Search

We report a case of postsurgical wound infection of polymicrobial etiology caused by Serratia marcescens and Pseudomonas aeruginosa following the use of a radial forearm free flap for oncological tongue reconstruction. S. marcescens was a producer of SHV-12 extended-spectrum beta-lactamase (ESBL). This is the first report from India of this ESBL. S. marcescens and P. aeruginosa were resistant to the empirical perioperative antibiotics administered. Delay in the recognition of the type of infection and in the institution of appropriate therapy resulted in total loss of the free flap.

Background and Objectives: Radical surgical extirpation in advanced breast cancer patients produces large defects that may not be suitable for primary closure. The primary aim in such cases is to achieve an adequate soft tissue cover expeditiously. Various methods, including skin graft, omentum, random flaps, and myocutaneous (MC) flaps, have been tried in the past; however, there is no consensus regarding the method of choice in such patients., Methods: A retrospective analysis of the breast cancer database of a single surgical unit was performed to find out the incidence of advanced breast cancer patients requiring an additional surgical procedure for soft tissue cover. A comparative analysis of two major groups, "MC flaps" and "thoraco-abdominal (TA) flaps," was performed in relation to operative time, blood loss, morbidity, hospital stay, and final outcome., Results: Forty (12.7%) out of 315 advanced breast cancer patients undergoing surgery required additional surgical procedures for soft tissue cover. MC flaps were used in 18 patients and TA flaps were used in 22 patients. The mean blood loss (192 +/- 77 ml vs. 40 +/- 19 ml), operating time (110 +/- 20 minutes vs. 35 +/- 7 minutes), and hospital stay (10 +/- 4 days vs. 5 +/- 2 days) were significantly less in the TA flap group., Conclusions: The results of the current study show a significant difference in the blood loss, operating time, and hospital stay between patients requiring TA and MC flap for soft tissue cover following mastectomy. In view of its simplicity and better results, we recommend that the TA flap should be used as a first option flap in advanced breast cancer patients requiring skin cover., (Copyright 2003 Wiley-Liss, Inc.)

Background: Nodal status is an important prognostic factor in oral cancer. Sentinel node studies may enable accurate identification of high-risk nodes without a formal neck dissection. Imprint cytology is an emerging tool to assist in the rapid intraoperative detection of nodal metastases with encouraging results in other solid tumors. This study was planned to evaluate a novel method of intraoperative staging using sentinel node biopsy and intraoperative imprint cytology in oral cancer., Patients and Methods: Thirty-two cases of oral cancer underwent sentinel node mapping using 1% isosulfan blue during the study period. The sentinel node was sent for evaluation by imprint cytology. The average time taken for reporting was 15 minutes. The result was compared with the final histopathology, which was taken as the "gold standard"., Results: Sentinel nodes (SLN) were identified in 30 cases (93.75% identification rate), with two false negatives. Intraoperative imprint cytology (IIC) could accurately predict the nodal status in 28 of the 30 patients. There was one false-positive result and one false-negative result. The overall sensitivity, specificity, and accuracy of IIC were 87.5%, 95.4%, and 93.3 %, respectively., Conclusion: Sentinel node biopsy along with IIC provides a reliable, inexpensive, and accurate method of intraoperative identification of the nodal status in oral cancer., (Copyright 2003 Wiley Periodicals, Inc.)

Objective: Reconstruction of locally advanced oral cancer presents a great challenge to the head and neck surgeon. The main goal of reconstruction is to provide intraoral lining and soft tissue cover. We discuss the use of Bipaddle pectoralis major myoculaneous flap (PMMF) and its modifications for reconstruction of complex oral defects following radical resection., Study Design: Retrospective analysis of prospective oral cancer data base., Setting: Tertiary Care Regional Cancer Center., Patients: Three hundred and ten patients were operated for oral carcinoma in this unit between 1993 and 2001. The oral cancer patients who required soft tissue reconstruction for lining and cover were analyzed. Patients in whom bipaddle PMMF were utilised were studied in terms of surgical technique, morbidity, function and cosmetic outcome., Results: Ninety-one (29.4 %) oral cancer patients required reconstruction for lining as well as cover. Of these, 54 (17.4 %) patients underwent a bipaddle PMMF flap reconstruction. Two horizontal skin islands were used in patients with lateral defects and two vertical islands in patients with central defects. There was no complication in 41 (76%) patients. Complete flap loss was seen in only one patient and differential flap loss in 2 patients (4 %) while seven (13 %) patients had only minor complication. All the patients received post-operative Radiotherapy. Good to average functional and cosmetic outcome was observed in 90% patients., Conclusions: Bipaddle PMMF offers an effective and leliahle reconstructive option for complex oral defects. By using certain technical modifications, majority of complex oral defects can be managed successfully using a Bipaddle PMMF. In a developing country like India with a large oral cancer disease burden Bipaddle PMMF should he used routinely for complex oral defects in view of its simplicity, versatility and reliability.

Aims of the Study: Isolated ipsilateral supraclavicular lymph nodal (IISCLN) metastasis was considered part of locally advanced breast cancer (LABC) previously but the recent staging system categorised this group to metastatic disease (stage IV). There is no clear consensus on intent of therapy in patients with IISCLN. A retrospective comparative analysis of IISCLN and LABC patients treated with a curative multimodality approach was performed to evolve guidelines on treatment approach in patients with IISCLN spread., Methodology: A total number of 670 patients with breast cancer treated in the Department of Surgical Oncology, IRCH, AIIMS, during the period between January, 1993 to December, 2000 were studied retrospectively. Out of these 16 (2.4%) patients with cytology proven isolated metastasis to ipsilateral SCLN without any other distant disease and 299 LABC patients were analysed. All patients received neoadjuvant anthracycline based chemotherapy, surgery, postoperative radiotherapy (50 Gy) including supraclavicular fossa. The relapse patterns and survival in both the groups were compared., Results: At a median follow up of 36 months (range 9-72 months) the total recurrence in the IISCLN group was 31% and in the LABC group was 26%, the systemic recurrence was equal at 25% in each group while the locoregional recurrence was 12% and 7% in the IISCLN and LABC groups respectively. The overall survival (OS) was 81% and 91% whereas the disease-free survival (DFS) was 12% and 7% in the IISCLN and LABC groups, respectively., Conclusion: Intent of therapy in metastatic breast cancer is palliative. However, patients with IISCLN metastasis have a relatively less aggressive biologic behaviour as compared to patients with spread to other distant sites. Results of the current study shows that the relapse patterns and survival of IISCLN group and LABC are comparable. Hence, despite being staged as metastatic disease, patients with IISCLN spread should be treated with combined modality approach for prolonged survival.

