Tracheo-esophageal Puncture (TEP) for Voice Rehabilitation in Laryngectomised Patients Blom-singer® Vs Provox® Prosthesis : Our Experience.

BACKGROUND: Stage III and IV cancers of larynx and hypopharynx often require total laryngectomy which leaves the patient with severe communication handicap. In such laryngectomised patients tracheo-esophageal puncture is the best way for voice rehabilitation using either Blom-Singer® prosthesis or Provox® indwelling valve. METHODS: A prospective comparative study of Blom-Singer® prosthesis and Provox® indwelling valves placed in Tracheo-esophageal Punctures (TEP) for voice rehabilitation following total laryngectomy was carried out at the Tata Memorial Hospital, Mumbai and Malignant Diseases Treatment Centre of Armed Forces, to assess their efficacy. This report comprises of our experience in 41 (39 males and two females) laryngtectomees who underwent TEP of which 15 patients were fitted with low pressure Blom-Singer® prostheses and 26 with Provox® indwelling prostheses. RESULTS: Prostheses related problems like granuloma formation, leakage, candidal growth over the valves and prosthetic decay were significantly less in the patients fitted with Provox® prosthesis. Dislodgement of prosthesis with closure of the tract or persistent fistula formation and creation of false passage, while reinsertion were problems encountered in the Blom-Singer group. After three months, speech assessment revealed a better quality of voice production and patient compliance in maintaining the prosthesis in the case of Provox® indwelling valve. CONCLUSION: In Indian scenario where illitracy amongst the patients hinders in maintainence of Blom-Singer® prosthesis, Provox® indwelling value is an appropriate choice for voice rehabilitation.

Pediatric tele-echocardiography: evaluation of transmission modalities.

Pediatric cardiology consultation has been effectively delivered outside the tertiary care setting through the use of tele-echocardiography. This study examined the effectiveness of several tele-echocardiography connections and the satisfaction of the referring physicians using these services. Studies were transmitted via either a shared fiber-optic (DS3) connection (two sites), a dedicated fast-copper (ISDN-PRI) link, or by courier from a nearby (25-mile) or distant (170-mile) site. Time intervals between when echocardiograms were performed locally until they were received, interpreted, and reported were prospectively recorded. Referring physician satisfaction was assessed through a survey. The critical time between when a remote echocardiogram was performed and when its result was reported to the referring physician was primarily determined by the mode of transmission. The time interval between performing an echocardiogram and receiving the study was significantly longer for echocardiograms sent from the 170-mile courier site (2474 +/- 295 min) than either the 25-mile courier site (474 +/- 151 min), DS3 (374 +/- 121 min), or ISDN-PRI (129 +/- 16 min). Regardless of the method of transmission, all referring physicians felt that the service improved their ability to manage children, and they would recommend the service to their colleagues. Those using the courier service from the 25-mile away site were more concerned about the availability of a pediatric cardiologist and image quality, presumably due to the delay in response times. The time interval data provided in this study and the assessment of physician satisfaction provide important data as echocardiography laboratories implement tele-echocardiography services.

Regeneration of plantlets in Sapindus trifoiatus L.

Continuous production of healthy plantlets of Sapindus trifoliatus L. was achieved via somatic embryos from long term cultures of an embryogenic mass (EM). A highly embryogenic culture of S. trifoliatus L. was obtained by recurrent embryogenesis from somatic embryos cultured on Murashige and Skoog's (MS) medium supplemented with kinetin (2.3 microM) and benzyladenine (8.8 microM). The cultures could be maintained without reduction of embryogenic competence for more than 20 months by subculture at 4 week intervals. About 90% mature somatic embryos on transfer to basal MS medium, germinated to plantlets, of which more than 70% survived when transferred to a sand and soil mixture in green house.

Management of tracheocutaneous fistula.

We describe a simple technique that utilises local skin flaps of closure of a large tracheocutaneous-fistula with a adequate support to the tracheal wall by double breasting of local flaps, thus avoiding the post-operative respiratory problems that can occur due to a single flap projecting into the tracheal lumen during inspiration.This technique avoids the complications associated with primary closure of fistulae & also the morbidity of waiting for secondary closure to occur. It also precludes the need for a more extensive operation in the form of muscle flap rotation. The fistulous tract does not need to be excised but forms a component of the repair.

p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India.

