Clinical characteristics with patterns of relapse and survival analysis of ovarian clear cell carcinoma.

AIMS: To analyze clinical characteristics, patterns of relapse, and treatment outcomes of clearcell carcinoma of the ovary (CCO). MATERIALS AND METHODS: Case files of 51 patients diagnosed with CCO between 2003 and 2010 were reviewed. RESULTS: The median age at diagnosis was 48 years (27-64 years). Fifty percent presented with nonspecific gastrointestinal symptoms. The median serum Ca125 was 74 IU/ml (6-1567 U/ml). Optimal cytoreduction was achieved in 32 (62.7%) patients. Of the 51 patients in this series, 34 (66.6%) had Stage I disease; Stage Ia in 12 (23.6%), Stage Ib in 1(1.9%), and Stage Ic in 21 (41.1%). Thirteen (25.6%) presented with Stage III and 4 (7.8%) with Stage IV. No patient had Stage II disease. All patients received 4-6 cycles of platinum-based combination chemotherapy. There were 18 relapses (35.2%), with disease-free intervals <6 months in 9, 6-12 months in 4, and >12 months in 5, respectively. Of them 33.3% had a recurrent pelvic mass. The median survival after relapse was 14 months. There were 13 deaths, 11 due to disease progression, 1 due to chemo toxicity, and 1 unrelated to disease. At a median follow up of 28 months, disease-free survival (DFS) and overall survival (OS) of patients with Stage I-Stage II (early) disease was 64% and 80%, respectively. In patients with advanced disease, that is, Stages III and IV, DFS and OS were 35% and 38%, respectively. CONCLUSION: CCO generally presents at an early stage but has a high propensity for relapse. Patients with early-stage disease have a relatively good prognosis as compared with those with advanced-stage disease.

An audit of histopathology reports of carcinoma endometrium: experience from a tertiary referral center.

BACKGROUND: The aim was to assess compliance to reporting minimum data sets in carcinoma endometrium reports, in a team of 13 pathologists, and also to analyze parameters such as. tumor size, type, grade, depth of myometrial invasion, lymph node yield, pTNM stage etc. MATERIALS AND METHODS: Reports of 114 cases of carcinoma endometrium, that were operated in-house during the years 2008 to 2010 were analyzed from the files of the Pathology department of our hospital. RESULTS: The median age was 58.04 years and median tumor size was 4 cm. Endometrioid adenocarcinoma was the most common type (82.5%), followed by malignant mixed Mullerian tumor (MMMT) (6.1%) and Serous carcinoma (3.5%). Grade 2 was the commonest tumor grade (42.1%). Less than half of myometrial invasion was seen in 50% of the cases and more than half of the myometrial invasion was seen in 46.5% of cases. (Information was not available in four cases). Parametrial involvement was seen in 5.3% cases. The pTNM stage was not mentioned in 71.9% reports. The median lymph node yield was 15. CONCLUSION: The compliance to adhere to and to provide minimum data information in carcinoma endometrium reports is generally good. Lymph node yield is reasonable. Mentioning of pTNM staging is to be done more meticulously. Use of proformas/checklists is recommended.

Amiodarone induced pulmonary toxicity in a case of atrial fibrillation.

Pulmonary opacities have many causes we are presenting a case of pulmonary opacity in a patient of breathlessness; who was on amiodarone for atrial fibrillation (AF).

Outcome of gestational trophoblastic neoplasia: experience from a tertiary cancer centre in India.

AIMS: Gestational trophoblastic neoplasms (GTN) comprise a spectrum of interrelated conditions originating from the placenta. With sensitive assays for human chorionic gonadotropin (ß-hCG) and current approaches to chemotherapy, most women with GTN can be cured with preservation of reproductive potential. The purpose of this analysis was to address the outcome of GTN from a developing country, as data are largely sparse from this region. MATERIALS AND METHODS: We undertook a retrospective review of GTN cases treated at our centre from 2001 to 2008. Patients of GTN were assigned to low-risk (score ≤ 6) or high-risk (score ≥ 7) categories as per the modified World Health Organization scoring system. The low-risk group was treated with single-agent methotrexate (MTX) and the high-risk group received the EMA/CO regimen. Salvage therapies were EMA/EP or BEP. Treatment was continued until serum ß-hCG values were normal for three consecutive chemotherapy cycles, after which the patients were kept on follow-up. RESULTS: In total, 70 GTN patients were treated at our institution during this period; 48 (68%) were low-risk and 22 (32%) were in the high-risk category. The median ß-hCG level was 50 000 IU/l. The lung was the most common site of metastasis, seen in 15 (21%) patients. Among 48 low-risk patients, 37 (77%) received chemotherapy, of whom 25 (68%) were treated with MTX and 24 (96%) achieved a complete response. Twelve low-risk patients (32%) received EMA/CO therapy; 10 (83%) achieved a complete response. The 22 high-risk patients received EMA/CO and of these 16 (73%) achieved a complete response, two (9%) progressed, two (9%) died of progressive disease and two (9%) were lost to follow-up. Grade 3/4 toxicities with MTX included mucositis in two (8%) and neutropenia in five (21%) patients. At a median follow-up of 16.6 months, overall survival in the low- and high-risk groups was 100 and 88.8%, respectively. CONCLUSION: Risk-stratified treatment of GTN was associated with acceptable toxicity and resulted in outcome that was comparable with international standards.

