Improved Overall Survival of Patients with Pancreatic Cancer through Multiagent Chemotherapy and Increased Rates of Surgical Resection.

BACKGROUND: Seminal trials have demonstrated improved survival in pancreatic adenocarcinoma with novel multiagent chemotherapy regimens. To understand the clinical ramifications of this paradigm shift, we reviewed our institutional experience. METHODS: This retrospective cohort study utilized a prospective database at a single institution to study all patients diagnosed with and treated for pancreatic adenocarcinoma between 2000 and 2020. RESULTS: 1,572 patients were included of which 36% were diagnosed before (Era 1) and 64% after (Era 2) 2011. Survival improved in Era 2 (Median survival 10 vs 8 months, HR .79; P < .001). The survival advantage for Era 2 was primarily seen in patients with high-risk disease (12 vs10 months, HR .71; P < .001). A similar trend was noted for patients undergoing surgical resection (26 vs 21 months, HR .80; P = .081) and with imminently resectable tumors (19 vs 15 months, HR .88; P = .4); however, this was not statistically significant. There was no survival advantage for patients with stage IV disease (4 vs 4 months). Patients in Era 2 were more likely to undergo surgery (OR 2.78; CI 2.00-3.92, P < .001). This increase was driven primarily by increased surgical resection for those with high-risk disease (42 vs 20%, OR 3.74; P < .001). DISCUSSION/CONCLUSIONS: This single institutional study showed improved survival after the shift to novel chemotherapy regimens. This was driven by improved survival for patients with high-risk disease and may be due to more effective eradication of microscopic metastatic disease with adjuvant chemotherapy and increased resection rates.

The Cost of Frailty in Complex Gastrointestinal Surgery.

BACKGROUND: Frailty is a syndrome characterized by decreased physiologic reserve related with aging; it has been associated with increased costs of health care. Factors driving its economic impact remain poorly understood. We examine the association between frailty, complications, and costs in complex gastrointestinal surgery. METHODS: Retrospective review of a prospective database encompassing elective complex gastrointestinal operations from 2017 to 2018 at a tertiary care hospital. Patients were categorized into non-frail (NF): MFI 0, pre-frail (PF): MFI 1-2, and frail (FR): MFI >2 based on the 5-Factor Modified Frailty Index. Linear regression models were applied. RESULTS: 612 patients were included; 268 (44%) were NF, 325 (53%) were PF, and 19 (3%) were FR. The FR group had a longer length of stay (7.26 days) compared to NF (5.05 days) or PF (5.67 days) (p = 0.031). The average total cost of care for all patients was $19,413.06 (CI 18,297.13-20,528.98). The cost for NF was $17,648.54 (CI 15,969.18-19,327.9), PF $20,435.70 (CI 18,911.01-21,960.4, p = .016), and FR patients was $26,809.36 (CI 20,511.9-33,106.81). A complication was observed in 91 patients (14.9%); of these, 76 (12.4%) were serious complications, as defined by NSQIP. There was no difference in incidence of complications (NF 14.93%, PF 14.46%, FR 21.05%, p = .734). On average, a complication added $12,656.67 regardless of frailty category. DISCUSSION: Frail patients are more costly and have a longer length of stay than their more robust counterparts. Complications were the major driver of costs after complex gastrointestinal surgery regardless of frailty status.

Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer.

BACKGROUND: This study was designed to better define the role of radiation (Neo-Rad) in addition to neoadjuvant multiagent chemotherapy (NAT) for the treatment of locally advanced pancreatic cancer. METHODS: Retrospective cohort study using the NCDB. Individuals with AJCC clinical T3/T4 pancreatic carcinoma who underwent resection and multiagent chemotherapy were included. Kaplan-Meier, logistic-regression, and Cox proportional-hazard models were used for analysis. RESULTS: A total of 2703 patients were included; 2039 had T3 and 664 had T4 tumors, and 1092 (40.4%) received Neo-Rad. Median follow-up was 22.5 months. During the study period, there was increased use of NAT and a decline in the use of Neo-Rad. Addition of Neo-Rad did not affect 30-day (2.51% vs. 3.24%, p = 0.272) or 90-day mortality (5.23% vs. 6.38%, p = 0.216). Neo-Rad was not associated with improved overall survival on univariable (25.95 vs. 24.7 months, p = 0.202), or multivariable analyses (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.85-1.05). Time from diagnosis to definitive surgery was increased by Neo-Rad (204 vs. 115 days, p < 0.001). Neo-Rad was associated with increased pathologic downstaging in T3 (32.8% vs. 14.4%) (odds ratio [OR] 2.90; 95% CI 2.30-3.66) and T4 tumors (88.9% vs. 77.8%) (OR 2.29; 95% CI 1.44-3.67); complete pathologic response (5.3% vs. 1.6%) (OR 2.89; 95% CI 1.73-4.83), and increased R0 resection rates (85.7% vs. 76.8%) (OR 1.79; 95% CI 1.44-2.23). CONCLUSIONS: The use of neoadjuvant therapy is increasing for the treatment of locally advanced pancreatic cancer. The addition of radiation to neoadjuvant chemotherapy is associated with improved antineoplastic effectiveness (downstaging, complete pathologic response), surgical resection (R0 rates), but has no effect on overall survival.

