Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.      

HIV-1tat induced apoptosis of T-cells is not mediated by TGF-β

Recent reports have demonstrated that the HIV-1 transactivator protein,tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-β (TGF-β). In this study we evaluated the ability of TGF-β to mediatetat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-β1 or a combination of tat and pan-specific TGF-β neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-β neutralizing antibodies, Jurkat cells that stably expresstat protein (Jurkat-tat) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1tat andrev) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-β does not play a significant role in mediatingtat induced T-cell apoptosis.     

Fatty infiltration of the liver: evaluation by proton spectroscopic imaging

The reliability of proton spectroscopic imaging in evaluating fatty infiltration of the liver was investigated in 35 subjects (12 healthy volunteers and 23 patients with fatty livers). With this modified spin-echo technique, fatty liver could be separated from normal liver both visually and quantitatively. On the opposed image, normal liver had an intermediate signal intensity, greater than that of muscle, whereas fatty liver had a lower signal intensity, equal to or less than that of muscle. In normal livers, the lipid signal fraction was less than 10%, while in fatty livers it was greater than 10% and usually exceeded 20%. With this technique, nonuniform fatty infiltration of the liver can be differentiated from hepatic metastases, and the technique may prove useful in the differentiation of some hepatic disorders.     

Mystery in the basement

56 year-old male presented to the University of Mississippi Medical Center emergency department (ED) with complaints of progressive shortness of breath, productive cough, fever, and malaise. His past medical history was significant for hypertension as well as a 60 pack-year history of smoking. Upon arrival to the ED he had a temperature of 103.6 degrees F, blood pressure of 80/40 mm Hg, a pulse of 110 beats per minute, respirations of 28 per minute, and an oxygen saturation of 50% on room air. He appeared to be in significant respiratory distress. Lung examination revealed diffuse bilateral rhonchi and wheezes in all lung fields. He was emergently intubated. Chest radiograph demonstrated a miliary pattern scattered throughout all lung fields in addition to parenchymal opacities. A complete blood count revealed a white blood cell count of 33,500 10(3)/microL, hematocrit of 37%, and platelets of 906,000 10(3)/uL. Blood urea nitrogen and creatinine were 27 mg/dL and 1.0 mg/dL, respectively. Initial ABG on 100% oxygen showed pH 7.15, pCO2 82 mm Hg, and pO2 62 mm Hg. Troponin I was negative. An electrocardiogram demonstrated sinus tachycardia. Blood and urine cultures were obtained.     

Thoracic wall involvement by Hodgkin disease and non-Hodgkin lymphoma: CT evaluation

Thoracic computed tomographic (CT) scans of 250 patients with newly diagnosed or recurrent lymphoma revealed thoracic wall involvement in 24 patients (11 with Hodgkin disease, 13 with non-Hodgkin lymphoma). Thoracic wall involvement occurred without contiguous mediastinal or parenchymal involvement in 17 patients. Of these, 13 patients had masses beneath the pectoralis muscles or within the breast, and four had masses arising from the ribs. Five additional patients had mediastinal masses with thymic involvement and parasternal extension through the thoracic wall. Pulmonary parenchymal lymphoma with thoracic wall invasion was noted in the remaining two patients. In five of nine patients receiving radiation therapy, treatment plans were modified by CT demonstration of thoracic wall lymphoma.     

Torque resistance after fixation of Jones fractures with intramedullary screws

BACKGROUND: Intramedullary screws frequently are used for fixation of Jones fractures of the fifth metarsal. While the ability of intramedullary screw fixation in fifth metatarsals to resist bending and tensile forces is well known, the ability to withstand torsion has not been studied. This paper compares the torsional stiffness of Jones fractures treated with 6.5-mm short- threaded intramedullary screws to those treated with 5.0-mm cannulated short-threaded intramedullary screws. METHODS: Nine fresh-frozen, matched pairs of cadaver fifth metatarsals had an acute Jones fracture simulated with an osteotomy. They were stabilized with intramedullary screws and then loaded to failure. RESULTS: The torsional stiffness of the metatarsals fixed with the 6.5-mm did not differ significantly from that using 5.0-mm screws. However, to achieve stability, the 5.0-mm screw had to be long enough to reach the metatarsal head and neck. This tended to straighten the normally curved fifth metatarsal bone and caused lateral gapping at the fracture site. CONCLUSION: Both 5.0-mm or 6.5-mm screws provide equal torsional rigidity, but 5.0-mm screws may need to be longer, which could potentially straighten the fifth metatarsal shaft in patients who have a curved fifth metatarsal.     

Torsional strains in the proximal fifth metatarsal: implications for Jones and stress fracture management

BACKGROUND: Reports of nonunion of proximal fifth metatarsal fractures treated by internal fixation indicate that current fixation methods do not always adequately address the stresses to which the bone is subjected during ambulation. In particular, the insertion sites of the peroneus brevis and peroneus tertius tendons on the fifth metatarsal suggest that their actions can impose torsional stresses on the areas of the bone in which Jones fractures and stress fractures occur. Intramedullary screw fixation, however, offers little resistance to rotation of the proximal and distal fragments relative to one another. METHODS: To determine the potential for the existence of torsional stresses in the fifth metatarsal during post-operative ambulation, a simplified cadaver model of single-limb stance was used in which cadaver feet were subjected to concurrent axial and tendon forces while monitoring the outputs of stacked rosette strain gauges placed at the typical sites of Jones and stress fractures. Principal strain and shear strain magnitudes and directions were measured. RESULTS: The shear strain magnitudes and strain axis directions indicated the presence of torsional stresses in the underlying bone potentially capable of causing internal rotation of the proximal fragment relative to the distal end of the bone. CONCLUSIONS: This finding has implications for the treatment of both Jones fractures and stress fractures of the proximal fifth metatarsal. An internal fixation device that has the capability to resist torsion as well as tension and bending would appear optimal to treat these fractures.     

A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status

BACKGROUND: Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC. METHODS: Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy. RESULTS: Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases. CONCLUSIONS: Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.