ 1.0 cm, lymphovascular invasion negative, well/moderately differentiated, margin negative resection) demonstrated improved OS with AC. Following propensity score matching based on key clinicopathologic features, AC remained associated with improved median OS (83.7 months vs 59.8 months, p < 0.01). However, in the cohort with body/tail tumors (101.2 months vs 95.0 months, p = 0.19) and those with all "good" prognostic features (95.9 months vs 90.6 months, p = 0.15), AC was not associated with improved survival. CONCLUSIONS: In resected, Stage IA PDAC, AC is associated with improved overall survival in the vast majority of patients; however, in select cohorts the role of AC is unclear. Further study is needed to tailor treatment to individual patients with PDAC.

Gender Disparities in Academic Productivity and Promotion Among Endocrine Surgery Faculty.

INTRODUCTION: Academic rank and metrics such as total publications (pubs) and H-index are indicators to measure academic achievement. This study aims to determine whether there are gender differences in academic productivity or faculty appointments among endocrine surgeons in the United States. METHODS: A database was generated from the American Association of Endocrine Surgeons (AAES) website. Community or academic practice was designated by institution affiliation and faculty appointment. Academic metrics, including pubs, H-index, and weighted-RCR (relative citation ratio), were obtained from public databases. RESULTS: A total of 258 AAES members were affiliated with an academic institution. The majority were men (58%). Overall, men in endocrine surgery had higher academic metrics: pubs (56.0 [26-134], 23.0 [11-56], P < 0.0001), H-index (19.0 [11-35], 9.0 [5-21], P < 0.0001), weighted-RCR (63.5 [22-193], 24.1 [8-74], P < 0.005) and rank (associate professor or professor, P < 0.0001). Subgroup analysis accounting for time in practice found no difference in total publications, weighted RCR, or faculty appointments between genders in practice for 0-5 y. However, among surgeons in practice for 6-10 y, men had higher academic metrics (pubs: 31.0 [16-79], 18.5 [9-33]; RCR: 46.0 [14-102], 13.3 [9-34]) and faculty appointments (all P < 0.05). CONCLUSIONS: There are gender disparities in academic productivity and faculty appointment among US endocrine surgeons. While junior faculty show no gender differences in most indicators of academic productivity or rank, men with 6-10 y in practice have higher average academic metrics and rank. Whether the absence of gender disparities among junior faculty is a sustainable reflection of recent efforts to encourage equal mentorship and professional opportunities or whether disparities will manifest as faculty progress remains to be determined.

Minimally Invasive Surgery for Resectable Adrenocortical Carcinoma: A Nationwide Analysis.

INTRODUCTION: The utilization of minimally invasive surgery (MIS) for adrenocortical carcinoma (ACC) remains controversial due to concerns regarding the quality of surgical resection and subsequent oncologic risks. Current guidelines recommend open resections for all cases of suspected ACC independent of size; however, there has been increased adoption of MIS for ACC over time. We sought to determine whether the rise in the utilization of MIS is associated with worse survival outcomes for ACC. METHODS: The National Cancer Database was queried for patients with ACC who underwent surgical resection between 2010 and 2017. Patient selection, oncologic outcomes, and overall survival were compared among patients who received an MIS approach (laparoscopic or robotic) versus an open approach. RESULTS: A total of 1483 patients underwent ACC resection with 982 (66.2%) patients undergoing an open approach and 501 (33.8%) receiving an MIS operation. The overall utilization of MIS for ACC increased significantly after 2013 (37.7% versus 29.5%, P < 0.01). There was no difference in overall survival between MIS and open resections on univariable (log-rank P = 0.12) analysis. On multivariable analysis, survival was improved in MIS patients versus open resection (Hazard ratio: 0.83, 95% CI: [0.70-0.99]). Notably, survival remained comparable among patients who underwent resection for large ACCs (6-10 cm, log-rank P = 0.66) and giant ACCs (>10 cm, log-rank P = 0.24), irrespective of operative approach. CONCLUSIONS: Our findings suggest that in appropriately selected patients with ACC, MIS can be performed safely without a significant decrease in overall survival, independent of size. We recommend consideration of a minimally-invasive approach for adrenal masses despite size >6 cm.

