Safety of eribulin mesylate and concomitant radiotherapy for metastatic breast cancer: a single-center experience.

AIM: This study evaluates, for the first time, the safety of eribulin in metastatic breast cancer patients concomitantly treated with palliative radiotherapy (RT). Patients & materials: A total of 17 patients were pretreated for metastatic breast cancer. Patients received eribulin mesylate and bone RT. RESULTS: The most frequent grade 3 hematologic adverse events were neutropenia (56%) and anemia (20%). Mean pain score decreased from 2 (baseline) to 0.7 (end of observation). Analgesic score remained stable (1.8 vs 1.6). Bone pain scores dropped within a few weeks and remained below baseline values throughout the analysis. The overall response rate was 29%, and the clinical benefit rate was 59%. CONCLUSION: Eribulin is characterized by a manageable safety profile also when combined with palliative RT.

Laparoscopic appendectomy performed by residents and experienced surgeons.

BACKGROUND: Laparoscopic appendectomy is widely performed by surgical residents, but its changing indications and outcomes have been poorly investigated. The aim of this study was to examine whether a difference exists in indications and outcomes between laparoscopic appendectomies performed by residents and those performed by experienced surgeons. METHODS: Between 1999 and 2007, 218 laparoscopic appendectomies were performed and recorded. Data were analyzed to compare operations performed by residents with those by experienced surgeons in terms of indications for surgery and severity of disease. Moreover, laparoscopic appendectomies were thoroughly compared regarding outcomes and complications. RESULTS: The residents had fewer conversions with laparoscopic appendectomy (8% vs 17%, P=0.04), and similar complication rates (12% vs 13%, P=0.16), compared with experienced surgeons. The median operating time was also comparable (67 minutes vs 60 minutes, P=0.23). However, patients operated on by residents had more emergencies (86% vs 70%, P=0.009), included more foreigners (27% vs 15%, P=0.03), and had intermediate to severe diseases, (81 vs 52%, P<0.001) than patients did operated on by experienced surgeons. CONCLUSIONS: Surgical residents performed more emergency laparoscopic appendectomies on foreign patients suffering from intermediate to severe diseases compared with experienced surgeons, with comparable surgical outcomes and lower conversion rates.

External accelerated partial breast irradiation for ductal carcinoma in situ: long-term follow-up from a phase 3 randomized trial.

INTRODUCTION: For a long time, accelerated partial breast irradiation (APBI) effectiveness for ductal carcinoma in situ (DCIS) has been debated, due to conflicting published results. Recent encouraging data from phase 3 trials reopened new perspectives for this radiation approach. The aim of the present study was to analyze the long-term efficacy and safety results of the series of patients with DCIS enrolled in the APBI arm of the APBI-IMRT-Florence phase 3 trial (NCT02104895). METHODS: Patients were treated in a phase 3 randomized trial comparing whole breast irradiation (50 Gy in 25 fractions to the whole breast, plus 10 Gy in 5 fractions to the tumor bed) to APBI (30 Gy in 5 nonconsecutive fractions) using the intensity-modulated radiotherapy technique. RESULTS: Overall, 22 patients were treated in the APBI arm. Median age was 62 years (mean 59; range 42-75 years). At a median follow-up of 9.2 years (mean 8.8; range 3.8-12.1 years), no contralateral invasive/DCIS occurrence, distant metastasis, or breast cancer-related death were recorded. The 5- and 10-year local recurrence, distant metastasis-free survival, and breast cancer-specific survival were 100%. The 10-year overall survival rate was 90.9%. No late toxicity at 5 and 10 years was recorded. CONCLUSIONS: Waiting for pending studies and mature follow-up, we confirmed the efficacy and safety of APBI for low-risk DCIS.

Laparoscopic ventral hernia repair: Results of a two thousand patients prospective multicentric database.

Laparoscopic incisional and ventral hernia repair (LIVHR) has been largely employed by the surgical community worldwide, despite the use of different types of mesh and fixation devices. A large nationwide prospective multicentric database collected 2005 operations from 8 high-volume centers, to investigate the perioeperative and long-term outcomes. The laparoscopic operations were completed in 1979 patients (98.7%), with a mean age of 60.7 years and a Body Mass Index of 28.8 kg/m2. Two hundred and one patient (18.8%) had a previous failed open repair. The average surface areas of the major defects were 47.4 and 18.2 cm 2 for postincisional and primary hernias. The mean operation time and postoperative stay were 94.4 min and s 3.7 days, respectively. We collected a total of 50 (2.5%) intraoperative and 414 (20.6%) postoperative complications, with reoperation needed in 38 cases (1.8%). After a mean follow-up period of 24 months, we recorded 62 (3.8%) confirmed recurrences. Length of surgery, hospital stay, and a previous recurrence were all risk factors for recurrence. Primary hernias had better perioperative outcomes compared to incisional hernias, except for the pain. The laparoscopic approach of both post-incisional and primary hernias seemed to be safe and feasible in short-to medium-term periods.

