The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis.

BACKGROUND: Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC. PATIENTS AND METHODS: A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI). RESULTS: Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference). CONCLUSIONS: Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.

Nutrition support in the pediatric total pancreatectomy with islet autotransplantation recipient.

For children with diminished quality of life and chronic pain caused by acute recurrent or chronic pancreatitis who are undergoing total pancreatectomy with islet autotransplantation, postoperative nutrition support has several unique characteristics. Surgical complications may lead to delays in nutrition support initiation or require modifications to the regimen. Early postoperative dysmotility requires the use of temporary enteral nutrition until this improves. The resultant complete exocrine pancreatic insufficiency necessitates lifelong pancreatic enzyme replacement therapy and fat-soluble vitamin supplementation. A low-oxalate diet is recommended to prevent kidney stones. Carbohydrate counting is needed for the provision of short-term insulin dosing and possibly long-term as well, depending on the transplanted islet yield. Children should have careful nutrition assessment and monitoring at several follow-up visits during the first year, then annually, and at any time with concerns.

Surveillance With Serial Imaging and CA 19-9 Tumor Marker Testing After Resection of Pancreatic Cancer: A Single-Center Retrospective Study.

OBJECTIVES: Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center. METHODS: We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence. RESULTS: We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis ( P =0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk ( P <0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72-0.95) and specificity of 87% (0.76-0.98) for identification of recurrence within 2 years of pancreatectomy. CONCLUSIONS: CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.

In Neoadjuvant FOLFIRINOX Chemotherapy for Pancreatic Ductal Adenocarcinoma, Which Response is the More Reliable Indicator for Prognosis, Radiologic or Biochemical?

BACKGROUND: In this era of increasing neoadjuvant chemotherapy, methods for evaluating responses to neoadjuvant chemotherapy are still diverse among institutions. Additionally, the efficacy of adjuvant chemotherapy for patients undergoing neoadjuvant chemotherapy remains unclear. Therefore, this retrospective study was performed to evaluate the effectiveness of methods for assessing response to neoadjuvant chemotherapy and the need for adjuvant chemotherapy in treating patients with non-metastatic pancreatic ductal adenocarcinoma. METHODS: The study identified 150 patients who underwent neoadjuvant FOLFIRINOX chemotherapy followed by curative-intent pancreatectomy. The patients were stratified by biochemical response based on the normalization of carbohydrate antigen 19-9 and by radiologic response based on size change at imaging. RESULTS: The patients were classified into the following three groups based on their response to neoadjuvant chemotherapy and prognosis: biochemical responders (BR+), radiology-only responders (BR-/RR+), and non-responders (BR-/RR-). The 3-year overall survival rate was higher for BR+ (71.0%) than for BR-/RR+ (53.6%) or BR-/RR- (33.1%) (P < 0.001). Response to neoadjuvant chemotherapy also was identified as a significant risk factor for recurrence in a comparison between BR-/RR+ and BR+ (hazard ratio [HR], 2.15; 95% confidence interval [CI] 1.19-3.88; P = 0.011) and BR-/RR- (HR, 3.82; 95% CI 2.41-6.08; P < 0.001). Additionally, regardless of the response to neoadjuvant chemotherapy, patients who completed adjuvant chemotherapy had a significantly higher 3-year overall survival rate than those who did not. CONCLUSIONS: This response evaluation criterion for neoadjuvant chemotherapy is feasible and can significantly predict prognosis. Additionally, completion of adjuvant chemotherapy could be helpful to patients who undergo neoadjuvant chemotherapy regardless of their response to neoadjuvant chemotherapy.

Functional sequelae after pancreatic resection for cancer.

