[Endoscopic resection of a rare gastric adenoma (pyloric gland adenoma) with transition into a well-differentiated adenocarcinoma]. / Endoskopische Resektion eines seltenen Magenadenoms (Pyloric-gland-Adenom) mit Übergang in ein gut differenziertes Adenokarzinom.

We present the case of a 76-year-old lady in whom the work-up for iron-deficiency anaemia resulted in the finding of a giant gastric polyp. The polyp could be completely removed endoscopically. The final histology showed the rare entity of a pyloric gland adenoma with focal transition into a well-differentiated adenocarcinoma. The patient is well after a follow-up of 12 months. Pyloric gland adenoma was first described in 1990. In spite of its benign histological appearance, a transition into adenocarcinoma has been reported in up to 30 % of the cases. Thus, although relatively rare, the gastroenterologist/endoscopist, as well as the pathologist should be aware of the entity of pyloric gland adenoma.

[Risk-adapted multimodal laboratory cervical screening---Pap test of the future?]. / Risikoadaptierte multimodale gynäkozytologische Krebsvorsorge. Pap-Test der Zukunft?

The objective of screening for cervical cancer is to reduce mortality and incidence of the disease. To date there is extensive and strong evidence that this can be achieved by cytology-based screening programs, which continue to be the mainstay of cervical prevention worldwide despite their inherent methodological limitations. This article presents a review on the utility of conventional, ancillary and experimental methods for cervical screening both as single tests and test combinations, and describes possible future directions for enhanced screening accuracy using risk-adapted protocols.

Unusual case of well-differentiated papillary thyroid carcinoma lacking thyroglobulin expression while still concentrating radioiodine.

We present an unusual case of a well-differentiated papillary thyroid carcinoma with bilateral lung metastases. Despite undetectable serum thyroglobulin (Tg) on thyroid stimulating hormone (TSH) stimulation and no immunohistochemical evidence of Tg expression in the primary tumour, the patient showed significant uptake of radioiodine in both lungs. After five cycles of high dose radioiodine therapy, the patient went into complete remission and therefore had an excellent response to radioiodine treatment. This case is a rare exception to the rule of Tg production as a prerequisite for differentiated thyroid cancers to concentrate radioiodine.

HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN). Impact of HPV analysis of anal lesions on diagnosis and prognosis.

BACKGROUND AND AIMS: Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were clinically correlated. METHODS: The study included biopsy samples from 87 patients who had been diagnosed with the following disease patterns: 47 invasive anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions. In 52 of these cases, a tumour was clinically suspected. All biopsies were retrospectively examined for microscopic indications of HPV infection. After microdissection, additional HPV analysis via PCR was carried out. RESULTS: In 38 of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the majority of which were HPV 16 (33/38=86.8%). In 29 of the 33 cases of AIN, HPV DNA was detected (87.9%), most of these in AIN III (15/16=93.8%). Histological markers of HPV infection were detected in all 87 cases. DISCUSSION: In our series, the clinical diagnosis of the invasive anal carcinoma had a high sensitivity of 93.6%, with a specificity of 80%. The positive predictive value was 84.6%, and the negative predictive value 91.4%. In contrast, AIN had been detected clinically in none of the cases. In this situation, especially with high-risk patients, our findings recommend anal HPV screening in combination with anal cytology and anoscopy. CONCLUSION: Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected. In individual cases, validation via HPV PCR must be considered.

Outcome of 60 neonates who had ARED flow prenatally compared with a matched control group of appropriate-for-gestational age preterm neonates.

