Duplex sonography of the mesenteric vessels--a critical evaluation of inter-observer variability.

INTRODUCTION: The number of publications concerning mesenteric Doppler sonography (mesDS) is immense and does not correlate with the frequency of its use in clinical practice. This is astonishing since it provides real time blood flow (perfusion) information without side effects. Despite uncontrollable parameters like the technical limitations in some situations the optimization of (possibly) controllable parameters like standardization, production of normal values and reduction of the investigator variability by evaluating stable parameters could change the situation. PATIENTS AND METHODS: 10 investigators experienced in abdominal sonography ("DEGUM-Seminarleiter") performed mesenteric Doppler sonography in 5 healthy subjects with 5 different machines. RESULTS: The portal vein at the confluence and the common hepatic artery provide a significant portion of investigations with intromission angles of more than 60°. Values of diameter, resistance index and pulsatility index of the celiac trunc could be obtained with inter-observer variability values below 25 %. The proper and the common hepatic artery show no differences in inter-observer variability values, whereas the intrahepatic measure point of the portal vein showed a higher reproducibility. DISCUSSION: We define frame conditions for future mesenteric Doppler studies: the portal vein should be investigated at the intrahepatic measure point. Pathophysiological studies should refrain from velocity parameters except in the case of larger vessels running in a straight course towards the probe.

Correlation between SonoVue enhancement in CEUS, HCC differentiation and HCC diameter: analysis of 130 patients with hepatocellular carcinoma (HCC).

PURPOSE: The aim of the study was to characterize SonoVue enhancement in hepatocellular carcinoma in correlation to both lesion diameter and histological differentiation of the lesion. MATERIALS AND METHODS: In a prospective study 130 patients (72 male, 58 female, 62 +/- 10 years) with HCC lesions detected by B-mode sonography were examined. After injection of 1.2 - 2.4 ml SonoVue, HCC lesions were examined continuously for up to 5 min using "low MI" sonography. RESULTS: Arterial hypervascularization was found in 72 % of the HCC lesions without correlation to the lesion diameter or histological grading, when analyzed for the total group. However, the analysis of the G 1 subgroup showed significant correlation between lesion diameter and arterial hypervascularization. Arterial hypervascularization was found in 95 % of the G 1 lesions > 3 cm but in only 43 % of the G 1 lesions < 3 cm (p < 0.001). In contrast, analysis of the remaining HCC lesions (without G 1) showed arterial hypervascularization in 69 % of the lesions < 3 cm and in 72 % of the lesions > 3 cm (n. s.) without correlation to the diameter. In the late phase in the G 1 subgroup, hypoechoic demarcation was found in 95 % of the G 1 lesions > 3 cm, but in only 64 % of the G 1 lesions < 3 cm (p < 0.001). In contrast, in the less differentiated HCC lesions (without G 1), hypoechoic demarcation was found in 91 % (HCC > 3 cm) and in 82 % (HCC < 3 cm) of the lesions (n. s.). CONCLUSION: In well-differentiated HCCs (G1) hyperechoic enhancement in the arterial phase and hypoechoic demarcation in the late phase correlate to the diameter.

Tumor-specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1,349 liver lesions in contrast-enhanced ultrasound (CEUS).

AIM: To evaluate the incidence and diagnostic accuracy of tumor-specific vascularization pattern in contrast-enhanced ultrasound (CEUS) in the differential diagnosis of liver tumors in clinical practice. MATERIALS AND METHODS: From May 2004 to December 2006 1349 patients (male 677, female 672) with a hepatic tumor lacking a definite diagnosis based on B-mode ultrasound and power Doppler ultrasound were examined at 14 hospitals by CEUS using a standardized protocol (pulse/phase inversion imaging, mechanical index < 0.4). Vascularity pattern and contrast enhancement pattern were analyzed in focal lesions during the arterial, portal, and late phase. The tumor-specific diagnosis established after CEUS was compared to histology (> 75 % cases) or in some cases to CT or MRI. RESULTS: The final diagnosis of 573 benign hepatic tumors included hemangiomas (n = 242) and focal nodular hyperplasia (n = 170), other benign lesions (n = 161). Tumor-specific vascularization pattern such as a wheel-spoke pattern and arterial hyperenhancement followed by isoenhancement in the late phase in FNH or a nodular peripheral enhancement and partial or complete fill-in pattern in hemangiomas could be assessed in the majority, but not all lesions. The diagnostic accuracy of CEUS was 83.1 % for all benign lesions and 82.2 % for hemangioma and 87.1 % for FNH. The final diagnosis of 755 malignant hepatic tumors included metastases n = 383, hepatocellular carcinoma n = 279 and other malignant lesions n = 93. Late phase hypoenhancement was seen in almost all liver metastases (94.7 %) The diagnostic accuracy of CEUS was 95.8 % for all malignant lesions and 91.4 % for liver metastases and 84.9 % for hepatocellular carcinomas. CONCLUSION: Tumor-specific vascularization pattern in CEUS have a high diagnostic impact on the overall high diagnostic accuracy of CEUS for the differential diagnosis of hepatic tumors in clinical practice.

