The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis.

BACKGROUND: Immunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated. METHODS: For this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS). RESULTS: Of the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021). CONCLUSION: The study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC.

Incidence of clinically relevant postoperative pancreatic fistula in patients undergoing open and minimally invasive pancreatoduodenectomy: a population-based study.

Purpose: Postoperative pancreatic fistula (POPF) remains a devastating complication of pancreatoduodenectomy (PD). Minimally invasive PD (MIPD), including laparoscopic (LPD) and robotic (RPD) approaches, have comparable POPF rates to open PD (OPD). However, we hypothesize that the likelihood of having a more severe POPF, as defined as clinically relevant POPF (CR-POPF), would be higher in an MIPD relative to OPD. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted pancreatectomy dataset (2014-2020) was reviewed for any POPF after OPD. Propensity score matching (PSM) compared MIPD to OPD, and then RPD to LPD. Results: Among 3,083 patients who developed a POPF, 2,843 (92.2%) underwent OPD and 240 (7.8%) MIPD; of these, 25.0% were LPD (n = 60) and 75.0% RPD (n = 180). Grade B POPF was observed in 45.4% (n = 1,400), and grade C in 6.0% (n = 185). After PSM, MIPD patients had higher rates of CR-POPF (47.3% OPD vs. 54.4% MIPD, p = 0.037), as well as higher reoperation (9.1% vs. 15.3%, p = 0.006), delayed gastric emptying (29.2% vs. 35.8%, p = 0.041), and readmission rates (28.2% vs. 35.1%, p = 0.032). However, CR-POPF rates were comparable between LPD and RPD (56.8% vs. 49.3%, p = 0.408). Conclusion: The impact of POPF is more clinically pronounced after MIPD than OPD with a more complex postoperative course. The difference appears to be attributed to the minimally invasive environment itself as no difference was noted between LPD and RPD. A clear biological explanation of this clinical observation remains missing. Further studies are warranted.

Role of minimally invasive surgery in the management of localized pancreatic ductal adenocarcinoma: a review.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with a minority of patients eligible for curative-intent surgical intervention. Pancreatic resections are technically demanding operations associated with considerable morbidity and mortality. Minimally invasive pancreatic resections (MIPRs), which include laparoscopic and robotic approaches, may enhance postoperative outcomes by lessening physiological impact of open surgery. A limited number of randomized-controlled trials as well as numerous retrospective reports have focused on MIPR outcomes and role in management of a variety of tumors, including PDAC. Today, MIPRs are generally considered acceptable alternatives to open surgery as a trend towards improved short-term metrics is observed. However, several questions remain regarding the oncological adequacy of MIPR's as long-term experience is less extensive compared to open techniques. This review aims to summarize existing evidence on MIPRs with a focus on PDAC.

Neoadjuvant Chemotherapy for Intrahepatic, Perihilar, and Distal Cholangiocarcinoma: a National Population-Based Comparative Cohort Study.

INTRODUCTION: Data supporting the utilization of neoadjuvant chemotherapy (NAC) in patients receiving resection for cholangiocarcinoma (CCA) remains uncertain. We aimed to determine whether NAC followed by resection improves long-term survival in intrahepatic (iCCA), perihilar (hCCA), and distal (dCCA) cholangiocarcinoma, analyzed separately. METHODS: Patients undergoing surgery for iCCA, hCCA, and dCCA, receiving either none, NAC, or adjuvant chemotherapy (AC) from 2010 to 2016 were identified from the National Cancer Database (NCDB). Cox regression was performed to account for selection bias and to assess the impact of surgery alone (SA) versus either NAC or AC on overall survival (OS). RESULTS: There were 9411 patients undergoing surgery for iCCA (n = 3772, 39.5%), hCCA (n = 1879, 20%), and dCCA (n = 3760, 40%). Of these, 10.6% (n = 399), 6.5% (n = 123), and 7.2% (n = 271) with iCCA, hCCA, and dCCA received NAC, respectively. On adjusted analyses, patients receiving NAC followed by surgery had significantly improved OS, compared to SA for iCCA (HR 0.75, CI95% 0.64-0.88, p < 0.001), hCCA (HR 0.72, CI95% 0.54-0.97, p = 0.033), and for dCCA (HR 0.65, CI95% 0.53-0.78, p < 0.001). However, sensitivity analyses demonstrated no differences in OS between NACs, followed by surgery or AC after surgery in iCCA (HR 1.19, CI95% 0.99-1.45, p = 0.068), hCCA (HR 0.83 CI95% 0.59-1.19, p = 0.311), and dCCA (HR 1.13 CI95% 0.91-1.41, p = 0.264). CONCLUSIONS: This study associated NAC with increased OS for all CCA subtypes, even in patients with margin-negative and node-negative disease; however, no differences were found between NAC and AC. Our results highlight that a careful and interdisciplinary evaluation should be sought to consider NAC in CCA and warrant the need of larger studies to provide robust recommendation.

