Productive HIV-1 infection of human cervical tissue ex vivo is associated with the secretory phase of the menstrual cycle.

Cervical tissue explants (CTEs) from 22 HIV-1 seronegative women were exposed to R5 HIV-1 ex vivo. Eight CTEs were productively infected in terms of HIV-1 p24Gag release in culture supernatants, whereas 14 were not. Nonetheless, both accumulation of HIV-1gag DNA and of p24Gag(+) CD4(+) T cells and macrophages occurred in both productive and, at lower levels, in nonproductive CTEs. Nonproductive CTEs differed from productive CTEs for higher secretion of C-C motif chemokine ligand 3 (CCL3) and CCL5. A post-hoc analysis revealed that all productive CTEs were established from women in their secretory phase of the menstrual cycle, whereas nonproductive CTEs were derived from women either in their secretory (28%) or proliferative (36%) menstrual cycle phases or with an atrophic endometrium (36%). Thus, our results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.

The role of DNA ploidy in postoperative management of stage I endometrial cancer.

BACKGROUND: Definition of high-risk stage I endometrial cancer (EC) patients who might benefit from adjuvant therapy (AT) is controversial. Decision is on the basis of traditional prognostic factors. We report our experience in which ploidy has found to play a role in clinical practice since 1999. PATIENTS AND METHODS: Two hundred and twenty-two patients with stage I EC with a median follow-up of 4.57 years were studied. After primary surgery, patients are chronologically divided in group A, from 1990 to 1998 (n = 141), receiving AT in IC stage and group B, from 1999 to 2003 (n = 81), receiving AT in case of DNA index >1.2 or stage IC grade 3 with unknown lymph node status. We analyzed prognostic factors, survival and relapse rate of the two groups. RESULTS: Since ploidy was introduced as a decision-making factor, only 30.6% (n = 11) of patients with stage IC received AT. Despite this considerable decrease of AT, no tumor-related deaths were reported in the group of patients with diploid IC stage who did not receive AT. Only DNA ploidy and age at diagnosis were independent predictors of overall survival. CONCLUSIONS: Our results indicate the important role of ploidy in order to identify high-risk patients who need AT and avoid overtreatment.

[18F]fluorodeoxyglucose positron emission tomography as a useful indicator of metastatic gestational trophoblastic tumor: preliminary results in three patients.

OBJECTIVE: The goal of this study was to evaluate the usefulness of positron emission tomography with [(18)F]fluorodeoxyglucose ([(18)F]FDG-PET) in detecting metastases in patients with gestational trophoblastic tumor (GTTs). METHODS: A retrospective study was conducted on three patients with GTTs who had been studied with [(18)F]FDG-PET and computed tomography (CT) after an increase in human chorionic beta-gonadotropin (betahCG) serum levels. PET scans were performed with a multiring whole-body positron emission tomograph 45 min after an intravenous bolus injection of [(18)F]FDG ( approximately 5.2 MBq/kg). CT studies were obtained on a spiral scanner prior and after administration of intravenous iodinated contrast material. Within a week of CT and [(18)F]FDG-PET studies, the patients underwent surgical procedures for histological diagnosis. RESULTS: In one patient, a lung lesion positive for neoplastic tissue with [(18)F]FDG-PET and negative with CT was confirmed to be a GTT metastasis at histology. In another patient, [(18)F]FDG-PET was negative, while CT was positive for the presence of lung metastasis; no viable tumor tissue was found at histological analysis. The remaining patient had a positive [(18)F]FDG-PET and CT study for lung metastasis; this was confirmed at histological analysis. In the same patient, both [(18)F]FDG-PET and CT depicted the presence of a liver lesion. Necrotic lesion regression after treatment was clearly documented with [(18)F]FDG-PET only. CONCLUSIONS: Our preliminary results suggest that [(18)F]FDG-PET may be useful for the assessment of metastatic disease in patients with GTTs.

Identification of high risk patients with endometrial carcinoma. Prognostic assessment of endometrial cancer.

