Simultaneous Hepatic and Visceral Resection: Preoperative Risk Stratification and Implications on Return to Intended Oncologic Therapy.

PURPOSE: Sequence of therapies for synchronous liver metastasis (LM) is complex, with data supporting individualized approaches, although no guiding tools are currently available. We assessed the impact of simultaneous hepatic and visceral resections (SHVR) on textbook outcome (TO) and return to intended oncologic therapy (RIOT), and provide risk-stratification tools to guide individualized decision making and counseling. METHODS: Patients with synchronous LM undergoing hepatectomy ± SHVR were included (2015-2021). Primary and secondary outcomes were TO and RIOT (days), respectively. Using multivariable modeling, a risk score for TO was developed. Decision tree analysis using recursive partitioning was performed for hierarchical risk stratification. The associations between SHVR, TO, and RIOT were examined. RESULTS: Among 533 patients identified, 124 underwent SHVR. TO overall was 71.7%; 79.2% in the non-SHVR group and 46.8% in the SHVR group (p < 0.001). SHVR was the strongest predictor of non-TO (right colon/small bowel: odds ratio [OR] 4.63, 95% confidence interval [CI] 2.65-8.08; left colon/rectum: OR 6.09, 95% CI 2.59-14.3; stomach/pancreas: OR 6.69, 95% CI 1.46-30.7; multivisceral: OR 10.9, 95% CI 3.03-39.5). A composite score was developed yielding three risk strata for TO (score 0-2: 89% vs. score 3-5: 67% vs. score ≥ 6: 37%; p < 0.001). Decision tree analysis was congruent, identifying SHVR as the most important determinant of TO. In patients with colorectal LM, SHVR was associated with delayed time to RIOT (p = 0.004); the risk-stratification tool for TO was equally predictive of RIOT (p < 0.01). CONCLUSIONS: SHVR is associated with reduced likelihood of TO and in turn delayed RIOT. As SHVR is increasingly performed in order to consolidate cancer care, patient selection considering these different outcomes is critical.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Surgical Approach does not Affect Return to Intended Oncologic Therapy Following Pancreaticoduodenectomy for Pancreatic Adenocarcinoma: A Propensity-Matched Study.

BACKGROUND: The effect of minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic and robotic pancreaticoduodenectomy (LPD and RPD, respectively), on compliance and time to return to intended oncologic therapy (RIOT) for pancreatic ductal adenocarcinoma (PDAC) remains unknown. PATIENTS AND METHODS: Patients with nonmetastatic PDAC were analyzed in the National Cancer Database (NCDB). Three groups were matched per propensity score: open pancreaticoduodenectomy (OPD) and MIPD, LPD and RPD, and converted and nonconverted patients. RIOT rates and time to RIOT were examined. RESULTS: A total of 14,135 patients were included: 11,834 (83.7%) underwent OPD and 2301 (16.3%) underwent MIPD. After score matching, RIOT rates (67.2 vs. 65.3%; p = 0.112) and RIOT within 8 weeks (57.7 vs. 56.4%; p = 0.276) were similar among MIPD and OPD groups, and approach was not a significant predictor of RIOT on multivariable regression. Neither RIOT nor time to RIOT were different among LPD and RPD groups (63.9 vs. 67.0%, and 58.4 vs. 56.9%, respectively). Compared with LPD, RPD was associated with lower conversion rates (HR 0.519; p < 0.001), and conversion was associated with longer median time to RIOT (10 vs. 8 weeks; p = 0.041). CONCLUSION: In this national cohort, approach did not impact RIOT rates or time to RIOT for patients with PDAC. While conversion was associated with longer median time to RIOT, readiness to commence adjuvant therapy was similar for LPD and RPD.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Prophylactic Perioperative Antibiotics in Open Pancreaticoduodenectomy: When Less Is More and When It Is Not. A National Surgical Quality Improvement Program Propensity-Matched Analysis.

