Sunitinib in patients with imatinib‑resistant gastrointestinal stromal tumor: A single center experience.

AIM: The outcome of patients with advanced gastrointestinal stromal tumor (GIST) has improved with the use of imatinib. Despite high response rates with this drug resistance eventually develops in nearly all patients. We present an analysis of prospectively collected data on sunitinib efficacy and safety in patients with imatinib‑resistant GIST. SUBJECTS AND METHODS: Between November 2006 and October 2007, patients with GIST were accrued in an approved sunitinib patient access protocol. Key eligibility criteria included tumor resistance to imatinib and/or patient intolerance to this drug. Patients received sunitinib at a starting dose of 50 mg once daily for 4 weeks in a 6 week cycle, with standardized dose modification titrated to toxicity. Patients were continued on sunitinib until disease progression or unacceptable toxicity. The endpoints were safety, overall survival (OS) and objective response rate (ORR). RESULTS: Fifteen patients, all of whom had imatinib resistance and none intolerance, with median age of 48 (26–69) years, were treated on the protocol. The most common sites of primary disease were small intestine (40%), stomach (26.7%) and retroperitoneal (26.7%). A median of 10 (1–47) cycles of sunitinib were delivered, 9 (60%) patients required dose reductions due to toxicity whereas dose delay of > 2 weeks was required in only one (6.7%) patient. There were no toxicity‑related drug discontinuations. Hypothyroidism (n = 4; 26.7%) and hand‑foot syndrome (n = 3; 20%) were the most common toxicities. There were no complete and 4 (26.7%) partial responses while prolonged disease stability was seen in 8 (53.3%) patients. At a median follow‑up of 81 months in surviving patients, the median progression‑free and overall survivals were 15.5 and 18.7 months, respectively. CONCLUSIONS: Sunitinib appears to be an effective and well‑tolerated treatment for Indian patients with imatinib‑resistant GIST with outcomes similar to that reported previously. Adverse effects can be reasonably well managed using a dose modification strategy.

Leptomeningeal metastasis in solid tumors with a special focus on lung cancer.

Leptomeningeal metastasis is a common problem in advanced solid tumor malignancies. A significant number of patients have underlying lung cancer. With the advent of better therapies, the management of leptomeningeal metastasis is gained more importance to improve survival and quality of live. This review article focuses on the epidemiology, clinical features, diagnostics and the recent management strategies directed towards leotomeningela metastasis from solid tumor, esp lung cancer.

Safety of 0.1% topical tacrolimus in the treatment of vitiligo.

Cure rates for vitiligo are significantly lower because of problems to different studies have reported different response rate and different adverse effect for the treatment of vitiligo. This study was conducted to evaluate the response rate and adverse effect of topical tacrolimus 0.1% ointment in the treatment of vitiligo patients in the department of Dermatology and venereology, Bangladesh Medical college (BMC), Dhaka from January 2010 to July 2010. In this clinical trial, 30 newly diagnosed vitiligo (focal and segmental) patients, aged between 10 to 50 years were assigned for therapy and to observe the response and adverse effect. Each individual lesion was treated with topical tacrolimus 0.1% ointment twice daily for three months. All the patients completed three months treatment and available for statistical analysis. The highest percentage 13(43.3%) was in the age of 11-20 years. Sex ratio revealed higher in case of female 18(60%), with a male-female ratio 1:1.5 and 5(16.67%) patients had vitiligo among their families. Repigmentation was observed in 8 (26.7%) subjects at the end of 4th week, 15 (50.1%) subjects at 8th week and 25 (83.3%) subjects after 12 weeks of therapy. 25 (83.33%) subjects did not complain any adverse effect (like pruritus, burning etc.) and 5 (16.67%) subjects were suffered from different adverse effect of drug, like pruritus observed in 2 (6.7%) subjects and burning in 6 (20%) subjects. This study found that tacrolimus 0.1% ointment to be safe in the treatment of vitiligo, with reduction in the number of vitiliginous spots by increased repigmentation significantly.