Germline mutation analysis of BRCA1 gene has demonstrated significant allelic heterogeneity. These differences represent historical influences of migration, population structure and geographic or cultural isolation. To date, there have been no reports of Indian families with mutations in BRCA1. We have screened for mutations in selected coding exons of BRCA1 and their flanking intron regions in three breast or breast and ovarian cancer families with family history of three or more cases of breast cancer under age 45 and/or ovarian cancer at any age. We have also analyzed 10 female patients with sporadic breast cancer regardless of age and family history, as well as 50 unrelated normal individuals as controls. Thus a total of 90 samples were analyzed for BRCA1 mutations using polymerase chain reaction-mediated site directed mutagenesis (PSM) and single stranded conformation polymorphism (SSCP) analysis for various selected exons followed by sequencing of variant bands. Eight point mutations were identified. Two deleterious pathogenic, protein truncating non-sense mutations were detected in exon 11 (E1250X) and exon 20 (E1754X) and six novel and unique amino acid substitutions (F1734S, D1739Y, V1741G, Q1747H, P1749A, R1753K). One complex missense mutation of exon 20 [V1741G; P1749A] was seen in two out of three families and another complex combination of missense and non-sense mutations of the same exon [V1741G; E1754X] was observed in only one family. These complex mutations exist only in breast cancer families but not in control populations of women. Three splice site variants (IVS20+3A>C, IVS20+4A>T, IVS20+5A>T) and two intronic variants (IVS20+21_22insG, IVS20+21T>G) were also detected. In the group of 10 sporadic female patients no mutations were found., (Copyright 2002 Wiley-Liss, Inc.)

Purpose: Mediastinal adhesions, caused by the transerosal spread of disease, inflammatory diseases, or preoperative chemoradiotherapy, can result in diffi-culties and major complications during transhiatal esophagectomy (THE). However, few studies have specifically addressed the incidence and management of inflammatory adhesions encountered during THE., Methods: We retrospectively analyzed the operative details and postoperative outcome of 70 patients who underwent THE between 1998 and 2000. Patients with inflammatory tracheoesophageal adhesions were identified and their operative records were reviewed for operative findings, intraoperative management, morbidity, and mortality. Patients with upper thoracic esophageal tumors and direct tumor spread to the airways were excluded from the analysis., Results: Eight (11.4%) of the 70 patients had inflammatory adhesions and esophagectomy was possible in 7 of these 8 patients. Due to poor pulmonary status, one patient required conversion to the trnsthoracic approach, but the other six were managed transhiatally. Three patients underwent subtotal esophagectomy, the esophagectomy was completed by the inversion extraction technique in two, one required extended transhiatal dissection, and esophagectomy could not be completed in one due to dense inseparable adhesions between the trachea and esophagus. There was no major airway injury or bleeding., Conclusions: Inflammatory tracheoesophageal adhesions may be encountered in patients undergoing THE in developing countries. Thus, an awareness of the possibility of these adhesions and suitable modifications of the operating procedures are necessary to prevent major complications.

Radiation is well known to increase the risk of cancer. Leukemias, skin cancers, osteosarcomas, thyroid cancers are some examples of radiation-induced malignancies. Radiation-induced carcinoma of the esophagus is extremely rare. We present a case of 42 year old patient who received radiotherapy for breast cancer and subsequently developed esophageal carcinoma.

Paucity of well-defined prognostic molecular markers severely hampers prediction of the clinical course of squamous cell carcinoma (SCC) of oral cavity. The aim of the study was to evaluate the prognostic significance of impairments in the expression of proteins involved in cell cycle regulation and locoregional spread in oral SCC of habitual betel and tobacco chewers. A prospective study was performed in 105 betel and tobacco consumers with oral SCCs during the period 1988-1999, to evaluate the prognostic relevance of impairments in the expression of proteins involved in cell cycle regulation and locoregional spread. Alterations in the expression of p53, pRb, p16, MDM2, p21, and Ets-1 proteins were determined by immunohistochemical analysis in formalin fixed, paraffin embedded tissue sections from oral SCCs. Analysis of multiple molecular biological factors showed overexpression of p53 in 69/105 (66%) cases, MDM2 in 72/105 (69%) cases, p21 in 57/105 (54%) cases and Ets-1 in 64/105 (61%) cases. Loss of pRb was observed in 58/105 (55%) cases and p16 loss was observed in 72/105 (69%) cases. Interestingly, multivariate analysis revealed loss of pRb as the most significant predictor of advanced tumour stage [P=0.001; Odd's Ratio (OR)=3.5] and overexpression of Ets-1 protein was an independent risk factor for lymph node metastasis (OR: 10.1; P<10(-6)). Multiple logistic regression models showed that pRb loss [Hazard's Ratio (HR): 3.93] and p53 overexpression (HR: 2.97) may serve as adverse prognosticators for disease free survival of the patients. The data demonstrate multiple impairments in p53/MDM2/p21/Ets-1 and p16/pRb pathways in betel and tobacco related oral tumourigenesis.

Purpose: To determine the association between the expression of P-gp with Ets-1 and p53 proteins in oral squamous cell carcinomas (SCCs)., Materials and Methods: Immunohistochemical analysis of Ets-1, P-glycoprotein (P-gp), and p53 proteins was carried out in 40 formalin-fixed, paraffin-embedded tissue sections from oral SCCs using specific antibodies for these proteins., Results: Expression of Ets-1 protein was observed in 27/40 (68%) cases, P-gp was overexpressed in 27/40 (68%) cases, and p53 accumulation was observed in 26/40 (65%) cases. Twenty-two of 27 (82%) SCCs showed concomitant overexpression of Ets-1 and P-gp underpinning an association between the expression of these two proteins ( P=0.007). Twenty-one of 27 (78%) Ets-1 overexpressing oral SCCs showed accumulation of p53 protein ( P=0.015). Nineteen of the 27 (70%) P-gp expressing tumours showed p53 accumulation. Concomitant Ets-1 and P-gp overexpression was significantly associated with poor prognosis ( P=0.002). In multivariate analysis using Cox's proportional hazards model, P-glycoprotein emerged as the most significant adverse predictor of disease-free survival (HR=6.2, P=0.003). The hallmark of the study was the significant association between the expression of Ets-1, P-gp, and p53 proteins in oral SCCs and their association with poor prognosis. Oral cancer patients showing concomitant expression of Ets-1, P-gp, and p53 proteins had shorter disease-free survival (median time of no recurrence=18 months) and worst prognosis ( P=0.001) as compared to the cases overexpressing any of these proteins., Conclusion: Concomitant expression of Ets-1, P-gp, and p53 proteins adversely affects the clinical outcome in oral SCCs.

