Gallbladder Cancer Incidentally Found at Cholecystectomy: Perioperative Risk Factors.

PURPOSE: Risk factors of gallbladder cancer (GBC) are not well-defined resulting in greater than 60% of GBCs being diagnosed incidentally following cholecystectomy performed for presumed benign indications. As most localized GBCs require more extensive oncologic surgery beyond cholecystectomy, this study aims to examine factors associated with incidentally found GBC to improve preoperative and intraoperative diagnoses. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Database from 2007 to 2017 was used to identify cholecystectomies performed with and without a final diagnosis of GBC. Univariate and multivariable logistic regressions were used to compare demographic, intraoperative, and postoperative characteristics among those with and without a diagnosis of GBC. RESULTS: The incidence of GBC was observed to be 0.11% (441/403,443). Preoperative factors associated with risk of GBC included age > 60 (OR 6.51, p < .001), female sex (OR 1.75, p < .001), history of weight loss (2.58, p < .001), and elevated preoperative alkaline phosphatase level (OR 1.67, p = .001). Open approach was associated with 7 times increased risk of GBC compared to laparoscopic approach (OR 7.33, p < .001). In addition to preoperative factors and surgical approach, longer mean operative times (127 min vs 70.7 min, p < .001) were significantly associated with increased risk of GBC compared to benign final pathology. CONCLUSION: This study demonstrates that those with incidentally discovered GBC at cholecystectomy are unique from those undergoing cholecystectomy for benign indications. By identifying predictors of GBC, surgeons can choose high risk individuals for pre-operative oncologic evaluation and consider better tools for identifying GBC such as intraoperative frozen pathology.

Do-Not-Resuscitate Orders and Outcomes for Patients with Pancreatic Cancer.

Background: The impact of the do-not-resuscitate (DNR) order on patients with pancreatic cancer remains uncertain. In this study, we evaluated whether DNR status was associated with in-hospital mortality and costs for inpatient stay among patients hospitalized with pancreatic cancer. Methods: Data were obtained from the National Inpatient Sample, Healthcare Cost and Utilization Project, which represents ∼20% of all discharges from US community hospitals; 40,246 pancreatic cancer admissions between 2011 and 2016 were included. Mortality was modeled using a logistic regression model; costs for inpatient stay were modeled using a multivariable generalized linear regression model. Results: The sample included 6041 (15%) patients with a documented DNR order. After controlling for covariates, patients with a DNR order had approximately six times greater odds of mortality compared with patients without a DNR order (odds ratio 5.90, p < 0.0001). Compared with patients who survived without a DNR order during the hospital stay, patients who had a DNR order and died during the hospital stay had significantly lower costs (-US$983; p = 0.0270), and patients who died without a DNR order during the hospital stay had significantly higher costs (US$5638; p < 0.0001). Patients who survived with a DNR order had costs that were not significantly different from patients who survived without a DNR order. Conclusions: The presence of a DNR order among patients with pancreatic cancer was significantly associated with higher mortality risk as well as lower costs for patients who died during the hospital stay. However, DNR status was not significantly associated with costs for pancreatic cancer patients who were discharged alive.

Twitter Conversations About Pancreatic Cancer by Health Care Providers and the General Public: Thematic Analysis.

