Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Peritoneal metastasis (PM) is the most common site of dissemination of gastric cancer (GC) and is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with PM remains controversial due to modest survival and significant morbidity. METHODS: We conducted a retrospective analysis of patients with GC and PM treated with CRS and HIPEC with cisplatin and paclitaxel for 90 min from June 2019 to December 2022. RESULTS: Twenty-two patients were included and received a median of 7 (interquartile range [IQR] 4-8) cycles of neoadjuvant systemic therapy. Seventeen patients (77%) underwent a single neoadjuvant laparoscopic HIPEC, and six (27%) patients received chemoradiation. The median Peritoneal Carcinomatosis Index at the time of CRS was 1 (IQR 0-4), and 21 patients (95%) underwent complete cytoreduction (CC-0). An R0 resection was achieved in 20 (91%) patients, and the median length of stay was 5.5 (IQR 4-7.5) days. There were six (27%) 90-day major complications (Clavien-Dindo grade ≥ 3), one (4%) Common Terminology Classification for Adverse Events (CTCAE) grade 4 cytopenia, and one (4%) acute kidney injury. The rate of anastomotic leak (all grades) was 14%, the 30-day readmission rate was 18%, and the 90-day mortality rate was 0%. At a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-, 2-, and 3-year PFS rates were 65%, 56%, and 40%, respectively, and the 1-, 2-, and 3-year OS rates were 96%, 78%, and 55%, respectively. CONCLUSIONS: CRS and HIPEC with paclitaxel and cisplatin is well tolerated and is associated with favorable oncologic and perioperative outcomes.

Value of Surgical Cytoreduction in Patients with Small Intestinal Neuroendocrine Tumors Metastatic to the Liver and Peritoneum.

BACKGROUND: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. METHODS: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. RESULTS: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12). CONCLUSIONS: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.

Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with de Novo Pancreatic Adenocarcinoma.

BACKGROUND: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy. METHODS: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS). RESULTS: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan-Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death. CONCLUSIONS: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.

Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy.

BACKGROUND: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

Supply and demand of hepatopancreatobiliary surgeons in the United States.

BACKGROUND: Hepatopancreatobiliary (HPB) surgery requires specialized training and adequate case volumes to maintain procedural proficiency and optimal outcomes. Studies of individual HPB surgeon supply related to annual HPB case demand are sparse. This study assesses the supply and demand of the HPB surgical workforce in the United States (US). METHODS: The National Inpatient Sample (NIS) was queried from 1998-2019 to estimate the number of HPB procedures performed. To approximate the number of HPB surgeons, models based on previous HPB workforce publications were employed. We then calculated the number of HPB surgeons needed to maintain volume-outcome thresholds at current reported levels of centralization. RESULTS: In 2019, approximately 37,335 patients underwent inpatient HPB procedures in the US, while an estimated 905-1191 HPB surgeons were practicing. Assuming 50% centralization and an optimal volume-outcome threshold of 24 HPB cases-per-year, only 778 HPB surgeons were needed. Without adjustment in centralization, by 2030 there will be a demand of fewer than 12 annual cases per HPB surgeon. CONCLUSION: The current supply of HPB surgeons may exceed demand in the United States. Without alteration in training pathways or improved care centralization, by 2030, there will be insufficient HPB case volume per surgeon to maintain published volume-outcome standards.

Early vs conventional onset pancreatic ductal adenocarcinoma: analysis of surgical and oncologic outcomes in patients undergoing curative intent resection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) impacts patients in their 60s, but its incidence in younger patients is increasing. We hypothesize that younger patients may have worse oncologic outcomes. METHODS: Patients who underwent curative pancreatic resection for PDAC between January 2011 and December 2021 at a single institution were analyzed. Early-onset pancreatic cancer (EOPC) was defined as pancreatic cancer diagnosed in patients ≤50 years. Clinical and survival outcomes were compared between EOPC and Conventional Onset Pancreas Cancer (COPC). RESULTS: A total of 1133 patients were identified, 65 (5.7%) were EOPC. Preoperative patient characteristics including sex, smoking status, alcohol habitus, diabetes mellitus, CA 19-9, and neoadjuvant therapy were similar between EOPC and COPC (p > 0.05). EOPC patients were more likely non-white (p = 0.03), had lower ASA scores (p = 0.02) and larger median tumor size (33 vs 28 mm, p = 0.04), but had similar pathological stages and rate of R0 resections (p > 0.05). Postoperative outcomes were similar (p > 0.05). There was no statistically significant difference in overall (HR 0.93, CI 0.64, 1.33; p = 0.68) or recurrence free (HR 1.05, CI 0.75, 1.48; p = 0.77) survival between the EOPC and COPC after adjusting for significant factors. CONCLUSION: Patients with EOPC who underwent surgical resection had similar oncological outcomes compared to patients with COPC.

