Risk factors for the development of triple-negative breast cancer versus non-triple-negative breast cancer: a case-control study.

The risk factors for breast cancer have been defined in several studies but there is deficient data for specific subtypes. We report here the pathological characteristics of a breast cancer cohort and risk factors for patients with triple-negative disease. In this case-control study, a prospective breast cancer cohort was evaluated for demographic, reproductive, obesity-related and other risk factors using a validated questionnaire. Tumors were characterized for routine pathological characteristics and immunohistochemical markers of basal-like breast cancer. Patients with triple-negative breast cancer (TNBC) constituted cases and those with non-TNBC were controls. Odds ratios (OR) were calculated for each risk factor and independent associations were tested in an unconditional logistic regression analysis. Between 2011 and 2014, 1146 patients were recruited, of whom 912 [TNBC 266 (29.1%), non-TNBC 646 (70.9%)] with sufficient pathology material were analysed. Reproductive factors of parity, breastfeeding, age-at-menarche, age at first full-term pregnancy and oral contraceptive use were not significantly associated with TNBC. Higher body mass index (BMI > 24.9 vs ≤ 24.9, OR 0.89, 95%CI 0.63-1.24, p = 0.49) was not significantly associated while lesser waist circumference (> 80 cm vs ≤ 80 cm, OR 0.64, 95%CI 0.45-0.9, p = 0.012) and lower waist-to-hip ratio were significantly associated (> 0.85 vs ≤ 0.85, OR 0.72, 95%CI 0.51-1.0, p = 0.056), with TNBC. History of tobacco use was not significantly associated while lower socio-economic status was borderline associated with TNBC (socio-economic category > 5 versus ≤ 5, OR 0.73, 95%CI 0.50-1.06, p = 0.106). No factor was significant after adjustment for covariates. Central obesity seems to be preferentially associated with non-TNBC, and lower socio-economic status with TNBC in India, while most other conventional risk factors of breast cancer show no significant association with TNBC versus non-TNBC.

Effect of Peritumoral Infiltration of Local Anesthetic Before Surgery on Survival in Early Breast Cancer.

PURPOSE: Preventing metastases by using perioperative interventions has not been adequately explored. Local anesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral infiltration of local anesthesia on disease-free survival (DFS). METHODS: Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumor size, and center. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively. RESULTS: Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P = .017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P = .019). The impact of LA was similar in subgroups defined by menopausal status, tumor size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection. CONCLUSION: Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228).[Media: see text].

Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study.

AIM: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. METHODS: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. RESULTS: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45-41.81%) and 22.41% (13/58, 95%CI: 11.68-33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08-96.00%) and 82.76% (48/58; 95%CI: 73.04-92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41-79.50%) and 50.00% (29/58; 95%CI: 40.40-67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. CONCLUSION: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.

Fatal non-occlusive mesenteric ischemia after esophagectomy.

Non-occlusive mesenteric ischemia (NOMI) is a disorder with an extremely high mortality. Salvage of affected patients requires early recognition and aggressive intervention to prevent intestinal gangrene. We present a case of NOMI developing after esophagectomy and discuss the pathophysiology diagnosis and therapy.

Multimedia article. Relaparoscopy for salvage surgery in anastomotic recurrence of rectal cancer: feasible and safe.

Laparoscopic approach to rectal cancer is technically challenging even for experienced laparoscopic surgeons. Therefore, in a locally recurrent rectal cancer not many surgeons would be keen to adopt the relaparoscopy approach. In this video article, we present a case of salvage laparoscopic abdominoperineal resection performed for an isolated anastomotic recurrence developed 13 months after a laparoscopic ultralow anterior resection.

A new scoring system for gallbladder cancer (aiding treatment algorithm): an analysis of 335 patients.

