[90Y]Yttria Alumino Silicate Glass Microspheres: A Biosimilar Formulation to "TheraSphere" for Cost-Effective Treatment of Liver Cancer.

Background: Selective internal radiation therapy (SIRT) using a suitable ß--emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (90Y) [T1/2 = 64.2 h, Eß(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [90Y]yttria alumino silicate ([90Y]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. Methods: YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20 and 36 µm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [90Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [90Y]YAS glass microspheres were administered in human patients. Results: [90Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (∼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [90Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. Conclusions: The study confirmed the suitability of indigenously prepared [90Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.

An unusual tumor presentation.

Germ cell cancer is the most common malignancy in men 15-35 years of age; 5% of malignant germ cell tumors are of extragonadal origin. The key to diagnosis and management is tumor histology. This point is highlighted in this case review. It also reinforces that germ cell tumor markers should be done in all young patients diagnosed with malignancy. We describe the case of a 21-year-old man who was diagnosed as having inoperable cancer of the ascending colon, which turned out to be extragonadal germ cell tumor after studies. This patient has responded very well to bleomycin, etoposide, and cisplatin chemotherapy.

The impact of nutritional status on the outcome of Indian patients undergoing neurosurgical shunt surgery.

Undernutrition is common in surgical patients, is frequently unrecognised and is strongly associated with adverse outcomes such as high rates of complications and mortality, worsening functional status and prolonged hospitalisation. Owing to the associated infection and symptoms such as repeated vomiting, a high prevalence of undernutrition is expected in hydrocephalus patients, which may contribute to their poor surgical outcomes. The aim of this study was to evaluate the influence of preoperative nutritional status on the outcome of Indian patients with hydrocephalus undergoing neurosurgical shunt surgery. One hundred and twenty-four consecutive patients undergoing scheduled hydrocephalus shunt surgery were studied prospectively. All patients underwent nutritional screening according to different parameters prior to surgery. The patients were classified into normally nourished and undernourished groups. The undernourished group was further subdivided into moderately and severely undernourished. The surgical outcome was compared between these groups. A high prevalence (53%) of undernutrition was observed in these patients. Postoperative complications such as shunt infection (P = 0.0023), shunt revision (P = 0.0074) and mortality (P = 0.0003) were significantly more common in undernourished patients compared with normally nourished patients. Serum albumin emerged as the most significant independent predictor of postoperative mortality. The present study demonstrated a high prevalence of undernutrition in hydrocephalus patients in India and its adverse influence on the outcome of shunt surgery. Early preoperative nutritional status screening and its optimisation may decrease the morbidity and mortality of shunt surgery for hydrocephalus.

Laparoscopic management of difficult recurrent choledocholithiasis.

The management of common bile duct stones has traditionally required open laparotomy and bile duct exploration. With the advent of endoscopic and laparoscopic technology in the latter half of the last century, endoscopic retrograde cholangiopancreatography and laparoscopic common bile duct exploration has become the mainstream treatment for common bile duct stones in most medical centers around the world. However, in some patients, endoscopic retrograde cholangiopancreatography is difficult and laparoscopy is challenging because of previous surgery. These facts are highlighted in this report.

Appendiceal mucocoeles and pseudomyxoma peritonei.

Mucocoele of the appendix occurs when obstruction of the appendiceal lumen results in mucus accumulation and consequent abnormal dilatation. The most important aetiology, from a surgical perspective, is either mucinous cystadenoma or cystadenocarcinoma. In the latter, a spontaneous or iatrogenic rupture of the mucocoele can lead to mucinous intraperitoneal ascites, a syndrome known as pseudomyxoma peritonei. Optimal management of mucoceles is achieved through accurate preoperative identification and subsequent careful resection. We report two cases and subsequently discuss the clinical presentation of mucocoeles, their association with pseudomyxoma peritonei and an optimal management of both conditions.

Tissue engineering of small intestine--current status.

Short bowel syndrome (SBS) has always posed a great threat to patients and has been one of the biggest challenges for doctors due to its high morbidity and mortality. So far, parenteral nutrition (PN) and small bowel transplantation remain the only viable therapeutic options. However, sepsis and liver failure associated with PN and limited availability of the donor organs and high graft rejection rates associated with transplantation have limited their use to a nonpermanent solution. Clearly, there is a need for an alternative therapy whereby increasing the absorptive surface area would help neonates and adults suffering from permanent intestinal failure. Techniques such as sequential intestinal lengthening are being explored in animal models with little success. Attempts to engineer small intestine since the late 1980s have achieved varying degrees of success in animal models with evolving refinements in biotechnology. The most encouraging results so far have been the generation of intestinal neomucosa in the form of cysts when intestinal epithelial organoid units isolated from neonatal rats were seeded onto biodegradable polymers before implantation in syngeneic adult rats' omentum. Although still experimental, continued attempts worldwide using cultured stem cells and improved polymer technology offer promise to provide an off-the-shelf artificial intestine as a novel therapy for patients with SBS. This article reviews the current status of progress in the field of small intestinal tissue engineering and addresses various types of cell sources and scaffold material having potential to be used in this field.