OBJECTIVE: To describe the course and outcome of fetuses with absent or reversed end-diastolic (ARED) flow in the umbilical artery (UA) and to examine the influence of prematurity according to gestational age at delivery. METHODS: Sixty pregnancies complicated by ARED flow in the UA were monitored by repeat Doppler measurements of arterial and venous vessels, non-stress tests (cardiotocogram (CTG)) and maternal investigations, and were delivered between 24 and 34 weeks. Fetal outcome was investigated and compared to a control group of appropriate-for-gestational age (AGA) preterm neonates, matched for gestational age. Mortality, birth weight, Apgar scores, postnatal cord arterial pH and need for ventilation were all recorded, as were cases of respiratory distress syndrome, bronchopulmonary dysplasia, persistent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, abnormal neurological findings and those requiring surgical intervention. Additionally, the group of fetuses with ARED flow was divided into three subgroups of different degrees of prematurity (delivery between 24 + 0 and 28 + 6 weeks, delivery between 29 + 0 and 31 + 6 weeks, and delivery after 32 weeks) and compared according to the above parameters. RESULTS: Pre- or postnatal death occurred in 16 cases. Comparing the 44 (61%) that were born alive with the AGA neonates, significant differences were found in birth weight (P < 0.001), arterial pH value (P < 0.001), bronchopulmonary dysplasia (P = 0.002) and intestinal complications (P < 0.01). Prematurity-related complications were: need for ventilation (P = 0.001), respiratory distress syndrome (P < 0.0001), periventricular leukomalacia (P = 0.002) and pathological neurological testing (P = 0.005). CONCLUSIONS: Neonates displaying ARED flow before birth are growth restricted, acidemic at delivery and are at high risk of developing bronchopulmonary dysplasia and intestinal complications. While perinatal mortality seems to be related to abnormal fetal Doppler velocimetry, age at delivery has a significant impact on short-term morbidity. After 32 weeks, morbidity is low and delivery should be considered. It could be speculated from our data that prolongation of pregnancy with Doppler velocimetry monitoring could help to reduce morbidity, although prolongation remains limited in most cases.

Can we detect cervical human papillomavirus (HPV) infection by cytomorphology alone? Diagnostic value of non-classic cytological signs of HPV effect in minimally abnormal Pap tests.

OBJECTIVE: Our aim was to assess the validity of non-classical cytological signs in minimally abnormal cervical smears for the prediction of HPV infection. METHODS: 164 ThinPrep monolayers were re-screened for mild nuclear changes, disorders of keratinisation, abortive koilocytes and 'measles cells', as well as degenerative changes. HPV DNA was detected by GP5+/6+ and MY09/MY11 consensus primer PCR assays. RESULTS: Seventy six of 164 cases (46.3%) had HPV positivity by PCR. All cytomorphological features studied were significantly associated with the presence of HPV. Mild nuclear changes had 100% sensitivity and 100% negative predictive value for HPV infection. CONCLUSIONS: Our results indicate that non-classic cytomorphological signs can improve the sensitivity of cytology for detecting HPV. Minimally abnormal Pap smears lacking mild nuclear changes (16%) in the present study--do not require further molecular HPV testing.

Feto-amniotic shunting -- experience of six centres.

AIM: Foeto-amniotic shunting is an ultrasound-guided, therapeutic intervention for drainage of persistent intracavital fluid retention in severely affected foetuses with a high risk of mortality. In order to weigh up the comparatively high risk of intervention against the possible benefit, we evaluated the value of different indications, the complication rate and the time span of drains in situ. PATIENTS AND METHODS: We made a survey of all level III ultrasound centres of German-speaking countries from 1993 to 2001. Six level III centres returned the questionnaire: forty-seven foeto-amniotic shunting procedures were performed in 30 foetuses [megacystis in 18 foetuses (three of these with urinary ascites), hydrothorax in eight foetuses, hydronephrosis in two foetuses, cystic adenomatoid malformation of the lung in one foetus, ovarian cyst in one foetus]. RESULTS: The median gestational age at time of shunting was 23.5 (range 16 - 33) weeks, at time of delivery 35 (range 23 - 41) weeks. The median time span of drains in situ was 19 (range 0 - 170) days. Altogether 18 of 30 foetuses (60 %) had a benefit of foeto-amniotic shunting. CONCLUSION: The best possible selection of pregnancies which might profit from foeto-amniotic shunting is required. The decisive criteria are the underlying defect as well as the severity and progression of the disorder.

