Faculty Bibliography

BACKGROUND: HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. OBJECTIVE: Here, we report a large series in the highly active antiretroviral therapy era comparing outcomes between HIV-positive and HIV-negative patients with anal cancer. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at an outpatient oncology clinic at large academic center. PATIENTS: A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. MAIN OUTCOME MEASURES: Data on patient characteristics, treatment, toxicity, and outcomes were collected. Overall survival, colostomy-free survival, local recurrence-free survival, and distant metastasis-free survival were analyzed. RESULTS: Median follow-up was 15 months. HIV-positive patients were younger (median, 52 vs 64 years; p < 0.001) and predominantly men (82% men vs 49% men; p = 0.001). There were no significant differences in T, N, or stage groups. HIV-positive patients had a significantly longer duration from biopsy to start of chemoradiation (mean number of days, 82 vs 54; p = 0.042). There were no differences in rates of acute toxicities including diarrhea, fatigue, or dermatitis. HIV-positive patients had significantly higher rates of hospitalization (33% vs 15%; p = 0.024). The 3-year overall survival rate was 42% in HIV-positive and 76% in HIV-negative patients (p = 0.037; HR, 2.335 (95% CI, 1.032-5.283)). Three-year colostomy-free survival was 67% in HIV-positive and 88% in HIV-negative patients (p = 0.036; HR, 3.231 (95% CI, 1.014-10.299)). Differences in overall survival rates were not significant on multivariate analysis. LIMITATIONS: This study was limited by its retrospective design and small patient numbers. CONCLUSIONS: In this cohort, HIV-positive patients had significantly worse overall and colostomy-free survival rates than HIV-negative patients. However, differences in survival were not significant on multivariate analysis. Additional studies are necessary to establish the etiology of this difference.

OBJECTIVE: To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital. METHODS: We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks >/=10 days were compared using t-test and chi(2) test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed. RESULTS: The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks >/=10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis. CONCLUSIONS: Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.

OBJECTIVE: Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. METHODS: Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. RESULTS: Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) >/=5 mug/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size >/=3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge >/=3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery >/=8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CONCLUSION: CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.

BACKGROUND: Small studies have demonstrated that patients who have both colorectal and renal cell carcinoma may be at increased risk for the development of additional malignancies. A possible genetic basis has been suggested. Our study describes the clinicopathologic features of these patients and clarifies the relationship of this cohort with Lynch syndrome (LS). METHODS: Patients with primary CRC and RCC treated at our institution were identified. Medical records were reviewed for demographic and clinical information. Immunohistochemical staining for mismatch repair (MMR) proteins was performed on tumor tissue when possible. RESULTS: During the study period, 24,642 patients were treated for CRC and 7,366 were treated for RCC at our institution. One hundred seventy-nine patients had both diagnoses, with 101 patients eligible for inclusion in our cohort. Tumors were typically early stage. The 2 cancers presented as synchronous lesions in 42% of patients. Thirty-two patients had 1 additional primary malignancy, 7 patients had 2 additional primary malignancies, and 3 patients had 3 additional primary malignancies. No patient had a family history that met the Amsterdam II criteria (AC) for LS, but 50% had family members with 1 malignancy. One of 10 colorectal tumors analyzed for the absence of MMR protein expression demonstrated the absence of MSH6, but the corresponding RCC demonstrated intact expression of all 4 MMR proteins. CONCLUSION: It is rare for patients to be diagnosed with both CRC and RCC. The clinicopathologic features of this cohort and the results of immunohistochemical analysis performed on a sample of these patients do not suggest LS. However, the high rate of additional carcinomas suggests a need for careful follow-up. Multicenter longitudinal studies are warranted to further understand the natural history and possible genetic basis for this entity.

