Opioid-Free Discharge After Pancreatic Resection Through a Learning Health System Paradigm.

Importance: Postoperative opioid overprescribing leads to persistent opioid use and excess pills at risk for misuse and diversion. A learning health system paradigm using risk-stratified pancreatectomy clinical pathways (RSPCPs) may lead to reduction in inpatient and discharge opioid volume. Objective: To analyze the outcomes of 2 iterative RSPCP updates on inpatient and discharge opioid volumes. Design, Setting, and Participants: This cohort study included 832 consecutive adult patients at an urban comprehensive cancer center who underwent pancreatic resection between October 2016 and April 2022, comprising 3 sequential pathway cohorts (version [V] 1, October 1, 2016, to January 31, 2019 [n = 363]; V2, February 1, 2019, to October 31, 2020 [n = 229]; V3, November 1, 2020, to April 30, 2022 [n = 240]). Exposures: After V1 of the pathway established a baseline and reduced length of stay (n = 363), V2 (n = 229) updated patient and surgeon education handouts, limited intravenous opioids, suggested a 3-drug (acetaminophen, celecoxib, methocarbamol) nonopioid bundle, and implemented the 5×-multiplier (last 24-hour oral morphine equivalents [OME] multiplied by 5) to calculate discharge volume. Pathway version 3 (n = 240) required the nonopioid bundle as default in the recovery room and scheduled conversion to oral medications on postoperative day 1. Main Outcomes and Measures: Inpatient and discharge opioid volume in OME across the 3 RSPCPs were compared using nonparametric testing and trend analyses. Results: A total of 832 consecutive patients (median [IQR] age, 65 [56-72] years; 410 female [49.3%] and 422 male [50.7%]) underwent 541 pancreatoduodenectomies, 285 distal pancreatectomies, and 6 other pancreatectomies. Early nonopioid bundle administration increased from V1 (acetaminophen, 320 patients [88.2%]; celecoxib or anti-inflammatory, 98 patients [27.0%]; methocarbamol, 267 patients [73.6%]) to V3 (236 patients [98.3%], 163 patients [67.9%], and 238 patients [99.2%], respectively; P < .001). Total inpatient OME decreased from a median 290 mg (IQR, 157-468 mg) in V1 to 184 mg (IQR, 103-311 mg) in V2 to 129 mg (IQR, 75-206 mg) in V3 (P < .001). Discharge OME decreased from a median 150 mg (IQR, 100-225 mg) in V1 to 25 mg (IQR, 0-100 mg) in V2 to 0 mg (IQR, 0-50 mg) in V3 (P < .001). The percentage of patients discharged opioid free increased from 7.2% (26 of 363) in V1 to 52.5% (126 of 240) in V3 (P < .001), with 187 of 240 (77.9%) in V3 discharged with 50 mg OME or less. Median pain scores remained 3 or lower in all cohorts, with no differences in postdischarge refill requests. A subgroup analysis separating open and minimally invasive surgical cases showed similar results in both groups. Conclusions and Relevance: In this cohort study, the median total inpatient OME was halved and median discharge OME reduced to zero in association with a learning health system model of iterative opioid reduction that is freely adaptable by other hospitals. These findings suggest that opioid-free discharge after pancreatectomy and other major cancer operations is realistic and feasible with this no-cost blueprint.

Educating surgical oncology providers on perioperative opioid use: A departmental survey 1 year after the intervention.

BACKGROUND AND OBJECTIVES: A department-wide opioid reduction education program resulted in a 1-month change in perceptions of opioid needs and prescribing recommendations for surgical oncology patients. This study's aim was to re-evaluate if early trends were retained 1 year later. METHODS: Surgical Oncology attendings, fellows, and advanced practice providers at a Comprehensive Cancer Center were surveyed 1-year after an August 2018 opioid reduction education program, to compare departmental and individual opioid prescribing habits. RESULTS: The September 2019 response rate was 54/93 (58%), with 41 completing both the post-education and 1-year follow-up surveys. The departmental and matched cohort continued to recommend a lower quantity of discharge opioids for all five index operations (by >50%) and expected less postoperative days to zero opioid needs, when compared to pre-education perceptions. Providers continued to agree that discharge opioid prescriptions should be based on a patient's last 24 hours of inpatient opioid use. There was universal agreement that each respondent's opioid administration had decreased in the past year. CONCLUSIONS: The initial 1-month improvements in perioperative opioid prescribing perceptions were retained 1 year later by Surgical Oncology providers who recommended fewer discharge opioids, faster weaning to zero opioids, and standardized patient-specific discharge opioid volume calculations.

