Histotyping of Indian thymomas: A clinicopathologic study from north India

Background & objectives: Thymomas are rare, but most common anterior mediastinal lesions. The histomorphologic spectrum of thymic epithelial tumours (TETs) in Indian population has not been explored in depth. This study was aimed to assess the histomorphology of TETs in the Indian patients and correlate clinical parameters with pathological features. Methods: It was a retrospective study conducted in a tertiary referral hospital in north India. All morphologically confirmed cases of TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinicopathological correlation and survival analysis were done. A comparative review from other published Indian studies was performed. Results: A total of 219 cases of TETs (138 resections and 81 biopsies) were identified. The most common histomorphologic type was B2, and the most frequent stage was I. Types A/AB were common in older age (P<0.01). Clinically, higher stage tumours were found mostly in men (P<0.01), and these were Type B thymomas (P<0.01). Myasthenia gravis was more common in women (P<0.02) and in lower stages (P<0.05). Survival analysis revealed significant association between recurrence and tumour stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified. Interpretation & conclusions: Our findings showed that the thymomas in Indian patients were most commonly Stage I tumours of B2 and AB histotypes. Resected thymic carcinomas were conspicuously absent in our study. More studies need to be done to establish the frequency and biology of TETs from India.

Prognostic significance of location of the primary tumor in operable breast cancers.

BACKGROUND: The prognostic significance of the primary tumor site in breast cancers is not established with only a few studies having evaluated the issue. MATERIALS AND METHODS: The relevance of a primary tumor site with respect to systemic disease relapse was evaluated in 187 patients with breast cancer treated with primary surgery and adjuvant chemotherapy, in whom the location of primary tumor was classifiable in any one of the three sites, namely: outer, periareolar, and inner, quadrants. Data was obtained from prospectively maintained records of breast cancer patients treated at a single surgical unit in a tertiary care center. RESULTS: The three groups were comparable with regard to demographic, pathological tumor, and treatment characteristics. In the multivariate analysis, patients with inner and periareolar quadrant tumors had a higher hazard for systemic disease relapse, (2.53, 95% CI: 1.18-5.42; P = 0.02, and 2.73, 95% CI: 1.04-7.14; P = 0.04, respectively) as compared to outer quadrant tumors. The projected five-year survival estimates in Kaplan Meier were 87%, 61%, and 69%, respectively, for outer, periareolar, and inner quadrant. On further substratification the difference was particularly noted in high risk inner quadrant tumors: age 45, premenopausal patients, tumor size> 2 cms, positive nodes and intermediate or high grade histology, as also in patients treated with breast conservation and CMF, Cyclophosphamide, Methorexate, 5 Fluorouracil chemotherapy. CONCLUSION: The location of the primary tumor influences survival in breast cancer with inferior outcome for tumors in inner and periareolar quadrants, especially in high risk groups and those treated with conservative approaches. The role of aggressive therapies merits investigation in these patients.

Effects of monosodium glutamate on food acceptance and toxicity of selenium in rats.

Food acceptance and toxic effects of feeding sodium selenite (Se) alone and in combination with monosodium glutamate (MSG), a taste enhancer were studied in the laboratory rat. Dose-dependent stimulation of daily food intake was observed with MSG offered in no-choice or bi-choice with the plain food. Consumption of pellets containing 0.05, 0.5 and 1.0% Se was significantly low than the plain or MSG containing pellets but their active ingredient was sufficient to cause mortality of rats. Food pellets containing both MSG and Se in no-choice feeding trial were not preferred by the rats, as their consumption remained low as compared to pellets containing only MSG. However, prior feeding on MSG containing pellets for two days increased the amount of intake of Se-containing pellets. No mortality of rats feeding on pellets containing different concentrations of MSG was recorded. Feeding on Se-containing pellets caused dose-dependent mortality on the third day of the trial. As compared to rats feeding on Se-containing pellets, the mortality rate was reduced in those provided Se in combination with MSG but the intake of active ingredient of Se in both these trials did not differ significantly. Decrease in death rate of rats feeding on Se in combination with MSG containing pellets suggested that addition of MSG to seleniferous food probably provide protection to some extent from the toxic effects of selenium. However, combination of excess doses of MSG and Se in food pellets caused mortality of all experimental animals.

