Real-world echocardiography in patients referred for mitral valve surgery: the gap between guidelines and clinical practice.

BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is a common disorder for which mitral valve surgery is an established therapy. Although surgical indications are clearly defined for the management of valvular heart disease, a gap exists between current guidelines and their effective application. The study aim was to provide an insight into the diagnostic information provided for cardiac surgeons before performing mitral valve surgery. METHODS: The source documents and echocardiographic studies of 100 patients, referred by nine hospitals, were screened for arguments for MR severity justifying referral for surgery. Details of the documented MR mechanism, mitral annulus (MA) size, tricuspid regurgitation (TR) severity and annulus size were also noted. RESULTS: According to the referring physician, MR was severe in 83% and moderate-to-severe in 17%. In the great majority of patients (98%) the MR mechanism was mentioned, although specific information on the prolapsing scallops was available in only 17% of cases. The recommended primary determinants of MR severity, vena contracta and proximal isovelocity surface area (PISA) were measured in only 22% and 31% of patients, respectively. In 94% of patients with available PISA information this was described only qualitatively. Correct image expansion using the zoom mode was performed in only 25% of these patients, and a correct adaptation of the Nyquist limit in only 6%. Tricuspid annulus measurements guiding the need for concomitant tricuspid valvuloplasty in patients with less than severe TR were reported in only 6% of patients. CONCLUSION: These data demonstrate a clear and important gap between current guidelines and real-world practice with regards to the echocardiographic diagnostic information provided to the surgeon before performing mitral valve surgery.

Clinical validation of a type-specific real-time quantitative human papillomavirus PCR against the performance of hybrid capture 2 for the purpose of cervical cancer screening.

To be acceptable for use in cervical cancer screening, a new assay that detects DNA of high-risk human papillomavirus (hrHPV) types must demonstrate high reproducibility and performance not inferior to that of a clinically validated HPV test. In the present study, a real-time quantitative PCR (qPCR) assay targeting the E6 and E7 genes of hrHPV was compared with Hybrid Capture 2 (hc2) in a Belgian cervical cancer screening setting. In women >30 years old, the sensitivity and specificity for intraepithelial neoplasias of grade 2 or worse (93 cases of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) and 1,207 cases of no CIN or CIN1) were 93.6% and 95.6%, respectively, and those of hc2 were 83.9% and 94.5%, respectively {relative sensitivity of qPCR/hc2 = 1.12 [95% confidence interval (CI), 1.01 to 1.23]; relative specificity = 1.01 [95% CI, 0.99 to 1.03]}. A score test showed that the sensitivity (P < 0.0001) and specificity (P < 0.0001) of the qPCR assay were not inferior to those of hc2 at the required thresholds of 90% and 98%, respectively. The overall agreement of hrHPV positivity between the two runs of the qPCR tests was 98.7% (95% CI, 97.5 to 99.4%), with a kappa value of 0.96 (95% CI, 0.83 to 1.00). The qPCR assay used in this study can be considered a reliable HPV assay that fulfills the clinical validation criteria defined for use in cervical cancer screening.

Small, smaller, smallest. Steps towards bloodless neonatal and infant cardiopulmonary bypass.

In open heart surgery in neonates and small children, the cardiopulmonary bypass circuit surface and the priming volume are relatively large in relation to patient size and blood volume. Therefore, the use of allogeneic blood is inevitable to maintain the optimal hematocrit level during bypass. To avoid the deleterious effects of blood transfusion, as well as to reduce the contact surface of blood with artificial materials, we stepwise reduced the bypass circuit size. Use of the commercially available minimized elements and an adjusted set-up of the system allowed us to reduce usage of allogeneic blood in the prime and during the bypass. However, other supplemental measures are needed to obtain asanguineous cardiopulmonary bypass for neonatal and infant patients.

Correlation between laminin-5 immunohistochemistry and human papillomavirus status in squamous cervical carcinoma.