Background: A pancreaticoduodenectomy (PD) offers the only chance of a cure for pancreatic cancer and can be performed with low mortality and morbidity. However, little is known about outcomes of a PD in octogenarians. Methods: Differences in two groups of patients (Group Y, <80 and Group O, >/=80 year-old) who underwent a PD for pancreatic adenocarcinoma were analysed. Study end-points were length of post-operative stay, overall morbidity, 30-day mortality and overall survival. Results: There were 175 patients in Group Y (mean age 64 years) and 25 patients in Group O (mean age 83 years). Octogenarians had worse Eastern Cooperative Oncology Group (ECOG) Performance Status (PS >/=1: 90% vs. 51%) and American Society of Anesthesiology (ASA) score (>2: 71% vs. 47%). The two groups were similar in underlying co-morbidities, operative time, rates of portal vein resection, intra-operative complications, blood loss, pathological stage and status of resection margins. Octogenarians had a longer post-operative stay (20 vs. 14 days) and higher overall morbidity (68% vs. 44%). There was a single death in each group. At a median follow-up of 13 months median survival appeared similar in the two groups (17 vs. 13 months). Conclusions: As 30-day mortality and survival are similar to those observed in younger patients, a PD can be offered to carefully selected octogenarians.

BACKGROUND: Excess use of intravenous fluid can increase post-operative complications. We examined the influence of intra-operative crystalloid (IOC) administration on complications following pancreaticodudenectomy (PD) for pancreatic adenocarcinoma. METHODS: We categorized 188 patients who underwent PD for adenocarcinoma (1990-2009) into two groups: Group I received <6,000 ml and Group II received >/=6,000 ml IOC. Differences between groups in length of stay, overall morbidity, and 30-day mortality were evaluated. RESULTS: There were 86 patients in Group I and 102 in Group II. Group I patients were older and with higher percentage of women, but similar in regards to performance status, ASA score, underlying comorbidities, and administration of neo-adjuvant treatment. Group II patients had longer operations, increased blood loss, and higher rates of intra-operative blood transfusions. There were two post-operative deaths, both in the Group II (P = 0.5). Post-operative overall morbidity was 45.7%, without differences between the two groups (44.2% vs. 47.1%, P = 0.7). Likewise, length of post-operative stay was similar in both groups (13.8 days vs. 14.5 days, P = 0.5). CONCLUSIONS: The volume of IOC increased with duration of surgery, intra-operative blood losses, and intra-operative blood transfusion, but did not correlate with post-operative morbidity. J. Surg. Oncol (c) 2011 Wiley-Liss, Inc

Introduction: Surgery offers the only chance for cure in patients with pancreatic cancer. Currently, pancreaticoduodenectomy can be performed with a mortality of under 5% and a morbidity of 40-50%. Little, however, is known about outcomes of pancreaticoduodenectomy (PD) in octogenarians. This manuscript details outcomes after PD for adenocarcinoma in patients 80 years and older. Methods: From our comprehensive pancreatic adenocarcinoma database of 248 patients, we identified 200 patients who underwent PD (1990-2009). We categorized patients into two groups, according to age at time of surgery: Group I (>= 80 year-old) and Group II (< 80 year-old). The study end-points were length of post-operative stay (LOS), overall morbidity, 30-day mortality, overall survival (OS). Differences between groups were evaluated using t-test or chi-squared test. Survival was compared using Kaplan-Meier analysis and log-rank test. Results: There were 25 patients in group I (mean age 83.1) and 175 patients in Group II (mean age 64.4). Octogenarians had worse ECOG performance status (PS >= 1 in 90% vs. 50.8%, p < 0.01) and ASA score (ASA 3- 4 in 70.8% vs. 47.4%, p < 0.01). The two groups were similar in regard to underlying co-morbidities (including coronary artery disease, COPD, diabetes, chronic renal failure), operative time, rates of portal vein resection, intraoperative complications, blood loss, pathologic AJCC stage, status of resection margins. Octogenarians had longer LOS (20 vs. 13.7 days, p=0.01) and higher overall morbidity (68% vs. 44%, p=0.03). There was a single death in each group (p=0.23). At median follow-up of 13 months older patients had a median OS of 17.3 months compared to 13.1 months in younger patients (p=0.06). Conclusions: Surgical morbidity and LOS are significantly increased in octogenarians. However 30-day mortality was not significantly increased and OS was superior (but not statistically significant) when compared to younger patients. The decision for PD should be individualized and offered to carefully selected octogenarians