BACKGROUND:  There is a growing interest in the pattern of consumption of health-related information on social media platforms. OBJECTIVE: We evaluated the content of discussions around pancreatic cancer on Twitter to identify subtopics of greatest interest to health care providers and the general public. METHODS:  We used an online analytical tool (Creation Pinpoint) to quantify Twitter mentions (tweets and retweets) related to pancreatic cancer between January 2018 and December 2019. Keywords, hashtags, word combinations, and phrases were used to identify mentions. Health care provider profiles were identified using machine learning and then verified by a human analyst. Remaining user profiles were classified as belonging to the general public. Data from conversations were stratified qualitatively into 5 domains: (1) prevention, (2) survivorship, (3) treatment, (4) research, and (5) policy. We compared the themes of conversations initiated by health care providers and the general public and analyzed the impact of the Pancreatic Cancer Awareness Month and announcements by public figures of pancreatic cancer diagnoses on the overall volume of conversations. RESULTS:  Out of 1,258,028 mentions of pancreatic cancer, 313,668 unique mentions were classified into the 5 domains. We found that health care providers most commonly discussed pancreatic cancer research (10,640/27,031 mentions, 39.4%), while the general public most commonly discussed treatment (154,484/307,449 mentions, 50.2%). Health care providers were found to be more likely to initiate conversations related to research (odds ratio [OR] 1.75, 95% CI 1.70-1.79, P<.001) and prevention (OR 1.49, 95% CI 1.41-1.57, P<.001) whereas the general public took the lead in the domains of treatment (OR 1.63, 95% CI 1.58-1.69, P<.001) and survivorship (OR 1.17, 95% CI 1.13-1.21, P<.001). Pancreatic Cancer Awareness Month did not increase the number of mentions by health care providers in any of the 5 domains, but general public mentions increased temporarily in all domains except prevention and policy. Health care provider mentions did not increase with announcements by public figures of pancreatic cancer diagnoses. After Alex Trebek, host of the television show Jeopardy, received his diagnosis, general public mentions of survivorship increased, while Justice Ruth Bader Ginsburg's diagnosis increased conversations on treatment. CONCLUSIONS: Health care provider conversations on Twitter are not aligned with the general public. Pancreatic Cancer Awareness Month temporarily increased general public conversations about treatment, research, and survivorship, but not prevention or policy. Future studies are needed to understand how conversations on social media platforms can be leveraged to increase health care awareness among the general public.

The Durability of EUS-Guided Chemoablation of Mucinous Pancreatic Cysts: A Long-Term Follow-Up of the CHARM trial.

Pancreatic cancer has known precursor lesions with potential to develop into malignancy over time. At least 20% of pancreatic cancer evolves from mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which are often discovered incidentally.1,2 Current guidelines for the management of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms include long-term surveillance, which is expensive and nontherapeutic, or surgical resection, which is associated with major risk and may not be an option for patients with significant concomitant illness.3.

Undertreatment of Pancreatic Cancer: The Intersection of Bias, Biology, and Geography.

Pancreatic cancer is the third leading cause of cancer deaths in the United States. Black patients with pancreatic cancer experience higher incidence and increased mortality. Although racial biologic differences exist, socioeconomic status, insurance type, physician bias, and patient beliefs contribute to the disparities in outcomes observed among patients who are Black, indigenous, and people of color.

Trends in Diagnosis and Treatment of Metastatic Cancer in the United States.

OBJECTIVES: Metastatic cancer has historically been considered fatal; however, there is a paucity of evidence characterizing the epidemiology of incidence, treatment, and outcomes in these patients. MATERIALS AND METHODS: Incidence rates, annual percent change (APC), descriptive epidemiological statistics, and odds ratios for survival were calculated using registry data from the Surveillance, Epidemiology, and End Results (SEER) and the National Cancer Database (NCDB), 1998 to 2015. RESULTS: There were a total of 1,055,860 patients with metastatic cancer. The most frequent primary cancers were lung (42.6%), colorectal (9.5%), and ovarian (5.5%). Metastatic lung and colorectal cancer incidence decreased, APC: -1.57 (P<0.001) and APC: -1.48 (P<0.001), respectively; metastatic pancreatic cancer incidence increased, APC: 0.62 (P=0.001). The use of local therapies decreased for almost all sites, and the use of systemic therapies increased across multiple sites: single-agent chemotherapy in kidney (2.54% increase/year), female breast (1.14% increase/year), and prostate cancer (1.08% increase/year); multiagent chemotherapy, most notably in pancreas (2.23% increase/year), uterus (1.81% increase/year), and colorectal cancer (1.54% increase/year). Increased utilization of immunotherapy was observed across the majority of sites, most notably in melanoma (2.14% increase/year). Patients diagnosed from 2006 to 2010 had 17.4% higher odds of surviving at least 60 months compared with 1998 to 2002. CONCLUSIONS: In this study, metastatic disease has been shown to have unique epidemiological patterns, and survival has improved. Continued research on metastatic disease is important in understanding and addressing the distinct health concerns of this population.