The morbidity and mortality of pancreatic cancer surgery has seen substantial improvement due to the standardization of surgical techniques, the optimization of perioperative multidisciplinary management and the organization of specialized care systems. The identification and treatment of postoperative functional and nutritional sequelae have thereby become major issues in patients who undergo pancreatic surgery. This review addresses the functional sequelae of pancreatic resection for cancerous and pre-cancerous lesions (excluding chronic pancreatitis). Its aim is to specify the prevalence and severity of sequelae according to the type of pancreatic resection and to document, where appropriate, the therapeutic management. Exocrine pancreatic insufficiency (ExPI) is observed in nearly one out of three patients at one year after surgery, and endocrine pancreatic insufficiency (EnPI) is present in one out of five patients after pancreatoduodenectomy (PD) and one out of three patients after distal pancreatectomy (DP). In addition, digestive functional disorders may appear, such as delayed gastric emptying (DGE), which affects 10 to 45% of patients after PD and nearly 8% after DP. Beyond these functional sequelae, pancreatic surgery can also induce nutritional and vitamin deficiencies secondary to a lack of uptake for certain vitamins or to the loss of absorption site in the duodenum. In addition to the treatment of ExPI with oral pancreatic enzymes, nutritional management is based on a high-calorie, high-protein diet with normal lipid intake in frequent small feedings, combined with vitamin supplementation adapted to monitored deficiencies. Better knowledge of the functional consequences of pancreatic cancer surgery can improve the overall management of patients.

Opioid-Free Discharge After Pancreatic Resection Through a Learning Health System Paradigm.

Importance: Postoperative opioid overprescribing leads to persistent opioid use and excess pills at risk for misuse and diversion. A learning health system paradigm using risk-stratified pancreatectomy clinical pathways (RSPCPs) may lead to reduction in inpatient and discharge opioid volume. Objective: To analyze the outcomes of 2 iterative RSPCP updates on inpatient and discharge opioid volumes. Design, Setting, and Participants: This cohort study included 832 consecutive adult patients at an urban comprehensive cancer center who underwent pancreatic resection between October 2016 and April 2022, comprising 3 sequential pathway cohorts (version [V] 1, October 1, 2016, to January 31, 2019 [n = 363]; V2, February 1, 2019, to October 31, 2020 [n = 229]; V3, November 1, 2020, to April 30, 2022 [n = 240]). Exposures: After V1 of the pathway established a baseline and reduced length of stay (n = 363), V2 (n = 229) updated patient and surgeon education handouts, limited intravenous opioids, suggested a 3-drug (acetaminophen, celecoxib, methocarbamol) nonopioid bundle, and implemented the 5×-multiplier (last 24-hour oral morphine equivalents [OME] multiplied by 5) to calculate discharge volume. Pathway version 3 (n = 240) required the nonopioid bundle as default in the recovery room and scheduled conversion to oral medications on postoperative day 1. Main Outcomes and Measures: Inpatient and discharge opioid volume in OME across the 3 RSPCPs were compared using nonparametric testing and trend analyses. Results: A total of 832 consecutive patients (median [IQR] age, 65 [56-72] years; 410 female [49.3%] and 422 male [50.7%]) underwent 541 pancreatoduodenectomies, 285 distal pancreatectomies, and 6 other pancreatectomies. Early nonopioid bundle administration increased from V1 (acetaminophen, 320 patients [88.2%]; celecoxib or anti-inflammatory, 98 patients [27.0%]; methocarbamol, 267 patients [73.6%]) to V3 (236 patients [98.3%], 163 patients [67.9%], and 238 patients [99.2%], respectively; P < .001). Total inpatient OME decreased from a median 290 mg (IQR, 157-468 mg) in V1 to 184 mg (IQR, 103-311 mg) in V2 to 129 mg (IQR, 75-206 mg) in V3 (P < .001). Discharge OME decreased from a median 150 mg (IQR, 100-225 mg) in V1 to 25 mg (IQR, 0-100 mg) in V2 to 0 mg (IQR, 0-50 mg) in V3 (P < .001). The percentage of patients discharged opioid free increased from 7.2% (26 of 363) in V1 to 52.5% (126 of 240) in V3 (P < .001), with 187 of 240 (77.9%) in V3 discharged with 50 mg OME or less. Median pain scores remained 3 or lower in all cohorts, with no differences in postdischarge refill requests. A subgroup analysis separating open and minimally invasive surgical cases showed similar results in both groups. Conclusions and Relevance: In this cohort study, the median total inpatient OME was halved and median discharge OME reduced to zero in association with a learning health system model of iterative opioid reduction that is freely adaptable by other hospitals. These findings suggest that opioid-free discharge after pancreatectomy and other major cancer operations is realistic and feasible with this no-cost blueprint.