Aim: The harmonic scalpel is recently emerging as an alternative surgical tool for dissection and haemostasis and has been extensively used in the field of minimally invasive surgery. We studied the utility and advantages of this instrument over electrocautery for performing modified radical mastectomy., Methods: The operative and morbidity details of twenty-three breast cancer patients who underwent modified radical mastectomy using the harmonic scalpel were compared with 23 matched controls operated with electrocautery by the same surgical team., Results: There was no significant difference in the operating time between the harmonic scalpel and electrocautery group (104 and 100 mins, p > 0.05). The blood loss (60 +/- 35 ml and 294 +/- 155, p < 0.001) and drainage volume (590 +/- 430 ml and 1,085 +/- 690 ml, p < 0.001) were significantly lower in the harmonic scalpel group. There was a significant reduction of drain days in harmonic scalpel group (mean five and nine days, p < 0.05). There was no significant difference in the seroma rate between two groups (16% and 22%)., Conclusion: Modified radical mastectomy using harmonic scalpel is feasible and learning curve is short. Harmonic scalpel significantly reduces the blood loss and duration of drainage as compared to electrocautery.

The pRb (p16-pRb-cyclin D1) and p53 (p53-MDM2-p21) pathways play a critical role in tumorigenesis. To evaluate which of these cell cycle regulatory proteins are related to patients' prognosis, a comprehensive analysis of alterations in these components was carried out in 100 ESCCs (oesophageal squamous cell carcinoma) using immunohistochemistry and correlated with clinicopathological parameters by univariate analysis. Overexpression of p53, MDM2 and cyclin D1 proteins was observed in 73, 42 and 67% of the cases, respectively, while loss of expression of p21, p16 and pRb was observed in 36, 45 and 75% of the cases, respectively. Multiple logistic regression analysis revealed that loss of p16 immunoreactivity was a significant risk factor for tumour stage (pT) (Odds Ratio (OR)=3.3), whereas the loss of pRb was a significant risk factor for nodal metastasis (pN) (OR=8.8). MDM2 overexpression emerged as the most significant risk factor for distant organ metastasis (pM) (OR=4.6). Of the ESCC patients who underwent oesophagectomy, 50 cases were followed-up for a maximum period of 44 months and median of 16 months. Survival analysis revealed that Cyclin D1 overexpression is an adverse prognosticator for disease-free survival, as well as overall survival, and tumour stage (pT) is an adverse prognosticator for disease-free survival. In conclusion, these data support a model of oesophageal cancer pathogenesis in which both the pRb and p53 pathways are inactivated and suggests an in-depth evaluation of the clinical utility of these putative markers is warranted.

Introduction: Adenocarcinoma of the stomach is usually advanced at presentation, and local or distant spread may preclude the option of primary curative resection. Neoadjuvant chemotherapy (NAC) has shown promise in downstaging initially unresectable disease. This pilot study was planned to assess the utility of NAC using Cisplatin and 5-Fluoro uracil in the management of initially unresectable gastric cancer., Patients and Methods: Ten patients with unresectable gastric adnocarcinoma were included. They received two cycles of cisplatin, 30 mg/m2 intravenously in combination with 5-Fluoro Uracil, 1000 mg/m2. They were restaged using Endoscopy and CT scan and taken up for exploratory laparotomy., Results: Eight of 10 patients (80%) had an objective response to chemotherapy. Six patients (60%) with initially unresectable disease could be offered curative surgery. The median survival was 10 months (range 1-60 months). There were two long term survivors (48 and 60 months respectively)., Conclusion: Neoadjuvant chemotherapy (NAC) is an effective option in downstaging initially unresectable gastric carcinoma. Complete response to chemotherapy also predicts long term survival.

Background: Venous access is crucial for cancer management for administration of drugs blood products, antibiotics and periodic sampling., Aims: To review our experience of long-term venous access devices used over a ten-year period and to analyse the outcome in cancer patients in Indian setting., Setting and Design: A retrospective analysis of data in a tertiary care Regional cancer centre., Patients and Methods: A total of 110 patients with various malignancies requiring long-term venous access were included in the study. A uniform open cut down procedure under local anaesthesia was used and silastic Hickman catheters were inserted in the cephalic or external jugular or internal jugular veins. A record of all complications and catheter loss and final out come were analysed., Results: A total of 111 catheters were used in 110 patients. Sixty-nine catheters were placed in cephalic, 40 in external jugular, and 2 in internal jugular vein. Duration of catheter indwelling period ranged from 7 to 365 days with a median of 120 days. In 90% of the cases the catheter tip was located either in superior vena cava or in right atrium. Total catheter related complications were observed in 37 (34.54%) patients and catheter loss rate due to complications was 15.4% (17/111)., Conclusions: Long-term venous access using Hickman catheter insertion by open cut down method is a simple, safe and reliable method for administration of chemotherapeutic agents, antibiotics and blood products. The incidence of various complications and catheter loss was acceptable and overall patient satisfaction was good.

The degradation of the extracellular matrix (ECM) is a major step in the process of tumor invasion and metastasis, mediated by matrix metalloproteinases (MMPs). Knowledge of alterations in the expression of stromelysin-2 (ST-2) or MMP-10 in human esophageal squamous cell carcinoma (ESCC) is meager. Immunohistochemical analysis of ST-2 expression was carried out in surgically resected ESCCs (50 cases) and paired distal histologically normal esophageal tissues (50 cases), correlated with clinicopathological parameters. Overexpression of ST-2 protein, in tumor cell cytoplasm and stromal elements, was observed in 37 of the 50 (74%) ESCCs localized in tumor cell cytoplasm and stromal elements. Low levels of ST-2 were observed in 8 of the 50 (16%) matched histologically normal esophageal tissues. Significant associations were observed between ST-2 overexpression and tumor size (r = 0.02, P = 0.04), local invasiveness of the tumor (r = -0.30, P = 0.002) and distant organ metastasis (r = -0.227, P = 0.02), suggestive of its involvement in development and progression of ESCCs. The data underscore the significance of ST-2 expression in context to the aggressive tumor characteristics observed in ESCCs in the Indian population, wherein extremely poor prognosis has been ascribed to extensive local invasion and metastasis.

Metastases to the peripheral bones of the extremities are rare. Such lesions are often diagnosed as inflammatory or infective in nature. We present a report of a case of simultaneous involvement of the peripheral bones of the extremities--the talus and the thumb of the left hand--with a brief review of pathophysiology and management.

