Therapy-related myeloid neoplasm after peptide receptor radionuclide therapy (PRRT) in 1631 patients from our 20 years of experiences: prognostic parameters and overall survival.

PURPOSE: To determine prognostic factors and overall survival (OS) in therapy-related myeloid neoplasm (t-MN) of patients after receiving peptide receptor radionuclide therapy (PRRT). METHODS: All patients treated from February 1999 until September 2019 at our center who had bone marrow biopsy-proven t-MN after PRRT were included. Patient characteristics, laboratory results, and all tumor-directed therapies before t-MN diagnosis were collected. Cox regression analysis was performed to identify parameters associated with OS. Receiver operating characteristic (ROC) curve analysis was used to define cutoff values as well as sensitivity and specificity of the parameters. RESULTS: Out of 1631 patients treated with PRRT, 30 patients developed t-MN comprising myelodysplastic syndrome (MDS) in 23 patients (77%) and acute myeloid leukemia (AML) in 7 patients (23%). The median OS of t-MN patients was 13 months (range 9.1-16.9 months): 6 months for AML and 15 months for the MDS subgroup, respectively. Higher platelet level was a significant prognostic parameter for longer OS (hazard ratio (HR): 0.99, P < 0.05). Using ROC analysis, the best cutoff value for thrombocyte count was 183.5 Gpt/L, resulting in a sensitivity of 92.3% and a specificity of 50%. Other factors, such as hemoglobin level, did not show a significant correlation with OS. CONCLUSION: Even rarely occurred, the OS is gravely compromised in t-MN patients after PRRT, and even less in the AML subgroup (6 months). Higher platelet value was a significant prognostic parameter for longer OS in t-MN patients.

[Pulmonary neuroendocrine neoplasms]. / Neuroendokrine Neoplasien der Lunge.

The pulmonary neuroendocrine neoplasms originate from the enterochromaffin cells which are diffusely distributed in the body. The incidence of these tumors has increased significantly in recent decades due to the available diagnostics. They make up about 1-2% of all lung tumors and 20-30% of all neuroendocrine neoplasms. The current WHO classification from 2004 divides them into typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). The major neuroendocrine biomarkers are chromogranin A, synaptophysin and CD56. TC have a low mitotic rate of <2 mitoses/2mm(2) (10 HPF), whereas the mitotic rate of the AC is 2-10 mitoses/2 mm(2) (10 HPF). The Ki-67 staining is helpful to distinguish typical and atypical carcinoids from the highly malignant LCNEC and SCLC. Clinically, the patient presents usually with cough, hemoptysis or bronchial obstruction. The occurrence of a carcinoid or Cushing's syndrome and a tumor-associated acromegaly are rare. Surgical resection with radical lymph node dissection is the treatment of choice for achieving long-term survival. Endoscopic resection of the endobronchial tumor growth is a good alternative for inoperable endobronchially localized tumors. Peptide receptor radionuclide therapy (PRRT) is a promising treatment option for patients with metastatic or unresectable pulmonary neuroendocrine tumors. New targeted therapies using angiogenesis inhibitors, mTOR inhibitors, and tyrosine kinase inhibitors are being tested for their effectiveness in many previous studies. Typical carcinoid tumors metastasize less frequently than AC, the 5-year survival rate of patients with TC being over 90%. Patients with AC have a 5-year survival rate between 35% and 87%. The highly malignant LCNEC and SCLC, on the other hand, have a 5-year survival rate between 15% and 57%, and <5% respectively. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach and decision-making in multidisciplinary tumor conferences to ensure a personalized treatment approach. Therefore patients with a neuroendocrine neoplasm of the lung should be treated in specialized centers.

[The relevance of PET/CT for the surgical management of neuroendocrine neoplasms]. / Bedeutung der PET/CT für die Chirurgie neuroendokriner Neoplasien.