Second echelon node predicts metastatic involvement of additional axillary nodes following sentinel node biopsy in early breast cancer.

BACKGROUND: In many patients with early breast cancer, the sentinel lymph node (SLN) is the sole site of regional nodal metastasis. This subgroup of patients may not benefit from completion axillary lymph node dissection (CALND). AIMS: This pilot study evaluates the status of 2nd echelon (station) lymph nodes in the axilla as a predictor of additional positive nodes in the axilla in the presence of sentinel node metastasis. SETTINGS AND DESIGN: Cross-sectional study of 40 breast cancer patients. MATERIALS AND METHODS: Forty patients with invasive breast cancer underwent SLN biopsy followed by 2nd echelon lymph node biopsy in the same sitting. SLN mapping was performed using a combined technique of isosulfan blue and 99 mTc-sulfur colloid. SLNs (Station I) were defined as blue and/or hot nodes. These nodes were then injected with 0.1 ml of blue dye using a fine needle and their efferent lymphatic was traced to identify the Station II nodes. Then a complete ALND was performed. All the specimens were sent separately for histopathological evaluation. RESULTS: SLNs (Station I nodes) were successfully identified in 98% (39/40) patients. Of the 17 patients with a positive SLN, 8 (47%) patients had no further positive nodes in the axilla, 9 (53%) patients had additional metastasis in nonsentinel lymph nodes upon CALND. Station II nodes were identified in 76% (13/17) patients with a positive SLN. Station II nodes accurately predicted the status of the remaining axilla in 92% patients (12/13). STATISTICAL ANALYSIS: We calculated the Sensitivity, Negative predictive value, Positive predictive value, False negative rate and Identification rate. CONCLUSION: Station II nodes may predict metastatic involvement of additional nodes in the axilla.

Effect of preoperative short course famotidine on TILs and survival in breast cancer.

BACKGROUND: Histamine receptor antagonists have been shown to induce tumor-infiltrating lymphocytes (TILs) in colonic cancers and improve survival. The role of histamine receptor anatagonists in breast cancer is unclarified. AIM: To evaluate the role of histamine receptor antagonists in inducing (TILs) in breast cancer. METHOD: Forty-five patients with operable breast cancers (25 cases who received preoperative famotidine and 20 controls) were studied for the effect of famotidine in inducing TILs and survival in breast cancer. RESULTS: Significant TILs were seen in 75% (18/24) of cases as opposed to 35% (7/20) controls. In logistic regression analysis the only variable found to be predictive of TILs was famotidine, odds ratio 7.324 (1.693-31.686) P=0.008. In Cox's regression presence of TILs was favorably associated with improved disease free survival at a median follow up of 35.56 months. The hazard ratio for disease relapse was 3.327 (1.174-9.426) P=0.024 in TIL negative as compared to TIL positive patients. Famotidine use alone was not significant in the original model, however, on incorporation of quadrant of involvement in addition to other established prognostic factors in the above multivariate model, it assumed borderline significance with a hazard ratio for disease free survival 3.404 (1.005-11.531, P=0.049). CONCLUSIONS: Preoperative short course famotidine induces TILs in breast cancer. Patients with TILs demonstrable in tumor specimens had an improved disease free survival. Famotidine may improve disease free survival in breast cancer and these findings need validation in larger population subsets.

Neoadjuvant chemotherapy in squamous cell carcinoma of the esophagus using low dose continuous infusion 5-fluorouracil and cisplatin: results of a prospective study.