The high incidence of oral submucous fibrosis (OSF), a potentially malignant condition of the oral cavity, in the Indian subcontinent is causally associated with commonly prevailing habit of chewing areca nut and tobacco. Knowledge of molecular alterations in OSF is meagre. OSF is characterised by progressive accumulation of collagen fibres in lamina propria and oral submucosa. Colligin/HSP47 is a 47KDa stress protein which acts as a chaperone for collagen. We hypothesized that since colligin plays a vital role in folding and assembling collagen it may be involved in the pathogenesis of OSF. The present study was undertaken in tobacco and areca nut chewing Indian OSF patients to investigate the correlation, if any, between the expression of colligin and collagen type I proteins in OSF lesions. Immunohistochemical analysis showed overexpression of colligin and collagen type I proteins in 16/23 (70%) and 15/23 (65%) of OSF cases, respectively. The hallmark of the study was the significant association between the increased expression of type I collagen and its chaperone, colligin, in OSF lesions (P=0.0494). The data suggest that the increased levels of colligin in OSF may contribute to the deposition of collagen and consequent increased fibrosis in the oral submucosa in OSF lesions.

Purpose: The p16/cyclin D1/pRb pathway plays a critical role in tumourigenesis. We recently reported alterations in expression of tumour suppressor gene products, p16 and pRb in esophageal cancer. Knowledge of alterations in cyclin D1, a vital component of this pathway in esophageal carcinomas from the Indian subcontinent, where the etiology and pathogenesis may be confounded by various unique dietary and environmental factors, is presently scanty. In order to bridge the gap between the accentuating incidence of esophageal cancer and aberrations in the components of this vital pathway, we analysed cyclin D1 expression in esophageal squamous cell carcinoma in the Indian population., Method: Immunohistochemical analysis of cyclin D1 expression was carried out in paraffin-embedded sections of surgically resected esophageal squamous cell carcinomas (ESCC) (70 patients) and matched with histopathologically normal esophageal tissues from a distant site. The findings were correlated with clinicopathological parameters., Results: Overexpression of cyclin D1 was observed in the tumour nuclei in 41 out of 70 (59%) patients. We found concomitant alterations in 16 and cyclin D1 (p16-/CycD1+ phenotype) in 16 of the 70 patients (23%), while alterations of pRb and cyclin D1 (pRb-/CycD1+) were observed in 36 of the 70 (51%) patients of ESCCs. Cyclin D1 overexpression was significantly associated with the loss of p16 immunoreactivity (P = 0.005). The pRb- and p16-/pRb-/Cyc D+ phenotypes showed significant association with differentiation of the tumour (P = 0.005, 0.05, respectively). Kaplan-Meier analysis for disease recurrence showed increased disease recurrence in cyclin D1 overexpressed patients. Median time to disease recurrence in the cyclin D1+ group was 15 months as against 18 months observed in the cyclin D1- patients (P = 0.067; log-rank test)., Conclusion: Alterations in at least one of the components of the p16/cyclin D1/pRb pathway in majority of the 70 patients analysed herein, and concomitant alterations in all the three proteins in 19 patients (35%) underscore the critical role of this pathway in esophageal tumourigenesis. The results of the present study taken together with our previous findings on p16 and pRb alterations in ESCCs suggest that these alterations are not mutually exclusive and may cooperatively provide greater tumour growth advantage. The prognostic significance of alterations in the expression of these components cyclin D1, p16, and pRb remains to be established in a larger cohort.

Background: The incidence of colorectal cancer (CRC) shows a wide geographic variation and India along with other Asian and African countries has a low incidence. Most patients present with advanced disease and no uniform treatment guidelines are followed at present., Patients and Methods: An audit of 91 patients treated as per IRCH protocol between June 1994 and Jun 2000 in a single surgical unit was performed., Results: The mean age of patients was 45.3 years (18-90 years) and there was a predominance of rectal cancer patients (Rectal vs Colon = 76% vs 24%). Majority of the rectal cancers were low rectal cancers (67%) and abdominoperineal resection was the commonest surgical procedure performed(40). The inoperability rate was 24% and sphincter salvage rate was 13%. Seventy nine percent of patients had adenocarcinoma and 90% of CRC patients belonged to Astler-Collers stage B2 and C. A total of 37 patients also received adjuvant radiotherapy and only 39 out of 60 patients planned for adjuvant chemotherapy could complete the treatment. The operative mortality was 2.2% and morbidity was 18%. A total of 13 (14%) patients had relapse of disease (local 5, regional 3, distant 5)., Conclusions: A significant number of CRC patients in India present with advanced stage of disease and probably due to referral bias majority had low rectal cancers. By advocating multimodality protocols a good locoregional and systemic control can be achieved despite the advanced stage of presentation.

Breast conservation therapy for early breast cancer is an established but grossly under-utilized treatment option in India for various reasons. Breast conservation therapy was offered to 200 suitable breast cancer patients between June 1993 and June 1998. Fifty-one patients (25%) opted for breast conservation and the remaining preferred mastectomy. In patients agreeing to conservation therapy, surgery was performed first along with peroperative implantation of iridium-192 to deliver a boost. Whole breast irradiation of 45 Gy was delivered 3-4 weeks after the boost. Cosmesis was assessed at the end of 6 months from completion of therapy. The main reason for refusal of breast conservation therapy was fear of recurrence in the remaining breast (60%). There were no locoregional failures in our study at a median follow up of 42 months; one patient experienced a systemic relapse. Cosmesis was good to excellent in 80% of patients. Breast conservation therapy using peroperative iridium-192 implant provides excellent locoregional disease control and cosmesis. The results of our study indicate that patient preference for mastectomy is an important reason for the under-utilization of breast conservation therapy in India.

Iridium-192 interstitial brachytherapy is practiced infrequently in developing countries, even where head and neck cancer is a major neoplasm and the technique could provide good results. This report from India is presented as an audit to validate the benefit of brachytherapy. One hundred and six head and neck cancer patients were treated by interstitial brachytherapy alone (n = 29) or combined with external irradiation (n = 77). The oral cavity and the oropharynx together constituted 82% of the sites of implanted tumours; 75% were T(1-2)N0 status. Brachytherapy was carried out using afterloaded plastic catheters and the Paris dose prescription system was followed. External cobalt-60 beam portals covered the primary and the neck. The median duration of follow-up was 22 months. The median dose of brachytherapy used alone was 60 Gy. With combined treatment, the median external radiotherapy and brachytherapy doses were 50 Gy and 25 Gy respectively. The median brachytherapy dose rate was 0.5 Gy/h. Primary and nodal recurrences were recorded in 41/106 (38.7%) and 18/106 (17.0%) patients at median intervals of 15 and 13 months respectively. Implant site failure was more common after combined treatment than with brachytherapy alone (42.8% versus 27.5%), but it did not reach statistical significance in this analysis (P = 0.15). Kaplan-Meier actuarial 5-year estimates showed 52% and 87% disease-free and overall survivals. Iridium-192 interstitial implants in suitably selected head and neck cancer patients can improve the radiotherapeutic results, with the promise of organ conservation in 50%. In India, the practice should be established in more radiotherapy centres and could be utilized in 10,000-25,000 head and neck cancer patients annually.