Neuroendocrine neoplasms (NEN) are rare malignancies with a wide spectrum of metastatic potential which originate from the endocrine cells of the body and express somatostatin receptors. The (68)gallium somatostatin receptor positron emission tomography-computed tomography (PET/CT) technique is the most sensitive method of assessment of well-differentiated NENs and for the detection of cancer of unknown primary (CUP syndrome) NENs. Imaging with 18F-fluorodeoxyglucose (18F-FDG PET/CT) is indicated in poorly differentiated neuroendocrine carcinomas. The receptor-dependent imaging of NENs has a decisive impact on further management.

Vandetanib therapy in medullary thyroid cancer.

The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for the treatment of unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). In Europe it was approved in March 2012, but only for the treatment of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase inhibitor of several growth factors involved in cellular proliferation and angiogenesis, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In addition, vandetanib is an inhibitor of the RET (rearranged during transfection) gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare disease, for which no previous medical therapies are approved, vandetanib is the first drug shown to be effective in a large phase III trial treating patients with metastatic or locally advanced MTC. Common adverse events are diarrhea, nausea, hypertension, headache and QT prolongation that are manageable and are commonly outweighed by the benefits of vandetanib in terms of delaying disease progression and inducing tumor response.

Risk factors for haemorrhagic stroke: a case-control study.

A hospital based pair-matched case-control study was undertaken to identify risk factors for haemorrhagic stroke. The study took place in the Government Medical College Hospital, Nagpur, India, a tertiary care hospital. The study consisted of 166 hospitalised computerised tomography scan proved cases of haemorrhagic stroke (International Classification Diseases 9, 431-432), and an age and sex matched control per case. The controls were selected from patients who attended the study hospital for conditions other than stroke. The study included hypertension, serum total cholesterol, alcohol intake, smoking, diabetes mellitus, obesity, physical inactivity, type A personality, use of anticoagulants/antiplatelets, family history of stroke, history of cardiac diseases, past history of transient ischaemic attack, history of claudication and oral contraceptive use in women, as risk factors for haemorrhagic stroke. Bivariate analysis included odds ratio (OR), 95% confidence intervals (CI) for OR and McNemar's chi2 test. Multivariate analysis was carried out by conditional multiple logistic regression analysis. Attributable Risk Percent (ARP), Population Attributable Risk Percent (PARP) and their 95% CI were estimated for significant factors. On conditional multiple logistic regression five risk factors-hypertension (OR=1.9, 95% CI 1.5-2.5), serum total cholesterol (OR=2.3, 95% CI 1.4-4.9), use of anticoagulants and antiplatelet agents (OR=3.4, 95% CI 1.1-10.4), past history of transient ischaemic attack (OR=8.4, 95% CI 2.1-33.6) and alcohol intake (OR=2.1, 95% CI 1.3-3.6) were significant. Estimates of ARP and PARP for these factors confirmed their etiological and preventable role respectively. The current study recognised the significance of five risk factors, which are preventable. These risk factors may be considered for devising effective risk factor intervention strategy for haemorrhagic stroke.

Improvement in the information content of the Glasgow Coma Scale for the prediction of full cognitive recovery after head injury using fuzzy logic.

BACKGROUND: The objective of this study was to modify the existing Glasgow Coma Scale (GCS) into a fuzzy GCS by using fuzzy information representation and fuzzy inferencing. The study compared the information content of the existing GCS with the new fuzzy GCS for prediction of full cognitive recovery in patients with head injury. METHODS: A record-based study was conducted at the Government Medical College and Hospital, a tertiary care facility in Nagpur, India. The study, which covered the period from January 1 to December 31, 1997, included 253 patients with head injuries. Opinions of 17 clinical experts who routinely deal with head injury cases were used for the construction of the fuzzy GCS. RESULTS: By using the max operator for summarization, eye, motor, and verbal stimuli were all significantly associated with the possibility of full cognitive recovery with the fuzzy GCS (P < .001). Nonspecificity of the classical GCS, the min-operated fuzzy GCS, and the max-operated fuzzy GCS was comparable. A reduction in Shannon entropy was maximum with the max-operated fuzzy GCS. Min-operated fuzzy GCS better predicted a lack of full cognitive recovery. CONCLUSIONS: Fuzzy GCS substantially improves the information content for prediction of the possibility of full cognitive recovery after head injury. Eye, motor, and verbal stimuli all uniquely and significantly contribute to prediction of this possibility. We recommend the use of fuzzy GCS for prediction of the possibility of full cognitive recovery in patients with head injuries.