BACKGROUND: Surgery is the treatment of choice for localized esophageal squamous cell carcinoma (ESCC). Despite curative surgical resection, the majority of patients develop local and systemic recurrence with poor 5-year survival. AIMS: To study the role of low dose continuous infusion (CI) 5-fluorouracil (5-FU) and cisplatin as neoadjuvant chemotherapy in ESCC. SETTINGS AND DESIGN: A non-randomized prospective study conducted over a period of two years (1996-1998) in the Department of Surgery, All India Institute of Medical Sciences, India. MATERIAL AND METHODS: Twenty-two patients with ESCC were included in the study. Chemotherapy consisted of a continuous 30-day infusion of 5-FU (350 mg/m2/day) and cisplatin (7.5 mg/m2/day), 5 days/week for 4 weeks. All patients had surgery following chemotherapy. RESULTS: A full course of chemotherapy was completed in 18 patients (82%). Chemotherapy was not completed due to non-compliance (n=2), thrombophlebitis (n=1), and vomiting (n=1). Grade-1 haematological and hepato-toxicity was observed in four patients. Thirteen patients developed thrombophlebitis. After chemotherapy, improvement in dysphagia was observed in 13 of 22 (59%) patients. Radiological partial response was observed in 8 patients (36.4%). 19 patients underwent surgical resection (86.4%) with zero mortality. Post-operative morbidity was observed in six patients (27%). Complete and partial pathological response was observed in two (11%) and one patient (5.5%) respectively. The overall median survival was 18 months and 4-year survival was 42%. CONCLUSIONS: Low dose CI 5-FU and cisplatin is well tolerated with minimal toxicity. Histopathological response rates and survival figures are comparable with the more toxic neoadjuvant chemotherapeutic regimens.

Laparoscopic Management of Splenic Pseudocyst

Splenic cysts are rare entities. They are either true cysts or pseudocysts. Former is thought to be congenital or parasitic while the latter are considered post-traumatic. Developments in imaging and operative surgery have led to significant changes in the management of these cysts. We present a case of young male with a large splenic pseudocyst who was managed successfully by minimally invasive surgical approach. Pertinent literature is reviewed briefly.

Cystogenesis of antral follicles induced by dehydroepiandrosterone (DHEA) stimulates mast cell proliferation and maturation in the house rat (Rattus rattus) ovary.

Mast cell dynamics has been studied in relation to cystogenesis of ovarian follicles in the house rat. Immature rats were injected (s.c.) daily with DHEA (6.0 mg/100 g body weight) and were sacrificed on the day 8, 16 and 24 of the start of treatment. Ovarian sections of the treated rats had majority of the antral follicles undergoing atresia or in early stages of cystogenesis. Completely developed cysts were evident from the ovarian surface after 24 days of daily treatment. Treatment for 8 days resulted in significant increase in the number of alcian blue-positive ovarian mast cells. Ovaries after 16 days of DHEA treatment showed no marked change with regard to the number of total mast cells per unit area and staining characteristics. However, a significant rise in ovarian mast cell counts was recorded after 24 days of treatment and most of the cells contained safranin-positive red granules. This increase was attributed due to the increase in their number in medulla and stroma around the cystic follicles.

Effects of selenium toxicity on oestrous cyclicity, ovarian follicles, ovulation and foetal survival in rats.

Effects of intraperitoneal injections of sodium selenite (2.0 and 4.0 mg/kg body weight) to normally cycling female albino Wistar rats daily for 30 days, and of single injection either during proestrous or oestrous and at each stage of the 4-day oestrous cycle were determined on oestrous cyclicity, ovarian follicles, ovulation, implantation and pregnancy outcome on day 14 of gestation. Administration of selenite for 30 days had no effect on the duration of first two oestrous cycles but afterwards the rats remained at the dioestrus stage. Their ovaries developed cystic follicles. Selenite treatments during the oestrous cycle preceding mating affects the implantation and pregnancy outcome in a dose-related manner. Its single dose containing 2.0 mg/kg body weight administered either at proestrous or oestrous, though had no effect on different reproductive parameters investigated in this study but its daily dose during the 4 day oestrous cycle reduced the number of corpora lutea and implantations as compared to saline injected control female rats. Similar effects of a single dose of selenite (4.0 mg/kg body weight) when injected at proestrous were recorded. Higher dose of selenite at oestrous or throughout the cycle decreased the number of implantations, but in addition, also increased the resorption rate/litter on day 14 of gestation. The present studies clearly show that high selenium levels in the body during the oestrous cycle preceding mating affects the number of ovulations, implantations and live embryos depending upon its dose and stage of administration.

Video assisted thoracoscopic surgery (VATS) in the diagnosis of intrathoracic pathology: initial experience.

