Inhibition of SHH pathway mechanisms by arsenic trioxide in pediatric medulloblastomas: a comprehensive literature review.

Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment. Several new drugs aimed at SHH modulation are currently under development. This review focuses on the role of arsenic trioxide, a drug well established in clinical practice and probably an under-explored agent in medulloblastoma management, in the SHH pathway.

Transplanted chondrocytes inhibit endochondral ossification within cartilage repair tissue.

The aim of this study was to investigate the effect of transplanted chondrocytes on endochondral bone formation in cartilage repair tissue. In the knee joint of miniature pigs, cartilage lesions were treated by microfracturing and were then either left empty, covered with a collagen membrane, or treated by matrix-associated autologous chondrocyte transplantation. In control lesions, the subchondral bone plate was left intact (partial-thickness lesion). The repair tissues were analyzed after 12 weeks by histological methods focusing on bone formation and vascularization. The effect of chondrocytes on angiogenesis was assessed by in vitro assays. The presence of antiangiogenic proteins in cartilage repair tissue, including thrombospondin-1 (TSP-1) and chondromodulin-I (ChM-I), was detected immunohistochemically and their expression in chondrocytes and bone marrow stromal cells was measured by quantitative RT-PCR. Significant outgrowths of subchondral bone and excessive endochondral ossification within the repair tissue were regularly observed in lesions with an exposed or microfractured subchondral bone plate. In contrast, such excessive bone formation was significantly inhibited by the additional transplantation of chondrocytes. Cartilaginous repair tissue that resisted ossification was strongly positive for the antiangiogenic proteins, TSP-1 and ChM-I, which were, however, not detectable in vascularized osseous outgrowths. Chondrocytes were identified to be the major source of TSP-1- and ChM-I expression and were shown to counteract the angiogenic activity of endothelial cells. These data suggest that the resistance of cartilaginous repair tissue against endochondral ossification following the transplantation of chondrocytes is associated with the presence of antiangiogenic proteins whose individual relevance has yet to be further explored.

Laparoscopic partial posterior fundoplication improves poor oesophageal contractility in patients with gastrooesophageal reflux disease.

OBJECTIVE: To investigate the effect of partial posterior fundoplication on oesophageal contractility in patients with gastrooesophageal reflux disease (GORD). DESIGN: Follow-up study with 6 months of survey. SETTING: University hospital, Austria. SUBJECTS: 24 consecutive patients with GORD and poor oesophageal contractility. INTERVENTIONS: Laparoscopic partial posterior fundoplication. Oesophageal contractility was assessed manometrically. MAIN OUTCOME MEASURES: Changes in measurements of mean contraction amplitudes in the distal oesophagus, the number of contractions with amplitudes of less than 30 mmHg, the number of interrupted and simultaneous contractions, and the total number of defective contractions. RESULTS: 16 of the patients (67%) complained of dysphagia preoperatively, and none postoperatively. The mean (SEM) amplitudes in the distal oesophagus improved significantly (level 442.4 mmHg (3.5) compared with 31.8 mmHg (3.3), p = 0.03, and level 5-45.7 mmHg (3.8) compared with 32.6 mmHg (3.7), p = 0.02), the number of contractions with amplitudes below 30 mmHg decreased (18.0% (5.7) compared with 38.3% (6.2), p = 0.02), as did the number of interrupted or defected contractions (11.5% (3.6) compared with 26.3% (5.5), p = 0.03, and 29.5% (6.5) compared with 66.6% (5.1), p < 0.0001 respectively). There was no significant effect on the number of simultaneous waves (p = 0.11). CONCLUSIONS: Partial posterior fundoplication improves poor oesophageal body motility. This results in improvement of preoperative dysphagia.

Hand-assisted laparoscopic splenectomy for isolated splenic metastasis from an ovarian carcinoma: a case report with review of the literature.

A 56-year-old woman was found to have a solitary metastasis to the spleen from ovarian cancer. A hand-assisted laparoscopic splenectomy was carried out. The operative technique and advantages of this technique are discussed. Laparoscopy with mini laparotomy allows for manual manipulation of the spleen with the ability to control bleeding, and facilitates mobilization and removal of the specimen. Postoperative recovery is rapid. Review of the literature indicates that secondary metastasis to the spleen is quite common.

Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium.

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.

The surgical option for gastroesophageal reflux disease.

Gastroesophageal reflux disease is a common condition. Most patients can be managed with medications, but patients with refractory disease, particularly those with an incompetent lower esophageal sphincter, should be referred for surgery. The open Nissen fundoplication cures >90% of patients of their symptoms. The laparoscopic approach was first applied for patients with gastroesophageal reflux disease in 1991, and since then numerous reports evaluating the early experience with this technique have been published with results similar to the open procedure. Over the last 5 years, 595 laparoscopic antireflux procedures have been performed by us. There was 1 mortality due to an unrecognized duodenal perforation. Splenic injury did not occur compared to an incidence of up to 8.5% for the open procedure. A total of 9 patients required conversion to the open procedure for perforation, bleeding, or dissection difficulties. However, in the last 350 cases no conversions have been necessary. Most patients are now being discharged from hospital on the day after surgery with some patients being discharged on the same day as surgery. The overall reoperation rate, both for early postoperative morbidity and for late poor outcome, was 3.9% with follow-up ranging from 2 months to 5 years. The laparoscopic Nissen fundoplication achieves the same short-term outcome as the open procedure with significantly less postoperative morbidity and a shorter hospital stay.