Long-term followup after laparoscopic radical nephrectomy

PURPOSE: Laparoscopic radical nephrectomy has been shown to be less morbid than traditional open radical nephrectomy. The long-term oncological effectiveness of laparoscopic radical nephrectomy remains to be established. MATERIALS AND METHODS: At 3 centers patients undergoing laparoscopic radical nephrectomy before November 1, 1996 with pathologically confirmed renal cell carcinoma were identified. A representative group of patients undergoing open radical nephrectomy for clinical T1, T2 lesions was also identified. Staging, operative details and postoperative course were reviewed. Followup consisted of review of clinical, laboratory and radiological records. Kaplan-Meier analysis was performed. RESULTS: The study included 64 patients treated with laparoscopic and 69 treated with open radical nephrectomy with respective average ages of 60.6 and 61.3 years at surgery. On preoperative imaging open lesions were larger (6.2 cm., range 2.5 to 15) than laparoscopic radical nephrectomy lesions (4.3 cm., range 2 to 10, p <0.001). Pathology reports revealed no difference in specimen weight (425 and 495 gm., p = 0.146) or average Fuhrman grade (1.88 and 1.78, p = 0.476) between laparoscopic and open radical nephrectomy, respectively. Median followup was 54 months (range 0 to 94) for laparoscopic and 69 months (range 8 to 114) for open radical nephrectomy. Kaplan-Meier analysis with log rank comparison revealed 5-year recurrence-free survival of 92% and 91% for laparoscopic and open radical nephrectomy, respectively (p = 0.583). At 5 years cancer specific survival was 98% and 92% (p = 0.124), and nonspecific survival was 81% and 89% (p = 0.260) for laparoscopic and open radical nephrectomy, respectively. CONCLUSIONS: Laparoscopic radical nephrectomy confers long-term oncological effectiveness equivalent to traditional open radical nephrectomy.     

Management of ureterointestinal anastomotic strictures: comparison of open surgical and endourological repair

The established treatment for ureterointestinal anastomotic strictures is open surgical revision. In an effort to evaluate the efficacy of endourological surgery for this problem, we compared 7 patients (9 strictures) who underwent open revision to 6 patients (7 strictures) who underwent endoscopic incision and balloon dilation of the stricture. The success rate (that is patent ureter and no stent) was 89 per cent for the open revision group and 71 per cent (5 of 7) for the endoscopic group. All open revisions required use of general anesthesia, while 3 of the endoscopic procedures were performed with the patient under assisted local anesthesia. The endoscopic group had markedly shorter hospitalization, decreased blood loss, diminished patient discomfort and no postoperative complications. While the endoscopic procedure for ureteroileal anastomotic strictures is less successful than open revision, the lower morbidity, decreased cost and shorter hospital stay associated with the endourological approach favor its use over open revision. For elderly patients who fail initial endoscopic revision and for patients with metastatic transitional cell cancer, placement of an indwelling stent is a reasonable alternative. Given these guidelines, less than 30 per cent of the patients who suffer a ureteroileal anastomotic stricture will require open surgical revision.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.     

胰岛素样生长因子Ⅰ与肝纤维化

胰岛素样生长因子I(IGF-I)是体内普遍存在的多肽,循环系统中IGF-I主要来源于肝脏．在垂体生长激素的调控下,IGF-I对多种细胞如成纤维细胞、成骨细胞、平滑肌细胞等的有丝分裂均有调节作用．目前观点认为肝星状细胞(HSC)活化后可分泌大量胶原纤维,是肝纤维化时细胞外基质的主要来源．实验表明 IGF-I能够促进体外培养HSC增殖、活化并抑制其凋亡．而体内研究发现,肝硬化患者血清IGF-I浓度显著下降,外源性小剂量IGF-I 注射能够改善肝功能,为肝纤维化的治疗提供了新的理念．     

Molecular analysis of relapse in chronic myeloid leukemia after allogeneic bone marrow transplantation

Four patients with Philadelphia (Ph') positive chronic myeloid leukemia (CML) were studied before, after, and on relapse following allogeneic bone marrow transplantation (BMT). Southern analysis of DNA from cells collected before and at relapse after BMT was performed in order to investigate the origin of the leukemia at relapse. Using minisatellite probes we showed that the relapse occurred in cells of host origin in all four patients and this was confirmed with a Y chromosome specific probe in two male patients who had a female donor. Furthermore, using two probes for the breakpoint cluster region (bcr) on chromosome 22, we showed that leukemic cells at relapse bore identical rearrangements to those in the disease at time of presentation of each patient. We conclude that relapse in all four patients is due to re-emergence of the original leukemic clone.     

Methylation, a major mechanism of p16/CDKN2 gene inactivation in head and neck squamous carcinoma.

We studied 11 head and neck squamous carcinoma (HNSC) cell lines and 46 primary tumors for p16 gene status by protein, mRNA, and DNA genetic/epigenetic analyses to determine the incidence, the mechanism(s), and the potential biological significance of its inactivation. Of the 11 cell lines, only 1 showed intact p16 and 10 lacked its protein and mRNA; DNA analysis of these 10 cell lines showed 2 homozygous deletions, 6 methylations at exon 1 and 2, and 2 with no detectable abnormalities. In primary tumors, 16 (34.7%) of the 46 showed detectable p16 protein and mRNA; of these, 12 had no DNA abnormalities and 4 had only exon 2 methylation. Loss of p16 expression was found in three tumors with concurrent mutation at exon 2 and methylation at exon 2 (two) and both 1 and 2 (one). Of the 30 tumors that lacked p16 protein, 27 also lacked mRNA, 1 had detectable p16 mRNA, and 2 failed RT-PCR amplification. Twenty-two of the thirty tumors showed DNA alterations and eight manifested no abnormalities; DNA alterations comprised 6 homozygous deletions, 2 concurrent mutations and methylation of exon 2, and 13 with methylation at exon 1 and exons 1 and 2 (12 with methylation only and 1 with mutation) at exon 1. Except for patients' gender (P = 0.02), no significant correlation between p16 and clinicopathological factors was observed. We conclude that in HNSC 1) intragenic p16 alterations are infrequent events, 2) methylation of exon 1 constitutes a common mechanism in silencing the p16 gene, 3) p16 inactivation may play an important role in the early development and progression of HNSC, and 4) no association between p16 alterations and conventional clinicopathological factors was noted in this cohort.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。