We report our experience with the use of video-assisted thoracoscopic surgery [VATS] in the diagnosis of intrathoracic disease of unknown origin. In the last two years, 32 patients (18 males) underwent this procedure for diagnostic purposes. Of them, 18 patients had lung pathology, eight mediastinal and six pleural disease. All attempts at achieving a tissue diagnosis were unrewarding. In all of them, diagnostic thoracotomy was being contemplated to procure tissue for histopathological diagnosis. Diagnostic thoracoscopy was successful in providing tissue diagnosis in all the patients with lung disease; seven of the eight patients with mediastinal pathology and five of the six patients with pleural lesions. Diagnostic thoracoscopy was associated with minimal morbidity, short hospital stay, better cosmetic result and quicker return to work as compared to conventional thoracotomy. We conclude that video-assisted thoracoscopy is an excellent diagnostic tool to confirm tissue diagnosis in patients with undiagnosed chest diseases.

Adjuvant therapy in colorectal cancer.

Current evidence suggests that there is no role of adjuvant chemotherapy in stage I colon cancer. Patients with stage II colon cancer also do well without any adjuvant therapy with 5 year survivals of upto 80% with surgery alone. However, the role of adjuvant therapy in high risk stage II colon cancer (T4b) needs further evaluation. In stage III colon cancer adjuvant chemotherapy leads to definite survival advantage and is therefore strongly recommended. 5 FU and levamisole given for one year is the standard of care. 5 FU with leucovorin given for six months has shown good results and may become the standard of care in future. In rectal cancer, adjuvant treatment is not recommended for stage I tumours. In patients with stage II & III rectal tumours, a combination of chemotherapy and radiotherapy has given best results.

Quantitative assessment of changes and maturation of mast cells in the ovary of postnatal and adult rats, Rattus rattus.

Numerical changes in the distribution of immature mast cells in the different ovarian compartments of the immature and adult ovary of rats Rattus rattus have been studied using alcian blue-safranine staining method. Maturational changes of mast cells from the first day of birth to maturity of animal and during the oestrous cycle have also been determined. Immature animals were divided into five groups on the basis of their increasing body weights. All the mast cells in the ovary group of I and II were immature as they showed positive staining with alcian blue and appear to possess the proliferative capacity. Cells containing safranine-stained red granules were first observed in group III rats and they appeared simultaneously in hilus, medulla and cortical regions of the ovary. Total counts of immature mast cells per ovary increased significantly from group I to II, decreased in group III and thereafter no change was recorded in group IV and V. Mast cells in the ovary of rats of group I and II were mainly localized in the stroma, followed by medulla and hilus. In mature rats major part of cell population was concentrated in the hilar region. Alcian blue-positive mast cells were observed at all stages of oestrous cycle, their number per ovary was found to be highest at oestrus, intermediary at dioestrus and metoestrus, and lowest at pro-oestrus which suggested that new population of mast cells continue to differentiate in the cycling rat ovary.

Omental rhabdomyosarcoma presenting with pyrexia.

A 45-year-old man was admitted with pyrexia and intermittently palpable lump in the left lumbar region. Laparotomy revealed a primary omental tumor which on histological examination showed alveolar rhabdomyosarcoma of the omentum. Following surgery the fever subsided. Presentation of omental rhabdomyosarcoma with fever has not been reported earlier.

Failure of hCG to reverse incipient atretic changes induced in granulosa cells of rat ovarian follicles.

Surface membrane changes in the granulosa cells from follicles at different times following a single dose of PMSG have been investigated after the incubation of cells in media with and without hCG by spectrophotometric measure of concanavalin A-induced cellular agglutination rate. Agglutination rate and final level of agglutination of cells do not change from 24 to 48 hr but significantly rise at 72, 96 and 120 hr after PMSG administration. Incubation of cells in presence of hCG for 20 min decrease the agglutination level of cells at 24, 48 and 72 hr and no significant change was observed at 96 and 120 hr. The results, thus suggest that atretic changes when induced in the surface membrane of granulosa cells (after 72 hr of PMSG administration) cannot be reversed with hCG.

Effect of restricted feeding of prepubertal and adult male rats on fertility and sex ratio.

Food consumption per day per rat decreased in animals kept on restricted feeding schedules (2, 4, 8 and 12 hr) during adulthood but it remained unchanged in immature rats except in a group which was restricted to feed for 2 hr. The body weight gain decreased significantly in both the age groups. Epididymal sperm concentration did not change with feeding restriction in adult rats but decreased significantly in rats which attained puberty during the study period. Conception rate in females after mating with males under study decreased considerably. Percentage of female pups was greater in litters obtained after mating with males kept on 2, 4 and 8 hr per day feeding schedules during prepubertal period. The results, thus reveal that restricted feeding during prepubertal period decreases fertility and affects sex ratios in rats.