Reliability of the lung-to-head ratio in predicting outcome and neonatal ventilation parameters in fetuses with congenital diaphragmatic hernia.

OBJECTIVES: The ratio of the lung area (on the contralateral side of the hernia) to the head circumference, the lung-to-head ratio (LHR), has been proposed as a reliable tool in the assessment of the prognosis of congenital diaphragmatic hernia (CDH). An LHR < 0.6 has been associated with poor outcome whereas one > 1.4 has been associated with survival. We aimed to analyze the role of LHR in predicting fetal outcome and ventilation parameters in cases of isolated CDH in our center. METHODS: During the 40-month study period, 22 fetuses with an isolated CDH were delivered alive under optimized conditions at our perinatal center. LHR was measured at the time of diagnosis (median, 27 weeks' gestation). In addition to survival, postnatal ventilation parameters including pCO2, pO2, inspiratory O2 partial pressure, inspiratory pressure and oxygenation index were determined, as was the occurrence of pulmonary hypertension. RESULTS: The overall survival rate was 59%. The LHR was not able to predict fetal outcome reliably. There was no correlation between the liver herniation, LHR and fetal outcome. The prenatally determined lung size reflected in the LHR did not show any significant association with individual ventilation parameters. Eleven of 17 infants examined had signs of pulmonary hypertension and the LHR did not predict this condition. CONCLUSION: Our study cannot support the optimistic results reported by other groups on the use of LHR as a reliable predictor of outcome in fetuses with CDH. The LHR, as a reflection of lung size, correlates neither with survival patterns nor with various postnatal ventilation parameters.

Advanced dynamic flow -- a new method of vascular imaging in prenatal medicine. A pilot study of its applicability.

INTRODUCTION: Vascular imaging by means of colour Doppler sonography is an established method in prenatal diagnostics, especially in fetal echocardiography. In recent years, new techniques for the imaging of vessels have been developed, attaining B-scan quality. One example of such techniques is the Advanced Dynamic Flow. The goal of the study was the comparison of the practical application of ADF under routine conditions with the established colour Doppler method, on the same machine. AIM OF THE STUDY: Comparison of conventional colour Doppler sonography with Advanced Dynamic Flow. STUDY DESIGN: a prospective, systematic study. PATIENTS AND METHOD: We used a representative cross-section through the fetal vessels and also carried out complete fetal echocardiography. Between January 1 (st), 2002 and December 31 (st), 2002, 100 pregnant women between the 12 (th) to 40 (th) gestational week were examined. RESULTS: The success rate for visualisation of blood flow was the same or higher for Advanced Dynamic Flow in all areas, compared with conventional colour Doppler. These results could also be achieved in fetal echocardiography. CONCLUSION: The Advanced Dynamic Flow technique is a new method for vascular imaging with B-scan quality. It offers high resolution, good lateral discrimination and high sensitivity. The present prospective study has demonstrated that ADF achieves better vascular imaging than conventional colour Doppler sonography. The fact that ADF offers an almost three-dimensional imaging of vessels is particularly valuable. The ease of use of the ADF technique qualifies this method as a serious alternative to conventional colour Doppler sonography.

Meconium peritonitis and pseudo-cyst formation: prenatal diagnosis and post-natal course.

OBJECTIVES: Intra-uterine bowel perforation can occur secondary to a variety of abnormalities and cause sterile peritonitis in the fetus (generalised = type I). If sealing of the perforation does not take place, a thick-walled pseudo-cyst can form (type II). METHODS: Over a 12-year period, 21 616 pregnancies were screened for gastro-intestinal malformations using prenatal ultrasound. We identified 1077 cases suspicious of surgically correctable malformations. Post-natal diagnoses and outcome were worked up retrospectively. RESULT: We found 96 fetuses with suspected gastro-intestinal malformations. Prenatal bowel perforation with meconium peritonitis was confirmed in 11 cases. In 5 of these 11, the correct diagnosis had been predicted prenatally. One child presented as a fetal and neonatal emergency (case report). Ten of the eleven infants were operated on during their first day of life. Intra-operative findings were atresia (n = 4), meconium ileus (n = 6) and no obvious cause (n = 1). Two children suffered fatal complications. CONCLUSION: Meconium peritonitis and meconium pseudo-cysts as its special manifestation are assessable by prenatal diagnosis but present in different ways. They can present as fetal ascites or echogenic bowel and cause fetal or neonatal distress, requiring close observation and highly specialised care.

