A percutaneous large-needle aspiration biopsy technique for histologic examination of the testis in infertile patients

OBJECTIVE: To describe a relatively new percutaneous large-needle aspiration biopsy technique for histologic examination of the testis in infertile patients. DESIGN: Retrospective analysis of clinical and pathologic data. SETTING: Clinical and academic research environment. PATIENT(S): Sixty-six infertile patients who underwent testicular biopsy. INTERVENTION(S): Local anesthesia was induced through spermatic cord block with lidocaine, and a relatively large needle (usually 18- or 20-gauge) was introduced percutaneously into the testicle without a scrotal incision. MAIN OUTCOME MEASURE(S): The number of seminiferous tubules per histologic section of each testicular biopsy sample. RESULT(S): A mean of 74 seminiferous tubules were obtained in the histologic sections of each biopsy sample. This number varied according to the size of the needle used; it was 24.7 when a 21-gauge needle was used, 56.2 when a 20-gauge needle was used, and 103 when an 18-gauge needle was used. The biopsies were performed in the office. No significant hematomas occurred, no antibiotic prophylaxis was prescribed, and no postbiopsy medical or pharmacologic interventions were required. CONCLUSION(S): Tissue specimens as large as those obtained with open surgical biopsy can be obtained from the testicles of infertile patients with the use of a percutaneous technique that is easier, less costly, and safer than any previously reported.     

Cooperative transformation of 32D cells by the combined expression of IRS-1 and V-Ha-Ras

32D cells expressing v-Ha-Ras fail to show a transformed phenotype. Since Ras requires an active IGF-1R for transformation of fibroblasts, we asked whether expression of IRS-1 or Shc (two of the major substrates of the IGF-1R) could co-operate with oncogenic Ras in transforming 32D cells. We find that IRS-1, but not Shc, in combination with v-Ha-Ras generates a fully transformed phenotype in 32D cells. 32D cells expressing both IRS-1 and v-Ha-Ras (32D/IRS1/Ras) survive and proliferate in the absence of IL-3, do not undergo granulocytic differentiation in the presence of G-CSF and form tumors in nu/nu and syngeneic mice. In contrast, 32D cells expressing singly IRS-1 or v-Ha-Ras exhibit only a block in differentiation capacity. Over-expression of Shc proteins, by itself, promotes differentiation of 32D cells. Concomitant expression of IRS-1 and v-Ha-Ras synergistically phosphorylates ERK-1 and ERK-2 whereas a MEK inhibitor rapidly induces death of 32D/IRS1/Ras transformed cells. Furthermore, transformed 32D/IRS1/Ras cells display high levels of PI3-K activation and undergo rapid apoptosis when exposed to PI3-K inhibitors. The data indicate that: (1) a fully transformed phenotype in 32D cells is generated when a block in differentiation (v-Ha-Ras) is coupled with another differentiation block (IRS-1); (2) PI3-K and MAPK activity are required for the survival of transformed cells; (3) the signals generated by IRS-1 and oncogenic Ras converge on ERK and PI3-K resulting in high levels of activation.     

Comment on 'Cancer genetic counselling' by P. Mandich et al. (Ann Oncol 2005; 16: 171).

With the advent of genetic tests, genetic counselling is attractingincreasing attention, as also shown by the recent letter byMandich et al. [1], which addressed some aspects of our oncologist-basedmultistep model of cancer genetic counselling [2]. Perhaps thefeatures of our model can be appreciated if we explain the rationale     

Selective heparanase localization in malignant melanoma

Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate proteoglycans (HSPG), and its expression has been associated with increased growth, metastasis, and angiogenesis of tumors. Since metastatic melanoma cells express high levels of HSPG and because melanoma tumors grow highly vascularized, we analyzed melanoma tissue specimens for HPSE-1 expression from experimental animals as well as from patients. Laser capture microdissection microscopy was used to extract melanoma cell populations and to isolate them from adjacent tissue. In experimental animals, a 29-fold upregulation of HPSE-1 expression was detected by real-time PCR in metastatic melanoma compared to normal lung tissue. Additionally, immunohistochemistry (IHC) revealed selective HPSE-1 staining in human metastatic melanoma when compared to primary melanoma tumors from the same patient. IHC also showed a marked staining for the enzyme around blood vessels and in vascularized regions. Our results provide evidence demonstrating that HPSE-1 likely plays important roles in regulating the in vivo growth and progression of melanoma. These results further emphasize the importance that therapies designed to block HPSE-1 activity may aid in controlling this type of cancer.     

Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies

Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors who were treated before or during their reproductive years may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time to pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, end point, and germ cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm fluorescent in situ hybridization have corroborated the differences in germ cell susceptibilities. The available evidence indicates that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.     

Ninety-five percent insulin independence rate 3 years after pancreas transplantation alone with portal-enteric drainage

AIMS: Portal-enteric drainage (PED) might be particularly suitable for pancreas transplantation alone (PTA), since it has been associated with an immunologic advantage and achieves excellent metabolic results. We describe our experience with a consecutive series of 40 PTAs with PED. METHODS: Between April 2001 and March 2004, 40 consecutive PTAs were performed with PED. Recipients were selected according to the American Diabetic Association recommendations. Donors were selected according to standard criteria irrespective of HLA match, although matching for A and B loci was considered at the time of graft allocation. Immunosuppression consisted of induction treatment with basiliximab (n = 34) or thymoglobulin (n = 6), and maintenance therapy with steroids, mycophenolate mofetil, and tacrolimus. RESULTS: After a mean cold ischemia time of 690 minutes (range, 517-965 min) all pancreases functioned immediately. Three grafts were lost due to hyperacute or accelerated rejection. No graft was lost to vascular thrombosis, although 5 (12.5%) nonocclusive thromboses were identified and the grafts were rescued with intravenous heparin infusion. A repeat laparotomy was required in 7 recipients (17.5%) No patient required multiple repeat laparotomies, and none died. After a mean follow-up of 16.4 months (range, 1-36 mo), 2 recipients were diagnosed with rejection episodes, which were reversed with steroid boluses. Actuarial 3-year patient, and graft survival rates were 100% and 94.9%, respectively. The following parameters showed significant improvement compared with pretransplantation evaluation: hemoglobin A1C concentration, total and high-density lipoprotein cholesterol levels, arterial blood pressure, cardiac performance, retinopathy, proteinuria, and neuropathy. CONCLUSIONS: Pancreas transplantation alone with PED provides high rates of long-term insulin-independence.