Improvement of the Mair scoring system using structural equations modeling for classifying the diagnostic adequacy of cytology material from thyroid lesions.

The scoring system developed by Mair et al. (Acta Cytol 1989;33:809-813) is frequently used to grade the quality of cytology smears. Using a one-factor analytic structural equations model, we demonstrate that the errors in measurement of the parameters used in the Mair scoring system are highly and significantly correlated. We recommend the use of either a multiplicative scoring system, using linear scores, or an additive scoring system, using exponential scores, to correct for the correlated errors. We suggest that the 0, 1, and 2 points used in the Mair scoring system be replaced by 1, 2, and 4, respectively. Using data on fine-needle biopsies of 200 thyroid lesions by both fine-needle aspiration (FNA) and fine-needle capillary sampling (FNC), we demonstrate that our modification of the Mair scoring system is more sensitive and more consistent with the structural equations model. Therefore, we recommend that the modified Mair scoring system be used for classifying the diagnostic adequacy of cytology smears. Diagn. Cytopathol. 1999;21:387-393.

Differential protective effect of bacillus Calmette-Guerin vaccine against multibacillary and paucibacillary leprosy in Nagpur, India.

For this paper we conducted a secondary data analysis to test the hypothesis that a linear trend exists in the protective effect of bacillus Calmette-Guerin (BCG) vaccine against types of leprosy. We used data from two previous case-control studies to perform an unmatched test for linear trend. We observed that both the studies revealed a significant linear trend (P<0.00001). One study that estimated an insignificant protective effect of BCG against paucibacillary leprosy showed a significant departure from linearity. We conclude that, the protective effect of BCG vaccination is differential across severity of leprosy as it brings about a shift in the immune response to a higher level of cell mediated immunity. We recommend that future studies dealing with the protective effect of BCG against leprosy should also conduct an analysis for trend.

Risk factors and protective factors of pelvic inflammatory disease: a case-control study.

Risk factors and some protective factors for pelvic inflammatory disease (PID) in women were assessed in a case control study. Use of intrauterine device (OR = 3.98, p < 0.0001), sexual activity with multiple partners and younger age (ORs = 3.97, 1.9 and p = 0.0003, 0.0034, respectively), history of previous PID (OR = 4.08, p = 0.004) and history of minor gynecologic operation (OR = 3.07, p = 0.0158) were significant risk factors for PID. Pregnancy was a significant protective factor (OR = 0.25, p = .0074). Sterilisation had a significant protective effect (OR = 0.37, p = 0.0443) on multivariate analysis but not significant on univariate analysis. The results indicated that, almost half of the PID load on the population can be reduced by proper handling of four risk factors namely, use of IUD, sexual activity with multiple partners, history of previous PID and history of minor gynecologic operation (PARP = 0.2146, 0.1101, 0.0824 and 0.0794, respectively).

Sequential pattern of non-medical drug use in the drug career of opiate dependents in Nagpur, India.

A study was carried out in a group of opiate addicts who reported to various centers in Nagpur city, India, to know the sequential pattern of nonmedical drug use in the drug career of opiate dependents in Nagpur. The mean age of the study group was 28.2 years, the majority were males, educated up to 10th standard, employed in various occupations like petty business, vehicle driving, etc, with an average monthly income of Rs. 316. The average number of drugs ever used per person was 3.7 +/- 1.2, those recently used was 2.6 +/- 0.9 and currently used was 2.2 +/- 0.6. The study group experienced 13 drug types in their addict careers. Beedi¿cigarette was the first drug abused by the majority. Drug careers starting with beedi¿cigarette, progressing to alcohol and then to canabis and finally to heroin were observed in a majority of subjects. There appeared to be a shift from multidrug use to the singular combination of heroin and beedi¿cigarette currently. Use of all other drugs declined in favor of heroin as the career progressed. The study indicates that preventive programs should be directed at reducing the use of initial drugs like beedi¿cigarette and alcohol and also reducing the social acceptability of these drugs as measure for preventing progression to hard drugs like heroin.