Risks of Hypoparathyroidism After Total Thyroidectomy in Children: A 21-Year Experience in a High-Volume Cancer Center.

BACKGROUND: Hypoparathyroidism occurs relatively frequently after thyroid surgery in children. However, few studies have reported risk factors. We aimed to identify risk factors for hypoparathyroidism that occurred after total thyroidectomy for proven or suspected malignancy in children. METHODS: Children (aged ≤ 18 years) who underwent total thyroidectomy for neoplasm or RET germline mutation at our institution between 1997 and 2018 were included. We retrospectively reviewed demographics, surgical indications, perioperative and follow-up laboratory results, pathologic results, and duration of calcium/calcitriol supplementation. Risk factors for hypoparathyroidism were identified by multivariate analysis. RESULTS: Of 184 consecutive patients, 111 had undergone surgery for neoplasm; these diseases were primarily malignancies (106, 95.5%), predominantly papillary carcinoma (103, 92.8%). The remaining 73 patients had undergone early thyroidectomy for RET germline mutation. Among all patients, 67 (36.4%) had hypoparathyroidism: 61 transient and 6 permanent. In a multivariate analysis, central neck dissection (odds ratio 4.3, 95% confidence interval 2.0-9.1) and gross extrathyroidal extension (odds ratio 4.9, 95% confidence interval 2.0-12.1) predicted overall hypoparathyroidism; however, no significant factors were associated with permanent hypoparathyroidism. Most patients with permanent hypoparathyroidism (5 of 6) had undergone therapeutic central neck dissection. When central neck dissection was performed, younger children had a higher risk of overall hypoparathyroidism. CONCLUSIONS: In pediatric total thyroidectomies, central neck dissection and gross extrathyroidal extension were major predictors for overall hypoparathyroidism. Surgeons performing thyroidectomy in such patients should be aware of the relatively high risk, preserve parathyroid tissue to the extent possible, and be conscientious regarding postoperative calcium monitoring and replacement.

Home-Based Exercise Prehabilitation During Preoperative Treatment for Pancreatic Cancer Is Associated With Improvement in Physical Function and Quality of Life.

Purpose: To investigate relationships among physical activity, changes in physical function, and health-related quality of life (HRQOL) among patients with pancreatic adenocarcinoma enrolled in a home-based exercise prehabilitation program. Methods: Patients with resectable pancreatic adenocarcinoma receiving preoperative chemotherapy and/or chemoradiation were enrolled on this prospective, single-arm trial and were advised to perform ≥60 minutes each of moderate-intensity aerobic exercise and strengthening exercise weekly. Activity was measured via self-report and accelerometers, including moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and sedentary activity (SA). Physical function measures at baseline and restaging follow-up included 6-minute walk test (6MWT), 5 times sit-to-stand (5×STS), handgrip strength (HGS), 3-m walk for gait speed (GS), and the PROMIS Physical Function Short Form. HRQOL was measured via the FACT-Hep questionnaire. Results: Fifty participants with mean age 66 years (standard deviation = 8 years) were enrolled. The 6MWT, 5×STS, and GS significantly improved from baseline to restaging follow-up (P=.001, P=.049, and P=.009, respectively). Increases in self-reported aerobic exercise, weekly MVPA, and LPA were associated with improvement in 6MWT (ß=.19, P=.048; ß=.18, P=.03; and ß=.08, P=.03, respectively) and self-reported physical functioning (ß=.02, P=.03; ß=.03, P=.005; and ß=.01, P=.02, respectively). Increased weekly LPA was associated with increased HRQOL (ß=.03, P=.02). Increased SA was associated with decreased HRQOL (ß=-.02,P=.01). Conclusions: Patients with potentially resectable pancreatic cancer exhibit meaningful improvement in physical function with prehabilitation; physical activity was associated with improved physical function and HRQOL. These data highlight the importance of physical activity during treatment for pancreatic cancer.

