Outcome of Local Excision of Rectal Carcinoma

PURPOSE This study was designed to determine the results of patients with rectal adenocarcinoma treated with local excision.METHODS A retrospective, chart review was conducted for all patients treated with local excision for rectal adenocarcinoma from 1984 to 1998.RESULTS Sixty-four patients were retained for analysis. The median follow-up was 37 (range, 9–125) months. There were 15 local failures with a median time to local failure of 12 months. Seven patients were salvaged with further operation (4 by repeat local excision, 4 by abdominoperineal resection, and 1 by low anterior resection). The incidence of local recurrence increased with advancing stage of the carcinoma (T₁, 13 percent; T₂, 24 percent; T₃, 71 percent), histologic grade of differentiation, (well, 12 percent; moderately, 24 percent; poorly, 44 percent), and margin status (negative, 16 percent; close (within 2 mm), 33 percent; positive, 50 percent). Sixteen percent of carcinomas 3 cm failed compared with 47 percent for carcinomas > 3 cm. Nine percent (1/11) of T₂ patients treated with adjuvant radiation therapy recurred locally compared with 36 percent (5/14) without radiation therapy. Three of four T₃ patients who received radiation therapy failed locally compared with two of three who did not. Using the Kaplan-Meier method, the overall survival at five years was 71 percent, and disease-free survival was 83 percent. Actuarial local failure was 27 percent and freedom from distant metastasis was 86 percent. The sphincter preservation rate was 90 percent at five years.CONCLUSIONS Local excision alone is an acceptable option for well-differentiated, T₁ carcinomas, 3 cm. Adjuvant radiation is recommended for T₂ lesions. The high local recurrence rate in patients after local excision of T₃ lesions with or without adjuvant radiotherapy would mandate a radical resection.Reprints are not available.Poster presentation at the meeting of The American Society Colon Rectal Surgeons, Boston, Massachusetts, June 24 to 29, 2000.     

Applications of accelerator MS in pediatric drug evaluation

Accelerator MS (AMS) provides a novel method for obtaining and analyzing pharmacokinetics and pharmacodynamics in children. This paper reviews the scientific and ethical rationale for AMS in pediatric trials, the regulatory framework and general considerations with some specific examples of pediatric clinical trials using AMS. Microdosing in the context of this article refers to studies using a negligible amount (nanocuries) of (14)C as tracer, and AMS as a quantitative technique. The technology is by no means a panacea for the deficiency in pediatric clinical research; however, it lessens the challenges and provides the most quantitative tool for pediatric pharmacology studies.     

Lamotrigine in patients with epilepsy and comorbid depressive symptoms

PurposeThis open-label study evaluated the antidepressant qualities of lamotrigine (LTG) in people with epilepsy.MethodsEligible patients exhibited low to moderate depressive symptoms and required a change in antiepileptic drug (AED) therapy, but were excluded if they had a major depressive disorder (MDD). Lamotrigine was added onto a stable AED regimen, and self-report instruments were administered to evaluate changes in mood states. Evaluations were conducted at baseline, at the end of 19 weeks of adjunctive treatment, and 36 weeks following conversion to monotherapy.ResultsOne hundred and fifty-eight patients with epilepsy participated; 96 patients completed adjunctive treatment, and 66 patients completed monotherapy. Intent-to-treat analyses for all instruments showed improvement in depression scores after adjunctive LTG treatment. Improvement was maintained for those converted to monotherapy.ConclusionsThese data suggest that LTG may have antidepressant activity for patients with epilepsy and comorbid low to moderate depressive symptoms, and warrant a randomized controlled trial for validation.     