INTRODUCTION: We hypothesized that first-generation cephalosporins (G1CEP) provide adequate antimicrobial coverage for pancreaticoduodenectomy (PD) when no biliary stent is present but might be inferior to second-generation cephalosporins or broad-spectrum antibiotics (G2CEP/BS) in decreasing surgical-site infection (SSI) rates when a biliary stent is present. METHODS: The National Surgical Quality Improvement Program 2014-2019 was used to select patients who underwent elective open PD. We divided the population into no-stent versus stent groups based on the status of biliary drainage and then divided each group into G1CEP versus G2CEP/BS subgroups based on the choice of perioperative antibiotics. We matched the subgroups per a propensity score match and analyzed postoperative outcomes. RESULTS: Six thousand two hundred forty five cases of 39,779 were selected; 2821 in the no-stent (45.2%) versus 3424 (54.8%) in the stent group. G1CEP were the antibiotics of choice in 2653 (42.5%) versus G2CEP/BS in 3592 (57.5%) cases. In the no-stent group, we matched 1129 patients between G1CEP and G2CEP/BS. There was no difference in SSI-specific complications (20.3% versus 21.0%; P = 0.677), general infectious complications (25.7% versus 26.9%; P = 0.503), PD-specific complications, overall morbidity, length of stay, or mortality. In the stent group, we matched 1244 pairs. G2CEP/BS had fewer SSI-specific complications (19.9% versus 26.6%; P < 0.001), collections requiring drainage (9.6% versus 12.9%; P = 0.011), and general infectious complications (28.5% versus 34.1%; P = 0.002) but no difference in overall morbidity, mortality, length of stay, and readmission rates. CONCLUSIONS: G2CEP/BS are associated with reduced rates of SSI-specific and infectious complications in stented patients undergoing open elective PD. In patients without prior biliary drainage, G1CEP seems to provide adequate antimicrobial coverage.

Surgical approach to pancreaticoduodenectomy for pancreatic adenocarcinoma: uncomplicated ends justify the means.

BACKGROUND: Pancreaticoduodenectomy (PD) remains the cornerstone of managing pancreatic ductal adenocarcinoma (PDAC) of the pancreas head/neck, but it is associated with high morbidity. We hypothesize that, in absence of pancreatectomy-specific morbidity (PSM), minimally invasive PD (MIPD) provides improved short-term outcomes compared to open PD (OPD). METHODS: NSQIP pancreatectomy-targeted database 2014-2019 was utilized. PSM was defined as the occurrence of delayed gastric emptying (DGE) and/or post-operative pancreatic fistula (POPF). The cohort was divided into No-PSM and PSM groups. Propensity score match was applied in each group to compare outcomes of MIPD vs. OPD. RESULTS: 8,121 patients were selected. Patients were divided into No-PSM (N = 6267) and PSM (N = 1854) groups. In No-PSM group, we matched 1656 OPD to 552 MIPD patients. MIPD had longer operations (423 vs. 359 min; p < 0.001) but less overall morbidity (22.1% vs. 29.1%; p = 0.001) mostly attributed to less bleeding and sepsis. MIPD patients also had a one-day shorter median LOS (6 vs. 7 days; p = 0.005) and higher rates of home discharge (92.8% vs. 89.6%; p = 0.027). No difference was noted in mortality and 30-day readmission. In PSM group, 441 OPD were matched to 147 MIPD peers. MIPD had longer operations but without short-term benefits. General morbidity (61.2% vs. 61.9%), median LOS (12 vs. 12 days), mortality (2.7% vs. 1.8%), and readmission rates (32.7% vs. 26.5%) were similar. Same conclusions were drawn in the per-protocol analysis. CONCLUSION: PSM is common following PD for PDAC. In the absence of PSM, MIPD is associated with less postoperative morbidity and shorter LOS.

Patient-caregiver dyads in pancreatic cancer: identification of patient and caregiver factors associated with caregiver well-being.

We aimed to examine the psychosocial well-being in the pancreas cancer patient-caregiver dyad, and determine patient and caregiver characteristics that predict caregiver distress. This was a cross-sectional, observational study. Demographics and caregiving characteristics were gathered from patients and caregivers. Caregivers completed validated instruments investigating anxiety, depression, perceived stress and caregiver burden. Over a period of eleven months, 128 patient-caregiver dyads were enrolled. Patient and caregiver distress scores were not associated with patient clinical disease burden. Patient distress was a significant predictor of concurrent caregiver distress, anxiety, depression, and perceived burden. Younger caregivers were also associated with higher caregiver anxiety and perceived burden. Additionally, number of caregiving activities and caregiver overall health status were predictors of concurrent caregiver depression and perceived stress. Certain pancreatic cancer patient and caregiver variables may negatively impact the well-being of caregivers. Future efforts should focus on development and implementation of comprehensive caregiver support programs for those at risk for psychosocial distress.