BACKGROUND: Human papillomavirus (HPV) plays a critical role in the carcinogenesis of squamous cervical carcinoma. Integration of viral DNA into the host genome is a major contributing factor to malignant transformation. Viral load may influence integration. AIMS: To compare HPV status (type, viral load, integration status) between normal samples, carcinoma in situ and invasive carcinoma in order to elucidate the role of HPV in progression to invasive lesions. METHODS: The study population comprised 10 biopsy samples from each diagnostic group. Laminin-5 immunohistochemistry was performed to distinguish invasive carcinoma from non-invasive high-grade lesions. Real-time PCR was used to detect specific HPV types, viral load and integrated HPV, with quantification of viral E2 and E6 genes. RESULTS: Invasive carcinomas contained a higher number of laminin-5 immunoreactive cells as compared to non-invasive lesions. Almost all samples contained HPV, with a higher viral load and copy number of HPV16 integrated in E2 in cases of laminin-5 immunoreactivity and cases of invasive carcinoma. High HPV16 viral load was associated with more integrated copies in E2. CONCLUSIONS: HPV is important in progression from carcinoma in situ to invasive carcinoma. Viral load and HPV integration influence the development of cervical cancer towards invasiveness. Overall HPV status may be more predictive of patient outcome and may influence patient management.

Management of fixed subaortic stenosis: a retrospective study of 57 cases.

Although recommended by several investigators, the benefit of early surgery in patients with fixed subaortic stenosis has not been proved. Findings were reviewed of 57 patients with isolated fixed subaortic stenosis, including 27 surgically treated patients, with special emphasis on the occurrence of aortic regurgitation during a mean follow-up period of 6.7 years. The number of patients with aortic regurgitation increased preoperatively in the total group (23% at diagnosis to 54% after 3.7 years of follow-up). The prevalence of aortic regurgitation in the 27 surgically treated patients was higher (81%) than that in the nonsurgically treated group but remained unchanged after a mean postoperative period of 4.7 years. In all patients but one, aortic regurgitation remained of minor hemodynamic significance. One patient died during follow-up. After surgery, 15 patients (55%) showed a relapse; 11 redeveloped a subvalvular pressure gradient greater than 30 mm Hg and discrete subvalvular ridges (range 6 months to 24 years after surgery, mean 7 years). In those patients with fixed subaortic stenosis, follow-up did not reveal any benefit from early surgery. The unpredictable course and sometimes very severe progression of this disease make frequent and careful follow-up necessary.

Role of human papillomavirus in the carcinogenesis of squamous cell carcinoma and adenocarcinoma of the cervix.

Human papillomavirus (HPV) infection is the most common sexually transmitted disease, with more than 80% of the population infected at some time in their life. In rare cases, this infection may lead to cervical cancer. Virtually all squamous cell carcinomas and the overwhelming majority of adenocarcinomas of the cervix are HPV positive. HPV integration in the genome will lead to inactivation of the p53 pathway and the Rb pathway. Integration is essential for the onset of cervical carcinogenesis, but is probably not sufficient for progression to invasive cervical cancers. It is likely that several cofactors, such as environmental, viral and host-related factors, are necessary for the development of cervical cancer. There are several similarities and differences between the two major histological types. This article will address the role of HPV in cervical carcinogenesis as well as the molecular biology involved in the process.

Quantitative and morphological aspects of Unicryl versus Lowicryl K4M embedding in immunoelectron microscopic studies.

In this study we compared the recently commercialized electron microscopy embedding resin Unicryl with the well-known resin Lowicryl K4M with regard to morphological and immunohistochemical preservation properties. The standard embedding procedure recommended by the manufacturer for the use of Unicryl resulted in considerable morphological alterations of the tissue, with the appearance of large gaps in and between the cells of the examined tissue. Morphometric analysis pointed to a swelling of the extracellular matrix as the main cause of these morphological artifacts. A slight modification in the protocol to correct this artifact is proposed and tested. Immunohistochemically, tissue embedded in Unicryl resulted in a significantly stronger immunogold labeling than identical tissue embedded in Lowicryl K4M. From the results of this technical study, it can be concluded that Unicryl embedding is a valuable new tool to supplement the available techniques for immunoelectron microscopic studies.

Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum.

The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. Contractions to carbachol (0.01 - 0.3 microM) and to electrical field stimulation (EFS, 0.25 - 8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum. Atropine (1 microM) abolished all contractions to EFS and carbachol in control and inflamed ileum. DMPP (3 - 30 microM), a nicotinic receptor agonist, induced concentration-dependent contractions that were more pronounced in inflamed ileum as compared to control ileum. Hexamethonium (100 microM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum but not in control ileum. In control ileum, histamine (10 - 100 microM) and the histamine H(1) receptor agonist HTMT (3 - 10 microM) inhibited the contractions to EFS concentration-dependently without affecting the contractions to carbachol. The inhibitory effect of histamine and HTMT was prevented by the histamine H(1) antagonist mepyramine (5 - 10 microM) but not by the H(2)- and H(3)-receptor antagonists cimetidine and thioperamide (both 10 microM). In chronically inflamed ileum however, histamine (10 - 100 microM) and HTMT (3 - 10 microM) failed to inhibit the contractions to EFS. The histamine H(2) and H(3) receptor agonists dimaprit and R(-)-alpha-methylhistamine did not affect the contractions to EFS in control and inflamed ileum. The alpha(2)-receptor agonist UK 14.304 (0.01 - 0.1 microM) inhibited the contractions to EFS in control and inflamed ileum without affecting the contractions to carbachol. The effect of UK 14.304 was reversed by the alpha(2)-receptor antagonist yohimbine (1 microM). The inhibitory effect of UK 14.304 on contractions to EFS was of similar potency in control and inflamed ileum. Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H(1) receptors is disturbed during chronic intestinal inflammation whereas the modulation by alpha(2)-receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.

Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus.

BACKGROUND: Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia. AIM: To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis. METHODS: In 229 type 1 diabetics (M/F: 135/94; age: 41 +/- 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients. RESULTS: Sixty-nine patients were PCA-positive. H. pylori infection was present in 72 patients and was negatively associated with HLA-DQA1*0103-B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501-B1*0201 (OR=1.9, P=0.032). PCA-positivity was linked to HLA-DQA1*0501-B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA-positivity was defined as a titre > or = 1/20 (OR=2.0, P=0.03), but not if > or =1/40 was the cut-off point. PCA-positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P < 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P < 0.0001). CONCLUSIONS: The HLA-bound susceptibility of H. pylori and PCA differed. PCA-positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.

Aortic root replacement with pulmonary autograft in children.

Between September 1988 and February 1993, 14 patients whose ages ranged from 3 months to 16 years (mean 11.1 +/- 4.3 years) underwent replacement of the aortic root with the autologous pulmonary root for aortic valve disease. The follow-up was 4 years (cumulative total of 25.2 patient-years). There was no early mortality. Late mortality (one patient) was 7.1% (95% confidence limits 0% to 21%). This patient had juvenile rheumatoid arthritis and died of consequent congestive heart failure with autograft failure 6 months after operation. Event-free survival after 4 years was 78.6% (95% confidence limits 50% to 95%). One patient was reoperated on because of autograft failure caused by a relapse of rheumatic fever. One patient operated on for critical neonatal aortic stenosis has subnormal exercise tolerance because of restrictive cardiomyopathy and pulmonary homograft regurgitation. The other 12 patients were in New York Heart Association functional class I at the end of follow-up. There was no prevalence of bacterial endocarditis. There were no signs of primary structural degeneration of the pulmonary autograft. During follow-up, in eight patients, increased anulus diameter of the pulmonary autograft could be demonstrated by precordial two-dimensional echocardiography, suggesting growth of the autograft. Our experience shows that aortic root replacement with the pulmonary autograft can be done with low mortality and morbidity in children with aortic valve disease. The operation seems to be contraindicated in children with juvenile rheumatoid arthritis because of the risk of recurrence of rheumatic disease in the autograft. The pulmonary autograft has also been shown to be susceptible to recurrence of rheumatic inflammation in children with a history of acute rheumatic fever. Despite pulmonary autograft replacement of the aortic valve in infants with critical valvular aortic stenosis and endocardial fibroelastosis, clinical results may be poor. Growth of the autograft is suggested by echocardiographic follow-up. We consider aortic root replacement with the pulmonary autograft the procedure of choice in children who require aortic valve replacement.