Nutritional Risks in Patients Undergoing Total Pancreatectomy Islet AutoTransplantation in the POST Consortium.

BACKGROUND AND AIMS: Total pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT. METHODS: The multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT. RESULTS: 348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up. CONCLUSIONS: Prevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies.

Neoadjuvant and Adjuvant Treatments for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: The Current Status of Pancreatic Ductal Adenocarcinoma Treatment in Japan.

Resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Although the outcome of technically resectable PDAC has improved with advances in surgery and adjuvant therapy, the 5-year survival rate remains low at 20% to 40%. More effective therapy is needed. Almost 15 years ago, the National Comprehensive Cancer Network guidelines proposed a resectability classification of PDAC based on preoperative imaging. Since then, treatment strategies for PDAC have been devised based on resectability. The standard of care for resectable PDAC is adjuvant chemotherapy after R0 resection, as shown by the results of pivotal clinical trials. With regard to neoadjuvant treatment, several recent clinical trials comparing neoadjuvant treatment with upfront resection have been conducted on resectable PDAC and borderline resectable PDAC, and the benefits and efficacy of neoadjuvant treatment for pancreatic cancer has become clearer. The significance of neoadjuvant treatment for resectable PDAC remains controversial, but in borderline resectable PDAC the efficacy of neoadjuvant treatment has been further recognised, although the standard of care has not yet been established. Several promising clinical trials for PDAC are ongoing. This review presents previous and ongoing trials of perioperative treatment for resectable and borderline resectable PDAC, focusing on the difference between Asian and Western countries.

Pancreatic Adenosquamous Carcinoma: Experience Within an Integrated Health Care System.

Introduction Adenosquamous carcinoma (ASC) of the pancreas is a rare form of pancreatic cancer with a worse prognosis than pancreatic ductal adenocarcinoma. The authors report on a retrospective study of 13 patients diagnosed with ASC in an integrated health care system. Methods A retrospective review was performed of all patients with pancreatic cancer identified between February 2010 and December 2018. Twenty-three patients were diagnosed with pancreatic ASC. Patient demographics, tumor characteristics, treatment modalities, and median survival were evaluated. Results Median overall survival was 8 months (standard devision [SD] = 18.6). Eight out of 13 patients who received surgery upfront had a positive surgical margin (62%). Eleven patients received adjuvant therapy. Median survival for patients who received multimodal treatment was 57 months (SD = 5.7) compared with 2.5 months for patients who received only surgery. Median survival for patients with negative pathologic margins was 17 months (SD = 23.6). One patient was receiving neoadjuvant chemotherapy (6 months into treatment without any evidence of metastatic disease). Discussion The high proportion of positive surgical margins and large tumor size upon presentation suggest that primary tumor downstaging should be considered. The positive results from recent prospective trials on neoadjuvant chemoradiation for pancreatic ductal adenocarcinoma could be a promising foundation of information for the treatment of ASC. Conclusion ASC of the pancreas is an extremely aggressive malignancy with poor prognosis. Further work is needed to determine the optimal multimodal treatment regimen.

Resection Versus Observation for Small (≤2 cm) Pancreatic Neuroendocrine Tumors.