Presentation, complications, and impact of concurrent malaria infection on anticancer therapy.

BACKGROUND: There is very limited data on the effects of malaria on on‑going anticancer therapy. MATERIALS AND METHODS: We performed a retrospective analysis of adult solid tumor patients who contracted malaria while on active anticancer therapy. We noted their demographic profile, clinical course and the effects of malaria infection on their on‑going anticancer therapy. Analysis was done with simple percentages. RESULTS: We analyzed 33 malarial episodes in 30 patients over 3 months. Plasmodium vivax was the most common type of infection (75%). Presenting symptoms included the typical triad of fever with chills and rigors. Malaria caused multiple complications, necessitating hospitalization in half of the patients and intensive care unit care in 1 of 8 patients. Common complications included thrombocytopenia (73%), anemia (67%), hyponatremia (66%), hepatic dysfunction (27%), and hypotension (12%). There were no deaths as a result of malaria. Malaria caused treatment delays with an average of 2.42 days per event. Plasmodium vivax caused more complications and therapy delays, average: 3.7 days per event, while non‑vivax malaria caused an average of 0.5 days delay per event. There was a high level of resistance to chloroquine. CONCLUSION: Malaria is a significant problem in adult solid tumor patients, leading to multiple complications and therapy delays.

Prevalence and aetiology of anaemia in lymphoid malignancies.

Background. We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies. Methods. Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the prevalence and a subgroup of 46 patients was analysed for the cause of anaemia. Results. Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients. Conclusion. Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out.

Review of Treatment of Reflex Sympathetic Dystrophy.

A review study was done by searching literature through PubMed. Reflex sympathetic dystrophy is a life altering disease pathogenesis of which are not yet clearly known likewise its management protocol has not been established. Treatment of longstanding Reflex sympathetic dystrophy is empirical and of limited efficacy. This disease may lead to dreadful squeal which may need amputation for their management and few of these patients may even develop suicidal tendency. Patient with Reflex sympathetic dystrophy usually present late. It was found that the clinical presentation of RSD are too much variable, although different modalities of treatment are used either alone or in combination, the outcomes are often unpredictable and of variable efficacy. Understanding of the treatment modalities and proper selection of treatment option are essential for best outcome. Preventive measure does play a role in management of these patients. Option of treatment includes pharmacological method, sympathetic nervous system interruption, use of calcitonin and bisphosphonate. More study is required to find out the mechanism that triggers the pain and other clinical manifestation so that a standardized protocol for its management can be developed.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India.

Background: This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. Materials and Methods: The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. Results: A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. Conclusions: The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Cyclic vomiting syndrome responding to amitryptiline.

A 7 year girl presented with history of recurrent vomiting and altered sensonium. Laboratory investigators were within normal limits. A diagnosis of cyclic vomiting syndrome was made and treated with amitryptiline with good results.

Thymoma Associated with Myasthenia Gravis in Infancy.

Thymomas are associated with various autoimmune disorders in adults, most commonly with myasthenia gravis (MG). In MG antibodies developed against acetylcholine (ACh) receptors, resulting weakness of muscle after repeated use and recovery following a period of rest. However, MG due to thymoma is extremely rare in pediatric age group.1We report an infant with MG due to invasive thymoma.

Granulocytic sarcoma.

We present two cases where GS was sole presentations, months before the diagnosis of AML.

Quantitation of proteinuria in nephrotic syndrome by spot urine protein creatinine ratio estimation in children.