Effect of Operative Time on Outcomes of Minimally Invasive Versus Open Pancreatoduodenectomy.

OBJECTIVE: To evaluate how operative time interacts with outcomes among different approaches to pancreaticoduodenectomy (PD). Minimally invasive PDs (MIPD), which include laparoscopic (LPD) and robotic (RPD) approaches, are increasingly performed in the USA. MIPD are generally associated with longer operative times (OT) compared to open PD (OPD). Increased OT is associated with inferior outcomes for OPD; however, the effect of OT on MIPD is not well understood. METHODS: National Surgical Quality Improvement Program (NSQIP)-targeted pancreatectomy dataset was utilized (2014-2019). Propensity score matching, logistic regression, and mixed effect modeling were performed to determine the effect of OT on outcomes following PD. OTs were stratified by quartiles for each approach, and outcomes were subsequently compared. RESULTS: Among 23,988 PDs, 22,185 were OPD and 1803 MIPD. Increased OT was associated with greater overall morbidity in all approaches. When comparing OT quartiles, MIPD was consistently associated with improved overall morbidity compared to OPD in matched cohorts. However, for upper quartiles, prolonged OT in MIPD was associated with significantly increased reoperation rates and mortality. The effect of OT on overall morbidity and other outcomes was comparable among LPD and RPD. CONCLUSIONS: In this study, increased OT was associated with incremental increases in overall morbidity after PD, irrespective of approach. While MIPD was associated with improved overall morbidity compared to OPD when stratified by OT quartile, higher mortality rates were observed with prolonged OT only with MIPD. Those data suggest that MIPD is a safe alternative to OPD when OT is optimized. NSQIP was used to compare the effect of operative time (OT) on outcomes following pancreaticoduodenectomy (PD), stratified by approach. Increased OT was associated with inferior outcomes following open, laparoscopic, and robotic PD. Surgeons should attempt to optimize OT, regardless of the approach to PD.

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.

Survival benefit of adjuvant chemotherapy following neoadjuvant therapy and oesophagectomy in oesophageal adenocarcinoma.

BACKGROUND: The evidence assessing the additional benefits of adjuvant chemotherapy (AC) following neoadjuvant therapy (NAT; i.e. chemotherapy or chemoradiotherapy) and oesophagectomy for oesophageal adenocarcinoma (EAC) are limited. This study aimed to determine whether AC improves long-term survival in patients receiving NAT and oesophagectomy. METHODS: Patients receiving oesophagectomy for EAC following NAT from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). To account for immortality bias, patients with survival ≤3 months were excluded to account for immortality bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival. RESULTS: Overall, 12,972 (91%) did not receive AC and 1,255 (9%) received AC. After PSM there were 2,485 who did not receive AC and 1,254 who did. After matching, AC was associated with improved survival (median: 38.5 vs 32.3 months, p < 0.001), which remained after multivariable adjustment (HR: 0.78, CI95%: 0.71-0.87). On multivariable interaction analyses, this benefit persisted in subgroup analysis for nodal status: N0 (HR: 0.85, CI95%: 0.69-0.96), N1 (HR: 0.66, CI95%: 0.56-0.78), N2/3 (HR: 0.80, CI95%: 0.66-0.97) and margin status: R0 (HR: 0.77, CI95%: 0.69-0.86), R1 (HR: 0.60, CI95%: 0.43-0.85). Further, patients with stable disease following NAT (HR: 0.60, CI95%: 0.59-0.80) or downstaged (HR: 0.80, CI95%: 0.68-0.95) disease had significant survival benefit after AC, but not patients with upstaged disease. CONCLUSION: AC following NAT and oesophagectomy is associated with improved survival, even in node-negative and margin-negative disease. NAT response may be crucial in identifying patients who will benefit maximally from AC, and thus future research should be focused on identifying molecular phenotype of tumours that respond to chemotherapy to improve outcomes.

Potential evidence of peritoneal recurrence in Stage-II colon cancer from the control arm of CALGB9581.