Fetal ovarian cysts: prenatal diagnosis, management and postnatal outcome.

OBJECTIVE: In female fetuses ovarian cysts represent the most important differential diagnosis for intra-abdominal masses. Analyzing our own patient population we investigated whether there was a connection between sonographic parameters and postnatal course, especially with regard to the need for surgical intervention. PATIENTS AND METHODS: This was a retrospective analysis of cases from the years 1986-1999. The pre- and postnatal data of 64 fetuses who were suspected prenatally to have an ovarian cyst were analyzed. The postnatal outcome was known for all the children. RESULTS: The diagnosis was made in all cases in the third trimester (median, 35; range, 26-40 weeks' gestation). In 34 of the 64 (53%) cases, resolution of the cyst occurred either prenatally (n = 18, 53%) or postnatally (n = 16, 47%). The cystic structure in the cases with resolution was isolated, smooth-walled (n = 29) or heterogeneous (n = 5). Postnatal surgery was performed in 30 of the 64 (47%) children. In 18 of the 30 children a fenestration of the ovary was performed (60%). In this group there were 13 children with an isolated, smooth-walled ovarian cyst and five children with a heterogeneous cyst. Twelve of the 30 (40%) children underwent an ovariectomy. Among these 12 children there were eight cases with a heterogeneous cystic structure and four cases with an isolated, smooth-walled cystic structure. Of the 30 cases that underwent surgery, 29 had a follicular cyst and one had an ovarian teratoma (with a heterogeneous internal structure). In three fetuses aspiration of cyst fluid was undertaken and subsequent resolution occurred in one case. The other two cases had to undergo postnatal fenestration. CONCLUSIONS: When an ovarian cyst is suspected prenatally, serial ultrasound monitoring should follow and delivery should take place in a perinatal center. The prenatal findings should also be checked postnatally by ultrasound. Prenatal aspiration of the cyst seems to be of no advantage and should be carried out only in special individual cases.

Prenatal diagnosis of intrapulmonary arteriovenous malformation: sonographic and pathomorphological findings.

Vessel malformations, which are very rare, can be diagnosed prenatally using color Doppler sonography. We present a case of a fetus which, at first prenatal presentation at 27 weeks, was diagnosed as having an intrapulmonary arteriovenous malformation. On the basis of the gray-scale sonographic findings of cardiomegaly and dilatation of the right pulmonary vein and right pulmonary artery, color Doppler sonography was performed which identified an arteriovenous malformation of the right lung. By means of pulsed Doppler sonography it was possible to determine the hyperdynamic blood circulation in the incoming and outgoing vessels of the vascular malformation: right pulmonary artery peak systolic velocity = 90 cm/s and end-diastolic velocity = 30 cm/s; right pulmonary vein peak systolic velocity = 60 cm/s and end-diastolic velocity = 30 cm/s. The fetus went on to develop hydrops as the result of an arteriovenous valve insufficiency. At 30 weeks' gestation a Cesarean section was performed and the neonate died due to respiratory and hemodynamic problems during catheter insertion. The autopsy provided pathoanatomical confirmation of the prenatal diagnosis of an arteriovenous malformation of the right lung. There was no evidence of hereditary hemorrhagic telangiectasia.

Fetal pulmonary venous flow pattern is determined by left atrial pressure: report of two cases of left heart hypoplasia, one with patent and the other with closed interatrial communication.