The ileocaecal junction.

The ileocaecal junction remains a controversial region of the gut. There are still a lot of questions concerning its anatomical structure and function. In this review, a concise overview is given of the recent and older literature on the embryology, anatomy, including the intrinsic and extrinsic innervation, and the pharmacology of this region. Based on the available data from the literature, evidence is accumulating for a sphincteric function.

Ki-67 immunocytochemistry in liquid based cervical cytology: useful as an adjunctive tool?

AIMS: To test the ability of Ki-67 to detect cytological lesions in a screening setting and its use as a surrogate marker of human papillomavirus (HPV) infection. METHODS: A study of liquid based cytology, HPV DNA testing by MY09/MY11 consensus polymerase chain reaction (PCR), type specific PCRs, and Ki-67 immunocytochemistry on a randomly selected series of 147 patients. RESULTS: Comparison of the number of Ki-67 immunoreactive cells/1000 cells in the different cytological groups showed that the HSIL group yielded a significantly higher mean count than did the other groups. The number of Ki-67 immunoreactive cells/1000 cells was significantly higher in HPV-16 positive samples than in samples containing infections with other high risk types. Receiver operating characteristic curves indicated a test accuracy (area under curve) of 0.68, 0.72, and 0.86 for atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL), and high grade squamous intraepithelial lesions (HSIL), respectively. Thresholds for 95% sensitivity were 0.07, 0.08, and 0.15 Ki-67 immunopositive cells/1000 cells for ASCUS, LSIL and HSIL, respectively. The threshold for 95% specificity was 1.9 Ki-67 immunopositive cells/1000 cells. CONCLUSIONS: Ki-67 immunocytochemistry can be applied to liquid based cytology. The accuracy and diagnostic indices of the test are good when compared with those of other techniques. As part of a panel of screening procedures, it could be used as an adjunct to liquid based cytology to identify HSIL, and as a surrogate marker of HPV-16 infection.

Human oesophagostomiasis: a histomorphometric study of 13 new cases in northern Ghana.

Oesophagostomiasis is an infrequently described and recognised parasitic infection in humans, caused by Oesophagostomum bifurcum. Although the disease is most often found in the northern part of Togo and the neighbouring part of Ghana, sporadic cases have been described in other parts of Africa and in Asia and South America: Uganda, Ivory Coast, Sudan, Kenya, Ethiopia, Indonesia, Malaysia and Brazil. Infection probably occurs by way of the ingestion of L3 larvae. These larvae penetrate the intestinal wall, especially that of the colon. Some of these larvae develop into young adult worms and return to the bowel lumen. Other larvae, however, develop into immature worms, which fail to settle in the lumen, forming abscesses in the bowel wall and causing pathology. In the literature 105 human cases have been described, many originating in the northern regions of Ghana and Togo. The present study was performed to evaluate 13 new cases originating in the northern part of Ghana (7 female and 6 male patients, aged between 2 and 60 years). Histopathologically, the patients could be divided into two groups: the first group showed multinodular disease, while patients in the second group presented with a single, nodular mass. In the first group, abscesses were seen throughout the colonic wall. The mean size of the cavities was 4.3+/-0.7 mm. There was no relation between the size and the localisation in the colonic wall. Abscesses were significantly larger in male patients than in female patients. There was no correlation with age. In the second group, histopathological examination showed a cyst of variable wall thickness with very limited inflammation. These cysts represented older lesions, often encapsulated in the mesentery. In conclusion, in this study we present 13 new cases of human oesophagostomiasis. The abscess formation was found to be organ specific, independent of age, and gender-related, producing a more intense tissue reaction in male patients.

