Cancer trends and burden among Armed Forces personnel, veterans and their families: Cancer registry data analysis from tertiary care hospital.

Background: Cancer incidence is rising across the globe. The incidence and patterns of various cancers among Armed Forces Personnel and Veterans is not known. We did the analysis of registry data maintained at our hospital. Methods: A retrospective analysis was performed of all patients registered at our hospital cancer registry between 01st January 2017 and 31st December 2019. Patients were registered with unique identification number. Baseline demographics and cancer subtype data were retrieved. Patients with histopathologically proven diagnosis and age ≥18 years were studied. Armed Forces Personnel (AFP) were defined as those who are in active service, and Veterans as those who had retired from service at the time of registration. Patients with Acute and Chronic Leukemias were excluded. Results: New cases registered were 2023, 2856 and 3057 in year 2017, 2018, 2019 respectively. AFP, Veterans and dependents among them were 9.6%, 17.8%, and 72.6% respectively. Haryana, Uttar Pradesh and Rajasthan represented 55% of all cases with male to female ratio 1.14:1 and median age was 59 years. The median age among AFP was 39 years. Among AFP as well as veterans, Head and Neck cancer was the most common malignancy. Cancer incidence was significantly higher in adults >40 years as compared to <40 years. Conclusion: Seven percent rise per year of new cases in this cohort is alarming. Tobacco-related cancers were the most common. There is an unmet need to establish a prospective centralized Cancer Registry to better understand the risk factors, outcomes of treatment and strengthen the policy matters.

Observational Study to Determine the Involvement of Level III Lymph Nodes in Case of Clinically Positive Level II Nodes in Carcinoma Breast.

Management of breast cancer has gradually shifted from era of radical surgery to present days of multimodality management and conservatism. Management of carcinoma breast is primarily multimodality of which surgery is one of the important roles to play. Our study is a prospective observational study to determine the involvement of level III axillary lymph nodes in clinically involved axilla with grossly involved lower-level axillary nodes. Underestimation of a number of involved nodes at level III shall result in inaccuracy of subset risk stratification leading to substandard prognostication. The enigma of not addressing presumably involved nodes thereby altering the staging vs acquired morbidity has always been a contentious issue. Mean lymph node harvest at the lower level (I and II) was 17.9 ± 6.3 (range: 6-32) while positive lower-level axillary lymph node involvement was 6.5 ± 6.5 (range: 1-27). The mean ± SD for level III positive lymph node involvement was 1.46 ± 1.69 (range: 0-8). Our prospective observational study though limited by the number and years of follow-up has demonstrated that the presence of more than three positive LN at a lower level increases the risk for higher nodal involvement substantially. It is also evident in our study that PNI, ECE, and LVI increased the probability of stage up-gradation. LVI was found to be a significant prognostic factor for apical LN involvement in multivariate analysis. On multivariate logistic regression > 3 pathological positive lymph nodes at the level I and II and LVI involvement elevated the risk of involvement at level III by 11 and 46 times, respectively. It is recommended that patients who have a positive pathological surrogate marker of aggressiveness should be evaluated perioperatively for level III involvement, especially in the setting of visible grossly involved nodes. The patient should be counseled and informed decision to perform complete axillary lymph node dissection with the added risk of morbidity should be contemplated.

Zinner Syndrome with Papillary Neoplasm: A Rare Case Report.

One of the uncommon urogenital malformations in males, which presents late in the second or third decades of life, is the congenital malformation of the seminal vesicle. Zinner syndrome is a rare condition comprising a triad of unilateral renal agenesis, ipsilateral seminal vesicle obstruction, and ipsilateral ejaculatory duct obstruction. Very few cases in the literature describe the malignant change in seminal vesicle cyst in Zinner syndrome. To the best of our knowledge, this is the first report of a papillary neoplasm of the seminal vesicle cyst developed in a patient with Zinner syndrome.

Surgical and Functional Outcomes of En Bloc Resection of Sacral Chordoma: a Retrospective Analysis.

Conventional chordomas occur most commonly in the sacral region. Currently, wide local excision remains the only hope for a cure in this disease. However, given the substantial morbidity caused by sacrectomy, a delicate balance needs to be established. This study elaborates our experience in managing these complicated cases with the help of a multidisciplinary team approach and outlines the various surgical and functional outcomes of sacrectomy. This was a retrospective observational study. Ten cases of biopsy proven sacral chordoma underwent en bloc resection by a posterior approach from 2011 to 2018 after multidisciplinary evaluation. Data collected and analyzed included demographics, extent of the disease, and operative parameters such as operative time, estimated blood loss, level of vertebral resection, level and number of the most caudal nerve roots preserved, surgical margins, soft tissue, or spinal reconstruction. Postoperative outcomes included time to recurrence and neurological function at 1 year. Mean size of the tumor was 116.1 mm. Three (30%) patients had positive margins. The median time to recurrence was 32 months. Four patients eventually succumbed to the disease due to local or distant recurrence. Bladder and bowel functions were excellent in those with preserved S3. Two patients remained wheelchair bound; the rest were able to walk with or without support. Management of sacral chordoma remains an onerous journey for both the treating surgeon and the patient. A multidisciplinary team approach, with careful preservation of sacral nerve roots, negative surgical margins, and excellent postoperative rehabilitation, can achieve optimum results.