The inactivation of p53 tumour suppressor gene vis-á-vis point mutation, overexpression and degradation due to Human Papilloma virus (HPV) 16/18 infection, was examined in chewing tobacco-associated oral cancers and oral leukoplakias from India. The analysis of mutations was assessed by polymerase chain reaction (PCR) with single strand conformation polymorphism (PCR-SSCP) of exons 5-9 on DNA from 83 oral cancer cases, and the mutations confirmed by direct nucleotide sequencing of the PCR products. p53 protein expression was evaluated by immunohistochemical analysis on paraffin-embedded sections of 62 representative oral cancer biopsies and 22 leukoplakias, using p53-specific monoclonal antibody DO-7. The presence of HPV16/18 was detected in the 83 oral cancer cases by PCR analysis using HPV L1 consensus sequences, followed by Southern hybridization with type-specific oligonucleotide probes. Forty-six per cent (38/83) of oral cancer tumours showed p53 alterations, with 17% (14/83) showing point mutations, 37% (23/62) with overexpression and 25% (21/83) with presence of HPV16 wherein the E6 HPV16 protein degrades p53. HPV18 was not detected in any of the samples. Ninety-two per cent concordance was observed between missense point mutations and overexpression of p53 protein. A significant correlation was not observed between p53 alterations in oral cancer and clinico-pathological profile of the patients. Twenty-seven per cent (6/22) of oral leukoplakias showed p53 overexpression. The overall p53 alterations in oral cancer tissues and oral lesions are comparable to data from the oral cancers reported in the Western countries with smoking and alcohol-associated oral cancers, and suggest a critical role for p53 gene in a significant proportion of oral cancers from India. The overexpression of p53 protein in leukoplakias may serve as a valuable biomarker for identifying individuals at high risk of transformation to malignant phenotype.

Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India.

The presence of high risk human papilloma virus (HPV) 16 and 18 was examined in 100 oral cancer patients of Indian descent, 80 patients with potentially malignant oral lesions and corresponding clinically normal mucosa from 48 of these patients. Additionally, presence of HPV-33, -6 and -11 was also studied in 86 oral cancers, 50 potentially malignant oral lesions and 30 corresponding normal oral mucosa. All the patients with oral cancer and oral lesions, were long term tobacco-chewers, and a majority of the patients were in Advanced Stages III and IV. The DNA samples were amplified by polymerase chain reaction (PCR) using HPV L1 consensus primers. Typing of HPV was performed by Southern hybridization analysis of the PCR products using HPV-16, -18, -33, -6 and -11 type specific oligonucleotide probes. HPV-16 was detected in 15 out of 100 (15%) oral tumours, 27 out of 80 (34%) potentially malignant lesions and 15 out of 48 (31%) of the corresponding normal mucosa in the patients with oral lesions. HPV-18 was not detected in any of the oral cancers, oral lesions and normal mucosa. HPV-33 and the low-risk HPV-6 and -11 were also not detected in the oral cancers, oral lesions and corresponding normal mucosa. A significantly higher prevalence of HPV-16 was observed in oral lesions (27 out of 80, 34%) as compared to oral cancers (15 out of 100, 15%). The observed difference of 19% (95% confidence interval [CI]: 6%, 31%), between these two proportions was statistically significant at the 5% level of significance. Our data indicates that HPV-16 may play a direct role in a certain proportion of oral cancers; whereas in a subpopulation of oral cancers HPV-16 infection may be vital in the early events associated with development of potentially malignant oral lesions, and the presence of the virus not essential in the progression of the oral lesion to frank malignancy.

Epstein-Barr virus in tobacco-induced oral cancers and oral lesions in patients from India.

We examined 103 oral squamous cell carcinomas (OSCC), 100 oral lesions consisting primarily of leukoplakia (82 cases), and 76 clinically normal mucosa specimens from the contralateral site in the oral cavity of individuals with oral lesions, for the presence of Epstein-Barr virus (EBV). Polymerase chain reaction (PCR) was used to amplify a 239 bp fragment of the BamHIL region of the EBV genome, followed by Southern blot hybridization with EBV oligonucleotide probe to increase further the specificity and sensitivity of the assay system. Since EBV seropositivity is frequent in populations, we also examined the peripheral blood cells (PBC) from 141 patients (50 oral cancer patients, 91 patients with oral lesions) for the presence of EBV. We detected EBV in 25 of 103 (25%) OSCC, 13 of 100 (13%) oral lesions, 3 of 76 (4%) clinically normal mucosa samples and 10 of 141 (7%) PBC. Our results indicate that EBV may contribute as one of the multiple factors in oral cancers, in a certain proportion of Indian patients.

Loss of p53 gene as a biomarker of high risk oral leukoplakias.

We have investigated loss of heterozygosity of p53 tumor suppressor gene in Indian oral cancer patients, individuals with premalignant leukoplakia lesions, and corresponding normal mucosa, to study the status of p53 alleles in oral cancer pathogenesis. Fifty oral cancers, and 42 oral leukoplakia lesions and corresponding clinically normal oral mucosa from 18 individuals, were analysed. Peripheral blood cells (PBCs) from all the individuals and 47 normal healthy volunteers were also included in the study. Polymerase chain reaction(PCR) of p53 Exon4, followed by restriction enzyme digestion with AccII due to the enzyme polymorphic site at Exon4 codon72, was used to detect homozygosity/heterozygosity of p53 alleles, and compared with the allelic pattern in the corresponding PBC. The PCR product subjected to AccII digestion detected 259 bp, 160/99 bp fragments indicating heterozygosity of p53 alleles in 69% of the 139 individuals. On comparison of the p53 allelic distribution in the lesions or tumour tissues, and corresponding PBC, LOH was observed in 20.5% oral tumors and 22% leukoplakias. However, there was no evidence of LOH in the clinically normal mucosa available from 16 individuals with leukoplakia. Our studies demonstrated LOH of p53 allele in early and advanced stages of oral cancers, as well as leukoplakias, perhaps indicating p53 LOH as one of the early events in oral carcinogenesis. Thus, p53 LOH may be useful as a biomarker in defining a certain population of high risk leukoplakias that may progress to oral cancer.

An overview of the initial experience with AK-2123 as a hypoxic cell sensitizer with radiation in the treatment of advanced head and neck cancers.

PURPOSE: AK-2123 (Senazole) is a nitrotriazole with a reported potential for hypoxic cell sensitization. The present study was conducted to evaluate hypoxic cell potentiation in patients with advanced head and neck cancer treated with discontinuous accelerated hyperfractionated radiation. METHODS AND MATERIALS: Histologically proven unresectable oro-pharyngeal cancers Stage T3-4, NO-3 and M0 were randomly allocated to receive discontinuous accelerated hyperfractionated radiation alone or with AK-2123. AK-2123 (880 and 990 mg) was administered as an i.v. infusion between the first and second fraction of radiation for 10 days in two groups of patients. Initial response as a surrogate end point has been analyzed for comparison and documented for follow-up status. RESULTS: A 100% complete response was observed in both the AK-2123-treated groups (880 mg and 990 mg), while a 44.4% complete response was observed in the control group. There were no treatment-related deaths. Neurotoxicity was not reported. CONCLUSION: AK-2123 (Senazole) when administered with discontinuous accelerated hyperfractionated radiation showed a significant potentiation that, therefore, requires further evaluation.

The Indian experience with immediate tracheoesophageal puncture for voice restoration.

A 3-year prospective study on primary tracheoesophageal puncture was carried out at Nanavati Hospital and Tata Memorial Hospital, Bombay, to assess its feasibility in a developing country and its success in vocal rehabilitation. We report our experience with primary tracheoesophageal puncture in 64 patients (57 males and 7 females) following surgical treatment for carcinoma of the pyriform fossa (45 cases) and endolarynx (19 cases). All patients underwent total laryngectomies with or without partial pharyngectomy and primary pharyngeal mucosal closure. Fifty-one patients underwent primary surgery followed by postoperative radiotherapy. At 3 months successful tracheoesophageal speech was achieved in 84% patients, although this percentage decreased to 67% at 9 months. There were no major complications. Successful vocal rehabilitation was related more to "patient factors" such as delays in seeking medical attention when prosthetic valves dislodged, improper use and care of the valves and inability to learn speech with the prosthesis. Overall, primary tracheoesophageal puncture was found to be feasible and should be used more extensively for vocal rehabilitation following laryngectomy in developing countries.

Restriction fragment length polymorphisms of the human N-myc gene in normal healthy individuals and oral cancer patients in India.