Persistent Mullerian duct syndrome is a rare, autosomal recessive intersex disorder characterized by the presence of completely developed Mullerian duct derivatives in an otherwise normally virilized male with a 46, XY karyotype. We discuss a rare presentation of this disorder, bilateral gonadal tumours with obstructive uropathy, and its management, together with a review of the literature.

Retinoids reverse potentially malignant lesions and inhibit the development of second primary cancers in patients with head-and-neck cancer. Many of the effects of retinoids result from modulation of gene expression by 2 distinct classes of nuclear receptor, RARs and RXRs; alterations in their expression can lead to tumorigenesis. To determine whether aberrations in expression of the receptors are related to the development of betel- and tobacco-related oral cancer, we used specific monoclonal antibodies against RARalpha and RARbeta to detect expression of these proteins in 30 histopathologically normal tissues, 45 potentially malignant lesions (leukoplakia) with histological evidence of either hyperplasia (31 cases) or dysplasia (14 cases) and 64 oral squamous-cell carcinomas (SCCs) by immunohistochemistry. Of the 30 normal oral tissues analysed, 8 cases showed detectable levels of RARalpha protein, while 10 cases did not show detectable RARbeta immunoreactivity. Immunostaining for RARalpha protein was observed in 12/31 (39%) hyperplastic lesions, 6/14 (43%) dysplastic lesions and 43/64 (67%) oral SCCs. Expression of RARalpha in oral SCC was significantly associated with the histological differentiation status of tumours (p = 0.016). In contrast, lack of detectable immunoreactivity was observed in 19/31 (61%) hyperplastic lesions, 8/14 (57%) dysplastic lesions and 21/64 (33%) oral SCCs. The hallmark of the study was the significant increase in RARalpha immunopositivity in oral SCCs compared to normal tissue (p = 0.0005) and hyperplastic lesions (p = 0.016). One intriguing feature was the significant decrease in RARbeta immunopositivity in hyperplastic lesions compared with normal oral mucosa (p = 0.05) as well as in oral SCCs compared with normal tissues (p = 0.0008).

In oral squamous cell carcinoma (SCC), the presence of lymph node metastasis is one of the most important prognostic factors, correlating locoregional spread, recurrence, distant metastasis and survival. However, the biological factors implicated and the mechanisms underlying these events are not completely elucidated. We reported Ets-1 expression in oral SCC and proposed that it may serve as a plausible marker of invasive potential and lymph node metastasis. Herein, we investigate the prognostic significance of Ets-1 expression in oral cancer. One hundred oral SCCs assessed for Ets-1 expression showed significant association with tumor stage (P = .027), lymph node involvement (P < 10(-6)) and distant organ metastasis (P = .007). The transcription factor Ets-1 regulates the expression of several genes involved in extracellular matrix remodeling that may account for its association with lymph node and distant organ metastasis. Kaplan-Meier survival analysis entailed significant association of Ets-1 expression in oral SCCs with reduced disease free survival (P = .0041), suggesting its utility as a prognosticator for oral cancer. In conclusion, these findings underscore the role of Ets-1 in oral tumor invasion and metastasis and may thus account for its association with diminished disease free survival.

Purpose: Alterations in the cell cycle regulatory p16INK4a/Cyclin D1/pRb pathway play a pivotal role in tumorigenesis. Knowledge of alterations in the tumor suppressor protein pRb and its negative regulator, p16CDKN2/MTS1/INK4a in esophageal squamous cell carcinoma (ESCC) from the Indian subcontinent is meager. To gain insight into the mechanisms underlying tumorigenesis and to search for diagnostic molecular markers for ESCC, we analyzed the expression of p16INK4a and pRb in ESCCs in the Indian population., Methods: Immunohistochemical analysis of pRb and p16INK4a proteins was carried out in paraffin-embedded sections from 61 surgically resected ESCCs and matched normal tissues, and the results correlated with clinicopathological parameters using chi square and Fisher's exact tests. Dual immunohistochemical analysis has been carried out to demonstrate the concomitant loss of expression of p16INK4a and pRb., Results: Fifty-nine of 61 (97%) cases showed aberration(s) in either or both of these proteins confirming their critical role in esophageal tumorigenesis. Loss of pRb was observed in 51 of the 61 (84%) and loss of p16INK4a was observed in 35 of 61 (57%) cases. Loss of pRb showed significant association with dedifferentiation of the tumor (P = 0.004). p16-/pRb-, and p16+/pRb- phenotypes were significantly associated with nodal metastasis (P = 0.017 and 0.027, respectively), while p16-/pRb+ phenotype was associated with dedifferentiation of the tumor (P = 0.012)., Conclusion: pRb/p16INK4a pathway plays a critical role in esophageal tumorigenesis in the Indian population. The dual hits (concomitant loss) of pRb and p16INK4a expression suggest that these two components are not mutually exclusive, and can both be altered in a significant proportion of primary ESCCs serving as putative diagnostic markers for esophageal cancer. However, the impact of dual hit on tumor behavior and disease prognosis remains to be determined.

Objective: The present case-control study was undertaken with the objective to study the nutritional risk factors associated with esophageal cancer., Methodology: One hundred and fifty diagnosed esophageal cancer patients and an equal number of healthy individuals constituted the patient and control groups, respectively. Dietary consumption pattern during the preceding 20 years prior to the diagnosis of esophageal cancer was assessed utilising the standard food frequency questionnaire method. Information on alcohol consumption, smoking habits, chewing of betel leaf with tobacco was also collected., Results: Multivariate analysis revealed that the risk of esophageal cancer was 7.81 times (p < 0.01) higher with daily consumption of alcohol. The risk increased to 3.16 times (p < 0.01) with the daily habit of chewing of betel leaf with tobacco. Nearly a two fold risk was observed when the consumption of "other vegetables" was less than four times per week. A 1.95 times (p < 0.01) increase in risk was observed with the daily habit of bidi smoking., Conclusion: Cancers in general are multifactorial in origin, and several environmental interactions are possible. It is not easy to quantify the contribution of diet to cancer risk. However, the results of the present study suggested that nutritional factors do play a role.