Frailty Cost: Economic Impact of Frailty in the Elective Surgical Patient.

BACKGROUND: Frailty in the surgical patient has been associated with increased morbidity, mortality, and failure to rescue. However, there is little understanding of the economic impact of frailty. STUDY DESIGN: A prospective database of elective surgery patients at an academic medical center was used to create a modified version of the Risk Analysis Index (RAI), a validated frailty index. This included 10,257 patients undergoing elective operations from 2016 to 2017. Patients were classified as not frail (RAI = 0), somewhat frail (RAI = 1 to 10), or significantly frail (RAI > 10). Cost, revenue, and income data were procured from the finance department. Univariate and multivariate analyses were performed. RESULTS: Frail patients were more likely to be older (65 years vs 50 years; p < 0.001) and inpatient (19% vs 36%; p < 0.001). General surgical, gynecologic, urologic, and cardiothoracic services operated on a higher percentage of significantly frail patients compared with orthopaedic, neurosurgical, and vascular (p < 0.001). On univariate analysis, frail patients were more likely to die (0% vs 0.4%; p < 0.001) and have increased length of stay (0.8 vs 2.1 days; p < 0.001), higher total cost ($6,934 vs $13,319), and lower net hospital income ($5,447 vs $3,129) (p < 0.001). On multivariate analysis, frailty was independently associated with increased direct cost (odds ratio [OR] 2.2; p < 0.001), indirect cost (OR 1.9; p < 0.001), total cost (OR 2.2; p < 0.001), and net income (OR 0.8; p < 0.001). Stratified by service line and inpatient vs outpatient status, frailty continued to be associated with increased direct cost, indirect cost, total cost, and decreased hospital income. CONCLUSIONS: Although a significant number of data exist on the impact of frailty in the surgical patient, the economic impacts have only limited description in the literature. Here we demonstrate that frailty, independent of age, has a detrimental financial impact on cost and hospital income in elective surgery.

Tumor mitotic rate is an independent predictor of survival for nonmetastatic melanoma.

BACKGROUND: Tumor mitotic rate is a known prognostic variable in Stage I melanoma; however, its importance is unclear in Stages II and III. METHODS: Patients diagnosed with nonmetastatic cutaneous melanoma from 2010 to 2014 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results registry. RESULTS: Of a total of 71,235 patients, the majority were white (94.7%), male (58.5%), and had a Stage I tumor (79.0%). On univariable analysis, 5-year disease-specific survival decreased with each increasing tumor mitotic rate category of 0-3, 4-10, and >10 mitoses/mm2 (Stage I 98.3%, 90.9%, 79.7%; Stage II 86.1%, 74.2%, 72.9%; and Stage III 72.5%, 58.6%, 49.7%). In multivariable models, tumor mitotic rate as both a continuous and categorical variable was associated with disease-specific survival for Stages I-III melanoma. Each unit increase in tumor mitotic rate increased the risk of death by 23% in Stage I, 5% in Stage II, and 3% in Stage III. Compared with the 0-3 tumor mitotic rate category, the risk of disease-specific mortality increased for tumors in the 4-10 and >10 categories for Stage I (RR 3.07 and 6.74, P < .0001), Stage II (RR 1.37 and 1.62, P = .0002), and Stage III (RR 1.24 and 1.35, P = .0004). CONCLUSION: In this cohort study, tumor mitotic rate is an independent predictor of survival for localized melanoma.

Current concepts in cutaneous melanoma: malignant melanoma.

Melanoma of the skin is one of the most clinically important skin and soft tissue lesions encountered by the practicing general surgeon. If it is properly diagnosed and treated in its early stages, its prognosis and outcome are uniformly favorable. The current concepts in malignant melanoma are discussed.

Laparoscopic resection of large adrenal tumors.

BACKGROUND: The maximum size of adrenal tumors that should be removed with a laparoscopic approach is controversial. It has been suggested that laparoscopic adrenalectomy is appropriate only for adrenal tumors < 6 cm in size. We report our experience with laparoscopic adrenalectomy in patients with adrenal tumors of > or =6 cm compared with patients with smaller tumors. METHODS: We retrospectively reviewed a consecutive series of patients who had a laparoscopic adrenalectomy. Patients were considered candidates for laparoscopic adrenalectomy if their computed tomography (CT) scan showed a well-encapsulated tumor confined to the adrenal gland. RESULTS: Sixty laparoscopic adrenalectomies were performed in 53 patients. Twelve of the adrenalectomies (20%) were for tumors that were > or =6 cm (median, 8 cm; range, 6 to 12 cm). There have been no local or regional recurrences, but one patient with adrenocortical carcinoma developed pulmonary metastases. When the 12 patients with large tumors were compared with the 36 patients with tumors < 6 cm, the median operative time (190 vs. 180 minutes; P =.32), operative blood loss (100 vs. 50 mL; P =.53), and postoperative hospital stay (2 vs. 2 days; P = 1.0) were similar. CONCLUSIONS: The size of an adrenal tumor should not be the primary factor in determining whether a laparoscopic adrenalectomy should be performed. Large adrenal tumors that are confined to the adrenal gland on CT can be removed with a laparoscopic approach.