Comparative analysis of hypervascular microcystic serous cystadenoma with MRI and immunohistochemistry.

PURPOSE: Cystic tumors of the pancreas are increasingly common lesions. Unlike mucinous cystic tumors, serous cystadenomas are benign lesions and do not pose a risk of cancer. Often seen in women in the 6th and 8th decades, they are rarely seen in younger women or in male patients. Serous cystadenomas do not require surgical treatment unless they produce symptoms due to compression. Sometimes they may be misdiagnosed as cystic neuroendocrine tumors and resected because of the contrast enhancement on contrast enhanced cross-sectional studies. The purpose of this article is a translational analysis of why a cystic tumor enhances. MATERIAL AND METHODS: The preoperative T2 HASTE, fat-suppressed T2 Turbo Spin Echo sequences, magnetic resonance cholangiopancreatography, diffusion weighted images, ex-vivo high-resolution T2 HASTE images of the post-operative pathologic specimen and immunohistochemical analysis with vascular marker CD31 were compared in a 58-yearold male patient with a pancreatic corpus microcystic serous cystadenoma. RESULTS: The nodular lesion is observed as fluid signal in T2 weighted sequences and enhancing in postcontrast series. Exvivo high-resolution MRI has also revealed cysts with millimetric different sizes and septations within the lesion. Evaluation with the CD31 vascular marker showed that fibrous septa between the cysts were dense vascular and stained. CONCLUSION: We show here that microcystic serous cystadenomas have intense vascularity of their septations that enhance in cross-sectional studies, especially when the cyst diameter is smaller. KEY WORDS: CD31, Microcystic, MRI, Serous cystadenoma.

[A safely resected case of hypervascular pancreatic giant tumor after preoperative arterial embolization].

A 73-year-old woman visited our hospital for a treatment of pancreatic tumor that increased steadily in size of 6 cm in diameter in 1999 to 13 cm in 2008, while remaining in asymptomatic condition throughout this follow-up time. The tumor was big and flowed from many vessels such as portal and superior mesenteric veins and the celiac and superior mesenteric arteries. These were critical for determining tumor respectability and the risk of massive intra-operative hemorrhage was felt to be considerable. Therefore, preoperative embolization of the tumor-feeding arteries arising from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was performed on the previous day of operation. Tumor resection with pancreaticoduodenectomy and partial resection of portal vein and reconstruction were performed. We got to SMA with the use of "paraduodenal mesenteric approach", we called, and we finished the operation without a blood transfusion. The final pathology confirmed the diagnosis of serous microcystic adenoma.

[Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma].

OBJECTIVE: To clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer. METHODS: Immunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens. RESULTS: EGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones (P < 0.01). EGFR positive expression rate in stage III-IV carcinoma tissues, poor differentiation and with ascites was higher than that in stage I-II carcinomas of well differentiation and without ascites (P < 0.05). MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters (P > 0.05). The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7%, respectively, significantly lower than that in cases with EGFR and LRP-negative expression (85.0% and 90.9%, P < 0.05). In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance (P < 0.01), and only LRP-positive expression and chemotherapeutic effect were independently related to survival time (P < 0.05). There was a correlation between EGFR and MVD (r = 0.548, P < 0.01), EGFR and LRP positive expression (P = 0.020). CONCLUSION: The expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer. LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.

Is serous cystadenoma of the pancreas a model of clear-cell-associated angiogenesis and tumorigenesis?

BACKGROUND: Similar to the other von Hippel-Lindau (VHL)-related tumors such as renal cell carcinomas and capillary hemangioblastomas, serous cystadenomas (SCAs) of the pancreas are also characterized by clear cells. Over the years, we have also noticed that the tumor epithelium shows a prominent capillary network. METHODS: Eighteen cases of SCA were reviewed histologically, and immunohistochemical analysis was performed for CD31 and vascular endothelial growth factor (VEGF) as well as the molecules implicated in clear-cell tumorigenesis: GLUT-1, hypoxia-inducible factor-1 (HIF-1alpha), and carbonic anhydrase IX (CA IX). RESULTS: There was an extensively rich capillary network that appears almost intraepithelially in all cases of SCA, which was confirmed by CD31 stain that showed, on average, 26 capillaries per every 100 epithelial cells. VEGF expression was identified in 10/18 cases. Among the clear-cell tumorigenesis markers, CA IX was detected in all cases, GLUT-1 and HIF-1alpha in most cases. CONCLUSION: As in other VHL-related clear-cell tumors, there is a prominent capillary network immediately adjacent to the epithelium of SCA, confirming that the clear-cell- angiogenesis association is also valid for this tumor type. Molecules implicated in clear-cell tumorigenesis are also consistently expressed in SCA. This may have biologic and therapeutic implications, especially considering the rapidly evolving drugs against these pathways. More importantly, SCA may also serve as a model of clear-cell-associated angiogenesis and tumorigenesis, and the information gained from this tumor type may also be applicable to other clear-cell tumors.

