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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.

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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.

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Tumor associated antigen (TAA) on oral squamous cell carcinoma (SCC) was characterized using the monoclonal antibody (MAb) 3F8E3. Flow cytometric analysis revealed a varying degree of reactivity of MAb 3F8E3 to TAA on oral tumor cells. Pretreatment of SCC cells with pronase and trypsin annulled the reactivity of MAb 3F8E3. Sodium metaperiodate (NaIO4) and neuraminidase marginally enhanced the binding of 3F8E3 on oral SCC cells. The studies indicate that the TAA recognized by MAb 3F8E3 on oral tumors is a protein moiety. On Western blotting MAb 3F8E3 showed reactivity to proteins with a molecular weight of 60-66 kDa on oral tumor lysates. MAb 3F8E3 reacted strongly to recombinant human hsp60 and 70 in ELISA. The results suggest that MAb 3F8E3 may react to an epitope expressed on a family of heat shock proteins.

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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.

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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.

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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.

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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.

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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.

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Synchronous primaries in head and neck cancer pose a difficult management problem. A rare case of Synchronous primary of vocal cord and oesophagus was treated at the same sitting by laryngo-pharyngo-oesophagectomy with gastric pull up. We report this case and review the literature in this report.

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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.

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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.

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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.

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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.

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We report a case of synchronous double primary neoplasms of the stomach and kidney. Immunohistochemistry confirmed the two primaries to be of different origin based on antigen expression.

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Peripheral blood monocytes and draining lymph node macrophages from patients with squamous cell carcinoma of the oral cavity, monocytes from patients with oral leukoplakia and those from healthy donors were assessed for FcR. HLA-DR expression and interleukin-1 (IL-1) production after activation with LPS or IFN gamma. Monocyte cytotoxicity was also tested after activation with LPS, IFN gamma, IL-2 singly, or in combinations at suboptimal concentrations. The results showed that the percentage of activated monocytes expressing FcR was significantly low in untreated oral cancer patients, however, the proportion of HLA-DR positive cells was normal. The unstimulated monocytes from oral cancer patients showed spontaneous generation of IL-1. Upon activation, few patients could produce IL-1 to normal levels. The unstimulated monocytes from untreated patients and treated patients with recurrence also exhibit significantly higher tumoricidal activity. Treatment of monocytes with combinations of two modulators (IFN gamma, LPS and IL-2) induced significantly higher cytotoxicity.

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A prospective, randomized trial was carried out to assess the value of elective versus therapeutic neck dissection in early squamous cell carcinoma of the oral tongue. Disease-free survival (median follow-up 20 months) was 52 percent versus 63 percent in patients who underwent hemiglossectomy alone and those who underwent hemiglossectomy and radical neck dissection, respectively (difference not statistically significant). Patients with a tumor depth of less than 4 mm did significantly better than those with a tumor depth of greater than 4 mm; they were also more likely to have uninvolved nodes at elective radical neck dissection compared with those with a tumor depth of greater than 4 mm. However, when the survival rates of patients in the two treatment groups were compared with respect to a tumor depth of 4 mm, there was no significant difference between the hemiglossectomy and the hemiglossectomy and radical neck dissection groups. A policy of interval elective radical neck dissection only in those with a tumor depth of greater than 4 mm may optimize cure rates and avoid neck dissection in those unlikely to develop neck recurrence.

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Lymphocytes from metastatic (met) and nonmetastatic (non-met) regional lymph nodes, LNL peripheral blood (PBL) and tumor infiltrating lymphocytes (TIL) of patients with squamous cell carcinoma of the oral cavity and healthy donors were investigated for CD3, CD4, CD8 and HNK-1 phenotypes, Natural Killer (NK) cell Activity, Antibody Dependent Cellular Cytotoxicity (ADCC) and proliferative response to mitogen (PHA). Modulation of NK cytotoxicity with recombinant Interferon alpha (IFN-alpha) was also investigated in some cases. Lymphocytes from met and non-met lymph nodes showed no variation in the percentages of CD3+, CD4+ and CD8+ cells, when compared with each other and with PBL of oral cancer patients. TIL showed significantly less proportion of CD3+ and CD4+ cells. The percentage of HNK-1+ cells was significantly lower in LNL and TIL when compared to PBL of oral cancer patients. The mitogen responses of met and non-met LNL were comparable to each other and better than that of PBL from the same patients, while, TIL showed significant impairment in mitogen responses. The NK cytotoxicity and ADCC of PBL from oral cancer patients were comparable to healthy donors which could be augmented by rIFN alpha. LNL and TIL showed almost negligible NK and ADCC activities and NK activity could not be modulated by rIFN alpha. The results thus demonstrate that in oral cancer patients, lymphocytes from three compartments viz. PBL, LNL and TIL showed differential effector functions. The metastatic status of LN did not affect the immunoreactivity of LNL.

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