PubMed HealthSearch

Biomedical subjects

A R Fakih

Publications and source records attributed to A R Fakih.

16 recordsLinked to original sources

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

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

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

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

Natural killer and lymphokine-activated killer cell-mediated cytotoxicity in patients with oral cancer.

Peripheral blood lymphocytes (PBL) from untreated and treated oral cancer patients, lymph node lymphocytes (LNL) from metastatic (met) and nonmetastatic (non-met) lymph nodes, and tumor infiltrating lymphocytes (TIL) were tested for natural killer (NK) and lymphokine activated killer (LAK) cell cytotoxicity using appropriate targets in a short-term chromium release assay. The results showed that while both NK and LAK functions of PBL from oral cancer patients were comparable to those of normal healthy donors, the NK activity of metastatic and nonmetastatic LNL and TIL was highly compromised. On the other hand, potent LAK activity could be generated from all three lymphoid populations. Individual patients showing low NK activity displayed good LAK cytotoxicity, indicating that endogenous cells with low NK potential have adequate ability to respond to interleukin 2 (IL-2). LAK activity tested on autologous tumour targets revealed that TIL were the best source of LAK cells. followed by PBL and LNL.

Cell Line

Elective versus therapeutic neck dissection in early carcinoma of the oral tongue.

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.

Adult

Monocyte/macrophage functions in patients with squamous cell carcinoma of the oral cavity.

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.

Carcinoma, Squamous Cell

Interleukin-2 mediated regulation of mitogen-activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity.

Peripheral blood lymphocytes (PBL) from patients with oral cancer (treated and untreated), oral leukoplakia and healthy donors; lymphocytes from metastatic and non-metastatic lymph nodes (met LNL and non-met LNL); and tumor infiltrating lymphocytes (TIL) were tested for proliferative response to mitogen PHA (phytohemagglutinin) and its augmentation by recombinant Interleukin-2 (rIL-2), for expression of Tac antigen (CD25) and for production of IL-2. Depressed PHA responses were found in PBL of treated and untreated patients, and in TIL. Addition of IL-2 could bring about 16% to 31% augmentation in lymphocyte response to PHA from all the three sources. PBL from 50% of healthy donors, 45% of patients with leukoplakia, 25% untreated oral cancer patients and 35% treated oral cancer patients showed IL-2 mediated augmentation of PHA response. While, 40% non-met LNL samples, 70% met LNL samples and only 23% TIL samples showed increased mitogen induced proliferation by IL-2. The augmented levels of PHA response of PBL from treated and untreated patients, and of TIL, were still below those of normal PBL. PBL from patients with leukoplakia, treated oral cancer patients and TIL showed depressed CD25 antigen expression. Depressed IL-2 production was observed only in PBL of leukoplakia patients. Thus the IL-2 mediated events of T cell activation from different lymphoid sources in patients with oral cancer did not correlate with their proliferative responses.

Adult

Immunoreactivity of lymphocytes from draining lymph nodes, peripheral blood and tumor infiltrates from oral cancer patients.

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.

Adult

Detection of circulating immune complexes in patients with squamous cell carcinoma of the oral cavity.

Circulating immune complexes (CICs) have been quantitated from the sera of untreated oral cancer patients and those treated with radiation or surgery using C1q binding assay in terms of percent binding activity (C1q BA) and microgram/ml equivalent of aggregated human gamma globulin (AHG). Sera from a total of 108 oral cancer patients and 47 normal healthy donors were evaluated for CICs. Out of these, 48 patients were tested before treatment and 60 were tested 6 months to 1 yr after treatment. Levels of CICs were elevated in 70.8% patients before treatment (mean % C1q BA 29.6 +/- 2.2) when compared to healthy controls (4.2% positive, mean % C1q BA 9.0 +/- 0.8). Treated patients showing no evidence of the disease had reduced CIC levels, only 11.7% patients showing C1q BA at the level of 13.2 +/- 1.4. On the other hand, treated patients showing recurrence of the disease had much higher CIC levels (mean % C1q BA 42.8 +/- 3.5, 92.3% positive) even higher than the untreated patients. Status of CIC levels as well as recurrence rate in patients treated with either radiation or surgery were comparable. One out of 4 individuals with premalignant changes such as oral leukoplakia showed elevated levels of CICs.

Adult

Cell-mediated immune status in patients with squamous cell carcinoma of the oral cavity.

Sixteen untreated patients with squamous cell carcinoma of the oral cavity were tested for in vitro immune status in comparison with the normal healthy donors. The parameters investigated were total leukocyte and lymphocyte counts, percentages and absolute counts of T- and B-cells in circulation, subsets of T-cells identified by the Fc receptors, phytohemagglutinin (PHA), and mixed lymphocyte culture (MLC) responses, natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities, and circulating immune complexes (CICs). Eight of these patients were retested 3 to 6 months after surgery. The results showed that there was an increase in leukocyte and lymphocyte counts, an increase in the percentage and absolute number of B-lymphocytes, an increase in the percentage of T-gamma cells, suboptimal PHA and MLC responses, normal NK and ADCC activities, and increased levels of CICs in untreated oral cancer patients. In the postoperative stage, except for a reduction in leukocyte and lymphocyte counts, other abnormalities remained unchanged. The CICs in treated patients correlated with the tumor load in that in three patients showing recurrence, the CIC level remained elevated, whereas in patients without evidence of the disease the CIC level was either low or comparable to the upper normal limits.

Adult

Completion thyroidectomy for thyroid carcinoma.

We have reviewed the charts of 149 patients who underwent completion thyroidectomies for cancer of the thyroid. The purpose of the study was to evaluate extent of residual disease in the thyroid, and morbidity and mortality of the operation. Residual cancer was found in 58% of the cases, the morbidity was low, and there was no operative mortality.

Adenocarcinoma