Southern blot hybridization with N-myc oncogene probes coding for different regions of the N-myc gene demonstrated three polymorphic restriction sites in the Indian population. The SphI and PvuII polymorphic pattern due to the SphI polymorphic site in the second intron and the PvuII polymorphic site in the 3'-region of the human N-myc oncogene respectively, was similar to that reported in the Japanese population. The allelic frequency distribution for SphI polymorphism did not differ significantly for the S1 and S2 alleles representing presence (allele S1) or absence (allele S2) of a SphI site. However, the allelic frequency distribution was distorted in the case of PvuII polymorphism, as the frequency of P1 allele (0.7) indicating presence of PvuII site, was higher than the P2 allele (0.3) indicating absence of PvuII site, in the Indian population. An additional polymorphic HindIII site localised in the second intron of the N-myc gene was also observed in both the Indian oral cancer patients and the normal healthy individuals, indicating that this RFLP was not tumor associated and may perhaps represent N-myc alteration in the Indian population.

Effect of testosterone on diethylstilbestrol toxicity and comparison to a recovery study in the rat epididymis and vas deferens.

Effects of diethylstilbestrol (DES) treatment (30 daily i.m. injections) in reproductive function in the male rat were investigated. These functions were evaluated with sperm counts, motility, fertility, morphology, serum testosterone, and a number of biochemical tests in rat epididymis and vasa deferentia. DES treatment resulted in a 15% loss of body weight and a 60 to 90% loss of weight of testes, epididymis, and vas deferens. Sperm parameters and fertility were reduced to nil by DES treatment. Likewise, the majority of the biochemical measures were severely depressed by the DES treatment. In general, the measured parameters were less affected or recovered with either testosterone cotreatment or 60 days of recovery, showing the role of androgen in maintaining functional integrity and metabolism. However, sperm parameters and fertility did not recover with testosterone cotreatment, which differs from withdrawal of treatment.

Recurrent ameloblastoma of the mandible and maxilla.

Sixteen cases of recurrent ameloblastomas of the mandible and maxilla seen over a 14 year period at the Tata Memorial Hospital were analysed with emphasis on recurrence patterns, type of primary surgery and surgical management. Seventy-five percent of the cases had conservative surgery at the first instance. In our experience, recurrent tumors could be excised widely even in unusual locations with good results.

Phaeohyphomycosis of the paranasal sinuses masquerading as a neoplasm: a case report.

A case of fungal infection of the paranasal sinuses simulating a neoplasm is reported. Fonsecaea pedrosoi, a dematiacious fungus, which has not been previously reported, was responsible for this unusual infection. Fungal infection may mimic malignant lesions of the paranasal sinuses; however, coexisting malignancy must be ruled out.

Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer.

The presence of epidermal growth factor receptor (EGF-R) gene was determined in 84 patients with squamous cell carcinoma (SCC) of the oropharyngeal region--a highly prevalent, chewing-tobacco associated malignancy in India, using Southern hybridisation analysis of DNA extracted from primary tumor tissues. We observed a 3- to 8-fold amplification of EGF-R gene in 19/66 (29%) of the SCCs of the oral cavity, and about 30-fold EGF-R amplification in 2/18 (11%) hypopharyngeal cancers. Dot blot analysis of total RNA from several tumour tissues, revealed overexpression of the EGF-R gene in the examined patients, with the EGF-R gene amplified. 4 patients with single copy EGF-R gene, did not exhibit overexpression of the gene. Within our sample set, no correlation was evident between EGF-R gene amplification and clinico-pathological parameters of the malignancy. The amplification and overexpression of the EGF-R gene observed in the primary tumour tissues of 25% (21/84) of the human oropharyngeal cancers, indicate possible involvement of the gene in the pathogenesis of these cancers.

Primary tracheo oesophageal puncture our initial experience.

Our initial experience of 9 primary tracheo oesophageal punctures with Blom Singer prosthesis is reported. Patient selection was based on motivation, intelligence and socioeconomic status. Excellent speech resulted in 7 out of 9 patients (77%), with 2 failures (23%). There were no major complications. The results are encouraging, but a larger study is required to determine the role of this procedure in our conditions.

Gastric transposition & deltopectoral flap for peristomal recurrence following total laryngectomy--a case report.

Stomal recurrence following laryngectomy presents a difficult problem with an incidence of 8.3-15%. Wide excision of the recurrence with mediastinal dissection, although the operation of choice,m is technically demanding and has a high morbidity and mortality. We recommend a technically easier procedure for reconstruction after palliative excision and present a case to illustrate it.