Implementation of an opioid reduction toolkit in pancreatectomy patients significantly increases patient awareness of safe practice and decreases amount prescribed and consumed.

BACKGROUND: Postoperative opioid abuse following surgery is a major concern. This study sought to create an opioid reduction toolkit to reduce the number of narcotics prescribed and consumed while increasing awareness of safe disposal in pancreatectomy patients. METHODS: Prescription, consumption, and refill request data for postoperative opioids were collected from patients receiving an open pancreatectomy before and after the implementation of an opioid reduction toolkit. Outcomes included safe disposal practice awareness for unused medication. RESULTS: 159 patients were included in the study: 24 in the pre-intervention and 135 in the post-intervention group. No significant demographic or clinical differences existed between groups. Median morphine milliequivalents (MMEs) prescribed were significantly reduced from 225 (225-310) to 75 (75-113) in the post-intervention group (p < 0.0001). Median MMEs consumed were significantly reduced from 109 (111-207) to 15 (0-75), p < 0.0001), as well. Refill request rates remained equivalent during the study (Pre: 17% v Post: 13%, p = 0.9) while patient awareness of safe disposal increased (Pre: 25% v Post: 62%, p < 0.0001). DISCUSSION: An opioid reduction toolkit significantly reduced the number of postoperative opioids prescribed and consumed after open pancreatectomy, while refill request rates remained the same and patients' awareness of safe disposal increased.

Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report.

BACKGROUND: Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered. CASE PRESENTATION: Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). CONCLUSIONS: Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.

Optimizing cancer cure dialog: an analysis of pancreatic cancer patients' views regarding survival and cure.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. Clinicians commonly refer to surgical therapy as resection with curative intent. However, PDA cure rates after resection remain unknown and the definition of cure remains vague. We investigated how patients (the majority undergoing resection), family members, and clinicians understand the concept of cure, to better inform discussions with patients regarding PDA prognosis. METHODS: In a prospective survey, cohorts were asked to indicate the best definition of cure from three choices: 5-year survival endpoint (typically used in the literature), a biological endpoint without biochemical or radiographic signs of disease (similar to the NCI definition), or a practical endpoint where life span approximates similarly aged patients without PDA. Fleiss' kappa statistic was calculated to measure inter-rater agreement. RESULTS: Patients, family members, and health care professionals (N = 200) agreed that renormalization of life expectancy was the preferred definition of cure in the context of pancreatic cancer. Inter-rater agreement was highest for the patient and family member groups (Fleiss' kappa 0.27 and 0.40, respectively, P < 0.001), while variability was observed between health care professionals (Fleiss' kappa 0.11, P < 0.001). CONCLUSIONS: In all groups surveyed, the probability for a normal life expectancy is the preferred long-term metric in patients with early-staged pancreatic cancer. Renormalization of life expectancy appears to be an important therapy goal for PDA patients and it is advisable to address this topic during clinical discussions.

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

CONTEXT.­: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. OBJECTIVE.­: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. DESIGN.­: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. RESULTS.­: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). CONCLUSIONS.­: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Distress, Depression, and the Effect of ZIP Code in Pancreaticobiliary Cancer Patients and Their Significant Others.

BACKGROUND: Distress screening of cancer patients is mandated by the American College of Surgeons Commission on Cancer. Clinical implementation remains limited, particularly in surgical oncology settings in individuals with pancreaticobiliary cancers. STUDY DESIGN: This study evaluated differences in mean distress scores based on the National Comprehensive Cancer Network Distress Thermometer & Problem List for patients with pancreaticobiliary cancers, benign pancreatic conditions, and for their significant others (SOs). The distress screening was conducted at the first office visit and postoperatively in a subset of those who had surgery. Distress Thermometer (DT) scores were dichotomized at ≤5 vs >5 and at ≥7 and correlated with Problem List items. The US ZIP Code database was used to correlate income range, percent poverty, and unemployment in the patient's self-identified ZIP code. Regression models were fitted to identify independent predictors of distress. RESULTS: A total of 547 patients and 184 SOs were evaluated. Thirty percent of patients had DT scores >5, with pancreatic adenocarcinoma patients reporting the highest levels of distress. SOs of pancreatic adenocarcinoma patients reported even greater distress than the patients themselves. As the number of pre-existing medical problems increased; so did DT scores. Distress correlated with physical and emotional problems and worry about insurance coverage and transportation. Higher income level predicted higher DT scores, although poverty predicted lower DT scores. Depression was present in 12% of the patients. Distress improved in those undergoing surgery. CONCLUSIONS: Distress and depression in pancreaticobiliary cancer patients and SOs are prevalent. The findings of this study have multiple actionable implications and require diagnosis, treatment, and referral to supportive care resources.

Repurposing the FDA-approved anthelmintic pyrvinium pamoate for pancreatic cancer treatment: study protocol for a phase I clinical trial in early-stage pancreatic ductal adenocarcinoma.