Background and Objectives: Modified radical mastectomy (MRM) remains the most commonly performed surgery for breast cancer today. Conventional surgery using scalpel and electrocautery is associated with moderate blood loss and morbidity in the form of haematoma, flap necrosis, prolonged axillary drainage, and seroma. This study was performed to evaluate the feasibility of using ultrasonic energy (harmonic scalpel) for MRM and to standardise the operative technique of harmonic scalpel MRM using various available accessories of the harmonic scalpel., Methods: Fourteen patients suffering from carcinoma breast planned for MRM were included in the study., Results: The learning curve of harmonic scalpel MRM was short. Harmonic scalpel is a multifunctional instrument and the whole operative procedure could be accomplished with the currently available accessories. No sutures or electrocautery were used. The mean blood loss was 57.5 ml and the mean operative time was 117 min. There were no hematomas or flap necroses, whereas one patient developed seroma. The mean postoperative drainage volume was 430 ml., Conclusions: In comparison to the historical data of conventional mastectomy, there seems to be a reduction in the blood loss and drainage volume using harmonic scalpel. Results of our study show that modified radical mastectomy using the harmonic scalpel is feasible and the learning curve is short, however, further studies are needed to assess the impact on morbidity.

Esophageal cancer (EC) in the Indian population presents in advanced stages with poor prognosis and warrants the identification of a non-invasive marker for early detection and better prognostic assessment. We have previously reported high prevalence of p53 protein accumulation in esophageal squamous-cell carcinomas (ESCCs). The present study was designed to determine (i) if esophageal cancer patients elicit a humoral immune response to intra-tumoral p53 protein accumulation and (ii) their relationship with p53 gene mutations. The goal was to compare the cellular events, p53 protein accumulation and gene mutations with the presence of serum anti-p53 antibodies (p53-Abs) and to assess the utility of serological p53-Ab analysis as a surrogate marker for p53 alterations in esophageal cancer. A high prevalence of circulating p53-Abs was observed in 36 of 60 (60%) ESCC patients. In a subset of 44 ESCCs, exons 5-9 of the p53 gene were examined for mutations by PCR and direct sequencing of PCR products. Mutational data have been correlated with p53-Abs and p53 protein accumulation in ESCCs. Circulating p53-Abs in ESCC patients were significantly associated with intra-tumoral p53 protein accumulation (p=0.0005). A strong correlation observed between humoral immune response against p53 protein, missense gene mutations and protein accumulation warrants the application of serological p53-Abs as a non-invasive surrogate marker in screening high-risk populations for early detection of malignancy., (Copyright 2000 Wiley-Liss, Inc.)

p21(waf1/cip1), an important regulator of the cell cycle, binds to PCNA and acts as a mediator of the growth suppressing and apoptosis promoting functions of p53. We report a hitherto unobserved polymorphism in the carboxy terminal domain (codon 149) of p21(waf1/cip1) gene, the domain encoding the PCNA binding motif. The codon 149 polymorphism (GAT-->GGT) was observed in 42 of 50 (84%) esophageal squamous cell carcinomas (ESCCs) and eight of 50 (16%) normal individuals. The resultant amino acid substitution from aspartate to glycine may have vital implication in PCNA mediated cell cycle regulation by p21(waf1/cip1). The second polymorphism at codon 31, involving a C-->A transversion at nucleotide 168 (AGC-->AGA) changing the amino acid from serine to arginine, was observed in 2/50 (4%) ESCCs at a relatively lower frequency in the Indian population than that reported in the West. No significant association was observed between p21(wap1/cip1) polymorphism at codon 149 and p21(wap1/cip1) protein expression in ESCC in this cohort of patients. Interestingly, the frequency of p21(wap1/cip1) variants (codon 149) in ESCCs (18 of 19 cases) with wild-type p53 was significantly higher than in tumors with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play an important role in esophageal tumorigenesis. Analysis of p21(waf1/cip1) expression in relation to p53 gene and protein status revealed its induction by p53-dependent as well as independent pathways in esophageal tumorigenesis.

Reactive oxygen metabolites (ROMs), including superoxide anion (O2*-), hydrogen peroxide (H2O2) and hydroxyl radical (*OH), play an important role in carcinogenesis. There are some primary antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) which protect against cellular and molecular damage caused by the ROMs. We conducted the present study to determine the rate of O2*- and H2O2 production, and concentration of malondialdehyde (MDA), as an index of lipid peroxidation, along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients. Forty-two age- and sex-matched patients with minor surgical problems, who had no history of any neoplastic or breast disorders, were taken as controls. The rate of O2*- production was significantly higher (p < 0.001) in BC patients than controls, irrespective of clinical stages and menopausal status. Similarly, H2O2 production was significantly higher in BC patients, especially in stage III and postmenopausal groups, as compared to the respective controls. MDA concentration was also observed significantly elevated in stage II (p < 0.001), stage III (p < 0.01), postmenopausal (p < 0.005), and premenopausal (p < 0.02) group as compared to their corresponding controls. SOD and GPx activities were found significantly raised in all the groups (p < 0.001), except the GPx activity was found a smaller alteration in stage IV (p < 0.02). On the contrary, CAT activity was found significantly depressed in all the study groups. The maximum depression was observed in stage II (-61.8%). Lower CAT activity in our study may be the effect of higher production of ROMs, particularly O2*- and *OH. SOD and GPx, however, were less effected by these higher ROMs production. The results of our study have shown a higher ROMs production and decreased CAT activity, which support the oxidative stress hypothesis in carcinogenesis. The relatively higher SOD and GPx may be due to the response of increased ROMs production in the blood. However, the higher SOD and GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the most dangerous *OH radical followed by MDA. Therefore, administration of CAT may be helpful in the management of BC patients. However, further elaborate clinical studies are required to evaluate the role of such antioxidant enzymes in BC management.

The proto-oncogene Ets-1 is a transcription factor known to regulate the expression of a number of genes involved in extracellular matrix remodelling. It has been postulated to play a role in angiogenesis, cell migration, and regulation of tumour invasion. In betel and tobacco-related oral tumourigenesis, oral squamous cell carcinomas (SCCs) having a poor prognosis often exhibit extensive local disease with spread into regional lymph nodes. At present, no tumour marker is available to predict the metastatic potential of oral carcinomas. To elucidate the involvement of Ets-1 in human oral tumourigenesis, 60 cases of oral SCC, 30 potentially malignant lesions, and 30 samples of normal oral mucosa were examined by immunohistochemistry and the findings corroborated with immunoblotting. The relationship of Ets-1 expression with the degree of differentiation, lymph node metastasis, and tumour stage was determined in oral SCCs. Ets-1 was not detected in the normal oral epithelium. Among the 60 cases of oral SCC, 35 cases (58 per cent) showed positive staining for the Ets-1 protein in tumour cells. In potentially malignant lesions, 14 of 30 cases (47 per cent) showed Ets-1 immunopositivity. Ets-1 expression correlated significantly with tumour stage ( p=0.01) and lymph node metastasis ( p=0.005). The presence of Ets-1 mRNA in oral SCCs was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). These findings suggest that overexpression of Ets-1 in potentially malignant lesions may be related to angiogenesis and its expression in oral SCCs may be one of the factors involved in tumour progression and lymph node metastasis., (Copyright 1999 John Wiley & Sons, Ltd.)

P-glycoprotein (Pgp) encoded by the MDR1 gene, a predictor of chemoresistance, may also serve as a prognosticator of clinical outcome in cancer patients. The mutant tumour-suppressor p53 protein has been shown to activate the MDR1 promoter, whereas the wild-type p53 represses this activity in cultured cells. We have described the differential expression of Pgp and p53 proteins in betel- and tobacco-related oral tumorigenesis in the Indian population. Herein, Pgp expression was analysed in relation to p53 protein accumulation in pre-malignant and malignant oral lesions by immunohistochemical and flow-cytometric analyses. The relationship between Pgp and p53 protein accumulation and clinicopathological parameters as well as prognosis was determined. Expression of Pgp was observed in 81% of oral squamous cell carcinomas (SCCs) and 71% of pre-malignant lesions. Sixty-five of 75 p53-positive oral SCCs and 21/24 p53-positive pre-malignant lesions showed expression of Pgp. Significant correlation between Pgp and p53 expression was found not only in oral SCCs but also in pre-malignant lesions. Co-expression of Pgp and p53 proteins was indicative of poor prognosis. Follow-up studies of 35 patients showed that 7 of 10 oral SCCs with accumulation of Pgp and p53 proteins also exhibited shorter disease-free survival (recurrence/metastases). Our findings provide clinical evidence for a significant association between Pgp and p53 protein expression in oral tumorigenesis and may account for the aggressive nature of the tumour and poor prognosis.

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.

p21waf1/cip1 protein, an inhibitor of cyclin dependent kinases, is a critical downstream target in the p53-specific pathway of growth control, and can also be induced by p53 independent pathways in relation to terminal differentiation. p21waf1 is also a putative tumour suppressor. Hence, we sought to determine whether this protein is abnormally expressed during betel- and tobacco-related oral oncogenesis. The aim was to determine whether a correlation exists between the expression profile of p21 and clinicopathological parameters of the patients, as well as with their p53 status. Immunohistochemical analysis showed that the expression of p21 protein in premalignant lesions was consistently elevated in the superficial, differentiated cells of the epithelium, while overexpression of the p53 tumour suppressor gene was observed in the basal proliferating layers of the epithelium. Our study demonstrated that p21 overexpression is associated with differentiation in proliferating dysplasias and squamous cell carcinomas (SCCs). The expression of p21 and p53 proteins was observed in 11/25 premalignant lesions. In 7 of these 11 cases, a heterogenous pattern of expression of p21 and p53 was observed. Four of these 11 premalignant and 30/51 malignant lesions showed concordant expression of both p21 and p53 proteins. The discordant p21 +/p53- phenotype was observed in 4/25 premalignant lesions and 5/51 oral SCCs. The p21-/p53+ phenotype was observed in 5/25 premalignant lesions and 7/51 oral SCCs. These results suggest that induction of p21 occurs by both p53 dependent and independent mechanisms during oral tumorigenesis.

p53 aberrations are early events in the pathogenesis of betel- and tobacco-related oral malignancies. Accumulation of p53 protein in oral lesions may elicit a humoral immune response against p53 protein in these patients. p53 antibodies (Abs) were analyzed in 183 sera obtained from patients with premalignant or malignant oral lesions and normal individuals by enzyme-linked immunoassay using recombinant p53 protein as antigen. These results were correlated with accumulation of p53 protein in patients' matched oral tissue specimens. Circulating p53 Abs were observed in 24 of 70 (34%) cancer patients and 15 of 50 (30%) patients with premalignant oral lesions. p53 Abs showed a significant association with increase in tumor size and dedifferentiation of tumors, factors indicative of poor prognosis. Expression of p53 protein was analyzed in 43 matched oral lesions (18 premalignant and 25 malignant cases). All the p53-seropositive patients (7 leukoplakia and 11 squamous cell carcinoma) showed elevated levels of p53 protein in matched oral lesions. However, the total number of patients seropositive for p53 Abs was lesser than that of patients exhibiting p53 protein accumulation in oral lesions. Four of the 63 normal healthy individuals who were heavy consumers of tobacco (smoking/chewing) and betel were found to be positive for p53 Abs. Detection of circulating p53 Abs in patients with premalignant oral lesions suggests that humoral immune response against p53 protein is an early event in oral oncogenesis and may be a surrogate marker for both p53 alteration and preclinical cancer.

Cyclin dependent kinase inhibitor 2/multiple tumour suppressor gene 1 (CDKN2/MTS1) and retinoblastoma (Rb) tumour suppressor genes play important roles in the regulation of the cell cycle. The protein products of these genes p16INK4 (p16) and pRb, respectively, like p53 protein inhibit progression from G1 to S phase. p16 exerts its function through inhibition of CDK4-mediated phosphorylation of pRb. The pRb/p16 pathway is a critical target for molecular aberration at the G1-S checkpoint in a wide range of primary human tumours. The expression of p16 and pRb proteins was analyzed by immunohistochemistry in 35 cases of oral squamous cell carcinomas (SCCs), 22 cases of premalignant oral lesions and 30 normal oral tissues. Lack of pRb expression was observed in 23/35 (66%) oral SCCs and 14/22 (64%) premalignant lesions. Lack of p16 expression was observed in 22/35 (63%) oral SCCs and 13/22 (59%) premalignant lesions. Weak p16 and pRb immunoreactivities were observed in normal oral mucosal epithelium. The status of p16 and pRb was correlated with clinicopathological characteristics of the patients. Alteration in p16 expression showed significant correlation with tumour staging and progression (P = 0.024). Alteration in pRb/p16 expression correlated with heavy consumption of betel and tobacco. Our results suggest that alterations in the p16/pRb pathway are early events in oral tumorigenesis and may be involved in the development of betel- and tobacco-related oral malignancies.

Malignant mesenchymal tumours of the breast are rare neoplasms. Their incidence varies from 1%-3% of all malignant breast tumours (1). Stromal sarcoma of the breast is an extremely uncommon tumour (2). We present a rare case of advanced stromal sarcoma of the breast successfully managed with radical surgery and radiotherapy.

From January 1993 to December 1995, complete records of patients with biliary neoplasms were analysed. A total of 124 patients were registered. Majority of patients were in the age range of 40-60 years (median 54 years). There were 38 males and 86 females. Histopathologically, adenocarcinoma was the commonest type (59%). Pain, jaundice and lump were noticed in 119, 54 and 77 patients respectively. Fifty six patients had associated gall stones. Ninety patients had metastatic disease at presentation. Majority of them (110/124) had advanced, inoperable disease and therefore were considered for palliative treatment. Only 14 patients (12%) were considered for curative treatment. Of these 14 patients, all the cases underwent surgery, 10 received radiotherapy and 10 received chemotherapy. Follow up was very poor. The survival of 14 patients, who received curative treatment, ranged from 2 months to 44 months with mean of 16 months.