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

PURPOSE: This trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone. MATERIALS AND METHODS: Patients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery. RESULTS: A total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03). CONCLUSION: Escalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

Identification of atypical glandular cells in pap smears: is it a hit and miss scenario?.

OBJECTIVE: Glandular cell abnormality (GCA) in Pap smears is uncommon. Detection is important as the possibility of underlying high-grade lesions is greater in this entity than in atypical squamous cells of undetermined significance. This study was undertaken with an aim to correlate GCA cases with histology, scrutinize its mimics and identify cytologic features to segregate significant lesions from benign. STUDY DESIGN: A total of 22,618 conventional Pap smears were retrospectively analyzed. In all, 74 GCA cases were identified, correlated with histology and reevaluated using parameters based on architectural pattern, cellular features and background. RESULTS: This study revealed 15 false positives. On review, 11 cases [1 adenocarcinoma, 5 atypical glandular cells (AGC), not otherwise specified, 5 AGC, favor neoplasia (FN)] were recategorized as reactive. Of 9 cases reported as cervical intraepithelial neoplasia on histology, cytodiagnosis in 5 was revised from AGC-FN to high-grade squamous intraepithelial lesion involving glands. Initial overall cytohistology concordance was 79.7%. Reevaluation of the smears, based on stringent cytomorphological criteria, enhanced overall agreement to 94.59%. CONCLUSIONS: A diagnosis of AGC has considerable clinical implications. Dissociated atypical cells, nuclear membrane, architecture and chromatin pattern are the key distinguishing features between neoplastic and benign lesions.

A cystic hepatic lesion: when to worry? / La lesión cística del hígado: ¿cuándo preocuparse?

A 16-year old female presented to hospital with abdominal pain. Features on computed tomography raised the possibility of biliary cystadenoma or cystadenocarcinoma. She underwent a liver resection, and histopathology confirmed a serous biliary cystadenoma. This case is presented to highlight the radiological features of this uncommon pre-malignant condition as well as to summarize a management algorithm for cystic liver lesions.

Una mujer de 16 años de edad acudió al hospital con un dolor abdominal. Las características observadas con tomografía computarizada apuntaban a un cistoadenoma biliar o un cistoadenocarcinoma como diagnósticos diferenciales. La paciente fue sometida a una resección del hígado, y la histopatología confirmó un cistoadenoma biliar seroso. Presentamos este caso para resaltar los rasgos radiológicos de esta condición premaligna rara, así como para resumir un algoritmo de tratamiento para las lesiones císticas de hígado.

A cystic hepatic lesion: when to worry?

A 16-year old female presented to hospital with abdominal pain. Features on computed tomography raised the possibility of biliary cystadenoma or cystadenocarcinoma. She underwent a liver resection, and histopathology confirmed a serous biliary cystadenoma. This case is presented to highlight the radiological features of this uncommon pre-malignant condition as well as to summarize a management algorithm for cystic liver lesions.

Simultaneous gallbladder and bile duct cancers: revisiting the pathological possibilities.

The pathogenesis of gallbladder cancer presenting synchronously with malignancy of the bile duct has not been clearly understood. The possible causes for the simultaneous presence of these tumors could be due to local spread, metastases, de novo multifocal origin, or as part of a field change in the extrahepatic biliary apparatus. In this article, we discuss the cases of four patients with simultaneous gallbladder and bile duct malignancies and analyze their individual pathologies to provide an explanation into the mechanisms that may play a role in such conditions.

Is there a role for estrogen and progesterone receptors in gall bladder cancer?