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates. METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug's PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer. ETHICS AND DISSEMINATION: This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05055323.

Intraoperative Cytologic Sampling for Resected Pancreatic and Periampullary Adenocarcinoma with Implications for Locoregional Recurrence-Free Survival.

BACKGROUND: We hypothesized that pancreatic and periampullary adenocarcinoma recurrence after surgical resection may be affected by the shedding of malignant epithelial cells during surgical dissection and that this may have implications for disease recurrence and survival. STUDY DESIGN: In this ongoing, investigator-initiated prospective randomized controlled trial, patients with pancreatic and periampullary adenocarcinoma were randomized intraoperatively, postresection into 3 study arms: peritoneal lavage using 10 L normal saline or distilled water, or control group with no lavage. Peritoneal fluid was sampled for cytologic analysis (cytospin, cellblock, immunohistochemistry-Ber-EP4 antibody) at 4 stages: (1) abdominal entry pre-dissection, (2) resection bed after tumor extirpation, (3) ex vivo resected specimen, and (4) resection bed postlavage. RESULTS: Between April 2016 and May 2018, 193 patients who underwent randomization for the study also underwent the described cytologic sampling. Of these, 167 patients (86.5%) were ultimately found to have pancreatic or periampullary adenocarcinoma. Before dissection (1) on cytospin analysis, 4.9% were positive, which rose to 10.2% intraoperatively (2), 16.7% ex vivo (3), and decreased to 4.3% (4) after lavage. Lymph node metastasis, margin involvement, and perineural invasion did not correlate with locoregional recurrence (LR). Tumor cells in the ex vivo cytospin (3) correlated with LR (odds ratio 3.8 [95% CI 1.6 to 9.2], p = 0.005) and LR disease-free survival (p = 0.007). Cox regression analysis revealed ex vivo cytospin positivity to be strongly associated with poorer LR disease-free survival (hazard ratio 2.26 [95% CI 1.16 to 4.42], p = 0.017). CONCLUSIONS: Cytologic sampling from ex vivo specimen irrigation after surgical resection of pancreatic and periampullary adenocarcinoma may have implications for LR, survival, and treatment, suggesting a possible cancer cell shedding phenotype.

Preparedness for Surgery: Analyzing a Quality Improvement Project in a Population of Patients Undergoing Hepato-Pancreatico-Biliary Surgery.

BACKGROUND: Approximately 20% of patients diagnosed with pancreatic cancer will be eligible for hepato-pancreatico-biliary (HPB) surgery. Studies indicate that high-quality patient education is pivotal in reducing anxiety, improving clinical and performance outcomes, and increasing patient satisfaction. OBJECTIVES: This quality improvement project sought to determine the perceived level of preparedness for patients undergoing HPB surgery and to identify information and knowledge gaps in preoperative education. METHODS: Convenience sampling was used to collect postoperative information via questionnaire from 50 patients regarding areas of importance. FINDINGS: Preoperative information gaps for patient and family education were identified. Improving preparedness for HPB surgery has the potential to improve clinical outcomes, increase quality and patient satisfaction, decrease length of stay, and reduce time to adjuvant therapy.

Enhancing Patient Outcomes while Containing Costs after Complex Abdominal Operation: A Randomized Controlled Trial of the Whipple Accelerated Recovery Pathway.

BACKGROUND: This study was designed to determine whether a standardized recovery pathway could reduce post-pancreaticoduodenectomy hospital length of stay to 5 days without increasing complication or readmission rates. STUDY DESIGN: Pancreaticoduodenectomy patients (high-risk patients excluded) were enrolled in an IRB-approved, prospective, randomized controlled trial (NCT02517268) comparing a 5-day Whipple accelerated recovery pathway (WARP) with our traditional 7-day pathway (control). Whipple accelerated recovery pathway interventions included early discharge planning, shortened ICU stay, modified postoperative dietary and drain management algorithm, rigorous physical therapy with in-hospital gym visit, standardized rectal suppository administration, and close telehealth follow-up post discharge. The trial was powered to detect an increase in postoperative day 5 discharge from 10% to 30% (80% power, α = 0.05, 2-sided Fisher's exact test, target accrual: 142 patients). RESULTS: Seventy-six patients (37 WARP, 39 control) were randomized from June 2015 to September 2017. A planned interim analysis was conducted at 50% trial accrual resulting in mandatory early stoppage, as the predefined efficacy end point was met. Demographic variables between groups were similar. The WARP significantly increased the number of patients discharged to home by postoperative day 5 compared with controls (75.7% vs 12.8%; p < 0.001) without increasing readmission rates (8.1% vs 10.3%; p = 1.0). Overall complication rates did not differ between groups (29.7% vs 43.6%; p = 0.24), but the WARP significantly reduced the time from operation to adjuvant therapy initiation (51 days vs 66 days; p = 0.005) and hospital cost ($26,563 vs $31,845; p = 0.011). CONCLUSIONS: The WARP can safely reduce hospital length of stay, time to adjuvant therapy, and cost in selected pancreaticoduodenectomy patients without increasing readmission risk.

