Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma.

PURPOSE: Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown. Materials and METHODS: We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation. RESULTS: Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P =.007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P =.009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P =.03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV. CONCLUSION: Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.     

Comparing reconstruction with ileocecal graft to jejunal interposition pouch after total gastrectomy in rats.

After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation.     

HISTOPATHOLOGIC STUDY OF CONJUNC-TIVA IN PATIENTS WITH HYPEREMIA DURING BIMATOPROST THERAPY

Purpose: Conjunctival hyperemia has been reported as a frequent side effect of bimatoprost, a prostamide with efficacious ocular hypotensive action. To investigate the possible inflammatory basis of the hyperemia, we analysed, by means of light microscopy, the conjunctival specimens of patients who developed ocular hyperemia during bimatoprost therapy and who underwent cataract surgery. Methods: Patients were divided in two groups;     

Assessment of quadriceps/hamstring strength, knee ligament stability, functional and sports activity levels five years after anterior cruciate ligament reconstruction

The purpose of this study was to examine individuals 5 years after ACL reconstruction and analyze changes involving strength, stability, function, and sports activities. Nineteen males and six females, mean age = 31.4 +/- 7.31 years, participated in this study. Fifteen subjects had received extraarticular and ten subjects had received intraarticular ACL reconstructions. Subjects completed a 100 point subjective functional activity questionnaire and a sports participation survey. Knee ligament stability was assessed during an objective knee examination. Isokinetic quadriceps and hamstring muscle strength were tested at 240 and 120 deg/sec using the Cybex II dynamometer. Anterolateral rotatory instability and positive Lachman were elicited on the operated leg for 80% of the subjects. No significant relationship was found between objective instability and the functional activity score. For the intraarticular group, a significant correlation (P less than 0.05) was found between increased quadriceps and hamstring strength on the operated leg and return to functional activities. Subjects' functional activity score was positively correlated (P less than 0.001) with their ability to participate in sports. Subjects participating in sports involving cutting and twisting motions were less successful in returning to their preinjury participation levels and reported more subjective complaints of pain, swelling, and/or instability. These results indicate that long-term progressive rehabilitation emphasizing increased quadriceps and hamstring strength to approximate the nonoperated leg may enhance successful return to functional and sports activities after ACL reconstruction.     

Mediastinal lymphoblastic lymphoma with an immature B-cell immunophenotype.

A 19-year-old woman presented with a large mediastinal mass, histologically shown to be malignant lymphoma of lymphoblastic type (LBL). Immunophenotypic and gene rearrangement analysis unequivocally demonstrated that the neoplasm was of B-cell lineage. The neoplastic cells expressed terminal deoxynucleotidyl transferase, the pan-B cell antigens CD19, CD20, and CD22, and were negative for immunoglobulins and numerous T-cell antigens tested. Southern blot analysis showed rearrangement of one allele of the immunoglobulin heavy chain gene while the immunoglobulin kappa and T-cell receptor beta chain genes were in the germline configuration. Thus, the immunophenotypic and molecular findings in this case correspond to an early stage of B-cell differentiation, the pre-pre B-cell stage as has been named by others. In contrast with LBL of immature T-cell lineage, precursor B-cell LBLs involving the mediastinum are truly rare. Occasional cases have been reported that have arisen elsewhere and subsequently involved the mediastinum at time of relapse or tumor progression. Well-documented examples of immature B-cell LBL arising in the mediastinum are virtually unreported. The site and cell population giving rise to this neoplasm is unknown. However, origin from precursors of normal thymic medullary B cells is proposed as one possibility.     

Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma.

A case of low-grade angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma is reported. Initially, an asymptomatic breast mass was detected. Excisional biopsy and axillary lymph node dissection revealed a 1.5-cm infiltrating ductal carcinoma with 21 negative lymph nodes. The neoplasm was staged as T1, N0, M0. The patient was entered in a research protocol and was treated with high-dose external beam (4,860 rad) and iridium implant (1,860 rad) irradiation. Seven years later the patient developed low-grade angiosarcoma of the breast skin. The lesion recurred following excision and eventually was treated by simple mastectomy. The patient never had evidence of lymphedema. Cutaneous angiosarcomas occurring as a complication of lumpectomy and radiation therapy for breast carcinoma are rare. In some reported cases the patients have had lymphedema, a known factor predisposing to angiosarcoma. Furthermore, almost all cases previously reported have been high grade. This case suggests that radiation therapy for breast carcinoma may also be complicated by low-grade angiosarcoma.     

