Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC) patients receiving TKIs.

Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia.

According to the 2008 revision of the World Health Organization (WHO) classification of myeloid malignancies, philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) include clonal, hematologic disorders such as polycythemia vera, primary myelofibrosis, and essential thrombocythemia.Recent years have witnessed major advances in the understanding of the molecular pathophysiology of these rare subgroups of chronic, myeloproliferative disorders. Identification of somatic mutations in genes associated with pathogenesis and evolution of these myeloproliferative conditions (Janus Kinase 2; myeloproliferative leukemia virus gene; calreticulin) led to substantial changes in the international guidelines for diagnosis and treatment of Ph-negative MPN during the last few years.The MPN-Working Group (MPN-WG), a panel of hematologists with expertise in MPN diagnosis and treatment from various parts of India, examined applicability of this latest clinical and scientific evidence in the context of hematology practice in India.This manuscript summarizes the consensus recommendations formulated by the MPN-WG that can be followed as a guideline for management of patients with Ph-negative MPN in the context of clinical practice in India.

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study.

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality.

Lungs on fire.

A 50-year-old man was diagnosed as classical Hodgkin's lymphoma stage III B. He had been a reformed smoker and has had a coronary artery disease as his comorbidity. He was started on adriamycin, bleomycin, vinblastine, dacarbazine (ABVD)-based chemotherapy. An interim disease evaluation was suggestive of metabolic complete response after four cycles of ABVD. After completion of his sixth cycle, he presented with low-grade fever, dry cough, generalised malaise and increasing dyspnoea on exertion. FDG (18 fluoro-deoxyglucose) positron emission tomography (PET)-CT revealed intensely FDG avid diffuse activity in mid and lower zone both lung fields. He was started on intravenous steroids along with broad spectrum antibiotic and antifungal cover. Clinical, radiological and laboratory assays did not reveal any infective pathology. He was diagnosed as bleomycin-induced pulmonary toxicity (BIP). Despite best supportive care, his pulmonary functions deteriorated and he developed cardiac arrhythmias. He finally succumbed to the irreversible chemotherapy toxicity of a curable malignancy.

Management of primary and metastatic triple negative breast cancer: perceptions of oncologists from India.

BACKGROUND: In order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive survey of practicing Indian oncologists. MATERIALS AND METHODS: A core group of academic oncologists devised two hypothetical triple negative cases (metastatic and early breast cancer, respectively) and multiple choice options under different clinical circumstances. The respondents were practicing oncologists in different Indian cities who participated in either an online survey or a meeting. The participants electronically chose their preferred option based on their everyday practice. RESULTS: A total of 152 oncologists participated. Just over half (53.8%) preferred taxane based chemotherapy as first-line chemotherapy in the metastatic setting. In the adjuvant setting, a taxane regimen was chosen by 61%. Over half of respondents (52.6%) underestimated the baseline survival of a patient with node positive triple-negative tumor and 18.9% overestimated this survival compared to the estimate of the Adjuvant! program. DISCUSSION: This data offers insight into the perceptions and practice of a diverse cross-section of practicing oncologists in India with respect to their therapeutic choices in metastatic and adjuvant settings in triple negative breast cancer.

Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

Favourable impact of intensity-modulated radiation therapy on chronic dysphagia in patients with head and neck cancer.

The aim of this study was to evaluate the impact of intensity-modulated radiation therapy (IMRT) on the incidence and severity of chronic dysphagia in patients with head and neck cancer. 62 evaluable patients with head and neck cancer who were treated with IMRT with or without concurrent chemotherapy were analysed. The majority of the patients (77.4%) had advanced locoregional disease. 45 patients underwent definitive IMRT and 17 received post-operative IMRT. Concurrent chemotherapy was given to 29 of the 45 patients treated with definitive IMRT. The average prescribed dose to clinical target volume (CTV)1 was 66-70 Gy (definitive IMRT) and 56-62 Gy (post-operative IMRT); 60 Gy to CTV2; 54 Gy to CTV3; and 50-52 Gy to the supraclavicular area. At a median follow-up of 19 months, 2-year actuarial locoregional control and survival was 77% and 74%, respectively. At 6 months after IMRT, chronic dysphagia was Grade 0 in 77.1% of patients, Grade 1 in 10.5% and Grade 2 in 12.3%. Acute mucositis showed no correlation with long-term dysphagia. The percutaneous endoscopic gastrostomy or nasogastric tube was removed in all of the patients within 8 weeks of completion of treatment. Xerostomia was Grade 0 in 61.4% of patients, Grade 1 in 31.5% and Grade 2 in 7% of patients. In conclusion, IMRT conferred a major favourable impact on chronic dysphagia in patients with locally advanced head and neck cancers, with satisfactory locoregional control.