BACKGROUND: We hypothesized that those patients with pancreatic neuroendocrine tumors (pNETs) ≤2 cm managed nonoperatively would have comparable disease progression to individuals undergoing an operation. METHODS: Patients diagnosed with nonfunctional pNETs ≤ 2 cm who were evaluated at a single comprehensive cancer center from 2010 to 2017 were selected from a cancer registry database. Clinicopathologic variables were obtained via retrospective chart review. Primary outcomes were overall and disease specific survival. Variables were compared between the 2 groups using chi-square and independent t-test. RESULTS: Fifty-two individuals had tumors ≤2 cm, of whom 75% had an operation, while 25% were observed. Each treatment arm had similar distributions of gender, race, and tumor location. The most common operation was distal pancreatectomy (n = 29) followed by pancreatoduodenectomy (n = 6). Nine patients had grade III postoperative complications and 4 had grade IV under Clavien-Dindo classification. The observation group was noted to have a mean disease progression interval of 80.9 months, while those who underwent an operation had a mean disease progression interval of 94.6 months (P = .246). CONCLUSIONS: Overall disease progression in patients with pNETs ≤ 2 cm without evidence of metastasis at the time of presentation is not different between those who underwent operation compared to those observed.

Significance of Zinc Replacement Therapy After Pancreaticoduodenectomy.

BACKGROUND/AIM: Recently, a decrease in serum zinc levels and the need for zinc preparations have been reported in the perioperative period of gastrointestinal surgery. In this study, we examined treatment outcomes among patients supplemented with zinc after pancreaticoduodenectomy (PD) and evaluated the significance of zinc replacement therapy. PATIENTS AND METHODS: From June 2020 to April 2021, 56 patients who received zinc acetate hydrate (50 mg/day) from postoperative day 3 after PD in our department were retrospectively reviewed. Patients' characteristics and preoperative as well as postoperative data, including serum zinc levels and surgical results at 1 month were reviewed. RESULTS: Preoperative zinc deficiency was present in 86.1% (46/56) of the patients. Moreover, despite zinc supplementation, 17.8% (10/56) of patients had postoperative zinc deficiency. A comparison between the low zinc level group (Zn <80 µg/dl) and the normal zinc level group (Zn ≥80 µg/dl) after surgery showed siginificant differences among patients with malignant diseases (vs. benign diseases, p=0.044), those undergoing open surgery (vs. minimally invasive surgery, p=0.036), and those with intraoperative blood loss ≥346 ml (vs. <346 ml: p=0.041) in the univariate analysis. Multivariate analysis revealed that zinc deficiency was significantly associated with open surgery [odds ratio (OR)=15.885, 95% confidence interval (CI)=1.77-142.01, p=0.013] and intraoperative blood loss (OR=9.329, 95% CI=1.50-57.74, p=0.016). CONCLUSION: In patients undergoing open PD for pancreatic cancer, zinc preparations of 50 mg may not be sufficient and further supplementation may be necessary.

Outpatient Pain Management in Children With Chronic Pancreatitis: A Scoping Systematic Review.

OBJECTIVES: Although pain management is central to pediatric chronic pancreatitis (CP) care, no evidence-based guidelines exist. In this scoping systematic review, we sought promising strategies for CP pain treatment in children. METHODS: We systematically reviewed literature on pain management in children and adults with CP, and 2 conditions with similar pain courses: juvenile idiopathic arthritis and sickle cell disease. RESULTS: Of 8997 studies identified, 287 met inclusion criteria. There are no published studies of analgesic medications, antioxidants, dietary modification, integrative medicine, or regional nerve blocks in children with CP. In adults with CP, studies of nonopioid analgesics, pancreatic enzymes, and dietary interventions have mixed results. Retrospective studies suggest that endoscopic retrograde cholangiopancreatography and surgical procedures, most durably total pancreatectomy with islet autotransplant, improve pain for children with CP. Follow-up was short relative to a child's life. Large studies in adults also suggest benefit from endoscopic therapy and surgery, but lack conclusive evidence about optimal procedure or timing. Studies on other painful pediatric chronic illnesses revealed little generalizable to children with CP. CONCLUSIONS: No therapy had sufficient high-quality studies to warrant untempered, evidence-based support for use in children with CP. Multicenter studies are needed to identify pain management "best practices."