Finding the Balance Between Reduced Opioid Prescribing and Patient-reported Pain Management Among General Surgery Patients.

OBJECTIVE: To compare patient-reported outcomes before and after implementation of evidence-based, procedure-specific opioid prescribing guidelines. BACKGROUND: The opioid epidemic remains a significant public health issue. Many institutions have responded by reducing opioid prescribing after surgery. However, the impact of this on patient-reported outcomes remains poorly understood. METHODS: Opioid-naïve adults undergoing 12 elective general surgery procedures at a single institution prospectively completed telephone surveys at median 26 days from discharge. Patients were compared before (March 2017-January 2018) and after (May 2019-November 2019) implementation of evidence-based, procedure-specific opioid prescribing guidelines. RESULTS: A total of 603 preguideline and 138 postguideline patients met inclusion criteria and completed surveys. Overall, 60.5% of preguideline and 92.5% of postguideline prescriptions fell within recommendations ( P <0.001), while refill rates were similar (4.5% vs 5.8%, P =0.50). A statistically significant drop in median morphine milligram equivalent prescribed was observed for 9 of 12 procedures (75%). No opioids were prescribed for 16.7% of patients in both cohorts ( P =0.98). While 93.3% of preguideline and 87.7% of postguideline patients were very/somewhat satisfied with their pain control, the proportion of patients who were very/somewhat dissatisfied increased from 4.2% to 9.4% ( P =0.039). CONCLUSIONS: Prescribing guidelines successfully reduced opioid prescribing without increased refill rates. Despite decreased prescribing overall, there was a continued reluctance to prescribe no opioids after surgery. Although most patients experienced good pain control, there remains a subset of patients whose pain is not optimally managed in the era of reduced opioid prescribing.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Oncologic Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Highly Selected Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients. PATIENTS AND METHODS: Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated. RESULTS: In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months. CONCLUSIONS: CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009).

Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis: Results from a Prospective Pilot Study.

INTRODUCTION: Resection of oligometastatic pancreatic ductal adenocarcinoma (PDAC) has historically been ineffective, however modern systemic chemotherapy has improved survival. Thus, re-evaluating safety and outcomes of surgical resection in selected patients with limited peritoneal metastasis (PM) warrants consideration. METHODS: From 2018 to 2021, patients with PDAC and positive cytology or limited PM without extraperitoneal metastasis and who had an objective response to ≥ 6 months of systemic chemotherapy were enrolled. Patients underwent laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin/mitomycin C. If amenable to a complete cytoreduction, patients went on to cytoreduction and HIPEC. RESULTS: Overall, 18 patients were enrolled and received a median of 14 (interquartile range [IQR] 12-17) cycles of chemotherapy; 16 (89%) patients received chemoradiation. Laparoscopic HIPEC was completed in 17 patients, with a median length of stay of 1 day, and no grade III complications or hematological toxicities were observed. All 18 patients subsequently underwent a complete cytoreduction (CC-0) along with definitive treatment of the primary tumor, with formal resection (7/18), irreversible electroporation (IRE; 10/18), or intraoperative radiation therapy (IORT; 1/18). Median PCI was 2 (IQR 0-4), median LOS was 7 days (IQR 6-8), and 7 (39%) patients were readmitted. Eight (44%) patients experienced grade 3 or higher complications, including one 30-day mortality. At a median follow-up of 16 months, the median progression-free survival was 20 months and the median overall survival was 26 months. CONCLUSION: Cytoreduction and HIPEC for selected patients with low-volume PM from PDAC is safe and feasible with favorable short-term outcomes. A phase II trial (NCT04858009) is now enrolling to further assess this multimodality approach in select patients.

Survival and Symptomatic Relief After Cytoreductive Hepatectomy for Neuroendocrine Tumor Liver Metastases: Long-Term Follow-up Evaluation of More Than 500 Patients.