BACKGROUND/AIMS: The concept of metaplastic and non-metaplastic types of gall bladder cancer and the likelihood of hormone receptor expression in the nuclei of tumour cells raised the possibility of a potential role for anti-estrogen therapy in gall bladder cancer. This study was carried out to determine the hormone receptors (ER/PR) expression level in gall bladder cancer using specific immunohistochemical assays and correlate it with patient and tumour histopathological characteristics. PATIENTS AND METHODS: Histopathological tumour specimens of 62 patients who underwent a radical cholecystectomy were analysed. Pronase pretreatment and primary monoclonal antibodies were used to perform immunohistochemical analysis for ER and PR. RESULTS: The histology was adenocarcinoma--predominantly, moderately to poorly differentiated (91%). Gallstones were present in 90% of the individuals. Of the 62 specimens analysed, 62 (100%) and 61 (98%) were negative for ER and PR, respectively. CONCLUSION: The high incidence of gallstone-related gall bladder cancer in India is associated with metaplasia and a tendency to poorer differentiation in the tumour histology. These tumours are consequently less likely to express hormone receptors. Thus, there does not seem to be a role for anti-hormone therapy in patients with histogenesis similar to that seen in India.

Efficacy of species specific anti-scorpion venom serum (AScVS) against severe, serious scorpion stings (Mesobuthus tamulus concanesis Pocock)--an experience from rural hospital in western Maharashtra.

BACKGROUND: Death caused by scorpion envenoming is a common event in the tropical and subtropical countries including many regions in India. Severe scorpion envenoming causes an autonomic storm producing multi-system organ-failure (MSOF) and death. OBJECTIVES: To determine the efficacy of Anti-scorpion venom serum (AScVS) in patients stung by scorpions (Mesobuthus tamulus concanesis Pocock--earlier called Buthus tamulus); to compare it with other modalities of therapy and to detect complications, if any, arising out of AScVS treatment. METHODS: Total 48 patients of severe, serious scorpion envenoming syndrome were studied during the period from 1992 to 2002. In 17 patients AScVS was the only mode of treatment. Others had received adjunctive therapy along with AScVS. RESULTS: 47 patients out of 48 scorpion sting victims recovered completely. Recovery period in patients given AScVS (10 hours) was faster than those who received alpha blockers (16-42 hours). No anaphylactic reaction with AScVS was observed. CONCLUSIONS: AScVS is effective and safe method of therapy in severe scorpion envenoming syndrome.

Portal hypertensive jejunopathy: a case control study.

BACKGROUND: Small bowel mucosa is a recognized potential source of bleeding in portal hypertension. However, the frequency of its involvement is not known. AIMS: To document the nature, severity and frequency of endoscopic and histologic changes in the jejunum in patients with portal hypertension. METHODS: Forty consecutive patients with portal hypertension and 43 patients with non-ulcer dyspepsia (controls) underwent push enteroscopy and jejunal, duodenal and gastric biopsies. Biopsies were randomized and examined by a blinded pathologist for inflammation and vascular dilatation, which was quantified by morphometry. RESULTS: Endoscopic jejunopathy was observed in 6 patients and none of the control subjects. All patients with jejunopathy had portal hypertensive gastropathy (PHG) and 5 had duodenopathy. Vascular dilatation was observed in 15 patients and 25 control subjects (p = ns). The degree of vascular dilatation was similar in both groups. Inflammatory changes were observed in 24 patients and 25 control subjects (p = 0.05). CONCLUSIONS: Endoscopic jejunopathy was present in 15% of patients with portal hypertension. These changes were mild in 83% of them. All patients with jejunopathy also had PHG. Histologic changes were similar in patients and control subjects.

Interleukin 10-deficient colitis: new similarities to human inflammatory bowel disease.

BACKGROUND: Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Disruption of the IL-10 gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this model. METHODS: Animals were bred in specific pathogen-free conditions and transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and 15 weeks of age. Barrier function was assessed by measuring intestinal permeability and antibody response to systemic endotoxaemia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (HIS) was calculated. RESULTS: The HIS increased progressively until 12 weeks, with an associated increase in intestinal permeability, and immunoglobulin (Ig) M and IgG EndoCAb. The HIS correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb. CONCLUSION: IL-10 knockout mice develop colitis with an associated disturbance in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL-10 knockout mouse shares these histological, physiological and biochemical features with human inflammatory bowel disease and is therefore suitable for therapeutic trials. A measure of endotoxaemia correlated directly with intestinal permeability in this model.