Immunofluorescent visualization of the excretory and gut system of Schistosoma mansoni by confocal laser scanning microscopy.

Conventional epifluorescence microscopy (CEM) and confocal laser scanning microscopy (CLSM) were used to visualize the excretory system and the gut on whole organisms of different life-cycle stages of Schistosoma mansoni. To visualize the gut system, an anti-circulating anodic antigen (CAA) monoclonal antibody (MAb) (120-1B10-A) was used, whereas the excretory system was immunohistochemically stained with an anti-flame cell MAb (51-4H8-A) and with a recently described anti-egg MAb (114-5B1-A). The CEM procedure resulted in clear images at low magnification but the signal-to-noise ratio on the higher magnification images was very poor. Using CLSM on the adult worm, the 114-581-A MAb demonstrated a well-defined system of canals that could be morphologically identified as the excretory system. The flame cells terminating the branches of the excretory canals showed a clear immunoreactivity with the 114-5B1-A MAb as well as with the specific flame cell MAb. The gut system could be visualized, using an anti-CAA MAb, as two well-defined bands throughout the length of the parasite. Application of the 114-5B1-A MAb on cercariae revealed a strong fluorescence on the cercarial surface, whereas no immunoreactivity could be detected on internal structures. Whole eggs showed a bright fluorescence of the egg shell, whereas miracidia showed immunoreactivity of the germinal cells located in the center of the organism. The CLSM procedure, especially with the recently introduced fast photon-counting option, provides a superior tool to investigate the three-dimensional localization of different epitopes on immunofluorescently stained whole mounts of multicellular organisms in comparison with CEM.(ABSTRACT TRUNCATED AT 250 WORDS)

Subaortic obstruction: intraoperative echocardiography as an adjunct to operation.

Fourteen patients undergoing operation for subaortic obstruction (membranous obstruction in 11 patients, tunnel obstruction in 2 patients, obstruction due to reduplicated mitral valve tissue in 1 patient) were evaluated by intraoperative epicardial echocardiography. In all 9 patients with "discrete" obstruction who underwent prebypass epicardial echocardiography, the septal and lateral attachments of the lesion were correctly demonstrated. The precise extent of tunnel stenosis was seen in both patients. The lateral attachment of the membrane in 4 patients and multiple extensions in another 2 were identified by the epicardial study (having been missed on precordial echocardiography). The discrete membrane was enucleated in 10 of the 11 patients and was partially resected in 1. One tunnel obstruction was completely relieved; the other was partially relieved. Reduplicated mitral valve tissue in the remaining patient was completely resected. Epicardial imaging after bypass showed remnants of the membrane in 2 patients. Intraoperative Doppler echocardiography and color flow imaging confirmed the absence of clinically significant residual gradients (less than 20 mm Hg) in all but 1 patient with tunnel obstruction. Epicardial imaging provided excellent morphological information about obstructive lesions of the left ventricular outflow tract and enabled immediate assessment of surgical repair.

The role of nitric oxide in serotonin-induced relaxations in the canine terminal ileum and ileocolonic junction.

The role of nitric oxide (NO) in 5-HT-induced non-adrenergic non-cholinergic (NANC) relaxations was studied on circular muscle strips of the canine ileocolonic junction (ICJ) and terminal ileum. During an acetylcholine-induced contraction, NO (10(-5) M) evoked a transient relaxation, whereas 5-HT (10(-4) M) caused an initial NANC relaxation followed by a contraction. This initial relaxation to 5-HT, but not the relaxation to NO, was significantly inhibited by the stereospecific inhibitors of the NO biosynthesis NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA). L-arginine, but not D-arginine, prevented the inhibitory effect of L-NMMA and L-NNA. The enantiomer of L-NMMA, D-NMMA, had no effect. Hemoglobin abolished the NO-induced relaxations and significantly inhibited the relaxation to 5-HT. From these experiments it is concluded that the 5-HT-induced NANC relaxation is mediated by NO or a NO releasing substance.