BACKGROUND: Distant metastases are the strongest predictor of poor prognosis for patients with neuroendocrine tumors (NETs). Cytoreductive hepatectomy (CRH) can relieve symptoms of hormonal excess and prolong survival for patients with liver metastases (NETLMs), but long-term outcomes are poorly characterized. METHODS: This retrospective single-institution analysis analyzed patients who underwent CRH for well-differentiated NETLMs from 2000 to 2020. Kaplan-Meier analysis estimated symptom-free interval and overall and progression-free survival. Multivariable Cox regression analysis evaluated factors associated with survival. RESULTS: The inclusion criteria were met by 546 patients. The most common primary sites were the small intestine (n = 279) and the pancreas (n = 194). Simultaneous primary tumor resection was performed for 60 % of the cases. Major hepatectomy comprised 27% of the cases, but this rate decreased during the study period (p < 0.001). Major complications occurred in 20%, and the 90-day mortality rate was 1.6%. Functional disease was present in 37 %, and symptomatic relief was achieved in 96%. The median symptom-free interval was 41 months (62 months after complete cytoreduction and 21 months with gross residual disease) (p = 0.021). The median overall survival was 122 months, and progression-free survival was 17 months. In the multivariable analysis, worse overall survival was associated with age, pancreatic primary tumor, Ki-67, number and size of lesions, and extrahepatic metastases, with Ki-67 as the strongest predictor (odds ratio [OR], 1.90 for Ki-67 [3-20%; p = 0.018] and OR, 4.25 for Ki-67 [>20%; p < 0.001]). CONCLUSION: The study showed that CRH for NETLMs is associated with low perioperative morbidity and mortality and excellent overall survival, although the majority will experience recurrence/progression. For patients with functional tumors, CRH can provide durable symptomatic relief.

Gastrointestinal Glomus Tumors: A Single Institution, 20-Year Retrospective Study.

INTRODUCTION: Glomus tumors are rare mesenchymal neoplasms composed of cells resembling those of the thermoregulatory glomus body, typically occurring in the skin and superficial soft tissues. Rarely do they occur in the gastrointestinal tract, in particular the stomach, where they have been the subject of case reports and small series. We present our institutional experience with gastrointestinal glomus tumors. METHODS: A retrospective review of all gastrointestinal glomus tumors was conducted across all three Mayo Clinic sites in Minnesota, Arizona, and Florida from 2001 to 2021. Patient characteristics, pathologic findings, imaging features, operative reports, and clinical outcomes were abstracted. Descriptive statistics were utilized to report outcomes. RESULTS: Nine patients with glomus tumors were identified (five men and four women). The median age was 53 [interquartile range (IQR), 44-69] y. Four patients presented with abdominal discomfort, three had anemia or bleeding, and two tumors were incidentally diagnosed. Computed tomography scans identified masses thought to represent gastrointestinal stromal tumors or neuroendocrine tumors in all patients. The tumors were localized to the stomach in all cases, specifically in the gastric antrum. Seven patients underwent preoperative endoscopy, including five with endoscopic ultrasonography. Endoscopic biopsies were interpreted as glomus tumors (n = 3), neuroendocrine tumors (n = 2), and nondiagnostic (n = 2). All patients underwent open (n = 3) or minimally invasive (n = 6) margin-negative resection by wedge resection (n = 5) or distal gastrectomy (n = 4). No nodal metastases were identified radiographically or on pathologic examination. The median tumor size was 2.5 [IQR 1.3-3.4] cm. All tumors showed at least in part typical glomus tumor morphology and smooth muscle actin expression. Aberrant synaptophysin expression was present in the two tumors initially classified as NET. Using the current WHO criteria, tumors were classified as histologically malignant (n = 1) and of "uncertain malignant potential" (n = 8). At a median follow-up of 15 [IQR 1-56] mo, all patients were asymptomatic and without recurrence. Two patients died of unrelated causes. No patients received adjuvant therapies. CONCLUSIONS: Our 20-year, single institution, 3-site experience with resected gastrointestinal glomus tumors suggests the rarity, predisposition to involve the gastric antrum, and potentially an indolent clinical behavior of many of these tumors. Long-term follow-up is warranted as some previously reported gastric glomus tumors have metastasized, including cases lacking morphologic evidence of malignancy. Surgical resection, with minimally invasive wedge resection alone, is likely sufficient for the management of most gastric glomus tumors.

Laparoscopic versus open liver resections for intrahepatic cholangiocarcinoma and gallbladder cancer: the Mayo clinic experience.

