Triple-negative breast cancers: Are they always different from nontriple-negative breast cancers? An experience from a tertiary center in India.

BACKGROUND: Triple-negative breast cancers (TNBCs) are known for early age at presentation, large tumor sizes, and overall poor prognosis. However, Indian studies are scarce with limited follow-up data. Hence, the present study is aimed at characterizing nonmetastatic TNBC patients in our population and comparing their outcome with non-TNBC subset. METHODOLOGY: This is a retrospective observational study of nonmetastatic breast cancer patients accrued over 14 years. The demographic, clinical, and pathological profiles of TNBCs and their patterns of recurrences and survivals were compared to that of non-TNBC. Overall and disease-free survival (DFSs) were calculated from the time of initiation of therapy to the occurrence of event, i.e., death or recurrence. RESULTS: TNBC constituted 21.8% of all patients. Patients with triple-negative subtype were significantly younger and more likely to be premenopausal. Higher proportion of TNBC presented in locally advanced stage and had a higher proportion of node-positive patients compared to their non-TNBC counterparts. Although taxane-based neoadjuvant therapy was associated with significantly higher pathological complete responses, recurrences occurred earlier in TNBC. Even though inferior overall and DFSs were encountered in TNBC, statistical significance could not be derived. CONCLUSIONS: TNBCs are a subset of tumors with a poorly understood tumor biology and behavior. Despite being labeled as having an aggressive tumor biology and behavior, not many differences are seen in their clinical outcomes when they present as locally advanced cases.

VSL#3 induces and maintains short-term clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial.

BACKGROUND: The probiotic mixture VSL#3 has proven efficacious in inflammatory bowel diseases and irritable bowel syndrome; however, its efficacy in microscopic colitis (MC) is being investigated. OBJECTIVE: To evaluate the safety and efficacy of a multistrain probiotic, VSL#3, in inducing clinical remission and achieving clinical response, as compared with mesalamine, in patients with active MC. METHODS: A randomised, open labelled study comparing the efficacy of 900 billion colony-forming units/day of VSL#3 (group (Gp) A) or 1.6 g of mesalamine/day (Gp B) for 8 weeks in 30 patients with MC was conducted. After a washout period of 2 weeks, Gp B received 8 weeks of VSL#3 and Gp A was off medication for the next 8 weeks. The primary end points were clinical remission and clinical response at 8 weeks. RESULTS: Of 30 patients, 15 were randomised in each arm. 11 patients in Gp A and 13 patients in Gp B completed 8 weeks of treatment. 5 (46%) of 11 patients in Gp A and 1 (8%) of 13 patients in Gp B attained clinical remission (p=0.022). Clinical response was seen in Gp A, as evidenced by a lower stool weight (377.6±104.5 g) as compared with Gp B (507±168.2 g; p=0.03). VSL#3 was effective in maintaining clinical response up to 10 weeks, even after discontinuation of therapy. Secondary end points like stool parameters, histology and well-being improved in both treatment groups. CONCLUSIONS: The probiotic VSL#3 was found to offer the benefit of inducing as well as maintaining short-term clinical response in patients with active MC. TRIAL REGISTRATION NUMBER: The clinical trial is registered with CLINICAL TRIAL REGISTRY INDIA; http://ctri.nic.in, CTRI No. "CTRI/2008/091/000086" (registered on: 23/06/2008).

Titers of anti-tissue transglutaminase antibody correlate well with severity of villous abnormalities in celiac disease.

GOALS: We reviewed our celiac disease (CeD) database to study if anti-tissue transglutaminase (tTG) antibody (ab) titers correlate with severity of villous abnormalities in Indian patients and to find out a cutoff value of anti-tTG ab fold-rise, which could best predict CeD. BACKGROUND: Guidelines for diagnosing CeD suggest that biopsy could be avoided in some patients with high anti-tTG ab titer. STUDY: We reviewed a cohort of 366 anti-tTG ab-positive individuals in whom duodenal biopsies were performed. Anti-tTG ab was obtained before initiation of gluten-free diet. Anti-tTG ab results were expressed in terms of fold-rise by calculating ratio of observed values with cutoff value. CeD was diagnosed if in addition to positive serology, patients had villous atrophy (>Marsh grade 2) and unequivocal response to gluten-free diet. RESULTS: The mean anti-tTG fold-rise in groups with Marsh grade ≤2 was 2.6 (±2.5), grade 3a was 4.0 (±3.9), 3b was 5.7 (±5.1), and 3c was 11.8 (±8.0). The positive likelihood ratio for diagnosing CeD was 15.4 and 27.4 at 12- and 14-fold-rise of anti-tTG ab titer, respectively. The positive predictive value of diagnosis of CeD was 100% when anti-tTG ab titer was 14-fold higher over the cutoff value. Fifty-seven (43.9%) individuals with anti-tTG titer rise <2-fold high also had CeD. CONCLUSIONS: As severity of villous abnormality increases, titer of anti-tTG also rises. Presence of villous atrophy can be predicted at very high anti-tTG ab titer. In contrast to emerging belief, mucosal biopsies should be performed even if anti-tTG ab titer is <2 times, because many patients with CeD have low titers.

Effect of pre-operative short course famotidine on tumor infiltrating lymphocytes in colorectal cancer: a double blind, placebo controlled, prospective randomized study.

BACKGROUND: Pilot studies have shown that histamine H2 receptor antagonists augment the natural immunity against cancer in colorectal and gastric cancer by enhancing lymphocytic infiltration in the tumors. However, a study of adjuvant ranitidine failed to show a significant benefit in colorectal cancer, possibly because of the immunosuppression exerted by blood transfusion and post-operative infections. The pre-operative use of H2 receptor antagonists may therefore be of greater benefit. Except for a pilot study using cimetidine, there are no trials that have evaluated the effect of pre-operative H2 receptor antagonists on tumor infiltrating lymphocytes in colorectal cancer. OBJECTIVE: To evaluate the efficacy of famotidine in augmenting tumor infiltrating lymphocytes in colorectal cancer. STUDY DESIGN: Double blind, placebo controlled, prospective randomized study. METHODS: Twenty-three patients with resectable colorectal cancer were randomized to receive famotidine (n = 11) or placebo (n = 12). Famotidine was given for 1 week pre-operatively in a dose of 40 mg per day p.o. After resection, the specimens were analyzed histologically for lymphocytic infiltration by a pathologist blinded to the two groups. Lymphocytic infiltration more than 50 cells per high power field, involving more than 50% of the tumor-normal tissue interface was considered significant. RESULTS: The two groups were comparable for age, gender, pre-operative carcino embryonic antigen (CEA) levels and pathological stage. Significant lymphocytic infiltration was seen in 63.6% (7 of 11) patients in the study group compared to only 8.5% (1 of 12) patients in the placebo group (P = 0.005). Despite fewer recurrences and a longer survival in the study group, the difference was not significant. CONCLUSION: This study shows that pre-operative famotidine may significantly enhance lymphocytic infiltration in colorectal cancer and may have potential for use as an anticancer agent in colorectal cancer.