Autoimmune hepatitis, autoimmune gastritis, and gastric carcinoid in a type 1 diabetic patient: a case report.

The history of a 45-year-old male type 1 diabetic patient is presented. At the age of 29 years, he was diagnosed to have an autoimmune hepatitis with incipient liver cirrhosis. Five years later, a successful liver/pancreas transplantation was performed. Eighteen months later, however, pancreatic insufficiency occurred due to thrombosis of the pancreatic graft. Besides these conditions, iron deficiency, pernicious anemia, and autoimmune gastritis were also diagnosed. Serum parietal cell antibodies (PCA) and intrinsic factor antibodies (AIF) were positive. At 45, this patient was found to have a gastric carcinoid tumor. The clinical importance of PCA is discussed with regard to chronic atrophic gastritis and pernicious anemia, which both predispose toward gastric carcinoid tumors. Autoimmune type 1 diabetic patients who have a high prevalence of PCA should be screened for gastric autoimmune manifestations and tumors, as the history of this patient illustrates.

The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer.

OBJECTIVE: The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome. STUDY DESIGN: Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival. RESULTS: The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association. CONCLUSION: In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.

Localization of nitric oxide synthase in enteric neurons of the porcine and human ileocaecal junction.

Recent studies, using pharmacological or indirect morphological techniques, suggest that the non-adrenergic non-cholinergic (NANC) control of the ileocaecal junction (ICJ) is largely regulated by nitric oxide (NO). In this study, NO synthase (NOS) has been localized immunocytochemically and enzyme histochemically, using NADPH-diaphorase (NADPH-d), in enteric neurons of the myenteric and submucous plexuses of the ICJ of man and pig. The myenteric plexus, as well as the outer submucous plexus of both the porcine and the human ICJ, harboured NOS-containing neurons, which varied widely in size and shape, but which all displayed a multidendritic, uniaxonal appearance. Compared to the myenteric plexus, significantly fewer NOS-containing neurons were encountered in the outer submucous plexus. Neurofilament immunohistochemistry following NADPH-d application made it possible to distinguish a variety of cells that stained for both markers. Some of the larger neurons were of the Dogiel type-I morphology, whereas others showed a type III or a type VI-like morphology. A large number of NOS-immunoreactive nerve fibers were detected in the enlarged circular muscle of the ICJ and in the adjacent ileum. No NOS staining was detected in the smooth muscle cells of the outer circular or longitudinal muscle layer. The latter finding, together with the abundance of NOS positive nerve fibers in the smooth muscle layer, suggest a neuronal origin for NO as an important inhibitory neurotransmitter in the ICJ.

Treatment policy of neuroendocrine small cell cancer of the cervix.

Small cell cancers of the cervix are very rare and aggressive tumours. It is difficult to manage these tumours. They are often diagnosed in an advanced stage and their prognosis is generally poor. There are no clinical trials, due to their rarity, that would suggest optimal treatment. The present report describes a patient with a neuroendocrine small cell cancer of the cervix Stage IB2 with a positive lymph node. The treatment consisted of radical hysterectomy and node dissection, adjuvant chemotherapy, chemoradiation and brachytherapy. Currently, after 52 months, the patient is well and free of disease. Since 1996, there has been a classification for neuroendocrine tumours (NETs) of the cervix in four categories (large cell, small cell, typical carcinoid and atypical carcinoid). The aggressive behaviour of neuroendocrine small cell cancer is demonstrated by the high percentage of early lymphatic node and vessel invasion (68 and 90%). Almost half of the patients with Stage I and II will recur with an estimated 5-year survival from 14% to a maximum of 55%. Multimodal therapy for these tumours appears to give good response but often implies severe side-effects.