Impact of Hepatic Metastasectomy in the Multimodal Treatment of Metastatic Breast Cancer.

BACKGROUND: Surgical management of hepatic metastases in patients with stage IV breast cancer remains controversial. The purpose of this study was to examine the impact of hepatic metastasectomy on long-term outcomes. METHODS: The 2004-2015 National Cancer Database was queried for all patients diagnosed with stage IV breast cancer with metastases isolated to the liver. Patient demographics, disease-, treatment- and outcome-related data were analyzed. RESULTS: Of 2,895 patients, only 90 (3.1%) underwent hepatic resection. Compared to patients who did not undergo metastasectomy, patients treated with metastasectomy tended to be younger (52 ± 12.7 versus 59.2 ± 14.6; P < 0.001) and have private insurance (74.4% versus 45.3%; P < 0.001). Independent predictors of metastasectomy included younger age (OR 0.98; CI 0.96-0.99; P = 0.01), lobular carcinoma (OR 2.26; CI 1.06-4.82; P = 0.03), and prior surgery of the primary site (partial mastectomy (OR 6.96; CI 3.47-13.95; P < 0.001) or total mastectomy (OR 5.74; CI 3.06-10.76; P < 0.001)). Compared to no metastasectomy, hepatic metastasectomy was independently associated with a 37% reduction in the risk of death (HR 0.63; CI 0.44-0.91; P = 0.01). CONCLUSIONS: Stage IV breast cancer with metastases to the liver is rare and few patients undergo hepatic resection. However, in this select patient population, hepatic metastasectomy was associated with a significant survival advantage when included in the multimodal treatment of synchronous stage IV breast cancer.

Rates, Predictors, and Outcomes of Portal Lymphadenectomy for Resectable Gallbladder Cancer.

INTRODUCTION: Lymphadenectomy (LND) is recommended following surgical resection of ≥ T1b gallbladder cancer (GBC). However, frequency and stage-specific survival benefits of LND remain unclear. PATIENTS AND METHODS: The National Cancer Database (NCDB; 2006-15) was queried for resected pathologic stage I-III GBC. LND performance, predictors of receiving LND, and LND association with overall survival (OS) were assessed. RESULTS: Of 2302 total patients, 1343 (58.3%) underwent LND. Patients who underwent LND were younger and more frequently had private health insurance, a negative surgical margin, higher pathologic T stage, and received adjuvant chemotherapy (all p < 0.001). LND rates were highest at academic centers (70.1%) relative to all other facility types (p < 0.001). LND was independently associated with improved OS [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.44-0.61]. LND was associated with improved OS for pT1b, pT2, and pT3 patients (all p < 0.05) on univariate analysis. LND was independently associated with improved OS in pT2 (HR 0.44, CI 0.35-0.56) and pT3 (HR 0.54, CI 0.43-0.69) patients. CONCLUSIONS: LND is associated with a 48% reduction in risk of death in patients with resectable non-metastatic GBC, with greatest impact in pT2-3 patients. Patients without LND have similar OS to patients with node-positive disease, highlighting the importance of LND. Underutilization of LND likely results in undertreatment of patients with undiagnosed nodal disease, which may contribute to unfavorable oncologic outcomes.

Dietary interactions and INR variability: retrospective evaluation of patients couples on oral anticoagulant therapy.

AIM: The association between dietary vitamin K intake and International Normalized Ratio (INR) variability in patients on oral anticoagulants treatment (OAT) has been evaluated in several studies. Changes in diet composition are known to lead to INR variability. We evaluated INR over time in married couples on OAT and non-cohabitant couples on OAT, to assess clinical relevance of the diet. METHODS: Among outpatients receiving OAT we selected 31 married couples. Husbands and wives were then matched by demographic and clinical characteristics to 31 men and 31 women on OAT not married nor living together. We analyzed 6,357 INR measurements recorded from February 1998 to November 2009. RESULTS: We found similar average INR values within married couples and also within non-cohabitant couples. Using mixed models we confirmed INR differences between seasons and the slightly lower INR in non-cohabitant couples compared to married couples; although statistically significant, they were of marginal clinical significance. CONCLUSION: Within both married and non-cohabitant couples, we did not find statistically or clinically significant differences between men and women over time. The lack of INR differences over time within non-cohabitant couples indicates that diet is not an important determinant of INR over time. Also seasonal INR variations and differences between married and non-cohabitant couples were of little practical importance.

Fludarabine treatment in B-cell chronic lymphocytic leukemia: response, toxicity and survival analysis in 47 cases.

BACKGROUND AND OBJECTIVE: Fludarabine monophosphate (FAMP) is a purine analog with specific therapeutic activity in B-cell chronic lymphocytic leukemia (CLL). Its current use as front-line therapy of CLL is still a matter of debate both because of the controversial results of the clinical trials so far reported and because of the toxicity profile of the drug. In order to contribute to clarifying the possible role of FAMP, we report a retrospective analysis of the results obtained with the purine analog in CLL patients in different phases of the disease. DESIGN AND METHODS: Forty-seven patients affected by advanced CLL, 36% untreated, 31.9% relapsed and 31.9% resistant, were treated with FAMP 25 mg/m2/day, either for 4 days every 3 weeks in 29 cases, or for 5 days every 4 weeks in 18. The median number of FAMP cycles was 6 (range 2-11). Response was defined according to total tumor mass (TTM) score reduction and toxicity was expressed according to WHO grading criteria. The median follow-up of the series was 13 months from the beginning of FAMP therapy. RESULTS: Out of 47 evaluable patients the response rate was 74.4%, with 34% complete response (CR). The overall response rate was 94%, 80% and 46.6% in untreated, relapsed and resistant cases, respectively; a significantly higher number of responses was associated with no previous treatment and number of FAMP cycles. Fifty-three percent of all cases and 58.8% of untreated ones did not experience any toxicity. Treatment-related side effects were mainly autoimmune phenomena in untreated patients and infectious complications in treated ones. One heavily pre-treated patient died because of neurologic complications. Median time to re-treatment was18 months (range 1-30) and was influenced by age and previous treatment. The overall median survival was 35.7 months with a significantly higher proportion of surviving cases among RAI 0-II stages, responders and patients receiving more than 5 FAMP cycles. INTERPRETATION AND CONCLUSIONS: The present report confirms the high efficacy of FAMP in previously pre-treated cases with acceptable toxicity and encourages its use as front-line treatment provided that the results of randomized trials demonstrate its superiority over conventional chemotherapy. The possible development of autoimmune phenomena should, however, be considered seriously.

Correlation between estrogen receptor levels and clinical response to ovariectomy in premenopausal women with advanced breast cancer.

From 1974 to 1980, according to a controlled clinical trial, 66 premenopausal women with advanced breast cancer underwent bilateral ovariectomy (BO). Of the hormonal parameters evaluated, the present study deals with estrogen receptors (ER). The relation between the presence or the absence of ER and clinical response was evaluated, without considering their concentration in neoplastic tissue. The response was evaluated in relation to threshold values of 5 fmol/mg protein (considered at the time of the study the cut-off value of negativity and positivity) and 10 fmol/mg protein (recently found to be a more accurate cut-off value). The results of BO in relation to different receptor status showed an analogous response. Furthermore, the higher the receptor concentration, the better the response to BO, especially when the concentration was higher than 25 fmol/mg protein.