Triple Negative Apocrine Carcinomas as a Distinct Subtype of Triple Negative Breast Cancer: A Case-control Study.

BACKGROUND: Invasive triple negative apocrine carcinoma (TNAC) of the breast is a rare type of triple negative breast cancer. Several studies reported significantly distinct prognosis for TNAC when compared with most of the non-apocrine triple negative (NATN) tumors. This is a case-control study reporting onoutcomes from our long-term single-center experience. PATIENTS AND METHODS: We analyzed the clinicopathologic features of a series of 46 TNAC tumors treated in a 15-year period. Tumor characteristics and outcomes have been compared with a homogeneous control series of 43 NATN tumors treated during the same follow-up period. Local relapse-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) have been evaluated. RESULTS: LRFS in the TNAC group was 85% and 78% at 5 and 10 years, respectively. LRFS in the NATN group was 90% and 79% at 5 and 10 years, respectively (hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.41-3.19; P = .80). DMFS in the TNAC group was 85% and 85% at 5 and 10 years, respectively. DMFS in the NATN group was 85% and 75% at 5 and 10 years, respectively (HR, 0.39; 95% CI, 0.14-1.08; P = .071). OS in the TNAC group was 86% and 83% at 5 and 10 years, respectively. OS in the NATN group was 86% and 63% at 5 and 10 years, respectively. OS was significantly better in the TNAC group (HR, 0.45; 95% CI, 0.20-0.99; P = .049). CONCLUSIONS: TNAC seems to represent a distinct group of triple negative breast cancer, characterized by a favorable long-term outcome when compared with NATN tumors.

Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial.

BACKGROUND: Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early-late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results. METHODS: Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2). FINDINGS: No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01). INTERPRETATION: Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited.

Impact of hormonal status on outcome of ductal carcinoma in situ treated with breast-conserving surgery plus radiotherapy: Long-term experience from two large-institutional series.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a heterogeneous disease, for which the best adjuvant treatment is still uncertain. Many attempts of risk-groups stratification have been made over time, developing prognostic scores to predict risk of local recurrence (LR) on the basis of features such as age, final surgical margins (FSM) status, grade, and tumor size. The aim of our analysis was to evaluate the patterns of recurrence from a two large-institutional retrospective series. PATIENTS AND METHODS: We collected data on 457 patients treated with BCS and adjuvant RT between 1990 and 2012. Final analysis was performed on 278 patients, due to missing data about hormonal status (HS). Patients were treated at the Radiation Oncology Unit of the University of Florence (n = 195), and S. Maria Annunziata Hospital (n = 83) (Florence, Italy). RESULTS: At a median follow up time of 10.8 years (range 3-25), we observed 20 LR (7.2%). The 5-year and 10-year LR rates were 4.9% and 10.2%, respectively. At Cox regression univariate analysis, estrogen receptor (ER) positive status (p = 0.001), HS positive (p = 0.003), and FSM <1 mm (p = 0.0001) significantly impacted on LR. At Cox regression multivariate analysis positive ER status maintained a protective role (p = 0.003), and FSM status <1 mm its negative impact (p = 0.0001) on LR rate. CONCLUSIONS: Our experience confirmed the wide heterogeneity of DCIS. Inadequate FSM and negative ER status negatively influenced LR rates. Tumor biology should be integrated in adjuvant treatment decision-making process.

Learning curve for laparoscopic ventral hernia repair.

PURPOSE: To test if there was any difference in the indications and early outcomes of laparoscopic ventral hernia repair (LVHR) during a 36-month period at a single institution. METHODS: From August 1999 to August 2002, 64 consecutive, unselected patients underwent attempted LVHR. The patients were retrospectively divided into two groups: group 1 included the first 32 patients, and group 2 included the second 32 patients. Data regarding patient demographics, results, and postoperative follow-up were compared between the groups. RESULTS: Demographic characteristics, types of hernia, preoperative records, and hernia defects were well matched between the groups. Four patients in group 1 required conversion to laparotomy for bowel injuries, whereas no conversion was required in group 2 (12% vs 0%, P = 0.11 [NS]). The operative times and complication rates were similar, but bowel injuries were significantly more common in group 1 (19% vs 0%, P = 0.02), including the patients who were converted. The analgesic requirement was small and the hospital stay short in both groups; the differences were not significant. Three recurrences were noted in group 1 and none were noted in group 2, although follow-up was not comparable in the second group. CONCLUSIONS: A learning curve is needed to decrease conversions and bowel injuries during LVHR. The improved experience could permit the treatment of larger defects laparoscopically.