OBJECTIVES: To verify the importance of DNA ploidy on clinical outcome in endometrial carcinoma and to investigate whether the prognostic information obtained by this variable is independent from other clinical-pathologic features. MATERIALS AND METHODS: Univariate and multivariate analysis of clinical and pathologic prognostic factors obtained from 203 consecutive cases of endometrial cancer, that had been surgically treated in our hospital, were performed. RESULTS: Significant prognostic factors according to the Kaplan-Meier method were age at the time of diagnosis, grade of differentiation, peritoneal cytology, node involvement, vascular invasion, myometrial infiltration and ploidy. At multivariate analysis only DNA ploidy resulted to be an independent variable. CONCLUSIONS: In our analysis DNA content is the only parameter which preserved prognostic significance in multivariate analysis.

Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: effect of highly active antiretroviral therapy.

To determine the effect of highly active antiretroviral therapy (HAART) on high-risk human papillomavirus (HR-HPV) infections and related cervical lesions, the virologic and cytologic markers of HPV infection were prospectively studied in 163 human immunodeficiency virus (HIV)-infected women, including 27 untreated, 62 treated with reverse transcriptase inhibitors, and 74 treated with HAART. A high prevalence of both infections with HR-HPV types (68%) and squamous intraepithelial lesions (SILs; low grade, 20.2%; high grade, 6.2%) was observed. The risks of infection and disease were inversely correlated with CD4 cell counts (P=.015 and P=.022, respectively). During the observation period (mean, 15.4 months; range, 6-24 months), CD4 cell counts increased significantly only in subjects receiving HAART (P<.001). Persistence of HR-HPV infection and progression of SILs were comparable in the 3 groups. These results indicate that, even in the era of HAART, HIV-infected women should be monitored carefully for the emergence of high-grade SILs and cervical cancer.

Human vasculogenesis ex vivo: embryonal aorta as a tool for isolation of endothelial cell progenitors.

SUMMARY: Vasculogenesis, the de novo formation of new blood vessels from undifferentiated precursor cells or angioblasts, has been studied with experimental in vivo and ex vivo animal models, but its mechanism is poorly understood, particularly in humans. We used the aortic ring assay to investigate the angioforming capacity of aortic explants from 11- to 12-week-old human embryos. After being embedded in collagen gels, the aorta rings produced branching capillary-like structures formed by mesenchymal spindle cells that lined a capillary-like lumen and expressed markers of endothelial differentiation (CD31, CD34, von Willebrand factor [vWF], and fms-like tyrosine kinase-1 [Flk-1]/vascular endothelial growth factor receptor 2 [VEGFR2]). The cell linings of these structures showed ultrastructural evidence of endothelial differentiation. The neovascular proliferation occurred primarily in the outer aspects of aortic rings, thus suggesting that the new vessels mainly arose from immature endothelial precursor cells localized in the outer layer of the aortic stroma, ie, a process of vasculogenesis rather than angiogenesis. The undifferentiated mesenchymal cells (CD34+/CD31-), isolated and cultured on collagen-fibronectin, differentiated into endothelial cells expressing CD31 and vWF. Furthermore, the CD34+/CD31+ cells were capable of forming a network of capillary-like structures when cultured on Matrigel. This is the first reported study showing the ex vivo formation of human microvessels by vasculogenesis. Our findings indicate that the human embryonic aorta is a rich source of CD34+/CD31- endothelial progenitor cells (angioblasts), and this information may prove valuable in studies of vascular regeneration and tissue bioengineering.

Metastatic placental site trophoblastic tumor. Report of a case with complete response to chemotherapy.

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasia, commonly insensitive to chemotherapeutic agents. CASE: We report on long-term remission in a patient with metastatic PSTT after etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine combination chemotherapy. The 27-year-old patient with metastatic lung PSTT was alive, without evidence of disease, > 40 months after treatment. CONCLUSION: Treatment with multiagent chemotherapy can produce long-term remission, even in patients with metastatic PSTT.

Acromegaly associated with a granular cell tumor of the neurohypophysis: a clinical and histological study. Case report.

Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma, and hypersecretion of GH-releasing hormone (GHRH) from a hypothalamic or neuroendocrine tumor accounts for other cases. The authors report on the unusual association of acromegaly with a granular cell tumor of the neurohypophysis. A 42-year-old woman with a 10-year history of acral enlargement, headache, and menstrual abnormalities was referred to our department for a suspected GH-secreting pituitary adenoma. The patient's basal GH levels were mildly elevated at 4.8 microg/L, were not suppressed in response to an oral glucose tolerance test, and increased paradoxically after administration of thyrotropin-releasing hormone. The patient's insulin-like growth factor-1 (IGF-1) level was elevated at 462 microg/L, whereas a magnetic resonance image of the sella turcica revealed an intra- and suprasellar lesion that was compatible with a diagnosis of pituitary adenoma. A transsphenoidal approach to remove the lesion, which was mainly suprasellar, was successful during a second operative attempt, resulting in the clinical and biochemical regression of the patient's acromegaly. Four months postoperatively, the patient's basal GH level was 0.9 microg/L and her IGF-1 level was 140 microg/L. Histological analysis of the operative specimen demonstrated a granular cell tumor of the neurohypophysis, which when stained proved negative for pituitary hormones and GHRH. This case represents the first reported association between a granular cell tumor of the neurohypophysis and acromegaly. Granular cell tumor of the neurohypophysis could be added to the restricted list of neoplastic causes of acromegaly secondary to hypersecretion of a GH-releasing substance.

Hashimoto's disease in a papillary carcinoma of the thyroid originating in a teratoma of the ovary (malignant struma ovarii).

Adenocarcinomas represent a relatively rare complication of a cystic teratoma of the ovary. Those of thyroid origin have been reported in only a few cases. In this paper we report a case of papillary carcinoma of the thyroid arising from a cystic teratoma. The patient had no thyroid symptoms, but because of the presence of antimicrosomal and antithyroglobulin antibodies the diagnosis of Hashimoto's disease was made.

Pre-operative chemoembolization of hepatocellular carcinoma in cirrhotic patients.

BACKGROUND/AIMS: The aim of the study was to evaluate clinical and pathological effects of transcatheter arterial chemoembolization (TACE) before surgical resection for hepatocellular carcinoma (HCC) in cirrhosis (55 patients); results were compared with a group of 45 patients undergoing surgical resection without TACE. METHODOLOGY: From March 1989 to December 1997, 55 cirrhotic patients, affected by surgically resectable HCC not larger than 5 cm with unifocal or bifocal tumor lesions, underwent TACE pre-operatively. RESULTS: Massive necrosis was observed in 26%, necrosis > 50% in 38% of lesions. Neoplastic cells were found in 47% of cases within the capsule or in the pericapsular tissue. Satellite nodules showed a low rate of necrosis. Mortality and morbidity in the pre-operative TACE group were 1.8% and 29%, respectively, and 4.4% and 33%, respectively, in the control group. One-, 3- and 5-year patient survival rates were 87%, 70% and 39%, respectively, versus 79%, 38% and 19%, respectively (p<0.02), in the control group. Disease-free survival was 40% and 28% at 3 years and 5 years with pre-operative TACE versus 20% and 11% (p<0.05). CONCLUSIONS: Pre-operative TACE can be performed with low morbidity. TACE can necrotize the main lesion and temporarily arrest portal diffusion of neoplastic cells by acting on microvascular infiltration. No evident effect on satellites and pericapsular neoplastic foci was observed. The long-term patients and disease-free survival rates were improved upon.

Myofibrosarcoma of the breast: review of the literature on myofibroblastic tumors and criteria for defining myofibroblastic differentiation.

A case of myofibrosarcoma of the breast is described. A 55-year-old woman presented with a small mammary nodule. A large recurrent lesions appeared a month later, and the patient died 11 months following initial presentation from diffuse pleuropulmonary metastases. Histologically, the primary tumor consisted mainly of spindled cells, arranged in fascicles and surrounded by varying quantities of dense hyaline collagen. The recurrent lesion had a more pleomorphic organization. In both lesions, there was positive immunostaining for vimentin, smooth-muscle actin, and fibronectin, and negative results for desmin, laminin, and type IV collagen. Electron microscopy revealed abundant rough endoplasmic reticulum, myofilaments with focal densities, and the fibronexus junctions and fibronectin fibrils characteristic of myofibroblasts. Given these cellular features and behavior, the tumor was interpreted as a malignant neoplasm showing myofibroblastic differentiation, i.e., a myofibrosarcoma. This case enlarges the group of myofibrosarcoma of breast, also with the demonstration of fibronexus and fibronectin fibrils. The paper emphasizes the criteria required for myofibroblastic differentiation and reviews lesions of the breast reported in the literature as myofibroblastic.

