[Segmental testicular infarction]. / Segmentaler Hodeninfarkt.

Segmental testicular infarction is a rare cause of acute scrotum and only a few cases have been reported. Torsion of the testis, testicular tumor and infection are important differential diagnoses. The present case report describes a 61-year-old man with left-sided testicular pain increasing over 24 h. The diagnosis of segmental testicular infarction was considered after color Doppler ultrasound of the left scrotum and it was confirmed by surgical exploration and pathological examination. Although it is uncommon, segmental testicular infarction should be taken into consideration when acute scrotal pain is encountered, especially for younger patients, since a testis-sparing treatment strategy can be performed.

Triple-negative phenotype is of adverse prognostic value in patients treated with dose-dense sequential adjuvant chemotherapy: a translational research analysis in the context of a Hellenic Cooperative Oncology Group (HeCOG) randomized phase III trial.

PURPOSE: It is well recognized that breast cancer is a heterogeneous disease. The purpose of the current study was to classify patients according to the immunohistochemical phenotype of their tumors in an effort to evaluate the outcome of the respective groups of patients and specifically of those with triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant chemotherapy. METHODS: A total of 595 patients with high-risk breast cancer were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67, EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin-embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67-positive). RESULTS: Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients with luminal A tumors had the best prognosis, with improved disease-free survival (log-rank, P = 0.033) and overall survival (P = 0.006) compared with the other three tumor subtypes. The three subtypes had an increased risk for relapse and death compared with luminal A in multivariate analysis, as well. No benefit from paclitaxel treatment was detected in any of the four subtypes or the total cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by quantitative RT-PCR identified patient groups that were comparable to the subtypes identified by IHC. CONCLUSIONS: The results of this study confirm that triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of adverse prognostic value in high-risk breast cancer patients treated with dose-dense sequential adjuvant chemotherapy.

Survivin and glycodelin transcriptional activity in node-positive early breast cancer: mRNA expression of two key regulators of cell survival.

INTRODUCTION: Glycodelin and survivin are key polypeptide regulators of cellular proliferation, apoptosis and angiogenesis. In view of contradictory reports on their functional role in tumors, we studied their transcriptional levels in localized breast cancer. PATIENTS AND METHODS: Glycodelin and survivin messenger ribonucleic acid (mRNA) was isolated and amplified by quantitative reverse-trancription PCR from paraffin-embedded breast carcinomas of 275 women. A normalized score was calculated by the use of GAPDH, RPL37A reference genes and was correlated with clinicopathologic/molecular parameters and patient outcome. RESULTS: A total of 272 patients were eligible, most harbored stage III node-positive breast carcinomas larger than 2 cm. Glycodelin mRNA was expressed in 68 patients (25%), more frequently in premenopausal women (P = 0.01) and those with HER2 mRNA-positive tumors (P = 0.02). Survivin mRNA was present in 263 tumors (97%) and its levels correlated significantly with high nuclear grade, VEGF mRNA and p53 mRNA presence (P < 0.05). At a median follow-up of 64 months, neither glycodelin nor survivin mRNA expression demonstrated prognostic utility for overall or disease-free survival at univariate and multivariate analysis. CONCLUSIONS: Glycodelin and survivin transcriptional activity are associated with adverse clinicopathologic and molecular characteristics of node-positive primary breast cancer but do not predict patient outcome. Further study is needed for illumination of their functional roles in tumorigenesis.

p53 and bcl-2 expression in locally advanced squamous cell head-neck cancer treated with platinum based chemotherapy and radiotherapy.

BACKGROUND: The role of apoptosis regulating oncoproteins in defining response to cytotoxic therapy remains poorly understood. Loss of wild type p53 function and bcl-2 protein overexpression are well known to inhibit the apoptotic pathway in in vitro studies. METHODS: We immunohistochemically examined the nuclear accumulation of mutant p53 and the cytoplasmic overexpression of bcl-2 proteins in 76 patients with locally advanced inoperable squamous cell cancer of the head and neck area. Patients were treated with platinum based chemotherapy and radiotherapy (37 with induction and 39 with concurrent chemotherapy). The median follow up period was 72 months. RESULTS: Thirty five (46%) cases were positive for p53 and 41 (54%) negative, whilst 19 (25%) and 57 (75%) cases were positive and negative for bcl-2 respectively. A high percentage of bcl-2 positive cells was associated with a low incidence of nodal involvement. A statistically significant higher percentage of p53 positive cells was observed in the group of patients with complete disappearance of the disease as compared to the group with residual disease after treatment (p = 0.01). High percentage of p53 positive cells and concurrent chemoradiotherapy was associated with better local progression free survival (p = 0.05 and 0.02). In multivariate analysis, the type of chemotherapy (concurrent vs. induction) was the only significant prognostic variable for local relapse (p = 0.02) and overall survival (p = 0.03). CONCLUSIONS: The present study provides evidence that p53 nuclear accumulation may be associated with better response to DNA damaging cytotoxic agents. The association of wild type p53 loss with decreased DNA repair enzyme activity is a possible explanation. Induction platinum based chemotherapy may contribute to the selection of clonogenic cells with a radioresistant phenotype.