Animal model for liver dysfunction using lomustine in Wistar rats.

AIM: To induce intrahepatic cholestasis in rats using lomustine 1(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU). METHODS: Doses of 10 mg, 20 mg and 30 mg/Kg body weight of CCNU were injected intraperitoneally in separate groups of animals. RESULTS: With 10 mg/Kg body weight of CCNU, serum bilirubin levels increased for up to 72 hours and then slowly returned to normal. With a dose of 20 mg/Kg body weight of CCNU, serum bilirubin, AST, ALT and alkaline phosphatase levels increased for 72 hours and then returned to normal over 4-5 weeks. With a dose of 30 mg/Kg body weight peak levels of serum bilirubin were reached on day 17. Pathological studies were carried out after injection of 30 mg/Kg body weight of CCNU. After 72 hours hepatocytes were normal, with minimal nonspecific inflammation and bile duct proliferation. After 16 days, triaditis was observed with deposition of collagen. Focal fibrosis was also noticed. There was no significant abnormality of hepatocytes. After 75 days, hepatocytes showed focal ballooning. Bile duct proliferation was seen invading the parenchyma. Nodules of hepatocytes separated by irregular fibrous bands indicated cirrhosis. CONCLUSIONS: An animal model of intrahepatic cholestasis has been developed using CCNU; this model may be used to assess the utility of hepatobiliary radiopharmaceuticals.

Probiotic therapy fails to improve gut permeability in a hapten model of colitis.

BACKGROUND: Studies in clinical and experimental inflammatory bowel disease (IBD) have shown disturbances in intestinal bacterial flora with an increase in potentially pathogenic and a decrease in protective organisms. It was hypothesized that Lactobacillus plantarum species 299 (LP299), a probiotic, would ameliorate colitis and improve intestinal permeability in experimental colitis. This study investigated the effect of LP299 in the trinitrobenzenesulfonic acid/ethanol (TNBS/E) rat model of colitis. METHODS: Twelve week old male Wistar rats were randomized to receive rectal instillates of either TNBS/E (n = 48) or saline (n = 16). For the next 7 days the animals were gavaged with 2.5 ml of oat fibre suspension containing 10(9) colony forming units (CFU) of LP299 (LP299/OF), oat fibre suspension alone (OF) or no treatment. At the end of the experiment rats received radiolabelled polyethylene glycol and urine was collected for 24 h to assess permeability. Animals were then anaesthetized and colons were harvested for colon macroscopic scoring (CMS). RESULTS: TNBS/E per rectum resulted in a greater CMS (P < 0.001) and gut permeability (P = 0.006) than saline. Administration of LP299/OF or oat fibre alone did not result in a reduction in CMS or gut permeability when compared to colitic controls. CONCLUSIONS: LP299/OF, when administered after TNBS instillation, does not reduce the severity of colitis or improve gut permeability in this hapten model of colitis.

Autopsy study of patients dying of bleeding diathesis.

Ten thousand & thirty seven autopsies performed from the year 1982 to 1992 were studied retrospectively, to find out the number of deaths due to bleeding diathesis. Eighty-seven (0.87%) patients died due to bleeding diathesis, out of which haemolytic uraemic syndrome (HUS) was seen in 9 cases (10.34%), disseminated intravascular coagulation (DIC) in 67 cases (77.01%) & 11 cases were grouped as miscellaneous. Martius scarlet blue stain was carried out to demonstrate fibrin & depending on the number of thrombi in the glomerulus & blood vessels, the lesions were graded as mild, moderate or severe. Kidney was the most common organ involved in all groups of bleeding diathesis. In DIC kidney & lung involvement was almost equal.

Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat.

Ricin is known to have diverse effects on the cells of different organs like liver, kidney, pancreas, intestines and parathyroid. Acute decrease in serum thyroid hormone level 24 h after ricin administration (1.5 micrograms/100 g) led us to suspect the toxic action of ricin on the thyroid. We monitored the lipid peroxidation (LP) and anti-oxidant status of the thyroid tissue to determine the role, if any, played by reactive oxygen species (ROS) in this pathology. An increase of 39% in LP and 47% in superoxide dismutase, along with a 8.5% decrease in catalase points to the imbalance in the antioxidant defence involving hydrogen peroxide and its univalent reduction product, the hydroxyl radical. Thyroid histopathology shows destruction of thyroid follicles and necrosis, which may be due to ROS and may partly explain the 50% reduction in circulating thyroid hormones seen after ricin administration.