BACKGROUND: Relapse of early-stage colon cancer (CC) after curative-intent resection occurs. We hypothesized that known risk factors for peritoneal metastases (PM) can define a high-risk state (HRS) that predicts recurrence and mortality. METHODS: CALGB9581 trial patients receiving no adjuvant treatment after stage-II CC resection were included. Positive radial margins, T4 invasion, obstruction/perforation or lymphovascular invasion defined the HRS. Cox proportional hazard models determined association with overall (OS) and disease-free survival (DFS). RESULTS: Median follow-up in 873 included patients was 8.1 years. Five-year OS was 85.8%. HRS+ patients had lower 5-year DFS (68.7 vs. 82.4%, P = 0.003) and OS (75.5 vs. 87.8%, P = 0.001). HRS+ was independently predictive of worse DFS and OS (HR 1.52 and 1.64, P < 0.01). Among recurrences, HRS+ patients showed shorter median OS (3.3 vs. 5.3 years, P = 0.01). CONCLUSIONS: HRS criteria identify a cohort of CC patients at high-risk of recurrence and death. Studies of novel surveillance techniques in such patients are warranted.

Adjuvant radiotherapy improves long-term survival after resection for gallbladder cancer A population-based cohort study.

BACKGROUND: Data supporting routine use of adjuvant radiotherapy (RT) compared to without RT (noRT) for gallbladder cancer (GBC) is unclear. This study aimed to determine whether RT improves long-term survival following resection for GBC. METHODS: Patients receiving resection for GBC followed by RT from 2004 to 2016 were identified from the National Cancer Database (NCDB). Patients with survival <6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of RT on overall survival. RESULTS: Of 7514 (77%) noRT and 2261 (23%) RT, 2067 noRT and 2067 RT patients remained after PSM. After matching, RT was associated with improved survival (median: 26.2 vs 21.5 months, p < 0.001), which remained after multivariable adjustment (HR: 0.82, CI95%: 0.76-0.89, p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (HR: 0.84, CI95%: 0.77-0.93), N1 (HR: 0.77, CI95%: 0.68-0.88), N2/N3 (HR: 0.56, CI95%: 0.35-0.91), margin status: R0 (HR: 0.85, CI95%: 0.78-0.93), R1 (HR: 0.78, CI95%: 0.68-0.88) and use of adjuvant chemotherapy (AC) (HR: 0.67, CI95%: 0.57-0.79). Benefit with RT were also seen in patients with T2 - T4 disease and in patients undergoing simple and extended cholecystectomy. CONCLUSION: RT following resection was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings may suggest addition of RT into multimodality therapy for GBC.

Adjuvant chemotherapy for perihilar cholangiocarcinoma: A population-based comparative cohort study.

BACKGROUND: Data supporting routine use of adjuvant chemotherapy (AC) compared to no AC (noAC) for perihilar cholangiocarcinoma (hCCA) is unclear. This study aimed to determine whether AC improves long-term survival following resection for hCCA. METHODS: Patients receiving resection for hCCA followed by AC or no AC from 2010 to 2016 were identified from the National Cancer Database (NCDB). Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival. RESULTS: Of 924 (56%) noAC and 719 (44%) AC, 320 noAC and 320 AC patients remained after PSM. After matching, AC was associated with improved survival (median: 28.2 vs 19.9 months, p < 0.001), which remained after multivariable adjustment (HR: 0.61, CI95%: 0.50-0.75, p < 0.001). On multivariable interaction analyses, the benefit of AC over no AC persisted irrespective of nodal status: N0 (HR: 0.62, CI95%: 0.41-0.92, p = 0.019), N1 (HR: 0.52, CI95%: 0.36-0.75, p = 0.001), N2 (HR: 0.31, CI95%: 0.11-0.90, p = 0.032), Nx (HR: 0.22, CI95%: 0.09-0.55, p = 0.001) and margin status: R0 (HR: 0.74, CI95%: 0.57-0.97, p = 0.026), R1 (HR: 0.31, CI95%: 0.21-0.47, p < 0.001). Stratified analysis by nodal, margin and AC status demonstrated consistent results. CONCLUSION: AC following resection for hCCA was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings suggest incorporation of AC into multimodality therapy for hCCA in all cases, where appropriate.

Tissue Diagnosis Is Associated With Worse Survival in Hepatocellular Carcinoma: A National Cancer Database Analysis.