Management of early hepatocellular carcinoma: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association.

BACKGROUND: There are many potential treatment options for patients with early stage hepatocellular carcinoma (HCC) and practice patterns vary widely. This project aimed to use a Delphi conference to generate consensus regarding the management of small resectable HCC. METHODS: A base case was established with review by members of AHPBA Research Committee. The Delphi panel of experts reviewed the literature and scored clinical case statements to identify areas of agreement and disagreement. Following initial scoring, discussion was undertaken, questions were amended, and scoring was repeated. This cycle was repeated until no further likelihood of reaching consensus existed. RESULTS: The panel achieved agreement or disagreement consensus regarding 27 statements. The overarching themes included that resection, ablation, transplantation, or any locoregional therapy as a bridge to transplant were all appropriate modalities for early or recurrent HCC. For larger lesions, consensus was reached that radiofrequency ablation and microwave ablation were not appropriate treatments. CONCLUSION: Using a validated system for identifying consensus, an expert panel agreed that multiple treatment modalities are appropriate for early stage HCC. These consensus guidelines are intended to help guide physicians through treatment modalities for early HCC; however, clinical decisions should continue to be made on a patient-specific basis.

Cancer outcomes are independent of preoperative CA 19-9 in anatomically resectable pancreatic ductal adenocarcinoma: A retrospective cohort analysis.

BACKGROUND AND OBJECTIVES: Current guidelines recommend neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) patients with anatomically resectable tumors but elevated CA 19-9. However, this recommendation is based on data from anatomically resectable and borderline resectable PDAC patients. Therefore, we analyzed the association of preoperative CA 19-9 with oncologic outcomes in a cohort of anatomically resectable PDAC patients. METHODS: A single-institution PDAC database from 2007 to 2015 included patients who underwent guideline-based staging and were anatomically resectable. Patients with bilirubin above 1.5 after decompression, nonsecretors of CA 19-9, and borderline resectable patients were excluded. Statistical analysis included frequency testing and regression modeling for recurrence and survival. RESULTS: One hundred forty-four PDAC patients were identified; 16 (11.1%) had elevated preoperative CA 19-9 ≥ 1000. A CA 19-9 level ≥1000 was not associated with demographic, clinical, or pathological factors. After adjustment for potential confounders, CA 19-9 levels (continuous, median, 500 U/mL, or 1000 U/mL cut-offs) were not associated with recurrence or overall survival (OS). CONCLUSIONS: Although guidelines recommend CA 19-9 to determine the management of anatomically resectable PDAC patients, CA 19-9 was not associated with recurrence or OS in this cohort. Our findings do not suggest that CA 19-9 alone should determine the PDAC treatment strategy.

The use of contralateral prophylactic mastectomy among elderly patients in the United States.

PURPOSE: Previous studies have reported increased rates of contralateral prophylactic mastectomy (CPM) in the United States among women with unilateral breast cancer. These trends have primarily focused on younger breast cancer patients. Given the growing aging population in the United States, we sought to determine whether CPM use is also increasing in elderly patients. METHODS: This population-based study identified patients in the surveillance epidemiology and end results (SEER) data. We determined the rate of CPM as a proportion of all surgically treated patients and as a proportion of all mastectomies. We compared the unadjusted CPM rates over the study period using the Cochrane-Armitage test for trend. We used a logistic regression model to test for the factors associated with CPM utilization. RESULTS: We identified 261,281 patients ≥ 65 years who underwent surgical treatment for breast cancer. For all patients treated with surgery for invasive breast cancer, the use of CPM increased from 1 in 2004 to 3% in 2014 (200% increase). Among mastectomy patients, the use of CPM increased from 3 in 2004 to 7% in 2014 (133% increase). Young age, non-Hispanic white race, lobular histology, higher grade, increased stage, negative lymph node status, and recent year of diagnosis were significantly associated with increased CPM rates. CONCLUSIONS: For elderly patients the use of CPM has continued to increase in the United States. These observations warrant concern in light of increasing evidence that CPM does not improve oncological outcomes and is associated with increased morbidity in older patients.