BACKGROUND: Data regarding laparoscopic liver resections(LLRs) for Gallbladder cancer(GBC) and Intrahepatic Cholangiocarcinoma(iCCA) are sparse. This study compared LLRs with open liver resections(OLRs) in a high-volume center. METHODS: Data of patients who underwent LLR or OLR for GBC or iCCA at Mayo-Clinic between 01/2016 and 04/2021 were retrospectively compared. Proportional hazards models were used to compare the approach on survival. RESULTS: 32 and 52 patients underwent LLR and OLR during the study period, respectively. 64 and 20 patients had iCCA and GBC, respectively. LLR had lower median blood loss (250 mL vs. 475 mL, p = 0.001) and shorter median length of stay compared to OLR (3.0 days vs. 6.0 days, p = 0.001). LLR and OLR did not differ in post-operative major complication (25% vs. 32.7%, p = 0.62), negative margin (100% vs. 90.4%, p = 0.15) and completeness of lymphadenectomy rates (36.8% vs. 45.5%, p = 0.59). The median number of harvested lymph node was 4.0 and 5.0 for LLR and OLR, respectively (p = 0.347). There were no associations between approach and 3-year overall and disease-free survival between LLR and OLR (49.8% vs. 63.2% and 39.6% vs. 21.5%, p = 0.66 and p = 0.69). DISCUSSION: With appropriate patient selection and when compared to OLRs, LLRs for GBC and iCCA are feasible, safe and offer potential short-term benefits without compromising on oncological resection principals and long-term outcomes.

Comparing Clinician Consensus Recommendations to Patient-reported Opioid Use Across Multiple Hospital Systems.

OBJECTIVE: We compare consensus recommendations for 5 surgical procedures to prospectively collected patient consumption data. To address local variation, we combined data from multiple hospitals across the country. SUMMARY OF BACKGROUND DATA: One approach to address the opioid epidemic has been to create prescribing consensus reports for common surgical procedures. However, it is unclear how these guidelines compare to patient-reported data from multiple hospital systems. METHODS: Prospective observational studies of surgery patients were completed between 3/2017 and 12/2018. Data were collected utilizing post-discharge surveys and chart reviews from 5 hospitals (representing 3 hospital systems) in 5 states across the USA. Prescribing recommendations for 5 common surgical procedures identified in 2 recent consensus reports were compared to the prospectively collected aggregated data. Surgeries included: laparoscopic cholecystectomy, open inguinal hernia repair, laparoscopic inguinal hernia repair, partial mastectomy without sentinel lymph node biopsy, and partial mastectomy with sentinel lymph node biopsy. RESULTS: Eight hundred forty-seven opioid-naïve patients who underwent 1 of the 5 studied procedures reported counts of unused opioid pills after discharge. Forty-one percent did not take any opioid medications, and across all surgeries, the median consumption was 3 5 mg oxycodone pills or less. Generally, consensus reports recommended opioid quantities that were greater than the 75th percentile of consumption, and for 2 procedures, recommendations exceeded the 90th percentile of consumption. CONCLUSIONS: Although consensus recommendations were an important first step to address opioid prescribing, our data suggests that following these recommendations would result in 47%-56% of pills prescribed remaining unused. Future multi-institutional efforts should be directed toward refining and personalizing prescribing recommendations.

Safety and Outcomes of Combined Pancreatic and Hepatic Resections for Metastatic Pancreatic Neuroendocrine Tumors.

BACKGROUND: Approximately 40-50% of patients with pancreatic neuroendocrine tumors (pNETs) initially present with distant metastases. Little is known about the outcomes of patients undergoing combined pancreatic and hepatic resections for this indication. METHODS: Patients who underwent hepatectomy for metastatic pNETs at Mayo Clinic Rochester from 2000 to 2020 were retrospectively reviewed. Major pancreatectomy was defined as pancreaticoduodenectomy or total pancreatectomy, and major hepatectomy as right hepatectomy or trisegmentectomy. Characteristics and outcomes of patients who underwent pancreatectomy with simultaneous hepatectomy were compared with those of patients who underwent isolated hepatectomy (with or without prior history of pancreatectomy). RESULTS: 205 patients who underwent hepatectomy for metastatic pNETs were identified: 131 underwent pancreatectomy with simultaneous hepatectomy and 74 underwent isolated hepatectomy. Among patients undergoing simultaneous hepatectomy, 89 patients underwent minor pancreatectomy with minor hepatectomy, 11 patients underwent major pancreatectomy with minor hepatectomy, 30 patients underwent minor pancreatectomy with major hepatectomy, and 1 patient underwent major pancreatectomy with major hepatectomy. Patients undergoing simultaneous hepatectomy had more numerous liver lesions (10 or more lesions in 54% vs. 34%, p = 0.008), but the groups were otherwise similar. Rates of any major complications (31% versus 24%, p = 0.43), hepatectomy-specific complications such as bile leak, hemorrhage, and liver failure (0.8-7.6% vs. 1.4-12%, p = 0.30-0.99), and 90-day mortality (1.5% vs. 2.7%, p = 0.62) were similar between the two groups. 5-year overall survival was 64% after combined resections and 65% after isolated hepatectomy (p = 0.93). CONCLUSION: For patients with metastatic pNETs, combined pancreatic and hepatic resections can be performed with acceptable morbidity and mortality in selected patients at high-volume institutions.