Role of enteral hyperalimentation in patients of carcinoma oesophagus.

The nutritional status of 24 patients of carcinoma oesophagus was assessed before and after central hyperalimentation with a liquid blenderized diet containing 3000-3500 cal and 100-120 g protein. The overall prevalence of malnutrition was found to be 70.8 per cent before the initiation of therapy. Of the various parameters used for assessment of nutritional status weight loss was the most common finding (91.6%) followed by alteration in midarm circumference, haemoglobin, triceps skin fold thickness, midarm muscle circumference and serum albumin. Enteral hyperalimentation for 10 days improved nutritional status by inducing significant gain in body weight (74.1%), triceps skin fold thickness (50%), midarm circumference (58%), midarm muscle circumference (62.5%) and serum albumin levels (91.6%). There was no significant change in haemoglobin levels.

Changes in catalase activity during follicular growth, atresia and luteinization in rat ovary.

Quantitative changes have been observed in the catalase activity during follicular growth, induced atresia and in corpora lutea of cycle and pregnancy. Large growing and preovulatory follicles showed higher enzyme activity as compared to the smaller follicles; the activity was mainly present in the thecal layer of the preovulatory follicle. After the blockade of ovulation with barbiturate, the activity increases significantly in the whole follicle and also in the thecal layers till third day of ovulation and afterward it declines on 5th day, suggesting that rise in catalase activity may exert a protective function against lytic actions of peroxide which is known to be produced in the ovary during several metabolic and steroidogenic events. The corpora lutea of the cycle showed significantly less enzyme activity than the corpora lutea of pregnancy. The significance of catalase activity during follicular and corpus luteum degeneration is discussed.

Chemotactic detection of incipient ovarian follicular atresia.

Chemotactic activity was measured in the follicular fluid collected from normal and atretic Graafian follicles isolated from the rat ovaries. The atresia of Graafian follicles was induced by pentobarbitone injections for 3 days beginning the day of proestrous. The chemotactic activity, as measured by direct morphological evaluation of cellular locomotion of individual cells and Boyden leading front assay, was significantly higher in follicular fluid from atretic follicles and it showed a progressive increase from day 1 to day 3 of blockade of ovulation. In vitro exposure of blocked follicles to PMSG and hCG on day 1, 2 and 3 failed to alter the chemotactic response of leukocytes towards follicular fluid of atretic follicles. Increased chemotaxis in the follicular fluid after 24 hr of blockade of ovulation appears to form an important criterion to identify atretic follicles well in advance, before the morphological symptoms of degeneration become apparent and the incipient change once induced in follicles is not reversed by gonadotropins.

Comparison of glucose-6-phosphate dehydrogenase activity in healthy and atretic follicles in rat ovary.

Changes in the glucose-6-phosphate dehydrogenase activity have been determined in relation to atresia of Graafian follicles in the rat ovary. Induction of atresia in follicles either due to absence of hCG in the hormonally stimulated immature ovaries or by repeated injections of pentobarbitone sodium to proestrous rats caused significant rise in the enzyme activity. Measurement of enzyme activity in isolated follicular compartments of healthy and atretic follicles revealed that it is significantly higher in the thecal tissue than the granulosa. Increase in enzyme activity in the atretic follicles than the healthy ones occurs due to its rise both in theca and granulosa cells. The significance of these changes in the enzyme activity in healthy and atretic follicles are discussed in relation to the precocious luteinization of cells in the follicular envelope with the onset of atresia.

Mast cell dynamics in relation to ovulation in rat ovary.

Quantitative changes in the total number and distribution of ovarian mast cells have been studied after administration of histamine and pentobarbitone sodium to rats at pro-oestrous stage. No significant differences in the total cell counts per section and percentage distribution in the hilar and stromal regions of the ovary were observed after blockade of ovulation with pentobarbitone as compared to control. However, after 24 hr of histamine treatment the number of cells was significantly less than that of oestrous stage but no change was seen relative to the pro-oestrous stage. The results suggest that the number of cells increases late in the pro-oestrous stage by invasion or differentiation in the stroma to maintain the requisite levels of histamine during ovulation.