Primary rhabdomyosarcoma of the larynx

Sarcomas constitute fewer than 1% of the head and neck cancers. They represent less than 1% of laryngeal cancers. Primary rhabdomyosarcoma of the larynx is an extremely rare malignancy. The available literature on this medical oddity is in the form of isolated case reports only. The purpose of this article is to add another case of primary rhabdomyosarcoma of a rare site, the larynx, of which only 36 cases have so far been reported in the world literature. The present patient, an eighteen-year-old boy is only the third case being reported from India among all reported cases of rhabdomyosarcoma of the larynx in the world literature.     

Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor–based orthotopic xenograft mouse models of pediatric glioma

Background

Seneca Valley virus (SVV-001) is a nonpathogenic oncolytic virus that can be systemically administered and can pass through the blood–brain barrier. We examined its therapeutic efficacy and the mechanism of tumor cell infection in pediatric malignant gliomas.

Methods

In vitro antitumor activities were examined in primary cultures, preformed neurospheres, and self-renewing glioma cells derived from 6 patient tumor orthotopic xenograft mouse models (1 anaplastic astrocytoma and 5 GBM). In vivo therapeutic efficacy was examined by systemic treatment of preformed xenografts in 3 permissive and 2 resistant models. The functional role of sialic acid in mediating SVV-001 infection was investigated using neuraminidase and lectins that cleave or competitively bind to linkage-specific sialic acids.

Results

SVV-001 at a multiplicity of infection of 0.5 to 25 replicated in and effectively killed primary cultures, preformed neurospheres, and self-renewing stemlike single glioma cells derived from 4 of the 6 glioma models in vitro. A single i.v. injection of SVV-001 (5 × 10¹² viral particles/kg) led to the infection of orthotopic xenografts without harming normal mouse brain cells, resulting in significantly prolonged survival in all 3 permissive and 1 resistant mouse models (P < .05). Treatment with neuraminidase and competitive binding using lectins specific for α2,3-linked and/or α2,6-linked sialic acid significantly suppressed SVV-001 infectivity (P < .01).

Conclusion

SVV-001 possesses strong antitumor activity against pediatric malignant gliomas and utilizes α2,3-linked and α2,6-linked sialic acids as mediators of tumor cell infection. Our findings support the consideration of SVV-001 for clinical trials in children with malignant glioma.     

Primary Obstructive Megaureter in Adults: Need for an Aggressive Management Strategy

Purpose: Primary obstructive megaureter (POM) is an uncommon disease in adults. We reviewed our experience with this disease to determine the clinical profile, management and prognosis of this disease in adults. Methods: We studied 37 adults with POM who presented from January 1989 to December 1998. Their clinical presentation, renal function, radiologic data, complications, treatment as well as the results and follow-up were studied. Results: The patients' age ranged from 13 to 52 years. Male : female ratio was 27 : 10. Seven patients had bilateral disease. All patients were symptomatic excepting 2. Complications at presentation were loin pain (26 cases), urinary infection (15 cases), calculus disease (17 cases), azotaemia (5 cases), and obstructive jaundice (1 case). Associated congenital anomalies included contralateral renal agenesis (2 cases), posterior urethral valve (1 case) and exstrophy of bladder (1 case). Thirty-four patients required surgical intervention. Of these, 26 patients underwent ureteroneocystostomy (UNC) with ureteral tailoring in 18 patients; 4 patients were treated endoscopically by ureteric meatotomy and stenting, 2 patients with nonfunctioning kidney by nephroureterectomy, 2 patients in advanced renal failure by percutaneous nephrostomy alone. In 4 out of 5 patients uraemia did not improve despite adequate drainage. Conclusion: The majority of adults with POM are symptomatic, have complications and require surgical correction. Complications of stone formation (46%) and renal failure (13.5%) are unusually common in adults. Once renal failure is advanced, intervention appears futile, therefore, it is imperative to treat these patients as soon as possible. Surgical correction by ureteric reimplantation is effective and has low morbidity.     

Extracorporeal management of poisonings

Extracorporeal methods have been an integral part in the management of poisonings. The elimination of a drug or toxin by extracorporeal techniques (ECT) is governed by the properties of the toxin and the chosen extracorporeal therapy. The various ECT include hemodialysis, hemoperfusion, hemofiltration, continuous renal replacement therapy and peritoneal dialysis, all of which have been used some time or another for the management of poisonings. This review highlights the concepts forming the basis for selecting one modality over the others.     

Accelerated osteoarthritis in the temporomandibular joint of biglycan/fibromodulin double-deficient mice

OBJECTIVE: To investigate whether the absence of biglycan and fibromodulin, two proteoglycans expressed in cartilage, bone and tendon, resulted in accelerated osteoarthritis in the temporomandibular joint (TMJ). METHODS: Histological sections of TMJ from 3-, 6-, 9- and 18-month-old wild-type (WT) and biglycan/fibromodulin double-deficient (DKO) mice were compared. Immuno-stainings for biglycan, fibromodulin and proliferating cell nuclear antigen (PCNA) were performed. RESULTS: Biglycan and fibromodulin were highly expressed in the disc and articular cartilage of the TMJ. At 3 months of age, both WT and DKO presented early signs of cartilage degeneration visible as small acellular areas under the articular surfaces and superficial waving. From 6 months of age, DKOs developed accelerated osteoarthritis compared to WT. At 6 months, small vertical clefts in the condylar cartilage and partial disruption of the disk were visible in the DKO. In addition, chondrocytes had lost their regular columnar organization to form clusters. At 9 months, these differences were even more pronounced. At 18 months, extended cartilage erosion was visible in DKOs when by comparison the thickness of the articular cartilage in WT controls was basically intact. PCNA staining was stronger in 3-month-old WT TMJ fibrocartilage than in 3-month-old DKO TMJ fibrocartilage suggesting that chondrocyte proliferation might be impaired in DKOs. CONCLUSION: The biglycan/fibromodulin double knock-out mouse constitutes a useful animal model to decipher the pathobiology of osteoarthritis in the TMJ.     

Evaluation of laparoscopic radical cystectomy for loco-regionally advanced bladder cancer

We studied the safety and feasibility of laparoscopic radical cystectomy (LRC) in patients with loco-regionally advanced bladder cancer and report the short-term oncological outcome. This study comprised a total of 13 patients (10 males, 3 females), who presented with myriad of symptoms and on imaging they were found to have radiologically evident advanced disease (6 pelvic lymphadenopathies, 10 extravesical tumor extensions, three prostate/seminal vesical invasions). In view of recalcitrant symptoms (hematuria, frequency and irritative voiding) all patients underwent LRC and bilateral modified pelvic lymphadenectomy with ileal conduit urinary diversion. Mean age of the patients was 56.3 years. Mean operative time was 310 min with an average blood loss of 556 ml. No major intra-operative complications were noted. One patient died in the post-operative period due to sepsis. Histopathology report revealed pT3b N0 in two patients; pT3b N1 in four; pT3b N2 in three; pT4a N0 in one, and pT4aN1 in three patients. Adjuvant chemotherapy was administered in nine patients. At mean follow up of 18 months (range 6–28), seven patients are alive and cancer-free, while two patients are alive with metastases. LRC provides an alternative approach for treatment of patients with loco-regionally advanced bladder cancer, who suffer from recurrent hematuria and severe irritative voiding symptoms, in whom open surgery was the standard approach hitherto. However, it should be considered experimental and should be attempted only by surgeons who have significant experience of laparoscopic pelvic surgery and advanced skills, and after discussing the potential risks and benefits with the patient.