BACKGROUND: Biopsy to achieve tissue diagnosis (TD) of hepatocellular carcinoma (HCC) risks needle tract seeding. With chest wall and peritoneal recurrences reported, TD could worsen cancer outcomes. We investigated HCC outcomes after TD compared to clinical diagnosis (CD), hypothesizing that TD adversely affects overall survival (OS). METHODS: The National Cancer Database (NCDB) Participant User File for liver cancer was reviewed, including patients with nonmetastatic HCC treated with major hepatectomy or transplantation. Clinical diagnosis patients were matched 1:1 to TD patients per propensity score. Survival was examined in the unmatched and matched cohorts. RESULTS: Of 172 283 cases, 16 366 met inclusion criteria. Mean age was 60.8 years, 12 100 (73.9%) were male, and 48.4% of patients received hepatectomies. Clinical diagnosis occurred in 70.4% of cases, and 29.6% underwent TD. Cox regression confirmed the diagnostic method as an independent predictor of OS in addition to age, Charlson-Deyo score, grade, delay of surgery, lymphovascular invasion, nodal stage, and procedure type, favoring transplantation over hepatectomy. After propensity matching on these factors, 4251 patients were matched from each group. In the matched cohort, patients with TD had a significantly lower OS than patients with CD (median: 65.5 vs. 85.6 ± 2.7 months, P < .001). The corresponding 5-year survival was lower in the TD group (47.6% vs. 60.9% P < .001). CONCLUSION: Hepatocellular carcinoma patients with preoperative TD had decreased OS compared to CD, which persisted after propensity matching. This study supports avoiding biopsy for HCC whenever possible.

Neoadjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma is Associated with Lower Post-Pancreatectomy Readmission Rates: A Population-Based Cohort Study.

INTRODUCTION: Despite neoadjuvant chemotherapy (NAC) being increasingly utilized and possibly associated with improved oncological outcomes, the impact of NAC on textbook outcomes following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) remains debated. METHODS: A retrospective review of the National Cancer Database of patients undergoing resection of non-metastatic PDAC from 2004 to 2016 was performed. Propensity score matching was used to account for treatment selection bias in patients with and without NAC (noNAC). A multivariable binary logistic regression model was used to analyze the association of NAC with length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. RESULTS: Of 7975 (11%) NAC patients and 65,338 (89%) noNAC patients, 2911 NAC and 2911 noNAC patients remained in the cohort after matching. Clinicopathologic and demographic variables were well-balanced after matching. After matching, NAC was associated with significantly lower rates of 30-day readmission (5.5% vs. 7.4%; p = 0.006), which remained after multivariable adjustment (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.60-0.92; p = 0.006). There were no significant differences in LOS and 30- and 90-day mortality in patients receiving NAC and noNAC. Stratified analyses by surgery type (i.e. pancreaticoduodenectomy [PD] and distal pancreatectomy [DP]) demonstrated consistent results. CONCLUSION: Receipt of NAC in PDAC patients undergoing DP or PD is associated with lower readmission rates and does not otherwise compromise short-term outcomes. These data reaffirm the safety of strategies incorporating NAC and is important to consider when devising policies aimed at quality improvement in achieving textbook outcomes.

Local Endoscopic Resection is Inferior to Gastrectomy for Early Clinical Stage T1a and T1b Gastric Adenocarcinoma: A Propensity-Matched Study.

BACKGROUND: The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of ER versus gastrectomy in node-negative cT1a and cT1b gastric adenocarcinoma. METHODS: Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2927; ER: n = 1157, gastrectomy: n = 1770) and T1bN0 (n = 2915; ER: n = 474, gastrectomy: n = 2441) gastric adenocarcinoma. Propensity score matching and Cox multivariable analyses were used to account for treatment selection bias. RESULTS: ER for cT1a and cT1b cancers was performed more frequently over time. The rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared with ER for cT1a cancers (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95; p = 0.013), and corresponding 5-year survival for gastrectomy and ER was 72% and 66%, respectively (p = 0.013). For cT1b cancers, gastrectomy had a significantly longer survival compared with ER (HR 0.77, 95% CI 0.63-0.93; p = 0.008), and the corresponding 5-year survival for gastrectomy and ER was 60% and 50%, respectively (p = 0.013). CONCLUSION: This study demonstrates ER is inferior in terms of long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis, and would thus maximally benefit from ER.

Impact of Neoadjuvant Systemic Therapy on Pancreatic Fistula Rates Following Pancreatectomy: a Population-Based Propensity-Matched Analysis.

INTRODUCTION: Postoperative pancreatic fistula (POPF) drives morbidity and mortality following pancreatectomy. Use of neoadjuvant chemotherapy (NAC) has recently increased in the treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC). This study examined the effect of NAC on POPF rates and postoperative outcomes in PDAC. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) Targeted Pancreatectomy dataset was queried to identify PDAC patients who underwent curative-intent pancreatectomies. Propensity score matching was used to stratify patients by receipt of NAC. Postoperative outcomes were compared and logistic regression applied to identify POPF predictors. RESULTS: Six thousand eight hundred sixty-three patients met the inclusion criteria; of those, 1908 (27.8%) received NAC and 4955 (72.2%) did not (NNAC). Two thousand sixty-two patients were matched 1:1 from each group. NAC patients had significantly lower POPF rates (9.0% vs. 14.5%; P < 0.001); the majority were categorized as grade A (5.1% vs. 9.5%). Overall 30-day morbidity was lower with NAC (40.4% vs. 49.5%; P < 0.001). Specifically, pneumonia (2.3% vs. 4.1%), organ space infections (7.9% vs. 13.2%), sepsis (5.2% vs. 8.0%), and delayed gastric emptying (10.1% vs. 14.8%) occurred less frequently in the NAC group. Postoperative mortality and unplanned reoperations were similar. On multivariate analysis, receipt of NAC was an independent predictor of decreased POPF rates (HR, 0.73 [0.56-0.94]; P = 0.016). Other factors included gland texture, duct size, male gender, and lower BMI. CONCLUSIONS: In this propensity-matched, population-based cohort study of PDAC patients, NAC was associated with lower POPF rates and overall major complications. Those findings suggest a modest protective effect of NAC from POPF.

Preoperative calcitriol reduces postoperative intravenous calcium requirements and length of stay in parathyroidectomy for renal-origin hyperparathyroidism.

BACKGROUND: Patients undergoing subtotal parathyroidectomy for renal-origin hyperparathyroidism often develop postoperative hypocalcemia, requiring calcitriol and intravenous calcium (Postop-IVCa). We hypothesized that in subtotal parathyroidectomy for renal-origin hyperparathyroidism, preoperative calcitriol treatment reduces the use of postoperative administration of intravenous calcium. METHODS: A retrospective chart review compared subtotal parathyroidectomy for renal-origin hyperparathyroidism patients who received preoperative calcitriol treatment with those patietns who did not receive preoperative calcitriol treatment at one institution. Preoperative calcitriol treatment loading doses were 0.5 mcg twice daily for 5 days. All patients received postoperative calcitriol and oral calcium carbonate. Postoperative administration of intravenous calcium was given for symptoms, calcium <7.0 mg/dL, or surgeon preference. The Fisher exact test was used to compare proportions. The Wilcoxon test was used to compare continuous data. Multivariable logistic regression adjusted for confounders. RESULTS: Included were 81 patients who received subtotal parathyroidectomy for renal-origin hyperparathyroidism (41 patients who received preoperative calcitriol treatment, 40 patients who did not receive preoperative calcitriol treatment). Preoperative calcitriol treatment use increased over time (0% 2004-2010, 69% 2011-2016). Groups who received preoperative calcitriol treatment and groups who did not receive preoperative calcitriol treatment were similar in preoperative serum calcium, vitamin D, parathyroid hormone, and median age (P > .05 for all). Patients who received preoperative calcitriol treatment less often required postoperative administration of intravenous calcium (34% vs 90% of patients who did not receive preoperative calcitriol treatment, P < .001). Median length of stay was 2.0 days shorter for patients who received preoperative calcitriol treatment versus patients who did not receive preoperative calcitriol treatment patients (P < .001). Factors associated with postoperative administration of intravenous calcium included not receiving preoperative calcitriol treatment, low preoperative calcium, and high preoperative parathyroid hormone. After multivariable adjustment, preoperative calcitriol treatment remained independently associated with reduced postoperative administration of intravenous calcium (OR 0.02, P < .001). CONCLUSION: Preoperative calcitriol therapy lowered use of postoperative administration of intravenous calcium by 56% and length of stay by 50% in subtotal parathyroidectomy for renal-origin hyperparathyroidism patients. We believe preoperative calcitriol treatment should become standard of care for subtotal parathyroidectomy for renal-origin hyperparathyroidism.

Cost-effectiveness of Maintenance Capecitabine and Bevacizumab for Metastatic Colorectal Cancer.

Importance: Unregulated drug prices increase cancer therapy costs. After induction chemotherapy, patients with metastatic colon cancer can receive maintenance capecitabine and bevacizumab therapy based on improved progression-free survival, but whether this treatment's cost justifies its benefits has not been evaluated in the United States. Objective: This study sought to determine the influence of capecitabine and bevacizumab drug prices on cost-effectiveness from a Medicare payer's perspective. Design, Setting, and Participants: The incremental cost-effectiveness of capecitabine and bevacizumab maintenance therapy was determined with a Markov model using a quality-of-life penalty based on outcomes data from the CAIRO phase 3 randomized clinical trial (RCT), which included 558 adults in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. The outcomes were modeled using Markov chains to account for patients who had treatment complications or cancer progression. Transition probabilities between patient states were determined, and each state's costs were determined using US Medicare data on payments for capecitabine and bevacizumab treatment. Deterministic and probabilistic sensitivity analyses identified factors affecting cost-effectiveness. Main Outcomes and Measures: Life-years gained were adjusted using CAIRO3 RCT quality-of-life data to determine quality-adjusted life-years (QALYs). The primary end point was the incremental cost-effectiveness ratio, representing incremental costs per QALY gained using a capecitabine and bevacizumab maintenance regimen compared with observation alone. Results: Markov model estimated survival and complication outcomes closely matched those reported in the CAIRO3 RCT, which included 558 adults (n = 197 women, n = 361 men; median age, 64 and 63 years for patients in the observation and maintenance therapy groups, respectively) in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. Incremental costs for a 3-week maintenance chemotherapy cycle were $6601 per patient. After 29 model iterations corresponding to 60 months of follow-up, mean per-patient costs were $105 239 for maintenance therapy and $21.10 for observation. Mean QALYs accrued were 1.34 for maintenance therapy and 1.20 for observation. The incremental cost-effectiveness ratio favored maintenance treatment, at an incremental cost of $725 601 per QALY. The unadjusted ratio was $438 394 per life-year. Sensitivity analyses revealed that cost-effectiveness varied with changes in drug costs. To achieve an incremental cost-effectiveness ratio of less than $59 039 (median US household income) per unadjusted life-year would require capecitabine and bevacizumab drug costs to be reduced from $6173 (current cost) to $452 per 3-week chemotherapy cycle. Conclusions and Relevance: Antineoplastic therapy is expensive for payers and society. The price of capecitabine and bevacizumab maintenance therapy would need to be reduced by 93% to make it cost-effective, a finding useful for policy decision making and payment negotiations.

Obstruction predicts worse long-term outcomes in stage III colon cancer: A secondary analysis of the N0147 trial.

BACKGROUND: Patients with colon cancer often present with obstruction. Large series have reported obstruction among the high-risk features, yet prospective data on its specific prognostic influence are lacking. We hypothesized that obstruction is an independent risk factor for poor prognosis in patients with stage III colon cancer. METHODS: N0147 was a trial conducted between 2004 and 2009 that randomly assigned patients with stage III colon cancer to adjuvant regimens of folinic acid (leucovorin calcium), fluorouracil, and oxaliplatin or fluorouracil, leucovorin, and irinotecan, with or without cetuximab. Patient-level data from the control chemotherapy-only arms were obtained. Patient, tumor, and treatment characteristics were abstracted. Disease-free survival and overall survival were estimated by the Kaplan-Meier method. Proportions were compared by χ2 and Fisher exact tests. Univariable and multivariable survival analyses were performed using Cox proportional hazards models. RESULTS: Of 1,543 patients with stage III colon cancer, 250 (16.2%) presented with obstruction. Patients with obstruction were equally likely to complete 12 cycles of adjuvant chemotherapy (75.9% vs 77.1%, P = .6). With median follow-up time of 30.9 months among survivors, five-year overall survival and disease-free survival were worse among patients with obstruction (overall survival 67.7% vs 78.0%, P < .001; disease-free survival 53.9% vs 67.0%, P < .0001). On multivariable analysis, obstruction remained significantly associated with worse survival after adjusting for T stage, N stage, performance status, age, sex, histologic grade, and body mass index (overall survival hazard ratio 1.57, 95% confidence interval 1.12-2.20, P = .001; disease-free survival 1.52, 95% confidence interval 1.18-1.95, P < .001). CONCLUSION: In this prospectively followed cohort of patients with stage III colon cancer treated with adjuvant chemotherapy, obstruction was associated with recurrence and worse survival. Moreover, this effect was independent of T and N stage and histologic grade. These results suggest that obstruction should be incorporated into novel risk-stratification models.