Primitive neuroectodermal tumors after prophylactic central nervous system irradiation in children. Association with an activated K-ras gene.

Three patients had supratentorial malignant brain tumors 7 to 9 years after prophylactic central nervous system (CNS) treatment for acute lymphocytic leukemia or malignant T-cell lymphoma. Therapy was administered at the age of 3 to 8 years and included cranial irradiation (total dose, 1800 to 2400 cGy) and intrathecal methotrexate. The brain tumors had histologic and immunohistochemical features of primitive neuroectodermal tumors (PNET), including neuroblastic rosettes, rhythmic arrangement of tumor cells, and immunohistochemical expression of glial, and in one patient neuronal, marker proteins. Using polymerase chain reaction-mediated DNA amplification from paraffin-embedded tissues and subsequent DNA sequence analysis, an activating point mutation was detected in the K-ras protooncogene in one tumor. This mutation was a G to A transition in position 2 of codon 12, substituting aspartate (GAT) for glycine (GGT). This type of mutation has not been observed before in human brain tumors, but it is frequent in radiation-induced murine lymphomas. These observations suggest that PNET can be induced after completion of the embryonal and fetal development of the human CNS. Oncogene-activating point mutations may represent a pathogenetic mechanism involved in the genesis of radiation-induced brain tumors.     

Two distinct monoclonal natural thymocytotoxic autoantibodies from New Zealand black mouse

Autoimmune-prone NZB and NZB x NZW F1 mice have a large amount of autoantibodies cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). We established two distinct monoclonal NTAs (NTA260 and NTA204) from a NZB mouse that react with the majority, but not all of these thymocytes. Flow cytometry analysis showed that NTA260 is positive on subpopulations of peripheral T cells from young mice, in which approximately 65% of CD4+ and 85% of CD8+ T cells were NTA260+. NTA260 also reacted with brain tissues of mice and rats, including Purkinje cells in the cerebellum. Western blot analysis showed that the molecular weight of NTA260 antigen was 55 kDa. In contrast to NTA260, NTA204 reacted with peripheral B cells but not with peripheral T cells in mice. NTA204 also reacted with peripheral blood granulocytes and bone marrow myeloid cells from both mice and rats. An immunofluorescence inhibition assay revealed the presence of autoantibodies with specificities of each NTA260 and NTA204 in the sera from NZB mice. As a selective decline in the subset of NTA260+ T cells but not NTA204+ B cells was observed with aging of NZB and NZB x NZW F1 hybrid mice, NTA260 is at least partly related to the observed immunological abnormalities of T cells in these autoimmune-prone New Zealand mice.     

Loss of heterozygosity on chromosome 10 is more extensive in primary (de novo) than in secondary glioblastomas

Glioblastomas develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytoma (secondary glioblastomas). There is increasing evidence that these glioblastoma subtypes develop through different genetic pathways. Primary glioblastomas are characterized by EGFR and MDM2 amplification/overexpression, PTEN mutations, and p16 deletions, whereas secondary glioblastomas frequently contain p53 mutations. Loss of heterozygosity (LOH) on chromosome 10 (LOH#10) is the most frequent genetic alteration in glioblastomas; the involvement of tumor suppressor genes, other than PTEN, has been suggested. We carried out deletion mappings on chromosome 10, using PCR-based microsatellite analysis. LOH#10 was detected at similar frequencies in primary (8/17; 47%) and secondary glioblastomas (7/13; 54%). The majority (88%) of primary glioblastomas with LOH#10 showed LOH at all informative markers, suggesting loss of the entire chromosome 10. In contrast, secondary glioblastomas with LOH#10 showed partial or complete loss of chromosome 10q but no loss of 10p. These results are in accordance with the view that LOH on 10q is a major factor in the evolution of glioblastoma multiform as the common phenotypic end point of both genetic pathways, whereas LOH on 10p is largely restricted to the primary (de novo) glioblastoma.     

Schwannoma mimicking pancreatic carcinoma: A case report

BACKGROUNDSchwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery.CASE SUMMARYA 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement.CONCLUSIONSchwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.     

The Use of a Circular Side Stapling Technique in Laparoscopic Low Anterior Resection for Rectal Cancer: Experience of 30 Serial Cases