In Nephrotic Syndrome the amount of protein excretion is a reflection of activity of disease. Quantitative measurement of proteinuria by a 24-hour urine collection has been the accepted method of evaluation. Recent studies have shown that calculation of protein/creatinine ratio in a spot urine sample correlates well with the 24-hour urine protein (24-HUP) excretion. A study was conducted to compare the accuracy of a spot urinary protein/creatinine ratio (P/C ratio) and urinary dipstick with the 24-hour urine protein. Fifty two samples from 26 patients of nephrotic syndrome were collected. This included a 24-hour urine sample followed by the next voided random spot sample. The protein/creatinine ratio was calculated and dipstick was performed on the spot sample. This was compared with the 24-hour urine protein excretion. The correlation between the three samples was statistically highly significant (p<0.001) for all levels of proteinuria. The normal value of protein/creatinine ratio in Indian children was also estimated on 50 normal children admitted in the ward without any renal diseases calculated to be 0.053 (SE of mean +/-0.003).

Systemic onset juvenile idiopathic arthritis--its unusual presentation.

We report a case of systemic onset juvenile idiopathic arthritis (SOJIA), the manifestations of which started with fever and skin rash followed by arthritis within neonatal age. Such presentation is extremely rare in the newborn. After exclusion of closely mimicking conditions like congenital infections, neonatal onset multisystem inflammatory disease (NOMID), neonatal; lupus erythematosus (NLE) diagnosis of SOJIA may be entertained even in a neonate where arthritis, fever and rash are the presenting features.

Juvenile idiopathic arthritis with peripheral gangrene.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder of the childhood and is manifested by synovitis with or without systemic features. Secondary vasculitis occurring in response to JIA is reflected clinically on different structures or systems of the body. Here is reported a rare case of systemic onset JIA (SOJIA) with vasculitis leading to peripheral gangrene.

Unexplained somatic symptoms--diagnostic window for mental disorders.

Prevalence of common mental diseases eg, anxiety disorders and depression in primary care, general practice and specialists clinics is high but theirdiagnosis in these settings are poor, main reason being the absence of psychological complaints by patients. Such patients commonly present with physical symptoms suggestive of systemic diseases but examination and investigations often fail to substantiate organic basis of these so-called unexplained somatic symptoms (USSs). Several studies have shown that patients with USSs suffer from anxiety and depression. But these USSs are mostly misinterpreted or ignored by clinicians resulting in poor rates of diagnosis. The study objective was to devise algorithm for better and early diagnosis of. mental diseases in a specialist clinic practice setting. Common USSs were interpreted as regards their symptom-correlates both physical and mental and documented while taking detailed history, physical examination and needed investigations to diagnose systemic diseases. The study was in phases during three years and included 1297 patients in four cohorts which included one group of 154 patients with common USSs, treated with long term antidepressants. Data of all patients were recorded in microsoft excel spread-sheets for analysis. Commonest presenting USSs were so-called "gas", "acidity" and "dysentery" expressed in vernacular terms. On elucidation these were found to mean wide varieties of physical symptoms-complexes that were not typical of specific systemic diseases; 85% in one group and 73% in another with these USSs and their symptom-correlates when positively screened for symptoms of neurotic diseases (ICD-10) after detailed history taking were found to have anxiety and depression. Psychiatric comorbidity with systemic diseases was found in various percentages in three different cohorts when these USSs were properly evaluated. By patients' own assessments, 84.4%, 88% and 90% of those presenting with USSs of so-called "gas", "acidity" and "dysentery" (with their symptom-correlates) and who were put on three different low dose antidepressant treatment groups had satisfactory to good results so long as they were being taken regularly. These common USSs and the underlying physical symptoms-correlates were eponyms of anxiety disorders and non-major depression. General practitioners and specialists eg, gastroenterologists, cardiologists, neurologists, etc, should heed the USSs as the starting point for early diagnosis and treatment of comorbid mental disorders along with the systemic diseases for better treatment compliance and outcome and quality of life. Training of physicians and medical students in the diagnosis and management of patients with USSs should be emphasised in clinical teaching programmes. An algorithm for early diagnosis and management of common mental disorders in general and clinic practice is suggested.