Impact of radiation therapy facility volume on survival in patients with cancer.

BACKGROUND: This study examined whether radiation therapy facility volumes correlate with survival after curative intent treatment of solid tumors. METHODS: The National Cancer Database was queried for patients with solid tumors treated with curative-intent radiation therapy from 2004-2013. Facilities were stratified into 4 volume categories: low, intermediate, high, and very high. Primary cancer sites were divided into neoadjuvant, adjuvant, or definitive radiation subgroups. Kaplan-Meier curves of 5-year postradiation survival probability, stratified by facility volume, were generated with log-rank tests for group comparisons. Cox proportional hazard models were used to evaluate the effect of facility volume on survival, adjusted for multiple covariates. RESULTS: There were 253,422 patients treated at 1289 facilities: 6231 received neoadjuvant radiation, 147,980 received adjuvant radiation, and 99,211 received definitive radiation without surgery. Among patients receiving neoadjuvant radiation, survival correlated with facility volume for patients with rectal cancer (hazard ratio [HR], 0.75; 95% CI, 0.6-0.94; P = .01). For cancers of the breast and uterus, patients receiving adjuvant radiation at very high-volume facilities (vs low volume) had improved survival (HR, 0.83; 95% CI, 0.77-0.90; P < .001 and HR, 0.77, 95% CI, 0.62-0.97; P = .03, respectively). For patients receiving definitive radiation for prostate, non-small cell lung, pancreas, and head and neck cancer, there was an improvement in survival for patients treated at very high-volume centers (P < .05). CONCLUSIONS: For select cancer patients, treatment with curative radiation at higher volume facilities is associated with improved survival. In particular, patients receiving radiation therapy in the definitive setting without surgery may benefit most from treatment at high-volume centers.

Pathologic upstaging in resected pancreatic adenocarcinoma: Risk factors and impact on survival.

BACKGROUND: Clinical and pathologic staging determine treatment of pancreatic cancer. Clinical stage has been shown to underestimate final pathologic stage in pancreatic cancer, resulting in upstaging. METHODS: National Cancer Database was used to identify clinical stage I pancreatic adenocarcinoma. Univariate, multivariable logistic regression, and Cox proportional hazard ratio were used to determine differences between upstaged and stage concordant patients. RESULTS: Upstaging was seen in 80.2% of patients. Factors found to be significantly associated with upstaging included pancreatic head tumors (OR 2.56), high-grade histology (OR 1.74), elevated Ca 19-9 (OR 2.09), and clinical stage T2 (OR 1.99). Upstaging was associated with a 45% increased risk of mortality compared to stage concordant disease (HR 1.44, p < .001). CONCLUSION: A majority of clinical stage I pancreatic cancer is upstaged after resection. Factors including tumor location, grade, Ca 19-9, and tumor size can help identify those at high risk for upstaging.

Adjuvant Chemotherapy After Neoadjuvant Chemotherapy for Pancreatic Cancer is Associated with Improved Survival for Patients with Low-Risk Pathology.

BACKGROUND: With limited evidence, the benefit of adjuvant chemotherapy (AT) after completion of neoadjuvant chemotherapy (NT) and surgical resection for patients with pancreatic adenocarcinoma is debated. Guidelines recommend 6 months of AT for patients receiving NT. However, the patient-derived benefit from additional AT remains unknown. METHODS: The National Cancer Database from 2006 to 2015 was used to identify patients undergoing NT. The chi-square test and multivariable logistic regression were used to identify differences between those receiving only NT and those receiving NT and AT. Survival analysis using the Kaplan-Meier method and the Cox proportional hazard ratio model was applied to the entire cohort and to subgroups with differing lymph node ratios (LNRs), tumor sizes, grades, and surgical margin statuses. RESULTS: Of the 3897 patients who received NT, 36.7 % received additional AT. Analysis of the entire cohort showed that associated survival was significantly improved with NT and AT compared with NT alone (hazard ratio [HR], 0.83; p < 0.001). In the subgroup analysis, the survival benefit of additional AT remained significant for those with negative nodal disease, an LNR lower than 0.15, low-grade histology, and negative margin status. Overall survival did not differ between those receiving NT only and those receiving NT and AT in the group with an LNR of 0.15 or higher, high-grade histology, and positive margins. CONCLUSION: This study identified an increasing trend in the use of AT after NT and showed an associated survival benefit for subgroups with low-risk pathologic features. These results suggest that the addition of AT after NT likely beneficial for these subgroups.