Immunoscintigraphy with 131I-labelled H17E2 monoclonal antibody compared with conventional lymphangiography and computed tomography in the detection of metastases in patients with testicular germ cell tumours.

131I-labelled H17E2 monoclonal antibody (MAb) was administered to 16 patients with germ cell tumours of the testis (GCT). Eleven patients had non-seminomatous GCT and five seminoma. The MAb was administered into the webs between the second and third toes of both feet in 12 patients and intravenously in four patients at a dose of 1.5-2mCi. 131I-labelled 2-118 MAb (non-specific) was administered subcutaneously into the webs between the second and third toes of both feet in two patients and intravenously in one patient with non-seminomatous GCT. All three patients had only computed tomography (CT) scan. Patients were scanned immediately after until 7 days post-injection. For comparison all patients had CT scan and eight out of 16 patients had conventional lymphangiography (LG). When the radiolabelled MAb was given subcutaneously, the immunoscan (IS) was true positive in 9/12 (75%) patients and true negative in 2/12 (16.5%) and equivocal in 1/12 (8.5%). The LG gave true positive results in 6/8 (75%) patients and true negative results in 2/8 (25%) and the CT scan true positive results in 8/12 (66.6%) patients, true negative results in 2/12 (16.3%) and false negative results in 2/12 (16.3%). There was an excellent correlation of IS images with the LG results (true positivity 100%). When the radiolabelled MAb was given intravenously, both IS and CT scan gave true positive results in four cases. Our findings showed that the true positivity of IS reached 93.8%, whereas that of CT scan 87.5%. In all three patients who had the 131I-labelled 2-118 non-specific MAb, the IS was false negative, whereas the CT scan was true positive. Thus, this procedure may offer information complementary to that provided by existing conventional imaging methods.

Immunoscintigraphy with 131I-labelled monoclonal antibodies HMFG2 and HMFG1 F(ab')2 versus abdominal CT scan in the detection of residual disease in ovarian cancer patients.

131I-labelled HMFG2 or HMFG1 F(ab')2 monoclonal antibody (MAb) was administered intraperitoneally to 15 patients with epithelial ovarian cancer who had completed chemotherapy and were in complete or good partial remission. Each patient received 2-3 mCi. Patients were scanned immediately after and until 7 days post-injection. In 3/15 patients the immunoscan failed because extensive adhesions from the previous surgery prevented MAb diffusion. Of the remaining 12 patients, 9 underwent second-look laparotomy (SL). Immunoscan was true positive in 8/9 (89%) patients and equivocal in 1/9 (11%), whereas the abdominal CT scan gave true positive results in 6/9 (67%) patients. In 8 out of 9 patients there was a good correlation between distribution of all sites of abnormal uptake and the surgical findings at SL. Of the 3 patients not undergoing SL, the immunoscan was positive in all, whereas clinical examination and abdominal CT scan were negative. All 3 patients relapsed after 3, 4 and 5 months. Thus the total true positivity of immunoscan reached 92%, CT scan remaining at 50%. Immunoscan with intraperitoneal administration of 131I-labelled MAbs can thus accurately detect the presence of residual disease in ovarian cancer patients and appears more sensitive than abdominal CT scan.

Immunoscintigraphy with 131I-labelled HMFG2 and HMFG1 F(ab')2 in the pre-operative detection of clinical and subclinical lymph node metastases in breast cancer patients.

Radiolabelled specific monoclonal antibodies (MAbs) HMFG2 and HMFG1 F(ab')2 and non-specific 11.4.1 and 4C4 F(ab')2 were injected into the webs between the 2nd and 3rd fingers of both hands in 31 patients with clinical diagnosis of breast cancer. We studied 10 patients with clinically obvious axillary lymph-node disease (group A) and 10 patients with clinically negative axilla (group B) using HMFG2, 5 patients with clinically negative axilla (group C) using HMFG1 F(ab')2 and 6 patients with clinically positive axilla (group D) using non-specific 11.4.1 and 4C4 F(ab')2 MAbs. In group A, 7 patients had true positive scans. There were also 3 false negative scans, due to problems related to proper iodination at the beginning of this study. In group B there were 4 true positive scans, 4 true negative, I false positive and I false negative. In group C there were 4 true negative scans. In one patient the radiolabelled antibody was arrested in the middle of the arm, because of lymphatic obstruction. In group D, there were 3 false negative scans with 11.4.1 antibody and 3 false negative scans with 4C4 F(ab')2 MAb. The results of immunoscintigraphy were in accordance with the histopathology and immunoperoxidase staining findings. These results indicate that this non-invasive approach can accurately detect metastatic involvement in the axillary lymph nodes and can be used for the diagnosis and staging of breast cancer.