Multimodal Treatment of Gastrointestinal Tract Tumors: Consequences for Surgery

Formerly an exclusive business of surgery, gastrointestinal (GI) tumors are nowadays increasingly approached with multimodal strategies. Neoadjuvant concepts have had a particularly far-reaching impact on surgery and have contributed to improved survival. Modern pre-treatment staging and risk assessment provide the basis for decision on one of three general treatment concepts (1) Early cancers, confined to the mucosal/submucosal layers, are approached with primary surgery, without prior antineoplastic therapy. (2) Systemically metastasized tumors receive merely palliative treatment. (3) Locally advanced cancers are increasingly approached with neoadjuvant strategies. The benefit from these preoperative protocols is proven for diverse entities, but is evidently confined to a specific subgroup patients, i.e., the responders to neoadjuvant treatment. These are the ones benefiting most from subsequent surgical resection, which is required to ensure complete removal of the residual tumor tissue, as complete tumor regression occurs very rarely and cannot be proven without a specimen. The fact that responders will benefit and non-responders will not benefit or will even deteriorate during the neoadjuvant treatment makes early response prediction most demanding. An amazing new approach is the use of position emission tomography with fluro-desoxyglucose (FDG-PET) to assess the "metabolic response," which is possible as early as 14 days after initiation of the neoadjuvant protocol. This strategy offers the chance for modulating the surgical approach in accord i.e., with such metrobolic response termination of the protocol and proceeding to resection in the case of nonresponse.The future of GI cancer surgery is multimodal therapy in a response-based fashion and requires reponse-based trials for further evaluation.     

Elbow joint laxity after experimental radial head excision and lateral collateral ligament rupture: efficacy of prosthetic replacement and ligament repair

The objectives of this experimental study were to investigate the effect of radial head excision and lateral collateral ligament (LCL) division on elbow joint laxity and to determine the efficacy of radial head prosthetic replacement and LCL repair. Valgus, varus, internal rotation, and external rotation of the ulna were measured during passive flexion-extension and application of a 0.75-Nm torque in 6 intact cadaveric elbows and after (1) either excision of the radial head or division of the LCL, (2) removal of both constraints, (3) isolated radial head prosthetic replacement, (4) isolated LCL repair, and (5) radial head replacement combined with LCL repair. Isolated radial head excision increased varus (mean, 4.8 degrees) and external rotatory laxity (mean, 7.1 degrees), as did isolated LCL division (mean, 14.1 degrees for varus; mean, 14.7 degrees for external rotation). After removal of both constraints, varus and external rotatory laxities were increased by 19.0 degrees and 20.1 degrees, respectively, compared with the intact specimens. Isolated radial head replacement reduced mean varus laxity to 14.6 degrees and mean external rotatory laxity to 14.8 degrees. Isolated LCL repair normalized varus laxity but resulted in a 2.9 degrees increase in external rotatory laxity. The combined procedures restored laxity completely. The radial head is a constraint to varus and external rotation in the elbow joint, functioning by maintaining tension in the LCL. Still, removal of both constraints induces severe laxity, and in this case, prosthetic replacement may substitute for the constraining capacity of the native radial head. The combination of LCL repair and radial head replacement restores laxity completely, but an isolated LCL repair performs almost as well, probably by compensating for the ligamentous tension lost from radial head excision.     

Composite resin in medicine and dentistry

Composite resin has been used for nearly 50 years as a restorative material in dentistry. Use of this material has recently increased as a result of consumer demands for esthetic restorations, coupled with the public's concern with mercury-containing dental amalgam. Composite is now used in over 95% of all anterior teeth direct restorations and in 50% of all posterior teeth direct restorations. Carbon fiber reinforced composites have been developed for use as dental implants. In medicine, fiber-reinforced composites have been used in orthopedics as implants, osseous screws, and bearing surfaces. In addition, hydroxyapatite composite resin has become a promising alternative to acrylic cement in stabilizing fractures and cancellous screw fixation in elderly and osteoporotic patients. The use of composite resin in dentistry and medicine will be the focus of this review, with particular attention paid to its physical properties, chemical composition, clinical applications, and biocompatibility.     

EC-coupling in normal and failing hearts

Systolic heart failure may be due to too few cardiomyocytes, or to reduced contractile function of the heart cells. In the latter situation the myocardial function is impaired and this condition is called myocardial failure. The pathophysiological mechanism behind this cellular defect is not known, but Ca2+ handling is altered. Although the most important trigger of sarcoplasmatic reticulum (SR) Ca2+ release, the L-type Ca2+ current, seems to be unaltered, SR Ca2+ load is reduced in human heart failure. This could explain the reduced contractility observed in failing hearts. Three possible mechanisms have been suggested to explain the reduction in SR Ca2+ load. They are leak through the SR Ca2+ release channel (RyR), impaired SR Ca2+ ATPase (SERCA) function and increased Na+/Ca2+-exchanger (NCX) function. Leak through RyR is not consistently found. Increased NCX function is probably secondary to a change in Ca2+ handling, and thus not a primary mechanism, but blockade of the NCX might have therapeutic potential. Reduced SERCA function is probably a primary mechanism for the observed systolic dysfunction, and further insight is to be gained through studies in genetically modified models.     

Unilateral hinged external fixation frame for elbow compression arthrodesis: the stepwise attainment of a stable 90-degree flexion position: a case report

We report a case of an elbow arthrodesis using a modular hinged external fixation device in a patient who sustained a complex high-energy injury. The extensive bone and soft-tissue loss and local infection precluded restoration of the articular anatomy. Other reconstructive options, including total elbow arthroplasty and allograft reconstruction, were not appropriate in this clinical situation. A transelbow hinged external fixator was applied with the elbow in extension. Subsequently, the hinge was brought gradually into 90 degrees of flexion as the elbow fused. Fixation and arthrodesis were successfully achieved by using this modular device, despite severe tissue loss and local septic complications. Furthermore, by gradually flexing the frame from full extension to 90 degrees , the need for flap coverage of the open wound was avoided.     

The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats

This report compares the effects of progesterone and its metabolite, allopregnanolone, on the early injury cascade (apoptosis) and long-term functional deficits after TBI. Progesterone (16 mg/kg) or allopregnanolone (4, 8, or 16 mg/kg) were injected at 1 h, 6 h, and then for 5 consecutive days after bilateral contusions of the frontal cortex in adult male rats. Within one day after injury, progesterone and allopregnanolone reduced both the expression of pro-apoptotic proteins caspase-3 and Bax, and apoptotic DNA fragmentation. Progesterone and allopregnanolone also reduced the size of glial fibrillary acid protein (GFAP)-positive astrocytes at the lesion site 24 h after injury. Compared to sham-operated controls at 19 days after injury, injured rats given either progesterone or any of three doses of allopregnanolone had equivalent numbers of ChAT-positive cells in the nucleus basalis magnocellularis. At 19 days post-injury, rats given progesterone or allopregnanolone (8 mg/kg) showed improved performance in a spatial learning task compared to injured rats given only the vehicle. These results provide evidence of the anti-apoptotic and anti-astrogliotic effects of progesterone and allopregnanolone and help to explain why better cognitive performance is observed after injury when animals are given either neurosteroid.     

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.     

Prevalence of, and risk factors for, HSV-2 antibodies in sexually transmitted disease patients, healthy pregnant females, blood donors and medical students in Tanzania and Norway

The prevalence of specific HSV-2 antibodies was studied in Tanzanian and Norwegian sexually transmitted disease (STD) patients (1095) and non-STD patients (488). Correlates to demographic and behavioural factors were evaluated. Seropositivity was determined by the non-commercial peptide-55 enzyme-linked immunoassay. The prevalence of HSV-2 antibodies was 70% in Tanzanian and 17% in Norwegian STD patients, 35% in Tanzanian blood donors and pregnant women, and 4, 7 and 14% in Norwegian medical students, blood donors and pregnant women respectively. A higher HSV-2 prevalence was associated with female sex, increasing age, previous STDs, history of genital HSV infection, coitarchal age (age at first intercourse) <15 years and HIV seropositivity. Compared to previous data, the prevalence of HSV-2 antibodies in Tanzanian STD patients has increased remarkably. In Norwegian STD patients our results are consistent with, or lower than, the prevalence previously reported in Western Europe. Demographic rather than behavioural factors were associated with higher prevalence of HSV-2 antibodies in STD patients.