Impact of Facility Surgical Volume on Survival in Patients With Cancer.

BACKGROUND: Increased facility surgical treatment volume is sometimes associated with improved survival in patients with cancer; however, published studies evaluating volume are heterogeneous and disparate in their patient inclusion and definition of volume. The purpose of this work was to evaluate uniformly the impact of surgical facility volume on survival in patients with cancer. METHODS: The National Cancer Database was searched for patients diagnosed in 2004 through 2013 with the 12 cancers most commonly treated surgically. Facilities were stratified by 4 categories using the overall population (low, intermediate, high, and very high), each including 25% of patients, and then stratified by each individual disease site. Five-year postsurgery survival was estimated using both the Kaplan-Meier method and corresponding log-rank tests for group comparisons. Cox proportional hazard models were used to evaluate the effects of facility volume on 5-year postsurgery survival further, adjusted for multiple covariates. RESULTS: A total of 3,923,618 patients who underwent surgery were included from 1,139 facilities. Of these, 40.4% had breast cancer, 12.8% prostate cancer, and 10.0% colon cancer. Most patients were female (65.0%), White (86.4%), and privately insured (51.6%) with stage 0-III disease (64.8%). For all cancers, the risk of death for patients undergoing surgery at very high-volume facilities was 88% of that for those treated at low-volume facilities. Hazard ratios (HRs) were greatest (very high vs low volume) for cancer of the prostate (HR, 0.66; 95% CI, 0.63-0.69), pancreas (HR, 0.75; 95% CI, 0.71-0.78), and esophagus (HR, 0.78; 95% CI, 0.73-0.83), and for melanoma (HR, 0.81; 95% CI, 0.78-0.84); differences were smallest for uterine and non-small cell lung cancers. Overall survival differences were greatest for cancers of the brain, pancreas, and esophagus. CONCLUSIONS: Patients treated surgically at higher-volume facilities consistently had improved overall survival compared with those treated at low-volume centers, although the magnitude of difference was cancer-specific.

Undertreatment of Pancreatic Cancer: Role of Surgical Pathology.

BACKGROUND: Current guidelines recommend treatment of early-stage pancreatic cancer with surgical resection and chemotherapy. Undertreatment can occur after resection when patients fail to receive adjuvant chemotherapy. Final pathologic results have the potential to bias providers to omit adjuvant chemotherapy, however, the association of surgical pathology and adjuvant chemotherapy is unknown. METHODS: Data from the National Cancer Database identified patients who underwent surgery for stage I or II pancreatic cancer. Chi-square tests and logistic regression were used to determine differences between patients receiving surgery followed by chemotherapy and those who had resection alone. Survival analysis of subgroups with favorable pathology (node-negative disease, tumor size ≤ 2 cm, well-differentiated histology) was performed by the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Of the 22,131 patients included in this study, 28% were considered undertreated (surgery alone). Favorable pathologic traits of negative lymph nodes, tumor 2 cm in size or smaller, and well-differentiated histology were associated with a 15-35% lower probability that adjuvant chemotherapy would be given than less favorable pathologic results (p < 0.001). Multivariable survival analysis showed significantly lower odds of mortality for patients who received resection and chemotherapy than for those who were undertreated among two subgroups: patients with node-negative disease (hazard ratio [HR] 0.774) and those with a tumor 2 cm in size or smaller (HR 0.771). CONCLUSION: The patients who had early-stage pancreatic cancer with favorable pathology after pancreatectomy were less likely than those with unfavorable pathology to receive adjuvant chemotherapy. This omission had significant survival consequences for subgroups with node-negative disease and tumors 2 cm in size or smaller. Recognition of patients with favorable pathology as an undertreated group is required for efforts to be directed toward encouraging guideline-concordant care and to combat undertreatment of pancreatic cancer.