Laparoscopic cholecystectomy: retrospective comparative evaluation of titanium versus absorbable clips.

We present a retrospective study of the use of titanium and absorbable clips during laparoscopic cholecystectomy. The aim was to determine any differences in outcome and costs. From January 1999 to February 2002, 690 patients who had successfully undergone a laparoscopic cholecystectomy were reviewed. According to the type of clip, we retrospectively identified two groups of patients: 199 in whom the surgeons had used absorbable clips (absorbable clip group, ACG) and 491 in whom the surgeons had used titanium nonabsorbable clips (titanium clip group, TCG). Data about demographics, operation, results, complications, and follow-up were collected and matched in the two groups. Demographics, concomitant surgery, and the American Society of Anesthesiologists (ASA) status were comparable between the two groups. Although the proportions of cases requiring urgent operation, intraoperative cholangiography, use of a fourth trocar, and use of drainage suction were similar, the difficulty score of the operation was lower (6.3 vs. 7.0, P =.03) and the operative time was shorter (44 vs. 61 minutes, P <.0001) in the ACG than in the TCG. Complications, hospital stay, and long-term results were satisfactory and comparable between the two groups. No correlation was found between clip type and the incidence of biliary tree injuries, bleeding, wound infection, or readmission. The cost of the two types of clips varied slightly (90 euros for each procedure). Despite the fact that absorbable clips are theoretically less likely to cause complications than metallic ones, we were not able to demonstrate any clinical advantage during laparoscopic cholecystectomy in this retrospective study. Furthermore, the results suggest that absorbable clips are preferred when the cholecystectomy presents fewer difficulties.

Laparoscopic treatment of ventral hernias: prospective evaluation.

We describe 50 patients who recently underwent laparoscopic surgery. Early results, complications, and follow-up data were collected prospectively. Of 50 patients, 34 had an incisional hernia, whereas 16 had a primary defect. Three trocars were inserted. EndoShears or Ultracision was used for tissue manipulation. The prosthetic mesh used was an expanded polytetrafluoroethylene (ePTFE) mesh, inserted through the first trocar and fixed with a helicoidal stapler. Patients were followed-up in the outpatient clinic (mean, 14 months). Every operation was successfully completed, and mean operative time was 103 minutes. There were two small bowel injuries (4%) repaired by minilaparotomy. Postoperative pain was limited. Bowel movements, ambulation, and discharge were prompt. We noted 4 cases of urinary retention (8%), 8 seromas (16%), and 1 prolonged ileus, which resolved on day 5 spontaneously. Mean postoperative stay was 4 days. One patient was readmitted after 4 weeks because of incomplete obstruction, resolved conservatively. There has been only 1 recurrence (2%), 8 months after the operation. The technique appears safe and efficacious.

Simultaneous aortoiliac reconstruction and renal transplantation: is it safe?

A 54-year-old man with an aortoiliac aneurysm and renal failure due to renal artery thrombosis was placed on a transplantation waiting list. The aneurysm had a 3 cm diameter and, therefore, did not require aortoiliac reconstruction, while its evolution was followed by ultrasound color-doppler every six months. The aneurysm was stable and two years later, when a cadaver kidney became available, a preoperative ultrasound color-doppler showed initial wall dissection. Therefore, an abdominal aneurysmectomy using a standard Dacron bifurcation graft and renal transplantation were successfully carried out. The patient had no associated complications and 24 months after transplantation and aneurysmectomy currently has good renal function and distal pulses. Only 20 cases of simultaneous aortoiliac reconstruction and renal transplantation have been reported in the literature. The excellent results of our case and those reported in the literature prove that patients who have both severe aortoiliac disease and end-stage renal failure can safely undergo simultaneous aortic reconstruction and renal transplantation. However, the atherosclerosis in these patients is a generalized process, so that in the pretransplant protocol special attention should be paid to detecting coronary artery atherosclerosis. In fact, coronary artery disease may have a priority claim to therapy because of the high risk of myocardial infarction. Our own policy is to put the patient back on the waiting list for renal transplantation after treatment for coronary artery disease. Furthermore, considering that the management for aortoiliac disease and kidney failure is safe in both simultaneous and staged cases, we think that the real issue is whether or not these patients with coronary atherosclerosis can be candidates for renal transplantation. We believe that each transplant centre has to develop its own general policy for these critically ill patients on the basis of its own experience.

Paclitaxel and bevacizumab in first-line treatment for HER2-negative metastatic breast cancer: single-center experience.