An immunohistochemical and ultrastructural study of pancreatic microcystic serous cyst adenoma with special reference to tumor-associated microvasculature and vascular endothelial growth factor in tumor cells.

Pancreatic microcystic serous cyst adenomas are rare exocrine tumors composed of small cysts lined by glycogen-rich cells. The disease may be sporadic or present as part of von Hippel-Lindau (VHL) syndrome. Four sporadic cases of pancreatic serous cyst adenoma were examined by conventional histological, immunohistochemical, and ultrastructural methods. In the present study, new findings include the immunohistochemical identification of vascular endothelial growth factor (VEGF) and the lack of PDX-1 (putative master transcriptional factor in pancreatic stem cells) in the epithelial tumor cells. Ultrastructurally, many small blood vessels were intimately associated with epithelial tumor cells and adjacent fibroblastic cells. The observations suggest the possibility that VEGF-containing tumor cells act in a paracrine fashion to stimulate neovascularization; that peripheral blood in the vascular lumen might be filtered or processed by the endothelial and epithelial tumor cells; and that filtrates might therefore be stored as serous inclusions. It is hypothesized that pancreatic serous cyst adenomas might be under the abnormal regulation of the VHL gene, just like VHL disease itself and certain types of renal cell carcinoma, showing the distinctive histology of a rich vascularity intimately related to epithelial lining cells of cysts accompanied by stromal fibroblasts/myofibroblasts and collagenous stroma.

Conventional and color Doppler sonography in preoperative assessment of ovarian tumors.

OBJECTIVE: To study the vascular patterns of ovarian tumors by color Doppler imaging (CDI) and compare the findings of conventional sonographic studies and CDI with histopathologic findings for the same tumors. METHODS: Fifty nonpregnant women scheduled for elective surgery for ovarian tumors were examined by sonographic scanning and CDI by the same physician. Sonographic morphology scores [SMSs] were used, and the pulsatility index (PI) and resistance index (RI) were calculated after locating vessels in and around the tumors by CDI. RESULTS: It was possible to obtain CDI results in 26 of the 50 women. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 71.43%, 73.33%, and 100%, respectively, for SMS. With CDI, the sensitivity, specificity, PPV, and NPV were 100%, 85.72%, 95%, and 100% for PI and 100%, 71.43%, 90.48%, and 100% for RI. RI sensitivity and specificity were identical to those of SMS, i.e., 100% and 71.43%, respectively, but PI specificity was better (85.72%). CONCLUSION: In this study, CDI was definitely better than SMS when color flow could be obtained through the tumors. The overall efficiency in diagnosing the nature of tumors is very high if SMS and CDI are both used in patients having ovarian tumors.

[Morphofunctional characteristics of microvessels in serous tumors of the ovaries].

High vascularization is noted in serous papillary ovarian tumors of a low malignancy grade, particularly in malignant serous ovarian tumors with low vascularization in benign neoplasms. Pronounced morphological changes in the vascular wall are found mainly in malignant tumors and tumors of a low malignancy grade where primitive blood vessels of a sinusoid type with a thin muscle wall prevail. Types of vascularization in the tumors studied are variable and this correlates with results of color doppler mapping.

[Analysis of prognostic factors for the extent of vascularity of serous ovarian cancer on the basis of CD34 antigen expression]. / Analiza wartosci rokowniczej poziomu unaczynienia raka surowiczego jajnika na podstawie oceny ekspresji antygenu CD34.

OBJECTIVES: Ovarian neoplasms are very important problem in medicine, because they account for 23% of all female genital neoplasms, and they are the cause of 47% deaths among women suffering from gynecological cancers. Progression of neoplasmatic disease depends also on dynamism of angiogenesis, because better oxygen and nutrition substances supply increase tumor growth. To increase the tumor volume of 1 mm3, the development of new vessels is needed, and that also increases the risk of distant metastases. AIM: The aim of the study was the evaluation of clinical parameters compared with histological and laboratory findings in serous carcinomas. The research analyzed of angiogenesis level (antigen CD34) in patients with ovarian cancers and in control group. MATERIALS AND METHODS: The material consisted of 41 cases of serous ovarian cancer. For clinical examinations we chose only patients who underwent primary surgical operation. The control group for CD34 levels were 15 patients with benign serous adenomas. The microscopic (200x) evaluation of blood vessel in paraffin samples were made by showing the reaction of endothelial CD34 antigen with DAKO serum (Monoclonal Mouse Anti Human CD34 class 1-N 1574 LSAB). RESULTS: The level of statistical significance for grading and total vessels' area was p = 0.01 (G1--0.037 mm2, G2--0.019 mm2, G3--0.015 mm2). No difference in vascularity was observed at the level of total vascularisation of serous ovarian cancers (0.021 mm2) and in benign serous adenomas (0.023 mm2). CONCLUSIONS: Among analysed clinical and laboratory parameters only histological grade (G) correlates significantly with the level of vascularisation of ovarian serous cancers.

Esophagogastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas in von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder characterized by extensively vascularized tumors and cysts in specific organs. Angiogenesis is a striking future of VHL disease with its characteristic cysts and well-vascularized tumors. The hypervascular nature of VHL lesions has been linked to the overproduciton of vascular endothelial growth factor (VEGF) through increased expression of hypoxia inducible factor-1alpha (HIF-1alpha). Here we describe a rare case of VHL disease with esophageal and gastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas, which, upon immunohistochemical examination, exhibited HIF-1alpha and VEGF expression. Rupture of esophageal varices was successfully treated with endoscopic injection sclerotherapy.

Three-dimensional power Doppler sonography: imaging and quantifying blood flow and vascularization.

OBJECTIVES: To assess the feasibility of imaging low-velocity blood flow in adnexal masses by transvaginal three-dimensional power Doppler sonography, to analyze three-dimensional power Doppler sonography data sets with a new computer-assisted method and to test the reproducibility of the technique. METHODS: A commercially available 5-MHz Combison 530 ultrasound system was used to perform three-dimensional power Doppler sonography transvaginally. A cube (= volume of interest) was defined enclosing the vessels of the cyst and the Cartesian characteristics were stored on a hard disk. This cube was analyzed using specially designed software. Five indices representing vascularization (the vascularization index (VI) or blood flow (the flow index (FI)) or both (the vascularization-flow index (VFI)) were calculated. The intraobserver repeatability of cube definition and scan repetition was assessed using Hartley's test for homogeneous variances. Interobserver agreement was assessed by the Pearson correlation coefficient. RESULTS: Imaging of vessels with low-velocity blood flow by three-dimensional power Doppler sonography and cube definition was possible in all adnexal massed studied. In some cases even induced non-vascular flow related to endometriosis was detected. The calculated F value with intraobserver repeated Cartesian file-saving ranged from 0 to 18.8, with intraobserver scan repetition from 4.74 to 24.8 for VI, FI 1, FI 2 and VFI 1; for VFI 2 the calculated F value was 64. The interobserver correlation coefficient ranged between 0.83 and 0.92 for VI, FI 1, FI 2 and VFI 1; for VFI 2 the correlation coefficient was less than 0.75. CONCLUSION: Vessels with low-velocity blood flow can be imaged using three-dimensional power Doppler sonography. Induced non-vascular flow was detected in endometriotic cyst fluid. Three-dimensional power Doppler sonography combined with the cube method gave reproducible information for all indices except VFI 2. These indices might prove to be a new predictor in all fields of neoangiogenesis. The clinical relevance remains to be determined.

Three dimensional ultrasound and power doppler in assessment of uterine and ovarian angiogenesis: a prospective study.

AIM: To determine whether three-dimensional power Doppler can improve the recognition of pelvic tumor morphology and angiogenesis. METHODS: Using this technique we analyzed 180 adnexal masses and 110 uterine lesions. Tumor volume, morphology, and vascularity were evaluated in each patient. Irregular and randomly dispersed vessels with complex branching depicted by comprehensive three dimensional display were suggestive of pelvic malignancy, while linear-like vascular morphology, single vessel arrangement and regular branching were typical for benign structures. RESULTS: Addition of qualitative analysis of vascular architecture of adnexal tumor to morphological parameters reached 96.15% sensitivity and 98.73% specificity. When endometrial lesions were prospectively analyzed, sensitivity and specificity were 91.67% and 98.49%, respectively. Because the lowest positive predictive value of 16.67% was obtained for myometrial lesions, this method should not be advised for their eva luation. CONCLUSION: Good results achieved by three dimensional ultrasound can be explained by improved recognition of the pelvic lesion anatomy, characterization of the surface features, detection of the tumor infiltration, and precise depiction of the size and volume. Three dimensional power Doppler imaging can detect structural abnormalities of the malignant tumor vessels, such as arteriovenous shunts, microaneurysms, tumoral lakes, disproportional calibration, coiling, and dichotomous branching. Therefore it enhances and facilitates the morphologic and functional evaluation of both benign and malignant pelvic tumors.