Preoperative Fluorouracil, Doxorubicin, and Streptozocin for the Treatment of Pancreatic Neuroendocrine Liver Metastases.

INTRODUCTION: While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors. METHODS: All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not. RESULTS: Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival [overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0-136.0) vs. 107.0 months (95% CI 78.0-136.0), p = 0.64] and recurrence-free survival [RFS, 25.1 months (95% CI 23.2-27.0) vs. 18.0 months (95% CI 13.8-22.2), p = 0.16] as patients who did not. Among patients who presented with synchronous liver metastases (n = 46), the median OS [97.3 months (95% CI 65.9-128.6) vs. 65.0 months (95% CI 28.1-101.9), p = 0.001] and RFS [24.8 months (95% CI 22.6-26.9) vs. 12.1 months (2.2-22.0), p = 0.003] were significantly greater among patients who received preoperative FAS compared with those who did not. CONCLUSIONS: The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.

State of the Science: Cancer Complementary and Alternative Medicine Therapeutics Research-NCI Strategic Workshop Highlights of Discussion Report.

In May 2016, the Office of Cancer Complementary and Alternative Medicine, Division of Cancer Diagnosis and Treatment, of the National Cancer Institute convened a special workshop focused on the State of the Science: Cancer Complementary and Alternative Medicine Therapeutics Research. The current state of the science, gaps, and future opportunities were reviewed and discussed by a distinguished panel of experts in this field of research, and the highlights of this meeting are reported herein.

Total Laparoscopic Management for Stage IV Colorectal Cancer Requiring Multivisceral Resection.

BACKGROUND: Surgical resection of all sites of disease, in combination with effective systemic chemotherapy, offers the only potential chance for cure for patients with stage IV colorectal cancer (CRC). Coordinated multistage resection using a minimally invasive approach may provide optimal oncologic outcome while potentially offering the benefit of decreased morbidity. PATIENT: A 66-year-old women presented with transverse colon cancer and synchronous metastasis (CRLM) in segment IV involving the middle hepatic vein and main left portal pedicle, as well as the left adrenal gland. Due to favorable response to neoadjuvant chemotherapy (FOLFOX/bevacizumab), the patient was considered for resection but developed some obstructive symptoms from the primary tumor, necessitating re-coordination of treatment sequencing from the 'liver-first' approach. METHODS: The first procedure combined laparoscopic subtotal colectomy (extracorporeal anastomosis) with left adrenalectomy. After restaging, CRLM was removed separately 2 months later via laparoscopic left hepatectomy extending beyond the middle hepatic vein. Successful completion of the two procedures depended on optimal patient/port positioning for the combined colon/adrenal surgery and the second-stage liver resection. Postoperative lengths of stay were 4 and 3 days, respectively, and were without complication. Adjuvant FOLFOX was initiated 21 days following liver surgery, and the patient has been disease-free for 36 months. CONCLUSION: This case illustrates the feasibility of the total laparoscopic approach to multivisceral resection for synchronous stage IV CRC in the context of a preplanned, staged multidisciplinary strategy. This approach may offer optimal cancer management, including early return to systemic therapy, shortened time intervals between stages, and minimal postoperative morbidity.1 - 3.

Prognostic Scoring System to Risk Stratify Parathyroid Carcinoma.

BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that lacks an established system for risk categorization. This study evaluated a prognostic scoring system for recurrence-free survival (RFS) of patients with parathyroid carcinoma. STUDY DESIGN: Patients diagnosed and confirmed to have parathyroid carcinoma and who were treated between 1980 and 2016 at The University of Texas MD Anderson Cancer Center were studied retrospectively. Univariate and multivariate Cox proportional hazards regression analyses of RFS were conducted. A prognostic scoring system was created based on multivariate analysis. RESULTS: Sixty-eight patients were evaluated. After a median follow-up of 4.6 years, 26 patients experienced a recurrence. The Kaplan-Meier RFS rates were 85% at 1 year (95% CI 77% to 95%), 67% at 2 years (95% CI 55% to 81%), and 51% at 10 years (95% CI 36% to 72%) after initial operation. Multivariate analysis demonstrated that age older than 65 years, serum calcium level >15 mg/dL, and vascular invasion were negatively correlated with RFS rate. Combining these adverse variables into a prognostic scoring system, we stratified patients into 3 risk groups: low (0 variable; 2-year RFS rate, 93%), moderate (1 variable; 2-year RFS rate, 72%), and high (2 variables; 2-year RFS rate, 27%) (p = 0.001 [log-rank test]; concordance index, 0.70; 95% CI 0.47 to 0.92). CONCLUSIONS: A prognostic scoring system using vascular invasion, age, and serum calcium level at initial parathyroidectomy can be used to predict RFS. This categorization might be helpful for clinical decisions relative to the timing and use of adjuvant therapy. Comprehensive validation using multiple cohorts will be needed to confirm applicability.