Cytomorphology of hibernoma: a report of 2 cases.

BACKGROUND: Hibernoma, a benign neoplasm of the brown fat, clinically and radiologically can mimic a lipoma or liposarcoma, especially in the retroperitoneum. As treatment modalities vary, an accurate preoperative diagnosis may help the surgeon to plan treatment. Hence cytologic features of 2 cases of hibernoma are described. CASES: Two middle-aged men diagnosed clinically as having lipomas were subjected to fine needle aspiration (FNA). Smears revealed typical hibernoma cells with a minor percentage of eosinophilic cells and mature adipocytes. CONCLUSION: FNA is a highly sensitive and specific tool for the diagnosis of hibernoma.

Characteristics of the beta-galactosidase-carboxypeptidase complex in GM1-gangliosidosis and beta-galactosialidosis fibroblasts.

Lysosomal beta-galactosidase (beta-Gal) occurs either alone in monomeric and dimeric forms, or in a high-M(r) complex with at least two additional proteins. One is neuraminidase and the second is the protective protein, which has also been shown to possess carboxypeptidase activity. beta-Gal activity is deficient in GM1-gangliosidosis as a primary defect, and is secondarily affected in galactosialidosis (GS), where the primary defect is the absence of protective protein activity. Fibroblasts from three patients with GM1-gangliosidosis, type 1, showed markedly reduced amounts of beta-Gal cross-reacting material (CRM), and a fourth appeared to have normal levels. A patient with type 2 GM1-gangliosidosis was also found to be CRM-normal. These findings demonstrate that patients with GM1-gangliosidosis type 1 are heterogeneous with respect to the level of residual beta-Gal protein. Fibroblasts from four patients with GS were strongly CRM-positive with an anti-beta-Gal antibody, as was a sample of brain from one of these patients, suggesting that the loss of beta-Gal activity is linked to a subtler change in the primary structure of the enzyme than has been previously thought. While three GS cell lines displayed reduced carboxypeptidase activity (to 32-42% of the control), one cell line was completely devoid of activity, demonstrating that while carboxypeptidase activity is a property of the protective protein this action is distinct and separate from its protective role. On direct immunoprecipitation with anti-beta-Gal antibody, a portion of the total carboxypeptidase activity co-precipitated with beta-Gal from extracts of normal and GM1-gangliosidosis cells, consistent with the presence of the complex in these cells. However, no carboxypeptidase activity was precipitable with this antibody from GS fibroblasts, suggesting the absence of complex from these cells. To examine this further, the various forms of beta-Gal were resolved by h.p.l.c. molecular-sieve chromatography. Three forms of beta-Gal activity were resolved in normal cells: a complex, a dimer and a monomer. Residual beta-Gal activity of GS cells resolved into two of these forms, the complex and the monomer. In normal and GM1-gangliosidosis cells a portion of the total carboxypeptidase activity co-chromatographed with the complex while the bulk of the activity occurred in a single 36,000-M(r) peak. Only the low-M(r) carboxypeptidase activity was detected in GS cells. This confirms our results on immunoprecipitation indicating that portions of the beta-Gal and the carboxypeptidase activities exist outside the complex in normal, GM1-gangliosidosis and GS cells. In summary, the loss of protective protein function from GS cells results in disproportionate loss of the dimeric and monomeric forms of beta-Gal activity, but does not result in the complete degradation of the protein.

Characterization of arylsulfatase C isozymes from human liver and placenta.

Arylsulfatase C and steroid sulfatase were thought to be identical enzymes. However, recent evidence showed that human arylsulfatase C consists of two isozymes, s and f. In this study, the biochemical properties of the s form partially purified from human placenta were compared with those of the f form from human liver. Only the placental s form has steroid sulfatase activity and hydrolyses estrone sulfate, dehydroepiandrosterone sulfate and cholesterol sulfate. The liver f form has barely detectable activity towards these sterol sulfates. With the artificial substrate, 4-methylumbelliferyl sulfate, both forms demonstrated a similar KM but the liver enzyme has a pH optimum of 6.9 while the placental form displayed two optima at 7.3 and 5.5. The molecular weight of the native enzyme determined with gel filtration was 183,000 for the s form and 200,000 for the f form and their pI's were also similar at 6.5. However, the T50, temperature at which half of the enzyme activity was lost, was 49.5 degrees C for the f form and 56.8 degrees C for the s form. Polyclonal antibodies raised against the placental form reacted specifically against the s and not the f form. They immuno-precipitated concomitantly greater than 80% of the total placental arylsulfatase C and steroid sulfatase activities while less than 20% of the liver enzyme was immuno-precipitable. In conclusion, the two isozymes s and f of arylsulfatase C in humans purified from placenta and liver, respectively, have similar KM, pI' and native molecular weight. However, they are distinct proteins with different substrate specificity, pH optima, heat-lability and antigenic properties. Only the s form is confirmed to be steroid sulfatase.