Rural-Urban Disparities in Pancreatic Cancer Stage of Diagnosis: Understanding the Interaction With Medically Underserved Areas.

PURPOSE: To estimate differences in pancreatic cancer diagnosis stage by rurality of patient residence and residence in a medically underserved area (MUA). METHODS: Using 2010-2016 Pennsylvania Cancer Registry data, we restrict our analysis to adults diagnosed with pancreatic cancer. We categorize each patient's residence by Rural-Urban Continuum Codes (RUCC): (1) metro; (2) nonmetro adjacent with population ≥20,000; (3) nonmetro adjacent with population <20,000; (4) nonmetro nonadjacent, and (5) completely rural; also by whether the county was a full MUA, partial MUA, or non-MUA. We examine the percent of patients diagnosed with local and locoregional stage of disease for each residential rurality and MUA status grouping. We estimate multivariate linear probability models of local and locoregional stage of diagnosis while controlling for demographics, insurance type, year, rurality, and MUA status. Finally, we estimate models interacting rurality with MUA status to disentangle the relative impact of each on diagnostic stage. FINDINGS: We find that no pancreatic patients living in completely rural areas were diagnosed at the local stage, the lowest of all categories of rurality. In adjusted models, we find that patients living in completely rural areas have significantly lower rates of local and local/regional stage of diagnosis. The estimates are attenuated slightly when controlling for MUA. CONCLUSIONS: We find significantly lower rates of early stage pancreatic cancer diagnosis for patients living in completely rural areas. While lack of primary medical care resources is an important factor, rural residence remains an important independent predictor in later stage of diagnosis.

Biliary Drainage Before and After Liver Resection for Perihilar Cholangiocarcinoma.

Perihilar cholangiocarcinoma (PHC) is a rare tumor that requires surgical resection for a potential cure. The role of preoperative biliary drainage has long been debated, given its treatment of biliary sepsis and decompression of the future liver remnant (FLR), but high procedure-specific morbidity. The indications, methods, and outcomes for preoperative biliary drainage are discussed to serve as a guide for perioperative management of patients with resectable PHC. Multiple studies from the literature related to perihilar cholangiocarcinoma, biliary drainage, and management of the FLR were reviewed. Commonly employed preoperative biliary drainage includes endoscopic biliary stenting and percutaneous transhepatic biliary drainage. Drainage of the FLR remains controversial, with most experts recommending drainage of the only in patients with an FLR <50%. Biliary drainage for resectable PHC requires a patient-specific approach with careful determination of the FLR and balancing of potential morbidity with the benefits of drainage.

Epidemiology of liver metastases.

AIMS: The objectives of this study were to (1) characterize the epidemiology of liver metastases at the time of primary cancer diagnosis (synchronous liver metastases), (2) characterize the incidence trends of synchronous liver metastases from 2010-2015 and (3) assess survival of patients with synchronous liver metastases. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 was queried to obtain cases of patients with liver metastases at the time of primary cancer diagnosis. The primary cancers with an incidence rate of liver metastasis >0.1 are presented in this analysis. RESULTS: Among 2.4 million cancer patients, 5.14 % of cancer patients presented with synchronous liver metastases. The most common primary site was breast cancers for younger women (ages 20-50), and colorectal cancers for younger men. As patients get older, a more heterogenous population of the top cancers with liver metastases emerges including esophageal, stomach, small intestine, melanoma, and bladder cancer in addition to the large proportion of lung, pancreatic, and colorectal cancers. The 1-year survival of all patients with liver metastases was 15.1 %, compared to 24.0 % in those with non-hepatic metastases. Regression analysis showed that the presence of liver metastasis was associated with reduced survival, particularly in patients with cancers of the testis, prostate, breast, and anus, and in those with melanoma. CONCLUSIONS: The most common primary sites for patients with liver metastases varied based on age at diagnosis. Survival for patients with liver metastasis was significantly decreased as compared to patients without liver metastasis.

Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis.

BACKGROUND: The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS. METHODS: A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome. RESULTS: A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant. CONCLUSION: These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed.