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Biomedical subjects

A R Fakih

Publications and source records attributed to A R Fakih.

At least 19 recordsLinked to original sources
PubMed2003

Radical radiation vs surgery plus post-operative radiation in advanced (resectable) supraglottic larynx and pyriform sinus cancers: a prospective randomized study.

AIM: Survival in head and neck cancers reflect loco-regional control. With an aim of organ and function preservation the present study was undertaken to compare local failure and survivals. MATERIAL AND METHODS: Between August 1991-December 1995, 72 patients with resectable advanced supraglottic cancers, were randomized to radical surgery followed by post-operative radiation therapy (Sx+PORT) (Arm I) or radical radiation therapy followed by salvage surgery (RRT+/-SSx) (Arm II). RESULTS: Sixty-four of 72 patients were evaluable, 55 were T3 (86%) and 9 were T4 (14%) tumors. In Arm I (n=35) with a mean follow-up of 24 months (2-86 months), 21 patients were alive without disease. Six patients had recurrence, one each at local and tracheostomy stoma, four had nodal recurrence only, and two developed 2nd primary in soft palate/tonsil and parotid at 15 and 18 months respectively. In Arm II (n=29), with a mean follow-up of 24 months (3-81 months), 14 patients were alive without disease. Thirteen patients had recurrence, eight had local (one patient had persistent disease), two nodal only, three loco-regional and two patients developed distant metastasis (lung). One out of eight local recurrence and 2/2 nodal recurrences were salvaged with Sx. There was a significant difference in disease-free survival between the two treatment arms, DFS (5 years) of 70% in Arm I vs 50% in Arm II (p=0.04), but did not have any impact on overall survival OAS (5 years); 73% vs 77% (p=0.79). Voice/laryngeal preservation was possible in 18/29 patients (62%) treated with RRT+/- Sx, without significantly affecting the OAS. "Pathological upstaging" was another significant finding seen in 64% of clinical T3 after radical surgery. CONCLUSION: RRT+/-SSx can be a feasible option in low volume, favourable resectable stage III and IV supraglottic lesions for better quality of life.

Adult↗
PubMed2000

Prognostic factors in head and neck soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas of head and neck constitute a heterogeneous group of rare malignant tumors occurring at rare sites. The purpose of this retrospective study is to evaluate the pathologic features, treatment modalities, outcome, patterns of failure, survival, and other prognostic factors. METHODS: The medical records of 72 patients whose tumors were diagnosed as head and neck sarcomas, treated at Tata Memorial Center between 1981 to 1995 were reviewed. Potential prognostic factors including age, gender, tumor size, histology, grade, and adjuvant treatment were evaluated. RESULTS: The overall and disease free survival at 5 years was 60% and 45%, respectively. The median survival and follow-up was 76 and 38 months, respectively. Thirty-two patients (44.4%) developed recurrence of which 13 patients were salvaged. The univariate and multivariate analysis showed tumor size and grade as important prognostic factors for the survival. CONCLUSIONS: Tumor size greater than 5 cm and high grade tumors were important prognostic factors for survival. Every effort should be made for early diagnosis and wide surgical excision. For localized recurrent tumors without evidence of distant metastasis, surgery should be attempted whenever possible. High rates of locoregional failure in head and neck area indicate the need for improved treatment strategies.

Adolescent↗
PubMed1999

Human gamma delta T cells recognize heat shock protein-60 on oral tumor cells.

In the present investigations, gammadelta T cells were isolated from the peripheral blood of oral cancer patients and analyzed for their immunophenotype and cytotoxic potential. Flow-cytometric analysis revealed a dominant population expressing Vgamma9 and Vdelta2 T-cell receptors. In a 4-hr 51Cr-release assay, activated gammadelta T cells showed specific cytotoxicity against Daudi Burkitt's lymphoma cells and fresh oral tumor cells. Cold target competition assays demonstrated that gammadelta T cells recognize a common ligand on Daudi and oral tumor cells. Expression of heat shock protein 60 (hsp60) molecules was detected on the surface of Daudi as well as oral tumor cells by flow cytometry and immunoprecipitation of surface biotinylated cells by anti-hsp60 monoclonal antibody (MAb). Such MAbs brought about a significant inhibition of cytotoxicity of gammadelta T cells against Daudi and oral tumor cells. The results suggest that gammadelta T cells isolated from the peripheral blood of oral cancer patients have the ability to lyse oral tumor cells. The lysis of oral tumor cells occurs via recognition of hsp60 on the surface of oral tumor cells.

Antibodies, Monoclonal↗
PubMed1999

Complications following gastric transposition after total laryngo-pharyngectomy.

AIMS: To investigate restoration of the pharynx after total laryngo-pharyngectomy (TLP), one of the major problems in head and neck surgery. METHODS: A retrospective analysis of 60 patients undergoing total laryngo-pharyngectomy with gastric transposition was performed between June 1991 and June 1996. The analysis focused on morbidity, mortality and long-term function following gastric transposition. RESULTS: The post-operative mortality was 8.3% and the peri-operative morbidity 31.2%. The average hospital stay was 15 days. Immediate restoration of swallowing was achieved in 83% of patients. CONCLUSIONS: Gastric transposition after total laryngo-pharyngectomy is a safe procedure and can be performed with low mortality, acceptable morbidity and good long-term function.

Adult↗
PubMed1997

Analysis of DNA ploidy and expression of tumour-associated antigens on human oral carcinomas xenografted in nude mice.

Human squamous cell carcinomas (SCC) of the oral cavity were successfully established as xenografts in nude mice. Tumours with higher malignancy scores and involvement of lymph nodes in patients were more readily accepted as xenografts in nude mice. The xenografted tumours were characterised with respect to morphology, histology, DNA index and expression of tumour-associated antigens (TAA). Flow cytometric analysis of cellular DNA content revealed that many of the xenografts retained the parent tumour DNA pattern while some of the xenografts showed progression to aneuploidy. All the xenografted tumours expressed TAA recognised by monoclonal antibody (MAb) 3F8E3. On Western blotting, MAb 3F8E3 recognised proteins of molecular weight 62-64 kDa on parent and xenografted tumours. In general, the xenografts reflect many of the characteristics of the tumours from which they were derived and may provide a useful model for investigating newer approaches of treatment and diagnosis.

Animals↗
PubMed1996

Limiting dilution analysis of proliferating and cytotoxic lymphocytes in the peripheral blood and tumours of oral cancer patients.

Frequencies of proliferating and cytotoxic lymphocytes from the peripheral blood and tumour tissue of oral cancer patients and healthy individuals were monitored using limiting dilution analysis. Significantly lower precursor frequencies of proliferating lymphocytes were observed in the peripheral blood and tumour tissue of oral cancer patients. A high frequency of natural killer (NK) cells but low cytotoxic T lymphocytes (CTL) was observed in the peripheral blood compartment of oral cancer patients as compared to healthy individuals. A marked reduction in both NK and CTL frequencies in the tumour tissue compared to the peripheral blood was observed. In the tumour tissues, increased percentages of activated CD4+ lymphocytes as compared to CD8+ lymphocytes were observed. Our results suggest that impaired proliferative and cytotoxic potential of tumour infiltrating lymphocytes may play an important role in the escape of tumour cells from the immune system.

Adult↗
PubMed1994

Perioperative chemotherapy in patients with oral cancer.

In the final report of a prospective, randomized controlled clinical trial, we report the results of using adjuvant perioperative chemotherapy in patients with oral cancer. Our study is based on the hypothesis of Goldie and Coldman. A total of 135 patients with alveolobuccal carcinoma, classified as clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The patients in the test arm of the study received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The patients in the control arm underwent observation. This analysis at 24 months showed a disease-free survival rate of 61% in the test arm versus 37% in the control arm, which is statistically highly significant (P < 0.01). Analysis of the recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P = 0.002). Our study provided further clinical evidence in support of the concepts of Goldie and Coldman that the timing of chemotherapeutic drugs is critical for a successful end result.

Adult↗
PubMed1993

Modulatory effect of cytokines on natural killer and antibody dependent cellular cytotoxicity directed to squamous cell carcinoma targets by lymphocytes from oral cancer patients.

Cells from solid tumours are generally poor targets for natural killer (NK) cytotoxicity and antibody dependent cellular cytotoxicity (ADCC). In this paper, we have analysed NK cytotoxicity and ADCC mediated by peripheral blood mononuclear cells from healthy individuals and oral cancer patients before and after modulation with recombinant interleukin-2 (rIL-2), on target cells derived from two squamous cell carcinoma (SCC) cell lines prior to and after treatment with recombinant interferon-alpha (rIFN alpha). Target SCC cell directed monoclonal antibody 3F8E3 was used in ADCC. The results showed that the unmodulated SCC cells were poor targets for NK and ADCC compared to standard targets (K562 cells and chicken red blood cells, respectively). Modulation of targets alone with rIFN alpha showed moderate increase in their susceptibility while rIL-2 treated effectors could significantly lyse even unmodulated targets. Combined treatment of targets with rIFN alpha and effectors with rIL-2 showed additive enhancement in NK and ADCC activity against SCC cells. Lymphocytes from treated patients with recurrent disease could not efficiently lyse SCC targets even after combined modulation.

Adult↗
PubMed1993

Craniofacial excision for recurrent osteogenic sarcoma of maxilla.

Two cases of recurrent osteogenic sarcoma of the antro-ethmoidal complex treated at our hospital by a craniofacial resection are presented. The imperative need to treat osteogenic sarcomas of the maxilla primarily by a radical approach such as a craniofacial resection is emphasized.

Adolescent↗
PubMed1992

Morbidity & mortality following craniofacial resections.

A seven year experience with twenty patients undergoing the craniofacial approach for excision of tumours of the paranasal sinus and orbit is presented. Results indicate a low postoperative morbidity and mortality with excellent cosmesis. Good palliation is achieved in the presence of extensive disease, while large tumours which would have been considered inaccessible can be resected. Its advantage recommend it as the treatment of choice for tumours of the orbit and paranasal sinuses.

Adult↗
PubMed1991

Perioperative chemotherapy in oral cancer.

This is an interim report of a study of perioperative adjuvant chemotherapy following radical surgery for oral cancer, based on the hypothesis of Goldie and Coleman. 135 patients of alveolobuccal carcinoma, clinically stage III and IV, were entered on the protocol. After a curative resection, they were randomized. The test arm received methotrexate 50 mg/m2 on the 3rd, 10th, and 17th postoperative days. The control arm was only observed. This analysis at 12 months showed a disease free survival of 71% in the test arm vs. 45% in the control arm, which is statistically highly significant (P less than 0.01). Analysis of recurrence pattern showed that recurrence at the primary site was dramatically reduced during the first 6 postoperative months (P less than 0.01). Our study provided further clinical evidence in support of the concepts of Goldie and Coleman that the timing of chemotherapeutic drugs is very critical for a successful end result.

Adult↗
PubMed1989

Lymphokine-activated killer-cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer.

Lymphokine-activated killer (LAK) cells, generated from peripheral blood lymphocytes (PBL) from patients with oral cancer or oral leukoplakia and from healthy donors showed comparable lysis of 6 target tumor cell lines, including 3 derived from head and neck and oral cancers. The tumor burden of the host did not appear to influence the systemic LAK activity. LAK activity of lymphocytes infiltrating the tumor tissues (TIL) was also comparable to that of the PBL. Both TIL and PBL showed a parallel increase in proportion of HNK-I+ and CD-25+ cells upon activation with IL-2. The lymph-node lymphocytes (LNL) from metastatic (met) and non-metastatic (non-met) draining lymph nodes, however, showed reduced LAK activity and an increase in CD8+ cells, in addition to CD25+ and HNK-I+ cells, when cultured with IL-2. When IL-2-activated LNL were co-cultured with autologous PBL during IL-2 activation of the latter, a strong suppressive effect was exerted by LNL. In contrast, IL-2-activated PBL did not suppress autologous LAK generation in spite of an increase in CD8+ cells seen after activation with IL-2. Frequency distribution of LAK precursors was significantly lower in LNL than in PBL from oral cancer patients. LAK precursor frequency in TIL was comparable to that of PBL. The results show that, in oral cancer, regional lymph nodes may not have adequate IL-2-inducible cytotoxic potential, due to a reduced number of LAK progenitors and possible activation of suppressor cells. Alternatively, TIL can be a potential source for LAK cell function.

Adolescent↗
PubMed1989

Prophylactic neck dissection in squamous cell carcinoma of oral tongue: a prospective randomized study.

This paper presents the first report of an ongoing prospective randomised clinical trial in early T1T2N0 carcinoma of the oral tongue. The problems of regular follow-up in an indigent population from the vast rural expanse of India has been successfully overcome in this trial by close personal follow-up. The trial addresses itself specifically to prophylactic vs. therapeutic surgical management of the neck in T1T2N0 patients with cancer of the oral tongue. Overall disease, free survival (median follow-up 22 months) is higher (64% vs. 47%) in the group receiving prophylactic neck dissection. Disease-free survival for those with positive nodes at prophylactic neck dissection was twice that of those who underwent a subsequent therapeutic neck dissection (57% vs. 28%). Contralateral neck node metastasis has been identified as a significant factor in neck failures in those patients undergoing simultaneous prophylactic neck dissection.

Adult↗