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA-DNA hybrids.

Dietary calorie restriction is a broadly acting intervention that extends the lifespan of various organisms from yeast to mammals. On another front, magnesium (Mg2+) is an essential biological metal critical to fundamental cellular processes and is commonly used as both a dietary supplement and treatment for some clinical conditions. If connections exist between calorie restriction and Mg2+ is unknown. Here, we show that Mg2+, acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA-DNA hybrids, or R-loops. In an R-loop accumulation model of Pbp1-deficient Saccharomyces cerevisiae, magnesium ions guided by cell membrane Mg2+ transporters Alr1/2 act via Mg2+-sensitive R-loop suppressors Rnh1/201 and Pif1 to restore R-loop suppression, ribosomal DNA stability and cellular lifespan. Similarly, human cells deficient in ATXN2, the human ortholog of Pbp1, exhibit nuclear R-loop accumulations repressible by Mg2+ in a process that is dependent on the TRPM7 Mg2+ transporter and the RNaseH1 R-loop suppressor. Thus, we identify Mg2+ as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes.

Correlates of Sun Protection and Sunburn in Children of Melanoma Survivors.

INTRODUCTION: Sunburns during childhood increase melanoma risk. Children of melanoma survivors are at higher risk, but little is known about their sunburn and sun protection. One study showed that almost half of melanoma survivors' children experienced sunburn in the past year. This study evaluated sunburn and sun protection in melanoma survivors' children, and relevant survivor characteristics from Social Cognitive Theory and the Health Belief Model. METHODS: Melanoma survivors (N=340) were recruited from a comprehensive cancer center. Survivors completed a baseline questionnaire administered by telephone to report on the behavior of their children (N=340) as part of an RCT of a sun protection intervention. Data were collected in 2008 and analyzed in 2015. RESULTS: In the prior 6 months, 28% of children experienced sunburn. "Always" or "frequent" sun protection varied by behavior: sunscreen, 69%; lip balm, 15%; wide-brimmed hats, 9%; sleeved shirts, 28%; pants, 48%; sunglasses, 10%; shade, 33%; and limiting time outdoors, 45%. Survivors' sunburn and sun protection were positively associated with these outcomes in children. Correlates of sunburn also included older child age and higher risk perceptions. Correlates of sun protection behaviors included younger child age; stronger intentions, higher self-efficacy, and more positive outcome expectations about sun protection; and greater number of melanomas in survivors. CONCLUSIONS: Melanoma survivors may have a heightened awareness of the importance of their children's sun protection, but their children are not routinely protected. Correlates of children's sunburn and sun protection suggest subgroups of survivors to target with interventions to improve sun protection.

Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer.