Correction to: Minimally Invasive Lymphadenectomy for Biliary Tumors: Stepwise Progress.

In the original article, Schelomo Marmor's last name is misspelled. It is correct as reflected here.

Completion of Adjuvant Chemotherapy After Upfront Surgical Resection for Pancreatic Cancer Is Uncommon Yet Associated With Improved Survival.

BACKGROUND: Multiple trials have demonstrated a survival benefit for adjuvant chemotherapy after resection of pancreatic adenocarcinoma. This study aimed to identify the rate for completion of adjuvant chemotherapy, factors associated with completion, and its impact on survival after surgical resection. METHODS: The Surveillance Epidemiology and End Results Medicare-linked data was used to identify patients who underwent upfront resection for pancreatic adenocarcinoma from 2004 to 2013. Billing codes were used to quantify receipt and completion of chemotherapy. Factors associated with completion of chemotherapy were identified using multivariable regression. Kaplan-Meier and Cox proportional-hazards modeling were used to examine survival. RESULTS: The inclusion criteria were met by 2440 patients. Of these patients, 65% received no adjuvant chemotherapy, 28% received incomplete therapy, and 7% completed chemotherapy. The factors associated with chemotherapy completion were nodal metastases and treatment at a National Cancer Institute-designated cancer center (p ≤ 0.05). Comorbidities decreased the odds of completion (p ≤ 0.05). The median overall survival (OS) was 14 months for the patients who received no adjuvant chemotherapy, 17 months for those who received incomplete adjuvant chemotherapy, and 22 months for those who completed adjuvant chemotherapy (p ≤ 0.05). More recent diagnosis, comorbidities, T stage, nodal metastases, and no adjuvant chemotherapy were associated with an increased hazard ratio for death (p ≤ 0.05). Evaluation of 15 or more nodes and completion of chemotherapy decreased the hazard ratio for death (p ≤ 0.05). CONCLUSIONS: Only 7% of the Medicare patients who underwent upfront resection for pancreatic cancer completed adjuvant chemotherapy, yet completion of adjuvant chemotherapy was associated with improved OS. Completion of adjuvant chemotherapy should be the goal after upfront resection, but neoadjuvant chemotherapy may ensure that patients receive systemic chemotherapy.

Surgical resection of lymph node positive intrahepatic cholangiocarcinoma may not improve survival.

BACKGROUND: Nodal positivity is a predictor of poor survival following resection for intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the impact of surgical resection on survival in patients with lymph node (LN) positive ICC. METHODS: An augmented version of the Surveillance, Epidemiology, and End Results program database was utilized to identify patients with LN-positive ICC without distant metastases from 2000 to 2014. Patients were stratified by treatment: chemotherapy alone or surgical resection with/without chemotherapy. Survival was evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: 169 patients who underwent treatment for LN-positive ICC were identified. 88% underwent surgical resection and 12% underwent chemotherapy alone. The median survival for patients who underwent surgical resection was not different from patients treated with chemotherapy alone (19 months 95% Confidence Interval (CI) 17-33 versus 20 months CI 10-27, p = 0.323). A cox-proportional hazard ratio model demonstrated that black race was associated with worse survival (p < 0.05), while surgical resection was not independently associated with survival. CONCLUSION: Surgical resection for patients with LN-positive ICC may not improve survival compared to chemotherapy alone. Pathologic LN evaluation should be performed prior to surgical resection, to improve patient selection and ensure receipt of optimal therapy.

Distribution of 21-Gene Recurrence Scores in Male Breast Cancer in the United States.

