Establishment and characterization of two primary breast cancer cell lines from young Indian breast cancer patients: mutation analysis.

Two novel triple negative breast cancer cell lines, NIPBC-1 and NIPBC-2 were successfully established from primary tumors of two young breast cancer patients aged 39 and 38 years respectively, diagnosed as infiltrating duct carcinoma of breast. Characterization of these cell lines showed luminal origin with expression of epithelial specific antigen and cytokeratin 18 and presence of microfilaments and secretary vesicles, microvilli, tight junctions and desmosomes on ultra-structural analysis. Both the cell lines showed anchorage independent growth and invasion of matrigel coated membranes. Karyotype analysis showed aneuploidy, deletions and multiple rearrangements in chromosomes 7, 9, X and 11 and isochromosomes 17q in both the cell lines. P53 mutational analysis revealed no mutation in the coding region in both the cell lines; however NIPBC-2 cell line showed presence of heterozygous C/G polymorphism, g.417 C > G (NM_000546.5) resulting in Arg/Pro allele at codon 72 of exon 4. Screening for mutations in BRCA1&2 genes revealed presence of three heterozygous polymorphisms in exon 11 of BRCA1 and 2 polymorphisms in exons 11, and14 of BRCA2 gene in both the cell lines. Both the cell lines showed presence of CD 44+/24-breast cancer stem cells and capability of producing mammosphere on culture. The two triple negative breast cancer cell lines established from early onset breast tumors can serve as novel invitro models to study mechanisms underlying breast tumorigenesis in younger age group patients and also identification of new therapeutic modalities targeting cancer stem cells.

Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors.

BACKGROUND & OBJECTIVES: Breast cancer is the second most common malignancy in Indian women. Among the members of the steroid receptor superfamily the role of estrogen and progesterone receptors (ER and PR) is well established in breast cancer in predicting the prognosis and management of therapy, however, little is known about the clinical significance of androgen receptor (AR) in breast carcinogenesis. The present study was aimed to evaluate the expression of AR in breast cancer and to elucidate its clinical significance by correlating it with clinicopathological parameters, other steroid receptors (ER and PR) and growth factors receptors (EGFR and CD105). METHODS: Expression of AR, ER, PR, epidermal growth factor receptor (EGFR) and endoglin (CD105) was studied in 100 cases of breast cancer by immunohistochemistry (IHC). Risk ratio (RR) along with 95% confidence interval (CI) was estimated to assess the strength of association between the markers and clinicopathological characteristics. Categorical principal component analysis (CATPCA) was applied to obtain new sets of linearly combined expression, for their further evaluation with clinicopathological characteristics (n=100). RESULTS: In 31 cases presenting with locally advanced breast cancer (LABC), the expression of AR, ER, PR, EGFR and CD105 was associated with response to neoadjuvant chemotherapy (NACT). The results indicated the association of AR+ (P=0.001) and AR+/EGFR- (P=0.001) with the therapeutic response to NACT in LABC patients. The AR expression exhibited maximum sensitivity, specificity and likelihood ratio of positive and negative test. The present results showed the benefit of adding AR, EGFR and CD105 to the existing panel of markers to be able to predict response to therapy. INTERPRETATION & CONCLUSIONS: More studies on the expression profiles of AR+, AR+/CD105+ and AR+/EGFR- in larger set of breast cancer patients may possibly help in confirming their predictive role for therapeutic response in LABC patients.

Study on predictive role of AR and EGFR family genes with response to neoadjuvant chemotherapy in locally advanced breast cancer in Indian women.