Cholesterol esterification and Niemann-Pick disease: an approach to identifying the defect in fibroblasts.

Fibroblasts from 13 patients with the clinical phenotype of type IIS, Niemann-Pick disease were evaluated for their ability to incorporate oleic acid into cholesterol esters via an LDL responsive mechanism. Eight patients displayed a severe deficiency (less than 8% of normal) of cholesterol ester (CE) synthesis while a clinically less affected group displayed intermediate levels (36% of normal) of synthetic capacity with no detectable overlap between these groups and the control range. There was no deficiency in cholesterol ester production in fibroblasts from a patient with Zellweger's disease, a disorder characterized by altered peroxisomes and abnormal peroxisomal cholesterol metabolism, while in I-cell disease, characterized by a primary deficiency of a phosphotransferase which results in altered targeting of lysosomal hydrolases, it was reduced to 25% of the control level. To further implicate lysosomal proteins in the etiology of type IIS, Niemann-Pick disease we measured the effect of correction (conditioned) medium, and the lysosomotropic agent, NH4Cl on cholesterol ester synthesis in fibroblasts. NH4Cl completely inhibited incorporation into CE by normal cells, thus mimicking the CE defect in type IIS, Niemann-Pick cells. Conditioned medium had no effect on incorporation into CE synthesis but medium conditioned in the presence of 10 mM NH4Cl stimulated incorporation into CE in the control but not in Niemann-Pick cells. When Niemann-Pick cells cultured in the presence of NH4Cl were challenged to synthesize CE in the absence of NH4Cl, a significant enhancement of CE synthesis was noted in representative cell lines from both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of lactate accumulation on Na+, K+-ATPase activity of ischemic and post-ischemic brain.

In this study the cerebral Na+, K+-ATPase activity as well as selected parameters of oxidative metabolism and electrophysiological function were assessed in normoglycemic and hyperglycemic rats which were exposed to ischemia produced by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. In hyperglycemic animals 0.5 h of ischemia was associated with massive accumulation of lactate (34 mumol X g-1) and enhanced Na+, K+-ATPase activity (116% control), whereas normoglycemic animals showed more moderate lactate accumulation (17 mumol X g-1) and normal Na+, K+-ATPase activity (102% control). In normoglycemic animals release of the carotid clamps and recirculation for 0.5-1.5 h was associated with a normalization of the lactate levels and a decrease in Na+, K+-ATPase activity (68-72% control). Restituted hyperglycemic animals showed metabolic changes which seemed related to the blood pressure, with hypotensive hyperglycemic animals showing continuing massive lactacidosis (30-35 mumol X g-1) and enhanced Na+, K+-ATPase activity (108-110% control), whereas normotensive hyperglycemic animals showed progressive decreases in lactate level (14-20 mumol X g-1) and normal or mildly suppressed Na+, K+-ATPase activity (88-97% control). These patterns of change suggest that the reperfusion of the post-ischemic hyperglycemic-hyperlactacidotic brain was inadequate or non-homogeneous.

The effects of imidazole-4-acetic acid on cerebral carbohydrate metabolism.

The effects of intravenous administration of 50-400 mg/kg imidazole-4-acetic acid (IMA) on the carbohydrate metabolism of the rat brain were assessed by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic--citric acid cycle metabolites. IMA (100-400 mg/kg) produced a spectrum of electroencephalographic (EEG) change ranging from desynchronization to electrical suppression which was associated with unchanged tissue contents of ATP, ADP, and AMP, increasing levels of phosphocreatine, glucose, and aspartate, and decreasing levels of pyruvate, lactate, alpha-ketoglutarate, and malate. The changes in glycolytic intermediates were present within 5 min of injecting IMA (200 mg/kg) and the pattern suggested a suppression of glycolysis. The EEG stage of electrical suppression with episodic spiking (400 mg/kg) was associated with a 30% reduction of cortical high-energy phosphate use. The lowest dose of IMA (50 mg/kg) resulted in episodic EEG desynchronization which was associated with no significant changes of the measured metabolites. The results indicate that IMA is associated with metabolite changes that are compatible with a state of cerebral depression and that the desynchronous EEG pattern is without a biochemical correlate of increased neuronal activity.

High pressure neurological syndrome: antagonistic effects of helium pressure and inhalation anesthetics on the dopamine-sensitive cyclic AMP response.

The antagonistic effects of helium pressure and certain inhalation anesthetics on the dopamine-sensitive cAMP response in the caudate nucleus of rat brain were examined. Helium pressure suppressed basal, dopamine-stimulated, and anesthetic-stimulated cAMP levels. These data indicate that by reversing the effects of pressure on dopaminergic transmission in the brain, inhalation ahesthetics may account for the improvement of some clinical symptoms of high pressure neurological syndrome (HPNS).