BACKGROUND: The 21-gene recurrence score (RS) is a RT-PCR assay estimating risk of distant recurrence in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2) breast cancer (BC). Studies validating RS are limited to women. Our objective was to assess RS distribution and factors associated with high-risk RS in male BC. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified men and women with ER+/HER2- BC from 2010 to 2013. Patients were categorized into risk groups using the traditional and the Trial Assigning Individualized Options for Treatment (TAILORx) cutoffs. Multivariable logistic regression determined factors associated with testing and high-risk TAILORx RS. RESULTS: We identified 1388 men and 154,196 women with ER+/HER2- BC. Twenty-five percent of men and 30% of women had RS testing. Mean age of tested men was 63; most were white (81%), had grade I or II tumors (67%), and had stage I or II (95%) BC. Factors associated with increased RS testing were younger age, recent year of diagnosis, lymph node negativity, and lower-stage tumors (p ≤ 0.05). By TAILORx, 21% of men had high-risk RS compared with 14% of tested women. Men with grade III and PR negative tumors were more likely to have a high-risk RS (p ≤ 0.05). Chemotherapy utilization was correlated with RS. CONCLUSIONS: Using a large population-based dataset, we found that compared with women, men were significantly more likely to have high-risk RS. Grade III and PR-negative BC were significantly associated with high-risk RS. Higher RS in men correlated with increased chemotherapy utilization.

Impact of pancreatectomy on long-term patient-reported symptoms and quality of life in recurrence-free survivors of pancreatic and periampullary neoplasms.

BACKGROUND: Long term patient-reported symptoms and quality of life (QOL) are important outcome metrics following cancer operations, but have been poorly described in patients who have previously undergone pancreatectomy. METHODS: We conducted a cross-sectional survey of recurrence-free survivors of pancreatic ductal adenocarcinoma, periampullary carcinomas, and pancreatic neuroendocrine tumors who had undergone prior pancreatectomy. QOL and symptom burden were measured using the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire, and psychosocial distress was measured using the Hospital Anxiety and Depression Scale. RESULTS: Of 331 eligible patients surveyed, 217 (66%) participated at a median of 53.3 (range, 7.6-214.8) months following pancreatoduodenectomy (PD, n = 165) or distal pancreatectomy (DP, n = 52). Among all patients, overall QOL scores were favorable and influenced by race, histology, and type of surgery. The most common significant symptoms reported were fatigue (82%), back pain (32%), and difficulty with digestion (31%). In general, PD survivors reported better QOL, lower levels of anxiety/depression, greater levels of diarrhea, and improved appetite, constipation, fatigue, anxiety, and depression (P < 0.05) than DP survivors. On both univariate and multivariate regression analysis, DP was negatively associated with QOL. CONCLUSIONS: Most disease-free survivors of pancreatic neoplasms report favorable QOL, but gastrointestinal and psychosocial symptoms may exist long after pancreatectomy. J. Surg. Oncol. 2017;115:144-150. © 2016 Wiley Periodicals, Inc.

Real time ex vivo chemosensitivity assay for pancreatic adenocarcinoma.

BACKGROUND: Patient-derived organoids (PDOs) and xenografts (PDXs) have been extensively studied for drug-screening. However, their usage is limited due to lengthy establishment time, high engraftment failure rates and different tumor microenvironment from original tumors. To overcome the limitations, we developed real time-live tissue sensitivity assay (RT-LTSA) using fresh tumor samples. METHODS: Tissue slices from resected pancreatic cancer samples were placed in 96-well plates, and the slices were treated with chemotherapeutic agents. The correlation between the chemo-sensitivity of tissue slices and each patient's clinical outcome was analyzed. RESULTS: The viability and tumor microenvironment of the tissue slices are well-preserved over 5 days. The drug sensitivity assay results are available within 5 days after tissue collection. While all 4 patients who received RT-LTSA sensitive adjuvant regimens did not develop recurrence, 7 of 8 patients who received resistant adjuvant regimens developed recurrence. We observed significantly improved disease-free survival in the patients who received RT-LTSA sensitive adjuvant regimens (median: not reached versus 10.6 months, P = 0.02) compared with the patient who received resistant regimens. A significant negative correlation between RT-LTSA value and relapse-free survival was observed (Somer's D: -0.58; P = 0.016). CONCLUSIONS: RT-LTSA which maintains the tumor microenvironment and architecture as found in patients may reflect clinical outcome and could be used as a personalized strategy for pancreatic adenocarcinoma. Further, studies are warranted to verify the findings.