We report two cases of fetal left heart hypoplasia with extremes of size of interatrial communication, i.e. a closed foramen ovale and an atrial septal defect. Doppler examinations of the pulmonary veins showed almost to and fro flow in the fetus with the closed foramen ovale and, in contrast, a normal flow velocity waveform in the fetus with the atrial septal defect, despite mitral atresia. Our observations support the importance of left atrial pressure in the creation of a pulmonary venous flow pattern in the fetus.

Reliability of prenatal sonographic lung biometry in the diagnosis of pulmonary hypoplasia.

OBJECTIVE: The purpose of the present study was to assess the value of biometric lung measurements for the diagnosis of severe fetal pulmonary hypoplasia by investigating whether a significant correlation between two-dimensional lung biometry measurements and autopsy findings could be established. METHODS: This was a prospective study carried out between 1995 and 1997. Nomograms for normal fetuses of the anterior-posterior and transverse inner thoracic diameters, which describe the growth and shape of the lung, were used as a basis for diagnosis of pulmonary hypoplasia in fetuses at high risk of developing the condition (the fetuses had bilateral renal agenesis or multicystic kidneys; chronic PROM <25 gestational weeks or hydrothorax). Pregnancy was terminated by abortion or intrauterine death in 29/43 high-risk fetuses and autopsies were performed. Only the 29 fetuses for which there were autopsy findings were included in the study. RESULTS: The best plane for diagnosing pulmonary hypoplasia was the four-chamber view. The diagnostic accuracy for this view as expressed by the sensitivity was 57% for the anterior-posterior diameter and 44% for the transverse diameter; as expressed by the specificity it was 42% for the anterior-posterior diameter and 50% for the transverse diameter. The results for the four-chamber view for the various high-risk conditions were as follows: for fetuses with chronic PROM we obtained sensitivities of 75% and 50% (anterior-posterior and transverse dimensions, respectively) and specificities of 80% and 60% (anterior-posterior and transverse dimensions, respectively). The sensitivities of lung biometry in fetuses with hydrothorax were 1% and 80% for the two diameters, but there was a low specificity. In fetuses with bilateral renal agenesis or multicystic kidneys we obtained sensitivities of 36% and 30% (anterior-posterior and transverse dimensions, respectively) and a specificity of 50% (anterior-posterior dimension). CONCLUSIONS: The present results show that two-dimensional lung biometry is not a suitable method for antenatal detection of pulmonary hypoplasia. However, in individual cases with high risk for pulmonary hypoplasia, lung biometry might prove to be an additional diagnostic parameter.

[Idiopathic sclerosing mesenteritis. Case report and differential diagnosis of a rare disease picture]. / Idiopathische sklerosierende Mesenteritis. Fallbeschreibung und Differentialdiagnosen eines seltenen Krankheitsbildes.

We report the case of a 78-year-old woman with the endoscopic tentative diagnosis of a malignant tumor of the colon ascendens (biopsy without malignancy) that was removed by right hemicolectomy. Extensive mesenteric infiltration and colonic obstruction seemed to confirm this diagnosis. Surprisingly histology revealed invasion by sclerosing mesenteritis. The differential diagnoses include inflammatory pseudotumor, tumor-like fibromatosis at traumatized sites, idiopathic retroperitoneal fibromatosis, sclerosing malignant lymphoma, liposarcoma and drug-induced sclerosing mesenteritis, as well as mesenteric infiltration and metastases. Though preoperative diagnosis is not possible in most cases, the intraoperative macroscopic appearance and the histopathologic picture are conclusive.

Chlamydia trachomatis in andrologic patients--direct and indirect detection.

BACKGROUND: Chlamydia trachomatis is considered to be the most common sexually transmitted disease in Germany. It is currently unclear whether chlamydial infection causes pathological conditions of the male accessory glands with consequences for male infertility. PATIENTS AND METHODS: Within the framework of several prospective studies the association between sperm quality, male accessory gland function and infection with C. trachomatis was investigated in men of couples with unexplained infertility. Chlamydial infection was determined by serologic methods and by proof of Chlamydia-specific DNA. As a marker of infection the direct determination of granulocytes in the ejaculate or the measurement of the polymorphonuclear (PMN) elastase concentration was used. The male accessory gland function was evaluated using the markers fructose, citric acid and alpha-glucosidase in the seminal plasma. RESULTS: Chlamydia-specific DNA in the ejaculate was present in between 3-5% of the subjects, which corresponds to its prevalence in the normal population. Chlamydia IgA antibodies were demonstrated with a frequency of 38% in seminal plasma (n = 834) using a genus-specific test (rELISA). Using other species-specific tests (MIF, SeroCT, IgA pELISA and ImmunoComb), Chlamydia IgA antibodies were found at frequencies of between 8 and 22%. CONCLUSION: Only in a few individual cases was it possible to show a connection between reduced sperm quality, disturbed male accessory gland function and indication of infection with Chlamydia, bacteria or Ureaplasma.

DNA cytometry confirms the utility of the Bethesda system for the classification of Papanicolaou smears.

BACKGROUND: Developed in 1989, the Bethesda System has largely replaced previous classifications of Papanicolaou (Pap) smears from the uterine cervix. The system is binary, dividing smears into two groups - low-grade, squamous, epithelial lesions (LSIL) or high-grade, squamous, epithelial lesions (HSIL). A third category, atypical squamous cells of undetermined significance (ASCUS), is used to classify minimal cellular changes that do not satisfy the criteria for the low- or high-grade categories. This study was designed to confirm the utility of this binary division and to compare the results with another classification system (the Munich II Nomenclature) that is not binary but contains three divisions or grades for dysplasia - low, intermediate, and high. METHODS: Pap smears were obtained from 593 women with a cytologic diagnosis of dysplasia based on the Munich System. Smears were then classified by the Bethesda System into LSIL or HSIL. Patients were followed for 2 years either with biopsy or repeat cytology. The initial smears were restained by the Feulgen method, and ploidy was evaluated by interactive DNA cytometry. RESULTS: Of 241 cases of LSIL, 39% were diploid, 57% polyploid, and 4% aneuploid. Of 352 cases classified HSIL, 4% were diploid, 17% polyploid, and 79% aneuploid. After 2 years of follow-up, 2 of 108 patients who were biopsied and who were originally classified as diploid progressed to cervical intraepithelial neoplasia/carcinoma in situ (CIN/CIS) whereas 109 of 217 patients who were aneuploid and biopsied were found to have CINIII/CIS. CONCLUSIONS: The two divisions of the Bethesda System, LSIL and HSIL, correlated with ploidy as evaluated by cytometry. Aneuploidy was found to be useful to separate cases of HSIL from those of LSIL as defined in the Bethesda System. Because of the binary division, use of a system with three divisions for dysplasia, such as the Munich II Nomenclature, creates a therapeutic dilemma because a single diagnostic category (usually the intermediate grade) may contain both self-limiting and progressive lesions. DNA cytometry of Pap smears was found to be useful as a routine procedure.

[DNA-cytometry in dysplasias of the uterine cervix]. / DNA-Zytometrie bei Dysplasien der Cervix uteri.

The diagnostic group of dysplasias has been described as "a group of diagnostic impotence". DNA-aneuploidy detected by image cytometry of Feulgen stained pap smears indicates a potentially progressive lesion, representing a high-grade lesion. DNA-cytometry can identify cases of dysplasias which are likely to progress: DNA-aneuploid dysplasias are HSIL. DNA-aneuploidy is the expression of an integral HPV infection. CIN-lesions with episomal HPV infections are DNA-diploid. With the newly developed laserscanning cytometer (LSC) of ThinPrep-Preparation an automatisation of ploidy measurement is possible in combination with HPV-PCR. We recommend DNA-Image-cytometry as a routine method for classification of uterine cervical borderline lesion into regressive and progressive.