Locally advanced breast cancer (LABC) remains a clinical challenge as the majority of patients with this diagnosis develop distant metastases despite appropriate therapy. We analyzed expression of steroid and growth hormone receptor genes as well as gene associated with metabolism of chemotherapeutic drugs in locally advanced breast cancer before and after neoadjuvant chemotherapy (NACT) to study whether there is a change in gene expression induced by chemotherapy and whether such changes are associated with tumor response or non-response. Fifty patients were included with locally advanced breast cancer treated with cyclophosphamide, adriamycin, 5-fluorouracil (CAF)-based neoadjuvant chemotherapy before surgery. Total RNA was extracted from 50 match samples of pre- and post-NACT tumor tissues. RNA expression levels of epidermal growth factor receptor family genes including EGFR, ERBB2, ERBB3, androgen receptor (AR), and multidrug-resistance gene 1 (MDR1) were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Responders show significantly high levels of pre-NACT AR gene expression (P = 0.016), which reduces following NACT (P = 0.008), and hence can serve as a useful tool for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced breast carcinoma. Moreover, a significant post-therapeutic increase in the expression levels of EGFR and MDR1 gene in responders (P = 0.026 and P < 0.001) as well as in non-responders (P = 0.055, P = 0.001) suggests that expression of these genes changes during therapy but they do not have any impact on tumor response, whereas a post-therapeutic reduction was observed in AR in responders. This indicates an independent predictive role of AR with response to NACT.

Recurrent laryngeal nerve and voice preservation: routine identification and appropriate assessment - two important steps in thyroid surgery.

INTRODUCTION: The aims of this study were to assess and compare vocal cord functions before and after thyroid surgery after intra-operative identification of recurrent laryngeal nerve. PATIENTS AND METHODS: Recurrent laryngeal nerve (RLN) is seen intra-operatively in all cases undergoing thyroid surgeries. Vocal cord functions including any voice change were evaluated by indirect laryngoscopy (I/L) and direct laryngoscopy (D/L) before and after surgery. RESULTS: Prospective study on 100 patients over 18 months with a total of 146 nerves at risk (NAR). Majority were women (n = 86) with mean age of 37.48 years (range, 13-60 years). RLN was seen in all patients and 19 patients complained of some change in quality of their voice after surgery. Evaluation by I/L and D/L at 6 weeks showed recurrent laryngeal nerve palsy (RLNP) in nine (47.36%) and five (26%) of these 19 patients respectively. Analysed according to total NAR, the incidence of voice change and temporary RLN palsy (I/L and D/L) at 6 weeks was still less at 13.01%, 6.16% and 3.42%, respectively. Voice change improved in all cases at 3 months with no RLNP palsy by I/L or D/L. All these 19 patients had undergone difficult or extensive surgery for malignancy, large gland, extratyhroidal spread or fibrosis. CONCLUSIONS: Despite identification and preservation of RLN, patients can develop postoperative voice change and RLNP although all voice change cannot be attributed to damaged RLN. Proper assessment of vocal cord functions by I/L and D/L laryngoscopy is required to rule out injuries to these nerves. Risk of damage is higher in patients undergoing more difficult surgery.

Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women.

BACKGROUND: Considerably little is known about the biological role and clinical significance of androgen receptor expression in breast cancer. The objectives of this study were to characterize AR-CAG repeat genotypes in a cohort of women with breast cancer and to determine the influence of AR on response to neoadjuvant chemotherapy and clinical outcome. MATERIALS AND METHODS: Genotyping of the AR CAG repeat region was done on 70 patients and 80 healthy aged- matched female controls. To assess response to NACT, tissue samples from 30 LABC cases were evaluated quantitatively by real time for AR mRNA expression. The clinical response was correlated with both the pre and post chemotherapy AR expression. The CAG alleles did not show differences between cases and controls when the mean of short, long and average length of both CAG alleles was considered. However, analysis when done defining short allele as CAGn < 20 (AR1) and the long as CAGn ≥ 20 (AR2), risk was found associated with AR2 allele with marginal significance (P = 0.09). Stratification by age of onset, FH, stage, grade ER and AR status failed to reveal any association with breast cancer risk. Genotype carriers with ≥ 20 CAGn showed decrease of AR mRNA expression although significance could not be established (P = 0.47). Tumours in responders had the higher AR mRNA expression levels in pre neo-adjuvant chemotherapy condition (p < 0.02) which got reduced after neoadjuvant chemotherapy and the difference was found to be significant (P = 0.014). CONCLUSIONS: Although, expansion of the CAGn in the AR gene doesn't show any major effect on breast cancer risk, patients with positive AR expression, pre neoadjuvant chemotherapy, were found to be good responders and a decrease in mRNA level of AR gene related to the chemotherapy-induced apoptosis could serve as an important independent predictor of response to NACT.

Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines.

In breast cancer, maspin, a serine protease inhibitor, can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. The clinical significance of maspin expression in breast cancer, especially in the sequence of ductal carcinoma in situ (DCIS)-invasive cancer-lymph node metastasis is well known in the Western countries, but its status in the rapidly increasing breast cancers in India remains unknown. The present study was designed to determine the clinical significance of maspin expression in invasive ductal carcinomas of breast (IDCs) in North Indian population and modulation of its expression by curcumin. Immunohistochemical analysis of maspin showed loss or reduced cytoplasmic expression in 36 of 59 (61%) tumors. Furthermore, breast cancer cells (MCF-7 (wild type p53) and MDA-MB-231 (mutant p53)) were treated with curcumin and the effect on expression of maspin gene at transcription and translation levels was analyzed by RT-PCR, immunofluorescence and Western blotting. Maspin expression was also correlated with p53 and Bcl-2 levels. Curcumin inhibited cell growth, induced apoptosis and upregulated maspin gene expression in MCF-7 cells and these findings were further correlated with the upregulation of p53 protein and downregulation of Bcl-2, suggesting maspin mediated apoptosis in MCF-7 cells. To our knowledge this is the first report showing the upregulation of maspin expression by curcumin in breast cancer cells and taken together with the clinical data suggests a potential therapeutic role for curcumin in inducing maspin mediated inhibition of invasion of breast carcinoma cells.

Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma of breast.

BACKGROUND: Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/beta-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast. METHODS: In the current study, we analyzed the expression patterns and relationships between the key Wnt/beta-catenin signaling components- E-cadherin, Slug and GSK3beta in IDCs of breast. RESULTS: Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3beta expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3beta. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001), and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3beta nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression. CONCLUSION: The present study for the first time provided the clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3beta with beta-catenin in implementing EMT in these cells.

Leydig cell tumor: an unusual presentation.

Leydig cell tumor is a benign tumor of the testis and malignant transformation, if present, is rare. The case presented here showed certain features of malignancy but no infiltration beyond the capsule or metastasis. The case could not be labeled as benign or malignant and patient is on follow-up. Differential diagnosis and clinical implications of a case in the borderline zone are discussed.

Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/beta-catenin signaling.

Abnormal activation of the Wnt/beta-catenin signaling pathway and subsequent upregulation of beta-catenin driven downstream targets-c-Myc and cyclin D1 is associated with development of breast cancer. The objective of our study was to determine if curcumin could modulate the key elements of Wnt pathway in breast cancer cells; an effect that might underscore its usefulness for chemoprevention/treatment of this malignancy. Curcumin showed a cytotoxic effect on MCF-7 cells with 50% inhibitory concentration (IC(50)) of 35microM; while IC(50) for MDA-MB-231 cells was 30microM. Treatment with low cytostatic dose of 20microM curcumin showed G(2)/M arrest in both breast cancer cells. The effect of curcumin (20microM) treatment on expression of Wnt/beta-catenin pathway components in breast cancer cells (MCF-7 and MDA-MB-231) was analyzed by immunofluorescence and Western blotting. Curcumin was found to effectively inhibit the expression of several Wnt/beta-catenin pathway components-disheveled, beta-catenin, cyclin D1 and slug in both MCF-7 and MDA-MB-231. Immunofluorescence analysis showed that curcumin markedly reduced the nuclear expression of disheveled and beta-catenin proteins. Further, the protein levels of the positively regulated beta-catenin targets-cyclin D1 and slug, were downregulated by curcumin treatment. The expression levels of two integral proteins of Wnt signaling, GSK3beta and E-cadherin were also altered by curcumin treatment. In conclusion, our data demonstrated that the efficacy of curcumin in inhibition of cell proliferation and induction of apoptosis might occur through modulation of beta-catenin pathway in human breast cancer cells.