Occult insulinoma with treatment refractory, severe hypoglycaemia in multiple endocrine neoplasia type 1 syndrome; difficulties faced during diagnosis, localization and management; a case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is a rare, complex genetic disorder characterized by increased predisposition to tumorigenesis in multiple endocrine and non-endocrine tissues. Diagnosis and management of MEN 1 syndrome is challenging due to its vast heterogeneity in clinical presentation. CASE PRESENTATION: A 23-year-old female, previously diagnosed with Polycystic Ovarian Syndrome (PCOS) and pituitary microprolactinoma presented with drowsiness,confusion and profuse sweating developing over a period of one day. It was preceded by fluctuating, hallucinatory behavior for two weeks duration. There was recent increase in appetite with significant weight gain. There was no fever, seizures or symptoms suggestive of meningism. Her Body mass index(BMI) was 32 kg/m2.She had signs of hyperandrogenism. Multiple cutaneous collagenomas were noted on anterior chest and abdominal wall. Her Glasgow Coma Scale was 9/15. Pupils were sluggishly reactive to light. Tendon reflexes were exaggerated with up going planter reflexes. Moderate hepatomegaly was present. Rest of the clinical examination was normal. Laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive of an insulinoma. Hypercalcemia with elevated parathyroid hormone level suggested a parathyroid adenoma. Presence of insulinoma, primary hyperparathyroidism and pituitary microadenoma, in 3rd decade of life with characteristic cutaneous tumours was suggestive of a clinical diagnosis of MEN 1 syndrome. Recurrent, severe hypoglycaemia complicated with hypoglycaemic encephalopathy refractory to continuous, parenteral glucose supplementation and optimal pharmacotherapy complicated the clinical course. Insulinoma was localized with selective arterial calcium stimulation test. Distal pancreatectomy and four gland parathyroidectomy was performed leading to resolution of symptoms. CONCLUSIONS: Renal calculi or characteristic cutaneous lesions might be the only forewarning clinical manifestations of an undiagnosed MEN 1 syndrome impending a life-threatening presentation. Comprehensive management of MEN 1 syndrome requires multi-disciplinary approach with advanced imaging modalities, advanced surgical procedures and long-term follow up due to its heterogeneous presentation and the varying severity depending on the disease phenotype.

Predicting pathologic venous invasion before pancreatectomy with venous resection: When does radiology tell the truth?

BACKGROUND: Patients factors in addition to radiological characteristics could predict the presence of pathologic venous invasion in patients undergoing pancreatectomy with venous resection. METHODS: We tested the predictive value of 6 radiological classification methods for predicting pathologic venous invasion-the Nakao, Ishikawa, MD Anderson, Lu, Raptopoulos, and National Comprehensive Cancer Network methods-on a cohort of 198 pancreatectomies (160 pancreaticoduodenectomies and 38 total pancreatectomies) with venous resection for pancreatic adenocarcinomas. Radiological and clinical factors determining pathologic venous invasion were identified by multivariable logistic analysis. RESULTS: Pathologic venous invasion was detected in 124 patients (63.2%). The multivariable logistic regression analysis identified Lu classification (odds ratio = 1.77, 95% confidence interval =1.34-2.35; P < .0001), elevated serum CA19-9 values (odds ratio = 1.97, 95% confidence interval = 1.00-3.90; P = .04), and preoperative neoadjuvant chemotherapy (odds ratio = 0.38, 95% confidence interval = 0.18-0.79; P = .009) as independent factors associated with pathologic venous invasion. Radiological tumor-vessel contact greater than 50% of the circumference or venous wall deformity was associated with a significantly higher rate of pathological venous invasion (80% vs 52%; P < .0001), deeper (media-intima) venous invasion (47% vs 25%; P < .0001), R1 resection (58% vs 41%; P = .03), higher transfusions (84% vs 66%; P = .005), and arterial resection rates (43% vs 27%; P < .0001). Tumor-vein circumference contact of >50% and/or venous wall deformity was still associated with significantly higher rates of pathologic venous invasion, regardless of whether neoadjuvant chemotherapy was used or not and CA19-9 normalized or not under preoperative treatment. CONCLUSION: Preoperative radiological detection of tumor-vein circumference contact >50% and/or venous wall deformity is associated with up to 80% of cases of pathological venous invasion. The combination of radiologic features with biological (CA19-9) and clinical (presence of preoperative chemotherapy) factors could better refine preoperatively the need for venous resection.