The aim of our analysis was to report the outcome and safety of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2-negative metastatic breast cancer. Between February 2009 and August 2011, 62 consecutive patients received paclitaxel 90 mg/m(2) on days 1, 8, and 15 and bevacizumab (BV) 10 mg/kg intravenously on days 1 and 15, every 28-day cycle. After 6 cycles of combined treatment, patients were given maintenance BV every 3 weeks (15 mg/kg) until progression disease or unacceptable toxicity. At time of analysis, median overall survival was 12.3 months (range 4.6-44.8 months), progression-free survival was 8.1 months (range 2.3-33.2 months), and time to treatment failure was 8.4 months (range 2.3-33.2 months). Our results confirmed the efficacy and the acceptable toxicity profile of bevacizumab plus paclitaxel as first-line regimen for metastatic breast cancer.

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy.

PURPOSE: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). METHODS AND MATERIALS: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. RESULTS: After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence. CONCLUSIONS: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype.

Prognostic role of human epidermal growth factor receptor 2 status in premenopausal early breast cancer treated with adjuvant tamoxifen.

BACKGROUND: Hormone therapy is the most prescribed systemic therapy for patients with breast cancer (BC). Some patients fail to respond to tamoxifen; one pathway seems to involve human epidermal growth factor receptor 2 (HER2) overexpression. To better understand this matter, we reviewed our single-center experience of premenopausal patients who were chemotherapy naive and treated with 5 years of tamoxifen for early-stage BC by focusing on estrogen receptor (ER), progesterone receptor, HER2 status, and Ki-67 proliferative index. PATIENTS AND METHODS: We reviewed 425 patients treated with tamoxifen for early-stage BC. Previous solid tumors, age less than 18 years, BC recurrences or contralateral tumor, tamoxifen discontinuation, adjuvant chemotherapy, and a follow-up shorter than 6 months were considered exclusions criteria of the study. RESULTS: At a mean follow-up of 8.1 years, the mean (SD) time to local relapse was 6.7 ± 3.6 years; range, 2.0-10.7 years), whereas the mean (SD) time to distant metastases was 4.7 ± 2.3 years; range, 2.2-8.8 years). HER2 status did not influence local relapse-free survival (log-rank test, 0.40), distant metastases-free survival (log-rank test, 0.72), and overall survival rate (log-rank test, 0.87). CONCLUSIONS: Resistance to tamoxifen is a complex trait, and its pathway is still unclear; in patients with BC, a multidisciplinary approach is highly recommended. In our experience, we did not find a statistically significant difference in tamoxifen treatment efficacy according to HER2 status.

Predictors of recurrence after laparoscopic ventral hernia repair.

Laparoscopic ventral hernia repair (LVHR) is widely used to manage ventral hernias, but predictors of hernia recurrence have been poorly investigated. This retrospective study investigated the influence of common risk factors on hernia recurrence. Data from 146 consecutive, unselected patients who underwent LVHR between 2000 and 2006 were collected. Demographic, clinical, and perioperative parameters were analyzed to identify predictable risk factors for hernia recurrence. Both univariate and multivariate Cox's regression analysis were employed. The overall recurrence rate was 8% (12 patients) after an average follow-up of 45 months. On univariate analysis, smoking (P=0.01) and earlier repair (P<0.00) were significantly different in recurred patients. However, only earlier repair was an independent predictor of multivariate Cox's regression analysis (hazard ratio 0.085, 95% confidence interval: 0.020-0.355; P=0.001). LVHR is a safe technique to repair ventral hernias. However, smokers with earlier failed repair attempts have a higher risk of recurrence.

Comparison of laparoscopic and open repair for primary ventral hernias.

We designed a retrospective clinical trial comparing laparoscopic primary ventral hernia repair (LPVHR) and open traditional repair (OPVHR). Demographics, perioperative data, results, and follow-up were examined to determine if there was any difference in the main outcomes. From January 2000 to December 2006, 28 consecutive, unselected patients, who successfully underwent LPVHR, were matched with 36 patients, who received OPVHR (with mesh) during the same period. The operating room records, clinical files, and outpatient sheets were examined. Patient demographics, results, and follow-up were compared in the 2 groups. Demographic characteristics, site of hernia, concomitant surgery, and defect size were comparable between the 2 groups, but the proportion of urgent procedures was higher in OPVHR patients (25% vs. 4%; P=0.03). The overall complication rates were similar, with some specific differences, whereas analgesic requirement and hospital stay were also comparable. The operative times were significantly longer for the LPVHR group (70 min vs. 35 min; P<0.000). Four recurrences were noted in both OPVHR and LPVHR patients, 11% versus 14%, respectively, with no significant difference (P=0.67). LPVHR seemed to be as safe as the OVHR in this study, although LPVHR increased operative time. The complications of each method should be taken into consideration before making the choice of the surgical approach.