Effectiveness of mass neonatal BCG vaccination in the prevention of pulmonary tuberculosis: a case-control study in Nagpur, India.

SETTING: Government Medical College, Nagpur, India, a tertiary care hospital. OBJECTIVE: To estimate the effectiveness of mass neonatal BCG vaccination in the prevention of pulmonary tuberculosis in Nagpur, India. DESIGN: A hospital-based pair-matched case-control study with a case of 1:3, including 144 cases of pulmonary tuberculosis and 432 controls. RESULTS: The overall vaccine effectiveness estimated in the present study was 60% (95% Confidence Interval [CI] 43%-72%). The protective effect was more in males in the age group 21-30 years. The prevented fraction was 39% (95% CI 24%-52%). CONCLUSION: The moderate effectiveness demonstrated in this study needs to be substantiated for other forms of tuberculosis by undertaking community-based case-control studies, before attempting to justify the use of mass neonatal BCG vaccination strategy as a part of the national programme.

Burns in pregnancy: effect on maternal and fetal outcomes.

Burn injury during pregnancy is known to have adverse effects on fetal and maternal survival. Any hope of reducing the high mortality lies in identifying the risk factors responsible for the poor maternal and fetal outcome. A prospective study cohort of 50 pregnant burned patients, a comparison cohort of 50 uncomplicated singleton pregnancies and another comparison cohort of 50 non-pregnant burned females were followed up for fetal and maternal survival or death at the Government Medical College & Hospital, Nagpur, India. The effect of maternal factors on the maternal and fetal survival were assessed. Most of the patients (64 per cent) were severely burned, i.e. > 60 per cent TBSA with 100 per cent fetal and maternal mortality. There was 50 per cent maternal and fetal loss in the 40-59 per cent TBSA group. A fetal loss of 11.1 per cent was noted in the 20-39 per cent TBSA group with no maternal loss. Survival analyses using the Kaplan-Meier survival analysis and the Cox Proportional Hazards model showed that TBSA burned was the only factor found to be statistically significantly (P < 0.0001) responsible for the adverse fetal and maternal outcome. Pregnancy did not alter the maternal survival. Adequate shock management and early excision with grafting could reduce the mortality figures. Prevention of injury during pregnancy still appears to be the best option.

A risk scoring system for prediction of coronary heart disease based on multivariate analysis: development and validation.

Considering the multifactorial disposition and the need of primordial prevention of coronary heart disease (CHD), a risk scoring system for the prediction of CHD was devised at Govt Medical College, Nagpur, India. In this pair-matched case-control study of 154 cases and 154 age and sex matched controls, socioeconomic status, physical inactivity, family history of CHD, type A personality characteristic, cigarette smoking, alcohol consumption, body mass index, diabetes mellitus, hypertension, total serum cholesterol and oral contraceptive use (in women) were studied for association with CHD. The additive risk scoring system based on the results of conditional multiple logistic regression identified five factors, namely, socioeconomic status, physical inactivity, diabetes mellitus, hypertension and toal serum cholesterol with statistical weights of 3,5,2,4 and 5 respectively. On back-validation using receiver operating characteristic (ROC) curve, a total score of 12 was found to be the cut off point above which there was increased risk of CHD. The overall predictive accuracy of this system-equivalent to the area under the ROC curve-was 0.7962 (95% Confidence Interval 0.7468-0.8455). On prospective validation using a separate group of 140 cases and 140 controls, the predictive accuracy was found to be 0.6964 (95% Confidence Interval 0.6341-0.7587). Future studies need to assess the risk scoring system in population based studies.