Laparoscopic Appendectomy and Cholecystectomy Timing Predicts Hand-Offs but Not Miscounts.

INTRODUCTION: Intraoperative hand-offs are poorly coordinated and associated with risk of surgical miscount. We evaluated hand-off patterns for nursing staff during two common operations hypothesizing that hand-off patterns would be associated with increased surgical miscounts and vary during operations performed standard versus nonstandard operating hours. METHODS: We retrospectively analyzed laparoscopic cholecystectomy (N = 3888) and appendectomy (N = 1768) from 2012 to 2021 at a single institution using electronic medical records. We evaluated intraoperative hand-off patterns and the presence of miscounts for operations performed during standard versus nonstandard hours. Standard operating hours were defined as M-F 7:30 am to 5:00 pm. RESULTS: Across 5656 operations, 10 cases had surgical miscounts and were significantly longer than those without (156.5 versus 101 min P = 0.0178). More than half (51.3%) of cases had no identified hand-offs, and 42.9% of cases occurred during nonstandard hours. Cases during standard versus nonstandard hours were more likely to have hand-offs (56.0% versus 38.9%), P < 0.0001 and had shorter interval between hand-offs (64 versus 75 min), P < 0.0001. The period between patient entry to the room and intubation, which includes initial counts, had a disproportionately high percentage of hand-offs (P < 0.0001). CONCLUSIONS: Variability in hand-off occurrence and frequency in operations performed during standard and nonstandard hours suggest that hand-offs are influenced by staffing patterns. Few surgical miscounts occurred but were associated with longer cases. Hand-offs disproportionately occurred between patient entry and intubation, with a potential for disruption of initial instrument counts. Future work optimizing hand-off coordination is an opportunity to mitigate risk to patients.

Surgery Is Underutilized in the Management of Tertiary Hyperparathyroidism.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is observed in up to 40% of renal transplant patients. Standard guidelines defining 3HPT and indications for operative intervention are not well described. METHODS: We conducted a retrospective, single-institution cohort study of patients who underwent renal transplant between January 1, 2012 and January 30, 2018, with a minimum of 13-month follow-up and at least 1 y of allograft function. We defined 3HPT as having elevated serum level parathyroid hormone (>88 pg/mL) after successful renal transplantation or multiple instances of elevated serum calcium starting at least 3 mo after transplant. We compared graft failure rates after stratifying the cohort based on management strategy: expectant, medical management with cinacalcet, and parathyroidectomy. RESULTS: Out of the 381 transplanted patients with functional grafts at 1 y, 178 patients (46.6%) were found to have 3HPT. One hundred twenty-nine patients (72.5%) were managed expectantly without medications, 35 patients (19.7%) were managed medically, and 14 patients (7.8%) were managed with parathyroidectomy. Twenty-two patients (17.1%) in the observation group had graft failure, 4 patients (11.4%) in the medically managed group had graft failure, and 0 patients in the surgery group had graft failure. Surgical intervention was associated with decreased renal allograft failure when compared to the combined cohort of nonoperative 3HPT patients (P = 0.03). All patients who underwent parathyroidectomy were cured and did not have graft failure as of December 30, 2019. Calcium elevation, but not PTH elevation, was associated with referral for parathyroidectomy on multivariable logistic regression analysis (P < 0.01). CONCLUSIONS: At our institution, the referral rate for parathyroidectomy among patients with 3HPT remains low. Parathyroidectomy was associated with high cure rates and reduced graft failure. Surgery may be underutilized in the management of 3HPT.

The volume-outcomes relationship in donation after circulatory death liver transplantation.