Report of a case of pericardial mesothelioma with liver metastases responding well to pemetrexed and platinum-based chemotherapy.

Pericardial mesothelioma remains a disease with a bleak prognosis. We report the case of a patient with metastases to liver and good response to pemetrexed and carboplatin-based combination chemotherapy and consequent prolonged progression-free survival.

Isolated intraorbital metastasis in breast carcinoma.

We report a case of metastases to the eye, in a 30 year old lady with carcinoma breast leading to isolated metastatic involvement of the lateral rectus muscle with no evidence of metastases at any other site in the body after a follow up of one year after completion of chemotherapy.

Pure choriocarcinoma of testis with rare gingival and skin metastases.

A 22-year-old man presented with complaints of gingival and skin lesions. Physical examination revealed the presence of two nodular lesions, one over the sternum, 3 cm in size, and another, on the right side of chin, 1 cm in size. There was another fleshy soft tissue deposit over the left lower gingiva, in the oral cavity. He had noticed these lesions ten days prior to his visit to the hospital. In addition, there was left testicular non-tender swelling which had been present for two months, but was not investigated. Fine-needle aspiration cytology from skin and gingival lesions was suggestive of metastatic deposits. Patient underwent left high orchidectomy, and histopathological examination was consistent with the diagnosis of pure choriocarcinoma. Although rare, cases of testicular neoplasms and especially choriocarcinoma of the testis leading to skin metastases have been reported, but case reports of choriocarcinoma of testis metastatic to gingiva have been reported exceptionally in the English literature. We report this unique case of a young man with pure choricarcinoma of testis with unusual gingival and skin metastases.

Spontaneous fracture and pulmonary embolization of a central venous catheter.

The use of peripherally inserted central catheter is occasionally complicated by fracture and embolization of the catheter fragment. Here we report a 28 year old male with acute myeloid leukemia, who had spontaneous fracture of the central venous catheter and subsequent migration of the catheter fragment through the heart and into the lower lobe of the right lung. The catheter fragment was retrieved by retrograde femoral vein catheterization.

Small cell carcinoma of the gall bladder: case report and review of literature.

Small cell carcinoma of the gall bladder is a very rare tumor. The neoplasm is highly lethal, metastasizes early, and may cause death shortly after diagnosis. Here we report a 56 year old male with small cell carcinoma of the gall bladder metastatic to the liver. He attained partial remission with 5 fluouracil, cisplatin based chemotherapy. However, the disease progressed after 3 months and salvage chemotherapy with docetaxel and caboplatin failed to produce any tumour response. He succumbed to the illness 13 months after cholecystectomy.

Comparisons between cellulase production by Aspergillus fumigatus in agitated vessels and in an air-lift fermentor.

Aspergillus fumigatus was cultured in disc-turbine-agitated vessels and in an air-lift fermentor. In the agitated vessels the yield of cellulase was reduced when the agitation rate was increased, although extracellular protein levels rose. The enzyme complex itself was shown to be exceptionally stable under conditions similar to those in the agitated vessels, so probably shear damage to the mycelium had occurred, liberating intracellular contents. These appeared to contain an inhibitor that could be removed by fabricated inorganic protein absorbents, such as kieselguhr and alumina. However, the inhibitor was not likely to be protease, since only relatively low levels could be detected and its identity has not been established. The use of an air-lift fermentor avoided the shear effects due to use of the disc turbine agitator in the conventional fermentors, and yields of enzyme were then found to increase by about 20%, maximum yields being obtained at maximum K(L)a values.

Serum amylase and its isoenzymes in cases of viral hepatitis.

Serum amylase (SA) and its isoenzymes were studied in 9 control cases and 26 cases of Viral Hepatitis (VH). A significant rise in SA level was found in VH cases (Mean value--287.15 + 100.64) as compared to control cases (Mean value--155.56 + 28.57). The value was markedly increased in 8 cases with hepatic encephalopathy (Mean value--388 + 57.21). Isoenzymes of SA were estimated in all the cases by means of polyacrylamide gel electrophoresis and a direct saccharogenic assay of amylase activity. Besides two regular peaks (Pancreatic and Salivary fractions) a third peak (Slowest of all) was noticed in 4 out of 9 control cases (44.5%) and 19 out of 26 cases of VH (73.1%). Out of 8 cases who developed hepatic encephalopathy during the course, 7 had this peak (87.5%). SA levels and its isoenzymes level correlated well with the extent of hepatic damage (SGPT and Serum bilirubin levels). The possibility of hepatic origin of the third peak has been discussed.