Lack of c-kit (CD117) expression in CD30+ lymphomas and lymphomatoid papulosis.

c-Kit receptor (CD117) is expressed by erythroid, megakaryocytic, and myeloid precursors and mature mast cells and has been reported to be expressed in CD30+ lymphomas such as Hodgkin's disease and anaplastic large-cell lymphoma. Imatinib mesylate, a well-established inhibitor of bcr-abl tyrosine kinase, and currently used for the treatment of patients with chronic myeloid leukemia, also inhibits c-kit receptor kinase activity. In view of the possible use of imatinib as experimental therapy for patients with c-kit-positive tumors, we assessed c-kit expression in CD30+ cell lines and lymphomas. The cell lines were assessed using multiple methods (RT-PCR, flow cytometry, and Western blot). c-Kit expression was also immunohistochemically assessed in 168 CD30+ lymphomas including 87 classical Hodgkin's disease, 63 anaplastic large-cell lymphoma, and 15 cutaneous anaplastic large-cell lymphoma. We also studied 18 cases of lymphomatoid papulosis, a CD30+ lesion closely related to cutaneous anaplastic large-cell lymphoma. Neither c-kit mRNA nor protein was detected in any of the cell lines assessed. Furthermore, treatment with imatinib did not inhibit proliferation of cell lines in vitro. Using immunohistochemistry, only one of 183 (0.5%) lesions was positive for c-kit, the positive case being an ALK-negative anaplastic large-cell lymphoma. Our data demonstrate that expression of c-kit receptor is exceedingly rare among CD30+ lymphomas and lymphomatoid papulosis, suggesting that c-kit receptor is unlikely to be an appropriate target for therapeutic options such as imatinib in patients with these tumors.     

Cyclooxygenase-2 inhibition increases gastric tone and delays gastric emptying in rats.

We evaluated the effects of cyclooxygenase-2 (COX-2) selective inhibitors, COX-1 selective inhibitor, or COX non-selective inhibitor on gastric emptying and intestinal transit of liquids, and evaluated the effect of a COX-2 selective inhibitor on gastric tonus (GT). Male Wistar rats were treated per os with saline (control), rofecoxib, celecoxib, ketorolac, rofecoxib + ketorolac, celecoxib + ketorolac, or indomethacin. After 1 h, rats were gavage-fed (1.5 mL) with the test meal (5% glucose solution with 0.05 g mL(-1) phenol red) and killed 10, 20 or 30 min later. Gastric, proximal, medial or distal small intestine dye recovery (GDR and IDR, respectively) were measured by spectrophotometry. The animals of the other group were treated with i.v. valdecoxib or saline, and GT was continuously observed for 120 min using a pletismomether system. Compared with the control group, treatment with COX-2 inhibitors, alone or with ketocolac, as well as with indomethacin increased GDR (P < 0.05) at 10-, 20- or 30-min postprandial intervals. Ketorolac alone did not change the GDR, but increased the proximal IDR (P < 0.05) at 10 min, and decreased medial IDR (P < 0.05) at 10 and 20 min. Valdecoxib increased (P < 0.01) GT 60, 80 and 100 min after administration. In conclusion, COX-2 inhibition delayed the gastric emptying of liquids and increased GT in rats.     

Comparison of Endovenous Treatment with an 810 nm Laser versus Conventional Stripping of the Great Saphenous Vein in Patients with Primary Varicose Veins

BACKGROUND: Patients with varicose veins seek medical assistance for many reasons, including esthetic ones. The development of suitable and more flexible instruments, along with less invasive techniques, enables the establishment of new therapeutic procedures. OBJECTIVE: To compare endovenous great saphenous vein photocoagulation with an 810 nm diode laser and the conventional stripping operation in the same patient. METHODS: Twenty patients selected for operative treatment of primary great saphenous vein insufficiency on duplex scanning were assigned to a bilateral random comparison. In all cases, both techniques were performed, one on each lower limb. Clinically, evaluation was assessed on the seventh, thirtieth, and sixtieth postoperative days. Patients underwent examination with duplex ultrasonography and air plethysmography during the follow-up. RESULTS: Patients who received endovenous photocoagulation presented with the same pain but fewer swellings and less bruising than the stripping side. Most patients indicated that the limb operated on by laser received more benefits than the other. There was only one recanalization and no adverse effects. The venous filling time showed better hemodynamics in both techniques. CONCLUSION: The endovenous great saphenous vein photocoagulation is safe and well tolerated and presents results comparable to those of conventional stripping.