Reduced-intensity conditioning using fludarabine and antithymocyte globulin alone allows stable engraftment in a patient with dyskeratosis congenita

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by the triad of nail dystrophy, mucosal leukoplakia, and reticular pigmentation. Bone marrow failure is the principal cause of early mortality, and stem cell transplantation is the only cure for these patients. However, the results of conventional hematopoietic stem cell transplantation (HSCT) for patients with DC are poor because of the high incidence of transplant-related complications. We describe the successful treatment of a 21-year-old male with DC by nonmyeloablative HSCT from a matched unrelated donor. The gene responsible for the X-linked form of DC was screened and hemizygosity for the mutation Gln31Lys was found, which is consistent with the diagnosis. The conditioning regimen consisted of only fludarabine and antithymocyte globulin. Additionally, a graft-versus-host disease (GVHD) prophylaxis was administered with cyclosporine A (CSA) and mycophenolate mofetil (MMF). The regimen was well tolerated, no severe posttransplantation complications were observed, and engraftment was rapid and complete (granulocytes on day +11 and platelets on day +13). Seven months after HSCT, the patient developed GVHD of the liver after tapering CSA which was successfully treated with prednisolone, CSA, and MMF. At the time of reporting, 3 years after HSCT, the patient remained in good clinical condition with minimal signs of chronic GVHD of the oral mucosa. Thus, we conclude that a low-intensity conditioning regimen might be sufficient to induce permanent engraftment by using matched unrelated donor HSCT in DC patients and may avoid severe organ toxicity. Although allogeneic HSCT in patients with DC will not cure the underlying genetic defect it may significantly prolong survival through effective therapy for hematologic complications.     

Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity

Interactions between central corticotropin-releasing factor (CRF) and serotonergic systems are believed to be important for mediating fear and anxiety behaviors. Recently we demonstrated that infusions of CRF into the rat dorsal raphe nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. The current studies were designed to study the CRF receptor mechanisms and pathways involved in this serotonergic response. Infusions of CRF (0.5 μg/0.5 μL) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 μL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25–50 ng/0.5 μL) or antisauvagine-30 (2 μg/0.5 μL), respectively. Medial prefrontal cortex serotonin levels were measured using in-vivo microdialysis and high-performance liquid chromatography with electrochemical detection. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal raphe nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central nucleus of the amygdala, a source of CRF afferents to the dorsal raphe nucleus. Activation of the central nucleus increased medial prefrontal cortex serotonin release. This response was blocked by CRF receptor type 2 antagonism in the dorsal raphe. Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the raphe nuclei.     

Abdominal angiostrongyliasis in Nicaragua: a clinico-pathological study on a series of 12 cases reports.

A retrospective study was done to determine the presence of abdominal angiostrongyliasis in Nicaragua. Twelve cases of this parasitic disease were found among 48 visceral specimens: small intestine, liver and testes. The patients with intestinal lesions presented symptoms of an acute abdomen, and in some instances, a tumor-like mass was palpated in the lower right quadrant. A thickening of the intestinal wall accompanied by necrosis and perforation were the most important macroscopic findings. One patient with hepatic localisation of Angiostrongylus costaricencis displayed a clinical picture of visceral larva migrans-like syndrome. The chief laboratory findings were leukocytosis and eosinophilia. The histopathological examination showed granulomas and heavy eosinophilic infiltration around the eggs and larvae of A. costaricencis. Also, an adult worm was seen in one biopsy.     

View combination in moving objects: The role of motion in discriminating between novel views of similar and distinctive objects by humans and pigeons

Humans and pigeons were trained to discriminate between views of similar and distinctive objects that rotated in depth coherently or non-coherently. We tested novel views that were either moving or static and were either between the training viewpoints or beyond them. With both types of motion, both species recognized views between the training viewpoints better than views beyond this range. Additionally, for humans, and to some extent for pigeons, when similar objects were learned via coherent motion, dynamic cues facilitated recognition of viewpoints predictable from the direction of motion. Overall, the results suggest that dynamic information may be added to object representations for both species.     

H3K27M-mutant diffuse midline gliomas should be further molecularly stratified: an integrated analysis of 669 patients

Journal of Neuro-Oncology - H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies...