The faith of non-surveilled pancreatic cysts: a bicentric retrospective study.

BACKGROUND: Incidental discovery of pancreatic cystic neoplasms (PCLs) is a common and steadily increasing occurrence. The aim of this study was to investigate a cohort of patients presenting with incidentally detected PCLs which were not included in a surveillance protocol, and to compare their risk of malignant evolution with that of systematically surveilled lesions. MATERIALS AND METHODS: A population of PCLs which did not receive surveillance over a period >10 years (population A) was selected at the Medical University of Vienna. A group of "low risk" branch duct intraductal papillary mucinous neoplasm ≤15 mm in size upon diagnosis undergoing a regular follow-up of at least 5 years at the University of Verona was selected as control (population B). The incidence of pancreatic cancer (PC), cumulative risk of PC and disease-specific survival were compared. RESULTS: Overall, 376 patients with non-surveilled PCLs were included in study group A and compared to 299 patients in group B. This comparison resulted in similar incidence rates of PC (1.6% vs 1.7%, p = 0.938), a strong similarity in terms of disease-specific mortality rates (1.3% vs 0.3%, p = 0.171) and the 5- and 10-year cumulative risk of PC (≅ 1% and 2%, p = 0.589) and DSS (≅ 100% and 98%, p = 0.050). CONCLUSION: The "price to pay" for a negligence-based policy in the population of non-surveilled PCLs was reasonable, and the incidence of PC was comparable to that reported for a population of low-risk cysts enrolled to a standardized surveillance protocol.

Metachronous hepatic resection for liver only pancreatic metastases.

BACKGROUND: The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. METHODS: We performed a retrospective, multicenter study including patients undergoing hepatectomy for metachronous PDAC liver metastases between 2004 and 2015 to analyze postoperative outcome and overall survival. All patients were operated with curative intent. Patients with oligometastatic metachronous liver metastasis with definitive chemotherapy (n = 8) served as controls. RESULTS: Overall 25 patients in seven centers were included in this study. The median age at the time of LR was 63.8 years (56.9-69.9) and the median number of metastases in the liver was 1 (IQR 1-2). There were eight non-anatomical resections (32%), 15 anatomical minor (60%) and 2 major LR (8%). Postoperative complications occurred in eleven patients (eight Clavien-Dindo grade I complications (32%) and three grade IIIa complications (12%), respectively). The 30-day mortality was 0%. The median length of stay was 8.6 days (IQR 5-11). Median overall survival following LR was 36.8 months compared to 9.2 months in patients with metachronous liver metastasis with chemotherapy (p = 0007). DISCUSSION: Liver resection for metachronous PDAC metastasis is safe and feasible in selected patients. To address general applicability and to find factors for patient selection, larger trials are urgently warranted.

Experiences with the standardized classification of surgical complications (Clavien-Dindo) in general surgery patients.

BACKGROUND: The standardized Clavien-Dindo classification of surgical complications is applied as a simple and widely used tool to assess and report postoperative complications in general surgery. However, most documentation uses this classification to report surgery-related morbidity and mortality in a single field of surgery or even particular intervention. The aim of the present study was to present experiences with the Clavien-Dindo classification when applied to all patients on the general surgery ward of a tertiary referral care center. METHODS: We analyzed a period of 6 months of care on a ward with a broad range of general and visceral surgery. Discharge reports and patient charts were analyzed retrospectively and reported complications rated according to the most recent Clavien-Dindo classification version. The complexity of operations was assessed with the Austrian Chamber of Physicians accounting system. RESULTS: The study included 517 patients with 817 admissions, of whom 463 had been operated upon. Complications emerged in 12.5%, of which 19% were rated as Clavien I, 20.7% as Clavien II, 13.8% as Clavien IIIa, 27.6% as Clavien IIIb, 8.6% as Clavien IVa, and 10.3% as Clavien V. No Clavien grade IVb complication occurred within the investigation. Patients having undergone more complex surgery or with higher scores experienced significantly longer lengths of hospital stay. CONCLUSION: The Clavien-Dindo classification can easily be used to document complication rates in general surgery, even though this collective was not included in the original validation studies of Clavien et al. and consisted of more heavily impaired patients.

Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy.

BACKGROUND: The potential for a fibrin sealant patch to reduce the risk of postoperative pancreatic fistula (POPF) remains uncertain. The aim of this study was to evaluate whether a fibrin sealant patch is able to reduce POPF in patients undergoing pancreatoduodenectomy with pancreatojejunostomy. METHODS: In this multicentre trial, patients undergoing pancreatoduodenectomy were randomized to receive either a fibrin patch (patch group) or no patch (control group), and stratified by gland texture, pancreatic duct size and neoadjuvant treatment. The primary endpoint was POPF. Secondary endpoints included complications, drain-related factors and duration of hospital stay. Risk factors for POPF were identified by logistic regression analysis. RESULTS: A total of 142 patients were enrolled. Forty-five of 71 patients (63 per cent) in the patch group and 40 of 71 (56 per cent) in the control group developed biochemical leakage or POPF (P = 0·392). Fistulas were classified as grade B or C in 16 (23 per cent) and ten (14 per cent) patients respectively (P = 0·277). There were no differences in postoperative complications (54 patients in patch group and 50 in control group; P = 0·839), drain amylase concentration (P = 0·494), time until drain removal (mean(s.d.) 11·6(1·0) versus 13·3(1·3) days; P = 0·613), fistula closure (17·6(2·2) versus 16·5(2·1) days; P = 0·740) and duration of hospital stay (22·1(2·2) versus 18·2(0·9) days; P = 0·810) between the two groups. Multivariable logistic regression analysis confirmed that obesity (odds ratio (OR) 5·28, 95 per cent c.i. 1·20 to 23·18; P = 0·027), soft gland texture (OR 9·86, 3·41 to 28·54; P < 0·001) and a small duct (OR 5·50, 1·84 to 16·44; P = 0·002) were significant risk factors for POPF. A patch did not reduce the incidence of POPF in patients at higher risk. CONCLUSION: The use of a fibrin sealant patch did not reduce the occurrence of POPF and complications after pancreatoduodenectomy with pancreatojejunostomy. Registration number: 2013-000639-29 (EudraCT register).

Gadoxetic acid-enhanced 3.0 T MR imaging versus multidetector-row CT in the detection of colorectal metastases in fatty liver using intraoperative ultrasound and histopathology as a standard of reference.

OBJECTIVE: To compare the diagnostic value of gadoxetic acid-enhanced MRI at 3.0 T with 64-row MDCT in the detection of colorectal liver metastases in diffuse fatty infiltration of the liver after neoadjuvant chemotherapy. METHODS: Twenty-three patients with colorectal liver metastases and at moderate to severe steatosis (25-90%) underwent prospectively preoperative tri-phasic MDCT (Somatom Sensation 64, Siemens) and gadoxetic acid-enhanced MRI (3-T Magnetom Trio, Siemens). All patients underwent surgical resection of liver metastases. Intraoperative ultrasound (IOUS) was carried out, which served as the standard of reference, together with histopathology. RESULTS: Overall, 68 metastases (range, 0.4-6 cm; 31/68 metastases [46%] ≤ 1 cm) were found at histology. MDCT detected 49/68 lesions (72%), and MRI 66/68 (97%, p < 0.001). For lesions ≤ 1 cm, MDCT detected only 13/31 (41.9%) and MRI 29/31 (93%, p < 0.001). Eight false-positive lesions were detected by MDCT, seven small lesions by MRI. There was no statistically significant difference between the two modalities in the detection of lesions > 1 cm (p = 0.250). IOUS detected all metastases and revealed two false-positive diagnoses. CONCLUSION: Gadoxetic acid-enhanced 3.0 T MRI is superior to 64-row MDCT in detecting colorectal liver metastases ≤ 1 cm during preoperative staging in patients with liver steatosis. A combination of MRI and IOUS may further improve the outcome of surgical treatment.

Hospitalization, frequency of interventions, and quality of life after endoscopic, surgical, or conservative treatment in patients with chronic pancreatitis.

OBJECTIVE: Patients with chronic pancreatitis usually have a long and debilitating history of disease with frequent hospital admissions, episodes of intractable pain and multiple interventions. The sequences of treatment at initial presentation, endoscopy, surgery, or conservative treatment may affect the time course and admissions needed for disease control, thereby determining quality of life and overall outcome. METHODS: A total of 292 patients with initial endoscopic, surgical, or conservative pharmacological treatment were retrospectively analyzed regarding frequency of interventions, days in hospital, symptom-free intervals, morbidity, and mortality. Quality of life (QoL) at the latest follow-up was measured by two standardized quality of life questionnaires (EORTC C30 and PAN26). RESULTS: Endoscopic treatment was initially performed in 150 (51.4%) patients, whereas 99 (33.9%) underwent surgery and 43 (14.7%) patients were treated conservatively at their initial presentation. Patients who underwent surgery had a significantly shorter time in the hospital (25.3 ± 24.6, 34.4 ± 35.1, 61.1 ± 37.9; P < 0.001), fewer subsequent therapies (0.43 ± 1.0, 2.1 ± 2.4, 3.1 ± 3.0; P ≤ 0.001), and a longer relapse-free interval (P = 0.004) compared with endoscopically treated patients. The overall complication rate was 32% both after surgery and endoscopy. Infectious-related complications occurred more often after surgical treatment (P ≤ 0.001), whereas patients after endoscopic intervention developed acute or chronic pancreatitis or pseudocyst formation (P = 0.023). CONCLUSIONS: Patients who undergo surgery as their initial treatment for chronic pancreatitis require less consecutive interventions, a shorter hospital stay, and have a better quality of life compared with any other treatment. Surgery should therefore be considered early for the treatment of chronic pancreatitis, when endoscopic or conservative treatment fails and patients require further intervention.

Selective resection of colorectal liver metastases.

AIMS: Safety of liver surgery for colorectal cancer liver metastases after neoadjuvant chemotherapy has to be re-evaluated. PATIENTS AND METHODS: Two hundred Patients were prospectively analyzed after surgery for colorectal cancer liver metastases between 2001 and 2004 at our institution. Special emphasis was given to perioperative morbidity and mortality under modern perioperative care. RESULTS: There was no in-hospital mortality and the perioperative morbidity was 10% (20/200). Four patients had to be reoperated due to bile leak or intraabdominal abscess. The remainder either had infectious complications or pleural effusion and/or ascites requiring tapping. Variables strongly associated with decreased survival were T, N, G and UICC (International Union against cancer) classification of the primary, hepatic lesions>5 cm and elevated tumour markers. Short disease free interval and neoadjuvant chemotherapy without response predicted impaired recurrence free survival (RFS). Multivariate analysis revealed lymph node status and differentiation of the primary, presence of extrahepatic tumour and gender as factors associated with decreased survival. Administration of neoadjuvant chemotherapy was not associated with higher postoperative morbidity or prolonged hospital stay. CONCLUSIONS: Modern dissection techniques and improved perioperative care contributed to a very low rate of surgery-related morbidity (10%) and a zero percent mortality which was also observed in patients pretreated with neoadjuvant chemotherapy prior to resection. Liver resection in experienced hands has become a safe part in the potentially curative attempt of treating patients with metastatic colorectal cancer.

The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection.

BACKGROUND AND AIMS: Major liver resection incurs a risk of postoperative liver dysfunction and infection and there is a lack of objective evidence relating residual liver volume to these complications. PATIENTS AND METHODS: Liver volumetry was performed on computer models derived from computed tomography (CT) angioportograms of 104 patients with normal synthetic liver function scheduled for liver resection. Relative residual liver volume (%RLV) was calculated as the relation of residual to total functional liver volume and related to postoperative hepatic dysfunction and infection. Receiver operator characteristic curve analysis was undertaken to determine the critical %RLV predicting severe hepatic dysfunction and infection. Univariate analysis and multivariate logistic regression analysis were performed to delineate perioperative predictors of severe hepatic dysfunction and infection. RESULTS: The incidence of severe hepatic dysfunction and infection following liver resection increased significantly with smaller %RLV. A critical %RLV of 26.6% was identified as associated with severe hepatic dysfunction (p<0.0001). Additionally, body mass index (BMI), operating time, and intraoperative blood loss were significant prognostic indicators for severe hepatic dysfunction. It was not possible to predict the individual risk of postoperative infection precisely by %RLV. However, in patients undergoing major liver resection, infection was significantly more common in those who developed postoperative severe hepatic dysfunction compared with those who did not (p=0.030). CONCLUSIONS: The likelihood of severe hepatic dysfunction following liver resection can be predicted by a small %RLV and a high BMI whereas postoperative infection is more related to liver dysfunction than precise residual liver volume. Understanding the relationship between liver volume and synthetic and immune function is the key to improving the safety of major liver resection.

Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines.

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine. Eight MTC cell lines were established from seven patients with MTC. IC(50) values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC(50) values were 3.5 +/- 1.2 nmol/liter for CPT and 8.2 +/- 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable. Given peak plasma concentrations of 65 +/- 20 nmol/liter for CPT and 1 micro mol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density.

OBJECTIVE: Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer. METHODS: Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors. RESULTS: Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05). CONCLUSION: Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.

Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism.

BACKGROUND: Nesidioblastosis in adults has been reintroduced into the differential diagnosis of organic hyperinsulinism by the description of 'noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS)'. MATERIALS AND METHODS: Pathologic specimens of all adult patients (n = 66) operated on for organic hyperinsulinism were re-examined. Five patients fulfilled the histomorphological criteria of nesidioblastosis. Retrospective review of clinical presentation, results of 72-h fasts, intravenous tolbutamide tolerance tests, pre- and intraoperative localization studies and surgical therapy was performed. RESULTS: In contrast to NIPHS, fasting tests became positive after 8-14 h. Tolbutamide tests were positive and preoperative imaging showed negative results in all patients. At first operation distal pancreatic resections were performed in three patients, resection of the pancreatic body in one patient and biopsy of the pancreatic tail in one patient. Two of three patients with recurrent disease had to be reoperated. One patient showed a coexistence of nesidioblastosis and multiple small insulinomas and is part of a kindred with autosomal dominantly inherited 'familial islet-cell adenomatosis'. CONCLUSIONS: Surgical exploration is indicated only after thorough biochemical diagnosis. An aggressive strategy for preoperative localization including selective arterial calcium stimulation testing seems justified. There may be a combination of nesidioblastosis and islet cell tumours. A link between beta-cell hyperplasia and progression to insulinoma based on not yet known genetic causes can be suspected.

A study of non-closure of the peritoneum at vaginal hysterectomy.

The aim of this case-controlled study was to determine whether non-closure of the peritoneum is detrimental in vaginal hysterectomy. 233 patients who underwent total vaginal hysterectomy (TVH) or laparoscopically assisted vaginal hysterectomy (LAVH) at the University of Vienna/Austria were analyzed. Cohorts of patients were formed according to their peritonealization status (open, n=117, vs closed peritoneum, n=116) and further stratified according to the type of surgical procedure: simple TVH ( n=115), TVH with concurrent vaginal repair and/or urinary incontinence surgery ( n=91) and LAVH ( n=27). No significant differences could be observed in analyzed surgical outcome (operation time, blood loss and analgesia). Complications (fever, infection, hemorrhage or revision) were similar whether the peritoneum was closed or not. After simple TVH, resumption of bowel function took place earlier in patients with open peritoneum than in those where it had been sutured (1.9 vs 2.4 days, P=0.001). No readmission for prolapse of the vaginal vault was recorded. Non-closure of the peritoneum at vaginal hysterectomy appears to be safe. Omission of peritoneal closure reduces the potential risk of injury and has a beneficial effect on bowel function.

Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer.

OBJECTIVES: The aim of this study was to investigate the impact of downregulation of KAI1 metastasis suppressor protein in epithelial ovarian cancer. In addition, correlation of KAI1 and p53 immunostaining was investigated. METHODS: Expression of KAI1 and p53 was immunohistochemically determined in 107 specimens of epithelial ovarian cancer stages I-IV. Survival of patients was investigated using uni- and multivariate analysis. RESULTS: Strong KAI1 expression was observed in 17.8% of cases, moderate in 27.1%, weak in 21.5%, and complete loss of KAI1 expression in 33.6%. Overexpression of p53 protein was observed in 45.8%. There was correlation of KAI1 expression neither with p53 expression nor with various clinical and histopathological parameters. Serous ovarian cancers showed significantly decreased staining intensity of KAI when compared to other histological types (P = 0.007). Univariate and multivariate analysis revealed that patients with strong or moderate expression of KAI1 had a significantly longer overall (P = 0.0013) and disease-free survival (P = 0.0048) when compared to those with low or absent expression. CONCLUSION: KAI1 downregulation is an independent prognostic factor in epithelial ovarian cancer, indicating dismal prognosis. Our study did not reveal a correlation between p53 status and KAI1 expression, suggesting that p53-independent mechanisms might be involved in the downregulation of KAI1.

DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1alpha and prognostic significance.

The multifunctional apurinic/apyrimidinic endonuclease (Ape1/ref-1) plays a key role in the human DNA base excision repair pathway. Ape1/ref-1 has also been shown to be involved in the redox control of transactivation activities of hypoxia-inducible factor (HIF)-1alpha. The aim of our study was to investigate the expression of these proteins in early stage invasive cervical cancer. Expression of Ape1/ref-1 and HIF-1alpha was detected immunohistochemically in 88 samples of cervical cancer stage pT1b. The levels of the proteins were compared and the prognostic influence of Ape1/ref-1 expression was investigated. Strong nuclear expression of Ape1/ref-1 was observed in 9 cases (10.2%), moderate in 22 cases (25%), weak in 17 cases (19.3%), and absent in 40 cases (45.5%). Furthermore, no correlation between Ape1/ref-1 and HIF-1alpha expression was observed (p=0.864). We also found no relationship of Ape1/ref-1 expression and survival (p>0.05, log-rank test). From these studies, we have concluded that in cervical cancer there is no correlation between the upstream redox regulatory protein of HIF-1, i.e., Ape1/ref-1, and HIF-1alpha expression. However, these studies do not address any functional relationship between the two proteins.

Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer.

Inhibitor of differentiation/DNA binding (Id) proteins are transcription factors, involved in cell cycle regulation and neoangiogenesis. Using immunohistochemistry, we investigated the prognostic influence of Id-1, Id-2, and Id-3 expression in 89 patients with cervical cancer stage pT(1b). In univariate and multivariate analysis, patients with strong or moderate expression of Id-1 had a significant shorter overall survival time (P = 0.0144, log-rank test) and disease-free survival time (P = 0.0107, log-rank test) compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.

Expression of hypoxia-inducible factor-1 alpha in oligodendrogliomas: its impact on prognosis and on neoangiogenesis.

BACKGROUND: Hypoxia-inducible factor (HIF)1 alpha is considered to play a key role in the adaptation of cells to hypoxia by stimulating angiogenesis via regulation of vascular endothelial growth factor and by metabolic adaptation to O(2) deprivation. METHODS: Expression of HIF-1 alpha protein and p53 was investigated by immunohistochemistry in 51 specimens of supratentorial pure oligodendrogliomas. Microvessels density (MVD) was determined by anti-CD34 immunostaining. The influence of HIF-1 alpha expression on survival was investigated using univariate and multivariate analysis. RESULTS: Strong expression of HIF-1 alpha was observed in 12 (23.5%) specimens, moderate in 21 (41.2%) specimens, and weak in 8 (15.7%) cases, and no expression was found in 10 samples (19.6%). There was no correlation of HIF-1 alpha expression with histologic grading (P = 0.428, Mann-Whitney test). Hypoxia-inducible factor-1 alpha expression and MVD showed a strong correlation (P < 0.001, r = 0.735, Spearman coefficient of correlation). Overexpression of p53 was observed in only two cases. Patients with strong or moderate expression of HIF-1 alpha had a significantly shorter overall survival rate compared with those with low or no expression in univariate (P = 0.0434; log-rank test) and multivariate analysis (P = 0.0187). CONCLUSIONS: Overexpression of HIF-1 alpha indicates a diminished prognosis in oligodendrogliomas, independent of p53 status. This finding may be explained by the strong vascularization of these tumors that prevents hypoxia and allows O(2) diffusion and henceforth tumor progression.

Signal-amplified colorimetric in situ hybridization for assessment of human papillomavirus infection in cervical lesions.

Detection and typing of human papillomavirus (HPV) infection may have a major impact in cervical-screening and follow-up. In this study various commercially available techniques for the detection of HPV were evaluated. HPV-status was determined in 86 samples of cervical cancer by PCR and direct sequencing, catalyzed signal amplified colorimetric DNA in situ hybridization (CSAC- ISH) (GenPoint system, DAKO), immunohistochemistry (IHC) and in 12 selected cases also by conventional, non-amplified ISH. Twenty-one samples of cervical intraepithelial neoplasias grade III (CIN III) were investigated by CSAC-ISH, conventional ISH and by IHC, in corresponding PAP smears HPV-detection and typing was performed by CSAC-ISH and Hybrid Capture test II (HC). In additional 20 PAP smears HPV typing was performed using HC and a novel immunocytochemical system for HPV detection and-typing. CSAC-ISH showed good correlation with PCR analysis in cervical cancers: In 87% of PCR positive cases, HPV infection was also detected by CSAC- ISH (66/76). HPV 16 was detected in 75% of PCR-positive cases (44/59), HPV 18 in 71% of PCR positive cases (5/7). CSAC-ISH detected HPV 31 in only 29% of PCR positive cases (2/7), and HPV 33 in 64% of PCR-positive cases (23/36). Nevertheless, CSAC-ISH- false negative cases for HPV 31 or 33 were nearly always combined infections with other HPV types, which were detectable by CSAC-ISH in most cases. CSAC-ISH revealed HPV infection in 20 of 21 HC-positive cervical smears, while in corresponding biopsies (CIN III) CSAC-ISH detected 100% of HPV infections. Conventional, non-amplified ISH showed significantly lower sensitivity compared with CSAC-ISH, and immunocyto- and -histochemistry were of very low sensitivity for detection of HPV. CSAC-ISH is an easy-to-handle method for detection and typing of cervical HPV infection, and shows sufficient sensitivity for clinical practice.

Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.

PURPOSE: To investigate the impact of expression of hypoxia-inducible factor (HIF)-1alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors. EXPERIMENTAL DESIGN: Expression of HIF-1alpha protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival. RESULTS: In 68.6% of ovarian cancers and 88% of borderline tumors, expression of HIF-1alpha was observed. There was a significant correlation of HIF-1alpha protein expression and MVD (P < 0.001). HIF-1alpha overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1alpha expression. Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors. CONCLUSIONS: HIF-1alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1alpha protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.

Paclitaxel-carboplatin chemotherapy does not cause encephalopathy in patients with ovarian cancer: a prospective EEG mapping study in 28 patients.

BACKGROUND: The objective of this study was to evaluate possible effects of a paclitaxel containing chemotherapy, on the central nervous system (CNS) in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. Patients were tested with resting EEG (R-EEG) before and after chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. A decrease of beta power and an increase of delta and theta power as well as a deceleration of the total centroid frequency clearly demonstrated a reduced vigilance in patients with ovarian cancer compared to healthy controls. On the other hand, the observed increase of beta power, a decrease of delta and theta power, and an acceleration of the total centroid from pre- to post-treatment demonstrated an improvement of vigilance in patients with ovarian cancer after treatment with paclitaxel/carboplatin. CONCLUSIONS: The results of this study suggest that chemotherapy consisting of paclitaxel and carboplatin does not cause adverse effects on the central nervous system. Improved vigilance was measured in patients with ovarian cancer after chemotherapy.

Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer.

Few data on the influence of lymphatic microvessel density (MVD) on survival in cancer are available since until recently there was no reliable immunohistological marker for lymphatic endothelium. Using an antibody staining podoplanin, a novel marker for lymphatic endothelium, lymphatic MVD in tissue samples of 85 patients with cervical cancer classification pT1b treated by radical hysterectomy was investigated. Survival was determined using univariate and multivariate analyses. Lymphatic MVD was also compared to MVD assessed by immunostaining against factor VIII-related antigen, which is considered a marker for blood vessels. Patients with >5 lymphatic microvessels/0.25 mm(2) field had significantly better overall survival (mean 91.8 months) than those with < or =5 lymphatic microvessels/field in univariate analysis (mean 113 months) (p = 0.0105, log-rank test). In multivariate analysis, lymphatic node involvement (p =0.0183), vessel infiltration (p =0.0158) and lymphatic MVD (p =0.0269) remained independent prognostic factors. No correlation between lymphatic MVD and various clinical and histopathological parameters was observed. Correlation between lymphatic MVD and MVD assessed by immunostaining against factor VIII was only weak (p = 0.004, r = 0.312, Spearman's coefficient of correlation). Our results suggest that increased lymphatic MVD is associated with favorable prognosis in early-stage cervical cancer.