BACKGROUND: There is currently no preoperative staging/scoring system available for gallbladder cancer. Unfortunately, in gallbladder cancer, patients manifest advanced stages of the disease. There is need for a methodology that can aid accurate preoperative staging and the subsequent treatment algorithm. We thus sought to validate a new scoring system, the Tata Memorial Hospital Staging System (TMHSS), for gallbladder cancer. METHODS: TMHSS is based on the cumulative impact of specific features of computed tomographic scan, presence or absence of jaundice, and serum cancer antigen 19-9 levels. This scoring system was first proposed in 2004. Patients with gallbladder cancer were enrolled onto the testing sample for TMHSS to ascertain its validity. A total of 335 consecutive patients with gallbladder cancer who sought care at the Tata Memorial Hospital between May 1, 2005, and December 31, 2006, were studied. Treatment was suggested on the basis of current existing protocols. Each patient was assigned a TMHSS score, and the treatment decision taken was compared with the algorithm generated for each individual score. Concurrence of the decision taken with the score generated algorithm was tested by the Kendall tau-b test. RESULTS: Ordinal-by-ordinal analysis of the value of the test was .75, which showed excellent concurrence and a statistically significant P value (P < .0001). CONCLUSION: TMHSS provides an excellent correlative treatment plan for patients with gallbladder cancer. It has the potential to reduce unnecessary surgical explorations and to direct patients to the ideal treatment strategy, thereby offering a degree of prognostication.

Can we do better than 'incidental' gallbladder cancer?

The term 'incidental' gallbladder cancer is used to describe the histopathologic surprise of a malignancy following simple cholecystectomy for presumed benign gallstone disease. However, there remains a persistent doubt, especially so in large volume centers - whether some of these cases should have been detected on preoperative imaging. Under the broad definition of 'incidental' gallbladder cancer are we condoning the fact that some of the 'missed' gallbladder cancers may actually have been 'potential' gallbladder cancers, or 'suspicious' gallbladder cancers? In this report we try to answer this question. There exists a group of patients in whom preoperative imaging raises the suspicion of gallbladder cancer but are yet subjected to a laparoscopic simple cholecystectomy, possibly because adequate heed was not paid to the preoperative imaging. In this situation, the correct strategy would be to subject the excised gallbladder to an intraoperative frozen section and conversion to open radical cholecystectomy if the disease is more than T1. On the basis of experience gained with this problem at the Tata Memorial Center, we attempt to introduce two new terms: 'Potential' gallbladder cancer and 'suspicious gallbladder cancer', to highlight these clinical situations so that the correct procedure is performed where indicated.

Bile cultures and sensitivity patterns in malignant obstructive jaundice.

BACKGROUND: Bactibilia is one of the important factors in the development of postoperative septic complications. We undertook this retrospective analysis to identify the organisms present in bile and their antibiotic susceptibility patterns in patients with malignant obstructive jaundice. METHODS: Bile specimens were obtained during endoscopic cholangiography (ERC; n=65), by flushing biliary stents (n=15), intra-operatively before incising the common bile duct (n=7) or during percutaneous transhepatic biliary drainage (PTBD; n=1). Eighty-eight samples from 65 consecutive patients were analyzed for their bacterial spectrum and sensitivity to antibiotics. Concomitant septic complications such as wound infection and cholangitis were also assessed. RESULTS: Of 65 patients (hilar block 39, distal block 26), 17 (26.1%) had bactibilia at initial ERCP; in addition, 3 of 7 bile specimens obtained during surgery, one collected during PTBD, and 13 of 15 stent flushings grew bacterial organisms. Cholangitis developed in 15 patients (12 with hilar block, 3 with distal block). Blood cultures were positive in 3 cases, and initial bile culture was positive in four patients with cholangitis. The most commonly found organisms were Escherichia coli (36.6%), Klebsiella pneumonia (18.3%), Pseudomonas aeruginosa (8.3%), Proteus vulgaris (8.3%) and coagulase-negative staphylococci (8.3%). The organisms found on ERC were similar to those found at wound cultures in 3 of the 4 cases who developed wound infection. Amikacin, gentamicin, cefotaxime, ceftazidime, and cefoperazone-sulbactam combination showed good activity against E. coli and K. pneumonia. CONCLUSION: Approximately one-fourth of patients with malignant obstructive jaundice have positive bile cultures at initial ERC. Post-ERC cholangitis is common in hilar blocks.