Adjuvant role of MIB1 index in differentiating serous ovarian tumors-preliminary report.

Atypically proliferating serous tumors (APST) account for 15% of all ovarian serous epithelial neoplasms. The differences between benign, borderline and malignant ovarian tumors is principally due to their cellular proliferative potential. By means of MIB1 expression we could recognize differences in proliferation among serous ovarian tumors, overcoming interobserver variability. Thirty-three patients with serous ovarian tumors, treated at S. Raffaele Hospital, University of Milan between November 1, 1992 and July 31, 1994 were used as study the population: 9 patients had serous cystoadenocarcinoma, 14 patients had APST and 10 patients had serous cystoadenoma. Pathological slides of all the cases were reviewed and immunohistochemical analysis was performed on formalin fixed, paraffin was embedded tissue. Pearson's Chi-square test and Fisher's exact test were performed for statistical evaluation. The percentage of MIB1 positive neoplastic cells ranged from, 0% to 2.1% (median 0.45%; mean 0.69%) in cystoadenomas, 1.3% to 7% (median 2.9%; mean 3.98%) in APSTs and 4.7% to 20.3% (median 6.95%; mean 9.51%) in cystoadenocarcinomas (p < 0.0001; F = 47.7). A High percentage expression of MIB1 in a serous tumor, initially diagnosed as APST, promoted a wider sampling of the surgical specimen confirming the presence of a carcinomatous component. MIB1 index is reported as representative of cellular proliferative potential. The analysis of MIB1 index provided valuable information in addition to that gained by conventional microscopic study in all cases where diagnostic difficulties arose in assessing APST.

Idiopathic sclerosing peritonitis associated with florid mesothelial hyperplasia, ovarian fibromatosis, and endometriosis: a new disorder of abdominal mass.

A 35-year-old woman underwent exploratory laparotomy for ovarian enlargement, massive ascites, and intestinal obstruction. Sclerosing peritonitis associated with florid mesothelial hyperplasia, ovarian fibromatosis, and endometriosis were diagnosed postoperatively. We add to the literature this new association of bilateral ovarian enlargement, sclerosing peritonitis, and florid mesothelial hyperplasia.

Myxoid metastases of melanoma: report of three cases and review of the literature.

We report three cases of melanoma whose metastases to skin and regional lymph nodes showed myxoid foci, findings absent in their cutaneous primary tumors.

Pancreatic adenocarcinoma: assessment of vascular invasion with high-field MR imaging and a phased-array coil.

OBJECTIVE: We performed this study to determine the value of MR imaging for assessing vascular invasion in preoperative staging of pancreatic carcinoma. SUBJECTS AND METHODS: In 73 consecutive patients with an established diagnosis of pancreatic duct adenocarcinoma, spin-echo T1-weighted and breath-hold multiplanar gradient-recalled (MPGR) images were obtained at 1.5 T with a phased-array coil before and after bolus injection of gadopentetate dimeglumine. Major peripancreatic vessels were evaluated for contiguity with tumor and tumor encasement. All patients subsequently underwent surgery. Results of unenhanced and enhanced MR imaging studies were compared with the histologic findings in the resected specimens of 49 tumors and with the surgical findings of 24 nonresected tumors. RESULTS: In 39 patients, tumor contiguity with adjacent vessels was found at pathologic examination. Of the remaining 34 patients, 10 had vascular encasement by tumor seen on pathologic examination of the resected specimen; the other 24 had unresectable tumors encasing adjacent vessels at surgical evaluation. In the assessment of vascular tumor contiguity, the accuracy was 85% for unenhanced spin-echo T1-weighted imaging, 87% for enhanced spin-echo T1-weighted imaging, 67% for unenhanced MPGR imaging, and 69% for enhanced MPGR imaging. In the assessment of vascular tumor encasement, the accuracy was 91% for unenhanced spin-echo T1-weighted imaging, 94% for enhanced spin-echo T1-weighted imaging, 74% for unenhanced MPGR imaging, and 76% for enhanced MPGR imaging. CONCLUSION: MR imaging is helpful for preoperative assessment of vascular involvement caused by pancreatic carcinoma. For this purpose, unenhanced and enhanced spin-echo T1-weighted images seem to be more accurate than images obtained with other pulse sequences.