Carcinoma developing in a fibroadenoma in a woman with a family history of breast cancer: a case report and review of literature.

INTRODUCTION: Malignant transformation of a fibroadenoma is rare with only about 100 cases reported in the world literature. Fibroadenoma occurring in middle aged woman with a strong family history of breast or ovarian cancer should be investigated with a high suspicion for malignancy. CASE PRESENTATION: A 35-year- old Indian lady operated previously for fibroadenoma of the right breast presented with a recurrent lump at the same site. She had a strong family history of breast carcinoma. Mammography and trucut biopsy was suggestive of infiltrating duct carcinoma. She was managed by lumpectomy and axillary lymph node dissection with a satisfactory outcome. There was no evidence of BRCA-1, BRCA-2 mutation on immunohistochemistry. CONCLUSION: Malignant change in a pre-existing fibroadenoma is rare, however in a middle aged woman with a family history of breast cancer it should be suspected. In the absence of any definite clinical and radiological criteria of diagnosing malignant change in a fibroadenoma, high suspicion index is mandatory. The management and outcome depends on the stage and grade of presentation.

Risk adjustment is crucial in comparing outcomes of various surgical modalities in patients with ileal perforation.

BACKGROUND: Using crude mortality and morbidity rates for comparing outcomes can be misleading. The aim of the present study was to compare the outcome of various surgical modalities without and with risk adjustment using Physiologic and Operative Severity Scoring for the enUmeration of Mortality and morbidity (POSSUM) score in cases of ileal perforations. METHODS: Prospective study on 125 patients of ileal perforations. Resection anastamosis (Group I) was done in 38 patients, primary repair (Group II) in 42 patients and 45 patients had an ileostomy (Group III). The disease severity was assessed in all patients using POSSUM score. The odds of death without and with risk adjustment using POSSUM mortality score were calculated for all groups RESULTS: Seventeen patients (14%) patients died and 99 (79%) developed postoperative complications. Using crude mortality rates Group I appeared to be the best treatment option with only 2 (5%) deaths followed by Group II with 5 (12%) deaths where as Group III had the worst outcome with 10 deaths (22%). However, Group III (ileostomy) patients had higher mean POSSUM mortality and morbidity score (55.55%, 91.33%) than Group I (28%, 75.26%) and Group II (27%, 73.59%). Taking Group I as the reference (odds ratio, OR1) odds of death were greatest in Group III (OR 5.14, p = 0.043) followed by Group II (OR 2.43, p = 0.306). With risk adjustment using POSSUM mortality score the odds of death decreased in Group III (OR 1.16 p = 0.875). For the whole group, there was a significant association between the POSSUM score and postoperative complications and deaths. Mean POSSUM mortality and morbidity score of those who died (63.40 vs.33.68, p = 0.001) and developed complications (66.32 vs.84.20, p = 0.001) was significantly higher. For every percent increase in severity score the risk of postoperative complications and death increased by 1.10 (p = 0.001) and1.06 (p = 0.001) respectively. CONCLUSION: Despite ileostomy patients having highest crude mortality and complication rates, after risk adjustment it was equally safe. Severity of the disease rather than the surgical option had a significant impact on the outcome in patients with ileal perforations.

Isolated colostomy site recurrence in rectal cancer-two cases with review of literature.