BACKGROUND: Donation after circulatory death (DCD) liver transplantation (LT) has become an effective mechanism for expanding the donor pool and decreasing waitlist mortality. However, it is unclear if low-volume DCD centers can achieve comparable outcomes to high-volume centers. METHODS: From 2011 to 2019 utilizing the United Network for Organ Sharing (UNOS) database, liver transplant centers were categorized into tertiles based on their annual volume of DCD LTs. Donor selection, recipient selection, and survival outcomes were compared between very-low volume (VLV, n = 1-2 DCD LTs per year), low-volume (LV, n = 3-5), and high-volume (HV, n > 5) centers. RESULTS: One hundred and ten centers performed 3273 DCD LTs. VLV-centers performed 339 (10.4%), LV-centers performed 627 (19.2%), and HV-centers performed 2307 (70.4%) LTs. 30-day, 90-day, and 1-year patient and graft survival were significantly increased at HV-centers (all P < .05). Recipients at HV-centers had shorter waitlist durations (P < .01) and shorter hospital lengths of stay (P < .01). On multivariable regression, undergoing DCD LT at a VLV-center or LV-center was associated with increased 1-year patient mortality (VLV-OR:1.73, 1.12-2.69) (LV-OR: 1.42, 1.01-2.00) and 1-year graft failure (VLV-OR: 1.79, 1.24-2.58) (LV-OR: 1.28, .95-1.72). DISCUSSION: Increased annual DCD liver transplant volume is associated with improved patient and graft survival.

Is endocrine and exocrine function improved following duodenal preserving pancreatic head resection over whipple for chronic pancreatitis?

BACKGROUND: The aim of our study was to evaluate the rates of treatment for post-operative exocrine pancreatic insufficiency (EPI) and diabetes mellites (DM) between Duodenal Preserving Pancreatic Head Resections (DPPHR) and Pancreaticoduodenectomy (PD) from a prospectively maintained database of patients with chronic pancreatitis. METHODS: 104 patients were identified for inclusion, 62 of whom underwent DPPHR and 42 underwent PD. Study endpoints included changes in treatment for EPI and DM. RESULTS: In the DPPHR group, the vast majority (n = 55) received a Frey procedure, with a small minority of patients undergoing a Beger procedure (n = 4) or Berne modification (n = 3). Patients in the DPPHR group had a lower rate of new persistent treatment for EPI post-operatively compared to patients who underwent PD (28.0% vs. 76.5%, p = 0.002). There was no difference in the rate of new onset DM, with low rates of new insulin dependent diabetics in both groups. Both groups had equal efficacy in terms of pain control, with 67.7% of the DPPHR group and 61.9% of the PD group remaining opioid free at long-term follow-up (p = 0.539). CONCLUSION: In patients with head-predominant chronic pancreatitis, DPPHR was associated with reduced rates of new EPI treatment and similar endocrine function compared with PD.

Total pancreatectomy and islet cell autotransplantation: a 10-year update on outcomes and assessment of long-term durability.

BACKGROUND: Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years. METHODS: Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively. RESULTS: Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months. CONCLUSION: This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.

Heterogeneity within molecular subtypes of breast cancer.

Breast cancer is the quintessential example of how molecular characterization of tumor biology guides therapeutic decisions. From the discovery of the estrogen receptor to current clinical molecular profiles to evolving single-cell analytics, the characterization and compartmentalization of breast cancer into divergent subtypes is clear. However, competing with this divergent model of breast cancer is the recognition of intratumoral heterogeneity, which acknowledges the possibility that multiple different subtypes exist within a single tumor. Intratumoral heterogeneity is driven by both intrinsic effects of the tumor cells themselves as well as extrinsic effects from the surrounding microenvironment. There is emerging evidence that these intratumoral molecular subtypes are not static; rather, plasticity between divergent subtypes is possible. Interconversion between seemingly different subtypes within a tumor drives tumor progression, metastases, and treatment resistance. Therapeutic strategies must, therefore, contend with changing phenotypes in an individual patient's tumor. Identifying targetable drivers of molecular heterogeneity may improve treatment durability and disease progression.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.