Surgeon-Led Imaging Review for Patients with Periampullary Disease: An Important Aspect of the Preoperative Consultation.

Background: The perceived benefit of utilizing patients' own imaging studies as a preoperative educational tool has not been studied. Methods: Pancreaticobiliary surgeons reviewed key findings of imaging studies with patients to educate about their diagnosis and inform treatment recommendations. Patient surveys were administered pre- and postvisit by an independent researcher to assess the impact of this practice. Results: Only 55% of patients stated that it was important to see their imaging studies before the consultation. However, after the visit, 90% of patients understood their disease process better, and 86% of patients had a clearer understanding of their planned operation having seen their imaging studies. This represents significant improvement in patients' understanding of their medical condition (p < 0.05). Conclusion: Reviewing imaging findings with patients is an underappreciated aspect of the surgical consultation. It is a powerful educational tool that takes little time, improves patient understanding, and enhances patient experience.

Genetic Drivers of Pancreatic Cancer Are Identical Between the Primary Tumor and a Secondary Lesion in a Long-Term (>5 Years) Survivor After a Whipple Procedure.

Background: A new mass in the remnant pancreas of a patient with previously resected pancreatic ductal adenocarcinoma (PDA) typically represents either a recurrence of the initial primary tumor or a second primary tumor. Recent advances in next-generation sequencing (NGS) strategies allow us to compare the genetic makeup of primary and secondary lesions. Case presentation: A 50-year-old Caucasian female presented for a surgical evaluation of a new biopsy-proven PDA at the junction of the body and tail of the pancreas. Six years prior, in 2011, the patient was found to have a T3N0M0 PDA of the pancreatic head, which was surgically resected with a classic Whipple procedure and concurrent hemicolectomy. Pathology showed pancreatic intraepithelial neoplasia grade 2 and PDA with negative surgical margins, positive perineural spread, and negative lymphovascular spread, and the patient received adjuvant chemotherapy and local radiation. In 2017, she was diagnosed with a new PDA lesion in the remaining pancreatic body far from the previous anastomosis site and was taken to surgery for a completion pancreatectomy and revision of the gastrojejunostomy. NGS was performed on both specimens. Both lesions shared identical mutations in KRAS, TP53, and CDKN2A genes. Amplifications of MYC and mutant KRAS were identified in the 2017 tumor and an ACVR1B mutation was identified in the 2011 tumor, but was not found in the 2017 tumor. Conclusions: This case demonstrates the ability to evaluate similarities between key genetic drivers from a resected primary tumor and a PDA lesion that presented in the same patient 6 years later. Histological analysis and NGS can be used to understand potential differences and similarities between lesions and may be useful in future studies as predictive markers or to provide insight into resistance mechanisms (e.g., MYC amplification).

A Persistent Solid Pseudopapillary Tumor of the Pancreas: Case Report and Brief Literature Review.

Background: Solid pseudopapillary tumors (SPTs) of the pancreas are uncommon neoplasms, first reported in 1934, well described by Frantz in 1959, and later further characterized by Hamoudi in 1970. Ninety percent of these tumors occur in young females in their second to third decade of life. An interesting case of a persistent solid pseudopapillary neoplasm is described in this report. Case presentation: A 24-year-old woman from a Middle Eastern country presented with an 8.2 × 7.6 cm heterogeneous-enhancing lesion growing within the uncinate process of the pancreas. She had first experienced symptoms at the age of 12 years. Imaging studies showed that the mass closely abutted the superior mesenteric vein as well as the superior mesenteric artery (SMA). The patient underwent an open cholecystectomy and a classic pancreaticoduodenectomy. During the resection, the SMA was transected due to tumor adherence. The vessel was subsequently reapproximated in an end-to-end manner. On the first postoperative day, thrombosis of the SMA occurred and a bile leak developed. The patient returned to the operating room for SMA embolectomy and for repair of a hepaticojejunostomy leak, with redo of the biliary-enteric anastomosis. Histopathological examination showed solid pseudopapillary-arranged cells and cystic areas, showing strong cellular immunoreactivity for CD56, CD10, vimentin, and ß-catenin, and weak diffuse staining for synaptophysin. The tumor stained negative for chromogranin A, trypsin, AE1/AE3, and E-cadherin. Molecular genetic analysis was negative for the MYB gene deletion. At nearly 1 year of follow-up, the patient is well with no evidence of tumor recurrence. Conclusion: SPTs of the pancreas should be included in the differential diagnosis of pancreatic tumors, especially in young women.