BACKGROUND: Colostomy site carcinomas are rare with only eight cases reported in the world literature. Various etiological factors like adenoma-cancer sequence, bile acids, recurrent and persistent physical damage at the colostomy site by faecal matter due to associated stomal stenosis have been considered responsible. Two such cases are being reported and in both cases there was no evidence of any local recurrence in the pelvis or liver and distant metastasis. Both patients had received adjuvant chemotherapy following surgery. CASE PRESENTATION: First case was a 30-year-old male that had reported with large bowel obstruction due to an obstructing ulcero-proliferative growth (poorly differentiated adenocarcinoma) at the colostomy site after abdomino-perineal resection, performed for low rectal cancer six years previously. Wide local excision with microscopically free margins was performed with a satisfactory outcome. Four years later he presented with massive malignant ascites, cachexia and multiple liver metastasis and succumbed to his disease. Second case was a 47-year-old male that presented with acute large bowel obstruction due to an annular growth (well differentiated adenocarcinoma) in the upper rectum. He was managed by Hartmann's operation and the sigmoid colostomy was closed six months later. Five years following closure of colostomy, he presented with two parietal masses at the previous colostomy site scar, which, on fine needle aspiration cytology were found to be well-differentiated adenocarcinomas of colorectal type. Surgery in the form of wide local resection with free margins was performed. He presented again after five years with recurrence along the previous surgery scar and an incisional hernia and was managed by wide local excision along with hernioplasty. Follow-up of nine years following first surgery is satisfactory. CONCLUSIONS: Colostomy site/scar recurrence of rectal carcinoma is rare and could be due to various etiological factors, although the exact causative mechanism is not known. Surgery with microscopically free margins is recommended in the absence of metastatic disease. Stenosis of the stoma is considered as one of the most important contributory factors and should be followed carefully.

Is an aggressive approach justified in the management of an aggressive cancer--the squamous cell carcinoma of thyroid?

BACKGROUND: Primary squamous cell carcinoma of the thyroid is an extremely rare neoplasm, with less than 50 cases reported in the world literature. The prognosis is poor with a median survival of less than six months. The death is usually secondary to progression of local disease as distant metastases are rare. CASE REPORTS: Three cases, two males and one female presenting with sudden increase in the size of long standing thyroid swellings and associated pressure effects on the aero-digestive tract are reported. Exhaustive clinical, endoscopic, and radiological examinations did not reveal any primary site of squamous-cell carcinoma as the likely source of the metastases, or of any contiguous spread from neighboring structures. Two cases were managed by combined modality therapy including curative surgery with radiotherapy and one by radiotherapy alone. CONCLUSION: Primary squamous cell carcinoma is a rare malignancy with a poor outcome inspite of combined modality therapy. Out of three reported cases, two succumbed to their disease within less than one year. Aggressive surgery in the form of curative resection along with adjuvant radiotherapy is recommended, the tumor being chemo resistant.

Qualitative and quantitative dermatoglyphic traits in patients with breast cancer: a prospective clinical study.

BACKGROUND: Breast cancer is one of the most extensively studied cancers and its genetic basis is well established. Dermatoglyphic traits are formed under genetic control early in development but may be affected by environmental factors during first trimester of pregnancy. They however do not change significantly thereafter, thus maintaining stability not greatly affected by age. These patterns may represent the genetic make up of an individual and therefore his/her predisposition to certain diseases. Patterns of dermatoglyphics have been studied in various congenital disorders like Down's syndrome and Kleinfelter syndrome. The prints can thus represent a non-invasive anatomical marker of breast cancer risk and thus facilitate early detection and treatment. METHODS: The study was conducted on 60 histo-pathologically confirmed breast cancer patients and their digital dermatoglyphic patterns were studied to assess their association with the type and onset of breast cancer. Simultaneously 60 age-matched controls were also selected that had no self or familial history of a diagnosed breast cancer and the observations were recorded. The differences of qualitative (dermatoglyphic patterns) data were tested for their significance using the chi-square test, and for quantitative (ridge counts and pattern intensity index) data using the t- test. RESULTS: It was observed that six or more whorls in the finger print pattern were statistically significant among the cancer patients as compared to controls. It was also seen that whorls in the right ring finger and right little finger were found increased among the cases as compared to controls. The differences between mean pattern intensity index of cases and controls were found to be statistically significant. CONCLUSION: The dermatoglyphic patterns may be utilized effectively to study the genetic basis of breast cancer and may also serve as a screening tool in the high-risk population. In a developing country like India it might prove to be an anatomical, non-invasive, inexpensive and effective tool for screening and studying the patterns in the high-risk population.

The expression of mismatched repair genes and their correlation with clinicopathological parameters and response to neo-adjuvant chemotherapy in breast cancer.

BACKGROUND: The DNA mismatch repair (MMR) pathway is an important post-replicative repair process. It is involved in the maintenance of genomic stability and MMR genes have therefore been named the proofreaders of replicating DNA. These genes repair the replicative errors of DNA and are thus imperative for genomic stability. The MMR genes have been found to be involved in promoting cytotoxicity, apoptosis, p53 phosphorylation and cell cycle arrest following exposure to exogenous DNA damaging agents. Loss of MMR function prevents the correction of replicative errors leading to instability of the genome, and can be detected by polymorphisms in micro satellites (1-6 nucleotide repeat sequences scattered in whole of the genome). This phenomenon, known as micro satellite instability (MSI), is a hallmark of MMR dysfunction and can be used as a marker of MMR dysfunction in colorectal and other malignancies. An alternative method for detection of MMR dysfunction is to test the expression of protein products of the MMR genes by immunohistochemistry (IHC), as mutations in these genes lead to reduced or absent expression of their gene products. Correlation between loss of MMR function and clinical, histopathological, behavioral parameters of the tumor and its response to chemotherapy in breast cancers may be of value in predicting tumor behavior and response to neoadjuvant chemotherapy (NACT). Neoadjuvant chemotherapy is an integral part of multimodal therapy for locally advanced breast cancer and predicting response may help in tailoring regimens in patients for optimum response. MATERIALS: After approval by the IRB (Institutional Review Board) and ethical committee of the hospital, 31 cases of locally advanced breast carcinoma (LABC) were studied to assess the correlation between MMR dysfunction, clinicopathological parameters and objective clinical response to neoadjuvant chemotherapy using immunohistochemistry. The immunohistochemical analysis for four MMR protein products--MLH1, MSH2, MSH6 and PMS2 was done in the pre NACT trucut biopsy specimen and after three cycles of NACT with C AF (cyclophosphamide, adriamycin, 5-fluorouracil) regimen, in the modified radical mastectomy specimen. RESULTS AND CONCLUSION: There was no significant correlation observed between expression of MMR proteins and age, family history, tumor size or histological type. However there was a statistically significant negative correlation between MLH1, MSH2 expression and histological grade. There was also a negative correlation observed between PMS2 expression after neo-adjuvant chemotherapy and clinical response. Cases with high post NACT expression of PMS2 were poor responders to chemotherapy. MSH6 was the most frequently altered MMR gene, with a negativity rate of 48% and the patients with high expression responded poorly to NACT. The study highlights the possible role of MMR expression in predicting aggressive tumor behavior (histological grade) and response to neoadjuvant chemotherapy in patients with LABC.

Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country--a prospective study.

BACKGROUND: An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving. Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury. METHODS: The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant. RESULTS: At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 +/- 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group. Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury. CONCLUSION: It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.

Is the routine drainage after surgery for thyroid necessary? A prospective randomized clinical study [ISRCTN63623153].

BACKGROUND: Drains are usually left after thyroid surgery to prevent formation of hematoma and seroma in the thyroid bed. This is done to reduce complications and hospital stay. Objective evaluation of the amount collected in the thyroid bed by ultrasonography (USG) can help in assessing the role of drains. METHODS: A randomized prospective control study was conducted on 94 patients undergoing 102 thyroid surgeries, over a period of fifteen months. Patients included in the study were randomly allocated to drain and non-drain group on the basis of computer generated random number table. The surgeon was informed of the group just before the closure of the wound Postoperatively USG neck was done on first and seventh postoperative day by the same ultrasonologist each time. Any swelling, change in voice, tetany and tingling sensation were also recorded. The data was analyzed using two-sample t-test for calculating unequal variance. RESULTS: Both groups were evenly balanced according to age, sex, and size of tumor, type of procedure performed and histopathological diagnosis. There was no significant difference in collection of thyroid bed assessed by USG on D1 & D7 in the two groups (p = 0.313) but the hospital stay was significantly reduced in the non-drain group (p = 0.007). One patient in the drain group required needle aspiration for collection in thyroid bed. No patient in either group required re-operation for bleeding or haematoma. CONCLUSION: Routine drainage of thyroid bed following thyroid surgery may not be necessary. Not draining the wound results in lesser morbidity and decreased hospital stay.

Clasp knife in the gut: a case report.

BACKGROUND: A wide range of foreign bodies has been retrieved from the gut and reported. The presentation may be in the form of complications like intestinal obstruction, perforation and formation of abscesses etc but there is no case report of a half open clasp knife being retrieved from the ileum, the patient having thrived, in spite of its presence for a period of eight months. CASE PRESENTATION: A 30-year-old administrative clerk had undergone emergency abdominal surgery eight months previously under mysterious circumstances at a remote district hospital and had recovered completely. Later the blade of a knife was accidentally detected when an X ray of the abdomen was done during a routine follow-up visit to his family physician. Surgery revealed a clasp knife in the ileum, which was retrieved. The presence of an entero-enteric fistula short circuiting the loop was the secret of his earlier survival. CONCLUSIONS: To the best of our information this is the first case-report of a clasp knife in the gut and of the patient thriving in spite of its presence. We report here the dramatic sequence of events.

Spontaneous Enterocutaneous Fistula 27-years Following Radiotherapy in a Patient of Carcinoma Penis.

BACKGROUND: Radiotherapy in the radical doses can produce severe and often irreversible damage to the gut in the form of fibrosis, necrosis and fistulae formation. A previous pelvic surgery makes the gut extra-vulnerable. This is on account of adhesions to the pelvic wall, unless special care is taken during surgery to keep it out of the harms way, during adjuvant radiotherapy. These effects range from acute, to sub acute and delayed chronic manifestations like in the reported case. CASE REPORT: A spontaneous low out put enterocutaneous fistula in a 68-year-old man following surgery and adjuvant radiotherapy given 27 years back for carcinoma penis is reported. Patient is making a satisfactory progress after three years of follow-up. CONCLUSION: High dose external beam radiotherapy is known to produce deleterious side effects ranging from mild radiation enteritis to the development of internal and external fistulae. The effects may be acute, subacute or chronic. Presentation as spontaneous enterocutaneous fistula 27 years after radiotherapy is rare.

Primary squamous-cell carcinoma of the thyroid gland: new evidence in support of follicular epithelial cell origin.

Primary squamous-cell carcinoma (SCC) of the thyroid gland is extremely rare. We had an opportunity to treat two such cases recently. Two elderly females presented with left lobe thyroid swelling that had a history of long-standing goiter. Fine-needle aspiration (FNA) of the thyroid nodule was done in both cases. FNA cytology showed an thyroid abscess in the first, and a Hürthle-cell neoplasm in the second case. Histopathologic diagnosis was a well-differentiated squamous-cell carcinoma with an adjacent area of lymphocytic thyroiditis in the first case, and a moderately differentiated squamous-cell carcinoma in association with a Hürthle-cell adenoma in the second case. Serial sections of the excised gland ruled out any other associated thyroid malignancy. Immunostaining for pan-cytokeratin, thyroglobulin, and calcitonin were performed. The tumor, comprising polygonal and spindle cells, showed positive staining for cytokeratin and thyroglobulin; however, calcitonin did not stain any structures. Exhaustive clinical, endoscopic, and radiological examinations, i.e., X-ray of the chest, contrast-enhanced computer tomography (CECT) of the neck and chest, and ENT checkup in both cases did not reveal any primary site of squamous-cell carcinoma as the likely source of the metastases, or any contiguous spread from neighboring structures. Both patients had ipsilateral nodal metastases, and both succumbed to the disease within 6 mo of histological diagnosis. The interesting observation in both cases was thyroglobulin positivity, indicating a follicular epithelial cell origin of the SCC.