The double-stapling technique using a circular stapler (CS) to create an end-to-end anastomosis is currently used widely in laparoscopic-assisted rectal surgery. However, a high rate of anastomotic failure has been reported. We report new side-to-side anastomosis creation using a CS, the so-called circular side stapling technique (CST). After excising the rectum at the oral and anal sides of the tumor with a linear stapler, a side-to-side colorectal anastomosis was made on the anterior wall of the rectosigmoid colon and the anterior or posterior wall of the rectum with a CS. Between 2012 and 2013, we recorded 30 serial cases of rectal-sigmoid or rectal cancer that were treated with laparoscopic-assisted surgeries using this method. In the 30 cases, the mean age was 68 ± 12 years, operating time was 288 ± 80 minutes, and blood loss was 66 ± 67 mL. None of the patients suffered from anastomosis leakage or postoperative anastomotic bleeding, and none complained of their stool habits. Three months after the last surgery in this cohort, no anastomosis strictures were reported. Based on these results, we propose an alternative method of side-to-side anastomosis for low anterior resection by using a CS to prevent staple overlap. Our experience indicates that the CST is easy and safe. Therefore, this method is a useful alternative to the current method used in laparoscopic surgery.Key words: Laparoscopy, Circular stapler, Colorectal cancer, Low anterior resectionLaparoscopic surgery for the treatment of colorectal disease has proven to be a safe and effective method compared with an open procedure.^1–3 Laparoscopy has the advantages of reduced blood loss, hospital stay, and use of anesthetics as well as a better cosmetic outcome. Although many clinical studies have demonstrated the advantages and low complication rates of laparoscopic colectomy and low anterior resection,^1–5 a high rate of anastomotic leakage has been reported in laparoscopic rectal surgeries. The reported incidence of leakage after laparoscopic surgery for the treatment of rectum varies from 6% to 17%.^1–3 Additionally, anastomotic leakage might raise concerns about local recurrence and may limit the patients prognosis.^6–8 Therefore, despite great advances in laparoscopic surgery, the risks of anastomotic complications persist to a greater extent than those for other colonic resections.^6,7Recent reports have included proposed methods for reducing anastomotic leakage, and recently a transanal drainage tube has been recommended, because the high pressure experienced in the rectum could cause anastomotic failure.⁹ Another group reported the use of anti-traction sutures supporting the anastomosis to reduce anastomotic leakage.¹⁰ Despite these proposals, anastomotic failure has not been completely resolved.In typical laparoscopic rectal surgery, a double-stapling technique (DST) with a circular stapler is used to create the anastomosis. This method is thought to be the only method available to complete an intracorporeal anastomosis of the rectum. However, the DST requires the excision of the stump of the staple line created by the linear stapler. Our previous endoscopic experience with anastomotic leakage shows that leakage occurs frequently at the point where the staples overlap in the DST.¹¹ In this study we demonstrate a new circular side stapling technique (CST), which does not require the excision of the linear staple line in a laparoscopic low anterior resection.     

Mutations in the Nijmegen breakage syndrome gene in medulloblastomas

PURPOSE: Cerebellar medulloblastoma is a highly malignant, invasive embryonal tumor with preferential manifestation in children. Nijmegen breakage syndrome (NBS) with NBS1 germ-line mutations is a rare autosomal recessive disease with clinical features that include microcephaly, mental and growth retardation, immunodeficiency, increased radiosensitivity, and predisposition to cancer. There may be functional interactions between NBS1 and the TP53 pathways. The objective of the present study is to assess whether NBS1 mutations play a role in the pathogenesis of sporadic medulloblastomas. EXPERIMENTAL DESIGN: Forty-two cases of medulloblastomas were screened for mutations in the NBS1 gene (all 16 exons) and the TP53 gene (exons 5-8) by single-stranded conformational polymorphism followed by direct DNA sequencing. RESULTS: Seven of 42 (17%) medulloblastomas carried a total of 15 NBS1 mutations. Of these, 10 were missense point mutations and 5 were intronic splicing mutations. None of these were reported previously as germ-line mutations in NBS patients. No NBS1 mutations were detected in peritumoral brain tissues available in two patients. Of 5 medulloblastomas with TP53 mutations, 4 (80%) contained NBS1 mutations, and there was a significant association between TP53 mutations and NBS1 mutations (P = 0.001). CONCLUSIONS: We provide evidence of medulloblastomas characterized by NBS1 mutations typically associated with mutational inactivation of the TP53 gene.     

Extracapsular spread of squamous cell carcinoma in neck lymph nodes: prognostic factor of laryngeal cancer

Fifty-two patients with laryngeal cancer who underwent radical neck dissections were studied to provide further information on the prognosis of various clinical and histopathological parameters. Extracapsular spread (ECS) was found in 31% of patients with N1 nodes, and in 60% of patients with histopathologically positive nodes. The 5-year survival rate of histopathological findings was as follows: patients with no pathological evidence of neck metastasis (81%), patients with neck metastasis confined to the lymph node (no ECS) (76%), and patients with ECS (17%). The difference in survival rate between patients with no ECS and patients with ECS was statistically significant (P = .001). Staging classification, T-stage classification, the number of malignant nodes, the diameter of malignant nodes, and combined therapy had no prognostic importance. The most significant factor was the presence of extracapsular spread.     

p53 mutations in primary human lung tumors and their metastases

In a total of 26 primary human lung tumors and 60 metastases derived from them, exons 5–8 of the p53 tumor suppressor gene were analyzed by single-strand conformation polymorphism and subsequent direct DNA sequencing of amplified DNA. Mutational inactivation of the p53 gene was identified in four of five squamous cell carcinomas, three of nine adenocarcinomas, and two of nine small-cell carcinomas, the overall incidence being 35%. Point mutations occurred at a similar incidence in exons 5–8, with a preference for G←T transversions. In seven of nine cases (78%), mutations were identical in the primary tumor and all of its metastases, indicating that in lung tumors, p53 mutations usually precede metastasis and that hematogenic and lymphogenic dissemination of tumor cells to other tissues is not associated with a selection against p53 inactivation. In one case, a kidney metastasis had the same mutation as the primary squamous cell carcinoma, whereas a liver metastasis had no mutation, indicating heterogeneity of the primary lung neoplasm and selective metastasis of mutated and nonmutated tumor cells to kidney and liver, respectively. Only in one liver metastasis was a mutation identified that was neither present in the primary lung tumor nor in a kidney metastasis, suggesting that occasionally p53 mutations occur after metastatic spread. © 1994 Wiley-Liss, Inc.