Total pancreatectomy as an alternative to high-risk pancreatojejunostomy after pancreatoduodenectomy: a propensity score analysis on surgical outcome and quality of life.

BACKGROUND: Total pancreatectomy (TP) is mentioned as alternative to pancreatoduodenectomy (PD) with high-risk pancreatojejunostomy (PJ) to avoid severe pancreatic fistula-related complications, but its benefit is controversial and comparative studies are scarce. METHODS: Cross-sectional single-center study among patients after PD with high-risk PJ versus patients after single-stage elective TP for any indication (2015-2017), using propensity scores to evaluate surgical outcomes and long-term quality of life (QoL) in three risk strata. EORTC QLQ-C30 and EQ-5D-5L were used for QoL assessment. RESULTS: Overall, 77 patients after TP (68.8%) and 102 patients after high-risk PD (34.5%) were included. Major morbidity (29.9% vs. 41.2%; p = 0.119) and 90-day mortality (5.2% vs. 8.8%; p = 0.354) did not differ significantly between TP and high-risk PD. Interventions for intra-abdominal fluid collections (9.1% vs. 23.5%, p = 0.011) and postpancreatectomy haemorrhage (6.5% vs. 18.6%; p = 0.018) were more often required after high-risk PD, but these differences did not remain after stratification. QoL was comparable after TP and high-risk PD (75% vs. 83%; p = 0.720), even after stratification. CONCLUSIONS: TP seems not to be inferior to high-risk PD regarding surgical outcomes and QoL. TP could be considered as an alternative to a very high-risk PD, but reluctance persists since TP does not appear to reduce mortality.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.

Centralization of pancreatic cancer treatment within an integrated healthcare system improves overall survival.

BACKGROUND: Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival. METHODS: We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed. RESULTS: Neoadjuvant chemotherapy use rose from 10% to 31% (p < .001). The median overall survival (OS) improved by 3 months after centralization (p < .001), but this did not reach significance on multivariate analysis. CONCLUSIONS: Our results suggest that in a large integrated healthcare system, centralization improves overall survival and neoadjuvant therapy utilization for pancreatic cancer patients.

Successful En Bloc Resection of Locally Advanced Pancreatic Tail Cancer with Colonic Perforation Following Neoadjuvant Chemotherapy: A Case Report.

BACKGROUND Distal pancreatic cancers may be unresectable at the time of diagnosis because these cancers are asymptomatic and readily infiltrate neighboring organs. Radical resection of a pancreatic tail cancer with colonic perforation is rare. We describe successful resection of a locally advanced pancreatic tail cancer with colonic perforation using a multidisciplinary approach. CASE REPORT A 66-year-old man presented to our hospital with a chief concern of high fever. Abdominal computed tomography revealed a pancreatic tail tumor infiltrating the neighboring organs and causing colonic obstruction with perforation, which resulted in an intra-abdominal abscess. Colonoscopy revealed obstruction of the descending colon by extramural invasion. Laboratory tests showed high tumor marker concentrations (carcinoembryonic antigen, 11.6 ng/dL; pancreatic cancer-associated antigen-2, >1600 U/mL). We clinically diagnosed locally advanced pancreatic tail cancer with an intra-abdominal abscess caused by colonic perforation. First, we performed transverse colostomy and percutaneous drainage. We then started neoadjuvant chemotherapy with FOLFIRINOX for tumor shrinkage and prevention of distant metastases. The therapeutic effect was a partial response, and no distant metastases was found. We therefore performed radical surgery comprising distal pancreatectomy with partial resection of neighboring organs. Although pathological examination revealed a pancreatic tail tubular adenocarcinoma with direct invasion of the neighboring organs, R0 resection was achieved. The patient was discharged with no perioperative complications. Tegafur/gimeracil/oteracil potassium were administered as adjuvant chemotherapy. The patient remained recurrence-free for 19 months after surgery. CONCLUSIONS We achieved successful en bloc resection of a locally advanced distal pancreatic cancer with colonic perforation by using a multidisciplinary approach.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.