Results after endoscopic treatment of postoperative upper gastrointestinal fistulas and leaks using combined Vicryl plug and fibrin glue

Background The incidence of clinically relevant anastomotic leaks after upper gastrointestinal surgery is approximately 4% to 20%, and the associated mortality is up to 80%. Depending on the clinical presentation, the treatment options include surgery, conservative treatment with or without external drainage or endoscopic treatment.Methods This report presents nine cases of anastomotic leaks or fistulae after surgery for upper gastrointestinal cancers that were treated by insertion of a Vicryl plug and sealing with fibrin glue. Under sedation, all nine patients underwent endoscopic lavage of the cavity at the site of anastomotic leakage. The entrance to the cavity then was filled with Vicryl mesh and sealed off with fibrin glue. After the procedure, the patients underwent endoscopy and a water-soluble contrast study for assessment of the result.Results Seven of the nine patients had complete healing of the anastomotic leak or fistula after one to two endoscopic treatments. In one case, the treatment failed immediately because of a large and direct tracheoesophageal fistula. Another patient experienced recurrent intrathoracic abscesses after initial technical success.Conclusions Postoperative upper gastrointestinal fistulas or anastomotic leaks can be managed successfully with little morbidity by means of endoscopic insertion of Vicryl mesh with fibrin glue, thereby avoiding repetitive major surgery and its associated risks.     

Chorea and related disorders

Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham's chorea is the most common form of childhood chorea, whereas Huntington's disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.     

Tissue disposition of 2'-O-(2-methoxy) ethyl modified antisense oligonucleotides in monkeys

This study examined the plasma pharmacokinetics, tissue distribution, and metabolism of three second generation antisense oligonucleotides in monkeys. Three groups of monkeys were treated with 10 mg/kg of each test compound by a single 2-h intravenous infusion. Oligonucleotide concentrations were measured in plasma, tissues, and urine using capillary gel electrophoresis (CGE). HPLC-MS was used to identify the metabolite(s) of the study compounds. Plasma-concentration-time profiles after infusion for the two phosphorothioate oligonucleotides were mono-exponential, but was bi- exponential for the phosphodiester oligonucleotide. Plasma clearance for the phosphodiester oligonucleotide was four- to sevenfold higher than the two phosphorothioate oligonucleotides, which was attributed to the plasma protein binding and reduced nuclease resistance. 2'-O-(2-methoxy) ethyl (MOE) modification at both 3' and 5' ends of a phosphorothioate oligonucleotide greatly enhanced the resistance to nucleases in plasma and tissue. MOE modification only at the 3' end enhanced the resistance to nucleases in plasma, but only moderately enhanced the resistance to nucleases in tissues. Urinary excretion was a minor elimination pathway for the phosphorothioate oligonucleotide, but was a major elimination pathway for the phosphodiester oligonucleotide. The results characterize the relationships between structure and disposition and will direct future modifications for therapeutic use.     

A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer

OBJECTIVE: Postoperative radiotherapy is frequently employed among breast cancer patients with positive surgical margins after mastectomy but there is little evidence to support this practice. This study examined relapse and survival among women with node-negative breast cancer and positive surgical margins after mastectomy. METHODS: Among 2570 women diagnosed between 1989 and 1998 and referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0 invasive breast cancer treated with mastectomy, 94 had positive surgical margins and formed the study cohort. Women with more established indications for postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease were excluded. Demographic, tumor, and treatment factors; relapse patterns; and Kaplan-Meier 8-year locoregional relapse-free, breast cancer-specific, and overall survival rates were compared between women who were treated with (n = 41) and without (n = 53) PMRT. RESULTS: Median follow-up time was 7.7 years. The distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen receptor status, and number of axillary nodes removed were similar between the two treatment groups. Six local chest wall recurrences (6.4%), 4 regional recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local relapse rates were 2.4% vs. 9.4% (p = 0.23), and regional relapse rates were 2.4% vs. 5.7% (p = 0.63), with and without PMRT, respectively. Trends for higher cumulative locoregional relapse (LRR) rates without PMRT were identified in the presence of age <==50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%). Statistical significance was not demonstrated in these differences (p > 0.10), possibly because of the small number of events. In patients with age >50 years, T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse occurred even with positive margins. PMRT did not improve distant relapse, 8-year breast cancer-specific and overall survival rates. CONCLUSION: This study suggests that not all patients with node-negative breast cancer with positive margins after mastectomy require radiotherapy. Locoregional failure rates approximating 20% were observed in women with positive margins plus at least one of the following factors: age <==50 years, T2 tumor size, grade III histology, or LVI. The absolute and relative improvements in locoregional control with radiotherapy in these situations support the judicious, but not routine, use of PMRT for positive margins after mastectomy in patients with node-negative breast cancer.     

Cellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney

Using morphological and molecular approaches, we characterized cisplatin-induced cell necrosis and apoptosis in rat kidney. Male Sprague-Dawley rats (n=5 per group) received a single intraperitoneal injection of either cisplatin (5 mg/kg) or saline, and were killed on day 5. Functionally, cisplatin-treated rats developed polyuric acute renal failure. Morphologically, kidneys of cisplatin-treated rats showed overt tubular necrosis associated with apoptosis in the corticomedullary junction. Cell necrosis was segment-specific and was distributed in radial fashion at the corticomedullary junction. The apoptosis was limited to discrete cells in apparently intact tubules in the vicinity of the necrosed tubules. The apoptotic changes were confirmed by TUNEL (TdT-mediated deoxyuridine triphosphate nick-end labeling) and staining for cleaved caspase-3. Analysis of outer medullary tissue for apoptosis-related molecules by RNase protection assay revealed a significant increase in the expression of pro-apoptotic mRNAs (caspases 1, 2, and 8, and Bax) in cisplatin-treated rats. On the other hand, the expression of mRNA for the anti-apoptotic Bcl-2 did not change, resulting in a decrease in relative ratio of Bcl-2/Bax, and thus favoring apoptosis. The above changes were paralleled by a marked increase in caspase-3 precursor, the executioner protease. Furthermore, these pro-apoptotic molecular changes were associated with a 3-fold increase in the activity of JNK1 in the outer medulla, but not in the cortex, of cisplatin-treated rat kidneys, localizing to the site of maximal apoptosis. Upregulation of JNK1 activity in the outer medulla was not accompanied by changes in the activities of ERK or p38 kinase. In conclusion, these data suggest that cisplatin-induced apoptotic cell death in native kidney may be mediated by cooperative activation of the JNK1 pathway and Bax in the outer medulla.     

Adjuvant radiation therapy after breast-conserving surgery in elderly women with early-stage breast cancer: controversy or consensus?

Breast-conservation therapy (BCT), which consists of breast-conserving surgery (BCS) and postoperative radiation therapy (RT), provides similar levels of local control and survival compared with mastectomy. Although the incidence of breast cancer increases with age and the proportion of elderly women in the population continues to increase, clinical trials of BCT have included few women aged > or = 65 years, limiting the ability to establish clear consensus regarding optimal therapy in this population. This article examines the literature on BCT in elderly women with early-stage breast cancer. A systematic search of the Medline and CancerLit databases was conducted to identify articles specifically addressing BCT in elderly women. The outcomes evaluated were local control, disease-free survival, overall survival, and treatment-related toxicities. The lack of consensus in breast-conservation management in elderly patients is highlighted by a paucity of prospective data and numerous retrospective series reporting diverse treatment approaches with conflicting results. The available evidence from BCT trials with and without age subgroup analyses support BCS with postoperative RT as the standard approach associated with the most favorable local control outcomes. A low-risk subset of patients in whom RT may be omitted without compromising local control remains to be defined. Despite these findings, the use of standard therapy significantly decreases with advancing patient age. Although data specifically addressing BCT in elderly patients are limited, age should not preclude consideration of standard treatment strategies to optimize local disease control. Modern clinical trials with representative samples of elderly patients evaluating cancer recurrence and survival as well as functional and quality-of-life outcomes are needed to define optimal breast-conservation management for this important patient population.     

Intraoperative consultation for renal lesions. Implications and diagnostic pitfalls in 324 cases

Intraoperative consultation rarely is requested for lesions in the kidney. Of 324 renal lesions submitted for gross or frozen section intraoperative consultation, 199 specimens were submitted for gross consultation only; no diagnostic pitfalls were noted. The clinical implications and diagnostic pitfalls in 125 specimens submitted for frozen section were the focus of our study. Frozen section intraoperative consultation was requested to evaluate surgical margins in partial nephrectomy specimens, solid renal mass in an unusual clinical or radiologic setting, synchronous renal and extrarenal masses, cystic renal lesion, ureteral surgical margins for transitional cell carcinoma, multiple renal masses, solid mass in a diffusely cystic kidney, and renal injury. Among the 125 cases, the diagnoses were deferred in 17 (6 renal cell carcinomas with granular cytoplasm, 7 cystic lesions, 3 metastatic tumors, 1 leiomyoma). The frozen section diagnoses were incorrect owing to limited sampling in 5 and misinterpretation in 4 (melanoma vs angiomyolipoma, lymphoma vs angiomyolipoma, benign cyst vs cystic renal cell carcinoma, metastatic renal cell carcinoma vs pheochromocytoma). Awareness of distinctive indications for frozen section intraoperative consultation and diagnostic pitfalls should improve diagnostic accuracy and facilitate proper management of these lesions.     

Photopolymerizable hydrogels for tissue engineering applications

Photopolymerized hydrogels are being investigated for a number of tissue engineering applications because of the ability to form these materials in situ in a minimally invasive manner such as by injection. In addition, hydrogels, three-dimensional networks of hydrophilic polymers that are able to swell large amounts of water, can be made to resemble the physical characteristics of soft tissues. Hydrogel materials also generally exhibit high permeability and good biocompatibility making, these materials attractive for use in cell encapsulation and tissue engineering applications. A number of hydrogel materials can be formed via photopolymerization processes mild enough to be carried out in the presence of living cells. This allows one to homogeneously seed cells throughout the scaffold material and to form hydrogels in situ. This review presents advantages of photopolymerization of hydrogels and describes the photoinitiators and materials in current use. Applications of photopolymerized hydrogels in tissue engineering that have been investigated are summarized.