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma.

BACKGROUND: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. METHODS: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). RESULTS: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P<.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13-0.40), and was highly correlated (P=.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor (P<.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9-153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2-0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1-0.4). CONCLUSIONS: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.

Outcomes of pancreatectomy with portomesenteric venous resection and reconstruction for locally advanced pancreatic neuroendocrine neoplasms.

BACKGROUND: While pancreatectomy with portomesenteric venous resection and reconstruction is commonly performed for locally advanced pancreatic adenocarcinoma, little is known regarding outcomes for pancreatic neuroendocrine neoplasms (panNENs). METHODS: Patients who underwent non-parenchyma-sparing pancreatectomy for panNENs at Mayo Clinic from 2000 to 2020 were retrospectively reviewed. Propensity score matching was performed and patient characteristics and outcomes compared. RESULTS: Of 867 eligible patients, 41 (4.7%) required vascular resection, including 38 patients who underwent portomesenteric venous resection only. Of these, 23 underwent pancreaticoduodenectomy or total pancreatectomy and 15 distal pancreatectomy. Patients who required portomesenteric venous resection had larger tumors, higher tumor grade, and higher disease stage. After propensity score matching to patients undergoing standard resection, the portomesenteric venous resection group had longer operative times, greater blood loss, and higher transfusion rates. While portomesenteric venous thrombosis was more common after venous resection, major complication rates and perioperative mortality were similar between the two groups, as were 5-year overall and progression-free survival. CONCLUSION: For patients with locally advanced panNENs, pancreatectomy with portomesenteric venous resection and reconstruction can be performed in selected patients at high-volume centers with acceptable perioperative morbidity and short- and long-term survival.

Integrated cancer networks improve compliance with national guidelines and outcomes for resectable gastric cancer.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community. METHODS: Patients with stage II to III gastric adenocarcinoma undergoing curative-intent resection (National Cancer Data Base, 2006-2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan-Meier analysis was used to assess survival. RESULTS: There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10-year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline-concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline-concordant care and 32.0 months for those who did not (P < .001, reference for all ORs: academic programs). CONCLUSIONS: Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community.

Optimizing Opioid-Prescribing Practices After Parathyroidectomy.

BACKGROUND: To help control opioid overprescription, we conducted a large institutional, 3-site initiative to provide discharge prescribing guidelines for different procedures. Our aim is to refine institutional guidelines for parathyroidectomy. METHODS: Patients undergoing parathyroidectomy completed a 28-question survey about opioid consumption. Discharge opioid prescription amounts were converted into morphine milligram equivalents (MMEs) and reported as median and interquartile range (IQR). Consumption was dichotomized into top quartile MME users (Q4) versus standard users (Q1, Q3). Univariate analysis compared opioid consumption. RESULTS: A total of 91 patients were included; 90% were opioid-naive. While the median prescribed was 75 (IQR 75, 150) MME, the median consumed was 0 (IQR 0, 20). Top users reported higher pain scores [median (IQR): 2 (2, 4)] compared to standard users [1 (0, 3), P = 0.01]. However, there was no difference in opioid consumption between unilateral neck exploration, bilateral exploration, or thyroidectomy and parathyroidectomy, P = 0.11. There was no difference in opioid consumption by age, sex, or BMI (all P > 0.05). Of those receiving a prescription, 94.6% had left-over opioids at the time of survey, resulting in 82% of prescribed opioids being unused. CONCLUSIONS: Over half of patients undergoing parathyroidectomy did not consume any opioid, and very few needed more than 2 d of opioid. Moreover, most patients did not dispose the unused opioids, which put these pills at risk of diversion and misuse. Surgical approach did not change consumption, illustrating that these guidelines are applicable to thyroidectomy given the similarity between techniques. We recommend prescribing nonopioid analgesics for patients undergoing parathyroidectomy.

Hepatic artery infusion pumps.

The preferential blood supply from the hepatic artery to liver tumors allows for the regional delivery of chemotherapy, commonly referred to as hepatic artery infusion chemotherapy via a subcutaneous pump. Hepatic artery infusion chemotherapy has been demonstrated to improve overall survival in select patients with colorectal liver metastasis and is a promising treatment for unresectable intrahepatic cholangiocarcinoma. This review focuses on the technical aspects of hepatic artery infusion pump placement.