BACKGROUND: A well-defined treatment strategy for elderly patients with resectable pancreatic cancer is lacking. Multiple reports have described highly selected older cancer patients who have successfully undergone pancreatectomy. However, multimodality therapy is essential for long-term survival, and elderly patients are at high risk for not receiving adjuvant therapy postoperatively. We sought to describe the treatment patterns and outcomes of a series of elderly patients with pancreatic cancer who were treated with a multimodality strategy that liberally used neoadjuvant therapy. STUDY DESIGN: We retrospectively reviewed treatment plans, short-term outcomes, and overall survival of all patients 70 years old and older, presenting to our institution over a 9-year period, who were treated for potentially resectable or borderline resectable pancreatic cancer. RESULTS: There were 179 (76%) of 236 patients treated with curative intent. Of these patients, 153 (85%) initiated neoadjuvant therapy: 74 (48%) subsequently underwent pancreatectomy and 79 did not due to disease progression (n = 46), insufficient performance status (n = 23), or other reasons (n = 10). Eleven (42%) of 26 patients who underwent surgery first received postoperative therapy. Among patients treated with curative intent, the median overall survival of all patients initiating neoadjuvant therapy (16.6 months [range 2.1 to 142.7 months]) was similar to that of patients undergoing resection primarily (15.1 months [range 5.4 to 100.8 months]), p = 0.53. After pancreatectomy, patients had a 2% in-hospital mortality rate and 91% were discharged home. CONCLUSIONS: Eighty-five percent of all patients 70 years old and older, who underwent pancreatectomy for potentially resectable or borderline resectable pancreatic cancer, received multimodality therapy. More than 90% were discharged home. These data demonstrate a potential role for neoadjuvant therapy in selecting elderly patients for surgery, and support further studies to refine individualized treatment protocols for this high-risk population.

Is surveillance imaging effective for detecting surgically treatable recurrences in patients with melanoma? A comparative analysis of stage-specific surveillance strategies.

OBJECTIVE: To guide resource utilization, we aimed to determine the impact of routine surveillance imaging for the detection of melanoma recurrences amenable to surgical resection with curative intent. BACKGROUND: The National Comprehensive Cancer Network guidelines for melanoma surveillance are largely consensus based. METHODS: Using single-institution, patient-level data (n = 1600), transition probabilities were calculated for a Markov model simulating the natural history of patients with stage I-III melanoma. As a base estimate, imaging was assumed to detect regional and distant recurrences of which 80% and 20% could be surgically treated with curative intent, respectively. Sensitivity analyses were conducted for all point estimates. For each disease stage, we calculated the number of surgically treatable regional or distant recurrence detected during 5 years per 10,000 patients undergoing computed tomography (CT) or positron emission tomography (PET)/CT scans at 6- or 12-month intervals. The associated positive and negative predictive values and life expectancy were also calculated and compared with clinical examination alone. RESULTS: At 5-year follow-up, CT or PET/CT at 6-month intervals detected surgically treatable regional or distant recurrence in 6.4% of patients with stage I, 18.5% of stage II, and 33.1% of stage III disease; 12-month intervals decreased the rates to 3.0%, 7.9%, and 13.0%, respectively. The high false-positive rates of CT (20%) and PET/CT (9%) resulted in overall low positive predictive values. However, both CT and PET/CT effectively predicted absence of disease. Life-expectancy gains were minimal (≤ 2 months) for all groups. CONCLUSIONS: The effectiveness of routine surveillance imaging for detecting treatable melanoma recurrences is limited. Even in patients with stage III disease, only minimal gains in life expectancy were achieved.

Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer.

OBJECTIVES: The purpose of this study was to determine the relationship between carbohydrate antigen (CA) 19-9 levels and outcome in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy (NT). METHODS: This study included all patients with borderline resectable pancreatic cancer, a serum CA 19-9 level of ≥40 U/ml and bilirubin of ≤2 mg/dl, in whom NT was initiated at one institution between 2001 and 2010. The study evaluated the associations between pre- and post-NT CA 19-9, resection and overall survival. RESULTS: Among 141 eligible patients, CA 19-9 declined during NT in 116. Following NT, 84 of 141 (60%) patients underwent resection. For post-NT resection, the positive predictive value of a decline and the negative predictive value of an increase in CA 19-9 were 70% and 88%, respectively. The normalization of CA 19-9 (post-NT <40 U/ml) was associated with longer median overall survival among both non-resected (15 months versus 11 months; P = 0.022) and resected (38 months versus 26 months; P = 0.020) patients. Factors independently associated with shorter overall survival were no resection [hazard ratio (HR) 3.86, P < 0.001] and failure to normalize CA 19-9 (HR 2.13, P = 0.001). CONCLUSIONS: The serum CA 19-9 level represents a dynamic preoperative marker of tumour biology and response to NT, and provides prognostic information in both non-resected and resected patients with borderline resectable pancreatic cancer.

Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival.

Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p < 0.001). The most common reason that NT (11 %) and SF (26 %) patients failed to complete MMT was early disease progression. The rates of PMC among NT and SF patients were similar. Among SF patients, 69 % with no PMC completed MMT versus 29 % after PMC (p = 0.040). PMC were associated with decreased OS in SF patients but not in NT patients. The impact of early cancer progression and PMC upon completion of MMT is reduced by delivery of nonoperative therapies prior to pancreaticoduodenectomy. NT sequencing is a practical treatment strategy, particularly for patients at high biological or perioperative risk.

Predictable criteria for selective, rather than routine, calcium supplementation following thyroidectomy.

OBJECTIVES: To identify patients at risk for symptomatic hypocalcemia and to make recommendations for safe, selective calcium supplementation. DESIGN: Retrospective review of consecutive patients undergoing thyroidectomy. Patients were divided into 2 groups. Group 1 (the "high-risk/calcium-yes" group) included patients who were found to have (1) postoperative symptoms of hypocalcemia (ie, tingling and numbness), (2) any postoperative serum calcium level of less than 7 mg/dL, or (3) a parathyroid hormone level of less than 3 pg/mL on postoperative day 1. Group 2 (the "low-risk/calcium-no" group) included all other patients. Demographic, operative, biochemical, and pathologic data, as well as postoperative calcium supplementation data, were recorded. Trends in serum calcium level and parathyroid hormone level were analyzed during the immediate postoperative period to identify specific factors unique to group 1. PATIENTS: A total of 156 patients who underwent a thyroidectomy. SETTING: Tertiary care center. RESULTS: Of the 156 patients reviewed, 78% were female, 70% had a malignant disease, and the median age at operation was 50 years. Thirty-four patients (22%) were in group 1, and 122 patients (78%) were in group 2. Twenty-nine (19%) patients had a parathyroid hormone level of less than 3 pg/mL within 24 hours after a thyroidectomy. Patients who underwent a central neck dissection (P = .001), had malignant disease (P = .01), or had a documented removal of the parathyroid gland (with or without autotransplantation) at operation (P = .013) were most likely to be classified into group 1. Forty-two percent of patients in group 2 had either a parathyroid hormone level of less than 6 pg/mL or a serum calcium level of less than 8 mg/dL on postoperative day 1, but all patients in group 1 who were symptomatic met these parameters. CONCLUSION: Limiting supplementation to patients with a parathyroid hormone level of less than 6 pg/mL or a serum calcium level of less than 8 mg/dL on postoperative day 1 may eliminate unnecessary calcium/vitamin D intake, phlebotomy, and follow-up assessments in up to 58% of patients undergoing thyroidectomy. Validation is required in a prospective setting.

Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer.

OBJECTIVES: To determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma. METHODS: One hundred ninety-four patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 2004 and 2008 were evaluated. The retroperitoneal dissection was performed directly along the superior mesenteric artery in all cases. A standard histopathologic protocol that measured the "superior mesenteric artery (SMA) margin distance" between cancer cells and the superior mesenteric artery was employed. RESULTS: Seventy-six percent of patients received neoadjuvant chemoradiation. The SMA margin was positive in 4% of patients but an additional 22% of patients with a negative margin had a SMA margin distance of ≤1 mm. Preoperative CT images overestimated the SMA margin distance in 73% of cases. Patients who received chemoradiation had longer SMA margin distances than those who did not. Patients who received chemoradiation and had a SMA margin of >1 mm had the lowest recurrence rates. Administration of neoadjuvant chemoradiation and lower estimated blood loss were independently associated with longer progression-free survival on multivariate analysis. CONCLUSIONS: Preoperative chemoradiation and meticulous dissection of the superior mesenteric artery maximize the distance between cancer cells and the SMA margin and may influence locoregional control.

Survival and quality of life of patients with resected pancreatic adenocarcinoma treated with adjuvant interferon-based chemoradiation: a phase II trial.