To determine whether the multidrug-resistance-gene product phospho-glycoprotein (P-gp) is implicated in progression of oral tumours and/or drug resistance, the expression of P-gp was examined in different stages of oral oncogenesis using monoclonal antibody C-219. Cryosections from normal (41 cases), dysplastic lesions (32 cases), untreated primary SCCs (50 cases) and recurrent tumours (31 cases) were used for immunostaining, and the results were corroborated by immunoblotting. Chi-square test for trend analysis showed a significant increase in P-gp immunopositivity across the normal, leukoplakia, primary oral SCC and recurrent SCC groups (p < 0.01). Expression of P-gp in dysplastic lesions showed significant association with severity of dysplasia, the level of P-gp protein being higher in severe and moderate dysplasia. Among the primary tumours, significant correlation was observed between P-gp positivity as well as level of P-gp expression and tumour stage. The recurrent tumours showed significant increase in P-gp expression as compared with untreated primary oral tumours. We conclude that differential expression of P-gp may be an index of the disease prognosis in oral-cancer patients in the context of the Indian population.

At the Institute Rotary Cancer Hospital, AIIMS, New Delhi, 246 patients of breast cancer were operated on from June 1993 to June 1996; 82 suitable patients were discharged within 48 h (short stay surgery, SSS) after surgery and 164 were discharged after 48 h (conventional stay surgery, CSS). After discharge, patients of both groups were followed in the outpatient clinic until the removal of sutures and drains. There was no mortality or readmission for a complication in either group. Mean post-operative hospital stay was 1.5 days in the SSS group, and 3.3 days in the CSS group. There was no statistically significant difference in the incidence of post-operative complications like wound infection (4.8% vs 4.2%), flap necrosis (6% vs 5.4%), seroma (14% vs 19%), and the average number of hospital visits (3.42 vs 3.2) in SSS and CSS groups, respectively. Patient acceptance of early discharge was good except in the day care group. The study supports the safety and feasibility of short stay surgery for breast cancer in certain circumstances for properly selected patients.

A case control study was conducted on 170 patients with oesophageal cancer. An equal number of healthy persons (attendants of patients) were included in the study as controls to identify nutritional risk factors for oesophageal cancer. The majority (55%) of the patients were of low socio-economic status and from Northern parts of India. They were predominantly male (66%). Increase in risk was associated with low consumption of green leafy vegetables, other vegetables and fresh fruits, milk and milk products. Heavy use of spices and use of very hot tea or food were also associated with increased risk. Differences in the past dietary consumption patterns of oesophageal cancer patients and controls suggest a role for nutritional factors in oesophageal cancer pathogenesis. At the same time substance abuse by cigarette or bidi smoking, alcohol consumption, paan and tobacco chewing also increased risk. After multivariate analysis, green leafy vegetables, other vegetables spices, bidi usage and fresh fruits provided protection against oesophageal cancer.

Over-expression of glutathione S-transferase pi (GST-pi) class isozyme is often associated with malignant transformation and/or drug resistance. To determine whether GST-pi is implicated in betel and tobacco related oral carcinogenesis and/or drug resistance, its expression was studied in oral untreated primary squamous cell carcinomas (SCCs), recurrent tumours and matched normal oral tissues by immunohistochemical and immunoblotting techniques. The GST-pi expression in primary tumours predominantly varied from mild to moderate levels and no significant difference in its expression was observed in the matched normal tissue surrounding these lesions. Mild to moderate levels of GST-pi expression in the oral mucosa of consumers of betel and tobacco observed in the matched normal tissues may support the physiological role of this detoxification enzyme in the metabolism of xenobiotics and elimination of toxic constituents of tobacco. The hallmark of the study is the significant increase in GST-pi expression in recurrent oral SCCs, compared to the matched normal tissues, as well as primary oral tumours, suggesting its potential role as an indicator of prolonged exposure to carcinogens, or prognosis of the disease.

Multidrug resistance (MDR) in human cancer is often associated with over-expression of the mdr-1 gene, which encodes a 170-kDa transmembrane protein, termed P-glycoprotein (P-gp). We evaluated the immunoreactivity of P-gp in oral tissues at different stages of tumorigenesis in the Indian population by flow cytometry, using the MRK-16 monoclonal antibody, which recognizes an external epitope of P-gp. The expression of P-gp was studied in human oral normal tissues (12 cases), dysplastic lesions (13 cases), primary untreated squamous-cell carcinomas (12 cases) and recurrent tumors (18 cases). Quantitative flow-cytometric analysis of P-gp expression showed a significant increase in P-gp levels in untreated primary oral tumors (p < 0.01) and in dysplastic lesions (p < 0.05) as compared with normal oral tissues. A marked significant increase in P-gp expression was observed in recurrent oral carcinomas as compared with normal oral tissues (p < 0.001) and dysplastic lesions (p < 0.01). Among recurrent tumors, a significant increase in the level of P-gp was observed in T4-stage tumors as compared with T3-stage tumors (p < 0.01). We conclude that P-gp is differentially expressed during oral tumorigenesis, and may be an indicator of the biological behavior of oral malignancies.

Over a 7-year period from 1987 to 1993, 41 male breast cancer patients were seen in the breast cancer clinic of the Institute Rotary Cancer Hospital (IRCH) at the All India Institute of Medical Sciences (AIIMS). Their mean age was 54.2 years; and duration of symptoms ranged from 1 to 84 months with a mean of 15.1 months. Breast lump was the commonest presenting symptom. Fine needle aspiration cytology (FNAC) was the commonest diagnostic procedure. The TNM stage distribution was stage I, 5; stage II, 13; stage III, 17; and stage IV, 6. Radical mastectomy (25/36) was the commonest surgical procedure. Locoregional radiotherapy was given in 15 patients. Thirty patients received systemic adjuvant therapy (chemotherapy or tamoxifen, or a combination of the two). Local or distant recurrence occurred in 8 patients (8/31, 28.3%). Actuarial overall and disease-free survival was 100% and 80.1% at 2 years and 91.7% and 66.7% at 4 years, respectively. On univariate analysis, axillary lymph node status and age were found to affect disease-free survival significantly. Advanced stage of disease at presentation is common in Indian patients and will continue to influence treatment policies. Neoadjuvant chemotherapy needs to be evaluated for locally advanced tumors to improve outcome. Multicentric studies are necessary to define the relative roles of tamoxifen and chemotherapy for adjuvant treatment.