PURPOSE: We conducted a phase II trial to assess the survival duration and quality of life of patients who received adjuvant interferon-based chemoradiation for pancreatic adenocarcinoma after pancreaticoduodenectomy. METHODS: Patients with a performance status of 0 or 1 were enrolled to receive interferon-alfa-2b (3 million units MWF), cisplatin (30 mg/m(2), 6 doses) and 5-fluorouracil (5-FU; 175 mg/m(2)/day), concurrent with external-beam radiation (50.4 Gy) and followed by 2 courses of systemic 5-FU. The protocol was modified to include an optional 9 day break in the middle of chemoradiation. Quality of life was assessed by use of validated instruments. RESULTS: Twenty-eight patients were eligible for analysis. The operation of 15 (54%) patients was performed at other institutions. All patients had T3 tumors, 22 (79%) had positive lymph nodes and 4 (14%) had positive (R1) margins. 24 (86%) patients completed therapy. In all, 25 (89%) patients experienced grade 3 toxicity and 3 (11%) patients were hospitalized. The most common grade 3 events were leukopenia (15, 54%) and neutropenia (12, 43%). No grade 4 toxicity occurred. Overall quality of life decreased during chemoradiation but returned to baseline thereafter and was stable throughout surveillance. 19 patients have died; the median follow-up of the 9 survivors is 62 months. The median OS duration of treated patients was 42.3 (95% confidence interval 30.5-54.2) months. CONCLUSIONS: Adjuvant interferon-based chemoradiation can be delivered safely and tolerably-though with substantial reversible toxicity-to patients of good performance status at an experienced cancer center. Therapy may be associated with an improvement in overall survival.

Current status of adjuvant therapy for pancreatic cancer.

In this article, we review the rationale for and outcomes associated with the use of adjuvant and neoadjuvant therapy for resectable and borderline resectable cancer of the pancreatic head and uncinate process. Localized pancreatic cancer is a systemic disease that requires nonoperative therapies to minimize the local and systemic recurrences that almost invariably occur in the absence of such therapy, even following complete surgical resection. A well-defined role exists for the systemic administration of gemcitabine or 5-fluorouracil in the postoperative setting. Although the survival benefit associated with adjuvant chemoradiation has not been as rigorously defined, its use is supported by extensive historic experience; chemoradiation should be considered particularly for patients at high risk for local recurrence. Delivery of chemotherapy and/or chemoradiation prior to surgery has multiple potential advantages, although the superiority of neoadjuvant therapy over standard postoperative therapy has yet to be demonstrated. Neoadjuvant therapy may be particularly beneficial among patients with borderline resectable cancers. Although the existing literature is confusing, and indeed controversial, available evidence suggests that systemic chemotherapy and/or chemoradiation should be offered to all patients with pancreatic cancer who undergo potentially curative resection. Well-designed prospective trials are needed to define the optimal adjuvant or neoadjuvant therapy strategy for these patients.

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

PURPOSE: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer.

PURPOSE: To study the safety of bevacizumab with capecitabine-based chemoradiotherapy. PATIENTS AND METHODS: Patients with inoperable pancreatic adenocarcinoma received bevacizumab 2 weeks before radiotherapy (50.4 Gy treating the primary tumor and gross adenopathy), every 2 weeks during radiotherapy (12 patients each at 2.5, 5.0, 7.5, and 10 mg/kg), and after radiotherapy until disease progression. Capecitabine was administered on days 14 through 52 (650 mg/m2 orally twice daily for the first six patients; 825 mg/m2 for the remaining patients). RESULTS: Significant acute gastrointestinal (43% grade 2; 4% grade 3), hand and foot syndrome (21% grade 2), and transient hematologic (8% grade 3 or greater) events were uncommon with protocol mandated dose reductions of capecitabine grade 2 toxicity (43% of patients). Among the first 30 patients treated, three patients had tumor-associated bleeding duodenal ulcers, and one had a contained duodenal perforation. No additional bleeding events occurred among the final 18 patients after patients with duodenal involvement by tumor were excluded. Nine (20%) of 46 assessable patients had confirmed partial responses until distant progression for a median of 6.2 months. Four patients have undergone pancreaticoduodenectomy without perioperative complication. The median survival was 11.6 months (95% CI, 9.6 to 13.6), from the start of protocol therapy. CONCLUSION: Concurrent bevacizumab did not significantly increase the acute toxicity of a relatively well-tolerated chemoradiotherapy regimen. However, ulceration and bleeding in the radiation field possibly related to bevacizumab occurred when tumor involved the duodenal mucosa. The encouraging efficacy end points suggest that the further study of bevacizumab with chemoradiotherapy is warranted.