Involvement of the CD95 (APO-1/Fas) receptor and ligand system in Helicobacter pylori-induced gastric epithelial apoptosis.

Helicobacter pylori infection is associated with chronic gastritis, peptic ulceration, and gastric carcinoma. The potential role of CD95-mediated apoptosis was investigated in a panel of gastric biopsies obtained from patients with H. pylori-associated chronic gastritis (n = 29) and with noninfected normal mucosa (n = 10). Immunohistochemistry revealed increased CD95 receptor expression in epithelial and lamina propria cells in chronic gastritis. By in situ hybridization, CD95 ligand mRNA was absent or low in normal mucosa but expressed at high levels in lamina propria lymphocytes and, unexpectedly, in epithelial cells in chronic gastritis. Apoptotic cells were rare in normal mucosa but were observed regularly in chronic gastritis in close proximity to CD95 ligand mRNA expression throughout the epithelial and lamina propria cells. In a functional analysis gastric epithelial cell lines were incubated with supernatants of H. pylori. Treatment with the cytotoxic isolate H. pylori 60190 but not with the noncytotoxic isolate Tx30a upregulated CD95 in up to 50% of gastric epithelial cells and induced apoptosis in these cells. H. pylori-induced apoptosis was partially prevented by blocking CD95, demonstrating the functional role of the CD95 system. These findings suggest that H. pylori-associated chronic gastritis involves apoptosis of gastric epithelial cells by activation of the CD95 receptor and ligand system.

Natural orifice transluminal endoscopic surgery (NOTES) in the mediastinum: long-term survival animal experiments in transesophageal access, including minor surgical procedures.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) within the peritoneal cavity is rapidly evolving, using transgastric, transcolonic, or transvaginal access. There is little experience with transesophageal NOTES access to the mediastinum. This prospective long-term animal survival study was performed to explore the feasibility and safety of transesophageal intrathoracic procedures including minor surgery. MATERIAL AND METHODS: Nine pigs were used for acute (n = 2) and up to 6-week survival studies (n = 7), followed by autopsy and histological investigation. The esophageal incision site was chosen using EUS; this was followed by endoscopic mediastinoscopy and therapeutic procedures such as mediastinal lymph node removal, saline injection into myocardium, and pericardial fenestration. The wall was closed using a suturing system or endoscopic clips. RESULTS: No acute complications were recorded with respect to mediastinal structures, pericardium, cardiac rhythm, or circulatory parameters. Removal of small mediastinal lymph nodes (n = 2) was feasible, but proved to be difficult. Other procedures, specifically at the heart were all successfully performed. Endoscopy after 4 - 6 weeks showed a well-healed esophageal incision. Autopsy with histology revealed no signs of mediastinitis, infection, bleeding, or pericarditis. The esophageal scar was found to be well healed in all cases, but with a muscular gap where clip closure had been used. CONCLUSIONS: Transmural esophageal incision and endoscopic partial mediastinoscopy including therapeutic procedures on the heart or mediastinum proved feasible in long-term survival animal studies. Clip closure of the defect was effective, but did not close the esophageal muscle layer. Other means such as endoscopic suturing appear to be preferable.

Narrow band imaging with magnification for dysplasia detection and pit pattern assessment in ulcerative colitis surveillance: a case with multiple dysplasia associated lesions or masses.

A 62 year old man with longstanding ulcerative colitis and previous endoscopic excision of two dysplasia associated lesions or masses (DALMs) was admitted to our endoscopy unit for evaluation and resection of other possible DALMs. He had previously been offered and refused colectomy because of comorbidity from Parkinson's disease. He had multiple polypoid and sessile lesions which were assessed using a third generation prototype narrow band imaging (NBI) colonoscope with magnification. Selected lesions were either biopsied or resected with a combination of endoscopic submucosal dissection and endoscopic mucosal resection techniques. We correlated the pit pattern and vascular pattern intensity seen with magnification NBI with histology of both inflammatory and dysplastic lesions. Dysplastic areas showed Kudo pit patterns II, IIIL, and IV and high vascular pattern intensity. Non-dysplastic and dysplastic areas of recurrence immediately adjacent to the scar from a previous endoscopic mucosal resection site were also assessed. This is the first case report where NBI has been shown to help in DALM detection and to distinguish dysplastic from non-dysplastic mucosa in ulcerative colitis.

Bronchioloalveolar carcinoma: a new cancer in Peutz-Jeghers syndrome.

Besides gastrointestinal hamartomatous polyposis and melanin spots in the skin and mucosa, patients with the Peutz-Jeghers syndrome (PJS) have repeatedly been observed with a variety of tumours, including lung cancer. Available data indicate an increased cancer risk among PJS patients, which suggests that the gene involved in PJS, STK11 on chromosome 19p13.3, may be a tumour suppressor gene. Herein, bronchioloalveolar carcinoma (BAC) of mucinous type is reported in a 22-year old male PJS patient with a novel germline frameshift insertion in exon 2 at codon 118 of the STK11 gene. Molecular studies of his BAC indicated loss of heterozygosity (LOH) in the region of STK11 on chromosome 19p13.3. This observation supports the hypothesis that STK11 is a tumour suppressor gene which is involved in the development of lung adenocarcinoma.

Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer.

In animal studies, glutamine (Gln) reduces chemotherapy-associated mucositis and mucosal atrophy. Therefore, this study examined the protective effects of a parenteral Gln supplementation in patients with metastatic colorectal carcinoma receiving 5-fluorouracil (5-FU)/calcium-folinate (CF) chemotherapy. In a prospective study, a total of 24 patients underwent three courses of 5-FU/CF chemotherapy and were randomised with (n = 12) or without (n = 12) glycyl-L-glutamine. Effects on gastrointestinal mucosa were assessed by endoscopic examinations and histomorphometric measurements. Clinical side-effects were documented according to the World Health Organisation grading. In the Gln group, a significant reduction in mucositis and ulcerations of the gastric (P < 0.01) and duodenal mucosa (P < 0.05) was documented after the third course of chemotherapy. In the same group, the villus height/crypt depth ratio was significantly higher after therapy than in the unsupplemented group (1st course P < 0.01; 3rd course P < 0.05). However, there were no significant differences in the incidence and severity of clinical side-effects. The results suggest that parenteral Gln supplementation protects the gastrointestinal mucosa against 5-FU/CF chemotherapy-induced damage.

Pouch-anal cancer after restorative proctocolectomy for familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) and idiopathic ulcerative colitis are both mucosal diseases that bear a significant risk of developing colorectal cancer. As a consequence, their surgical treatment is currently widely performed by restorative proctocolectomy with pelvic ileal pouch-anal anastomosis (IPAA). Herein we report a new case of cancer after IPAA that developed in a 33-year-old woman with FAP. Pouch-anal cancer was diagnosed 8 years after restorative proctocolectomy, including anorectal mucosectomy, for FAP with manifest cancer in the sigmoid colon. This case observation reemphasizes that the risk of cancer for FAP patients persists as long as any rectal mucosa remains after IPAA surgery.

Simultaneous gastric adenocarcinoma and MALT-type lymphoma in Helicobacter pylori infection.

A 79-year-old women with upper abdominal pain, vomiting and weight loss was found at endoscopy to have a large tumour mass in the gastric body. Histology of forceps biopsies revealed an adenocarcinoma of intestinal type. Gastrectomy was performed, but extensive lymph node metastasis precluded a curative surgical approach. Histopathological study of the specimen, however, revealed two distict malignancies, which arose in the setting of Helicobacter pylori-associated chronic gastritis with partial mucosal atrophy. One tumour was a gastric carcinoma, while the other was a primary B-cell lymphoma of the stomach (CD20-positive). The lymphoma comprised both a low-grade component (mucosa-associated lymphoid tissue- or MALT-type lymphoma), and a high-grade component (large cell lymphoma with CD30-positive giant cells). Infection with H. pylori was confirmed by the serological presence of IgG antibodies to H. pylori-antigens, including antibodies against the 128 kDa protein of the cytotoxin-associated gene (cagA gene) of H. pylori.

Histology of intestinal Whipple's disease revisited. A study of 48 patients.

Whipple's disease is an infectious disorder with intestinal and extra-intestinal manifestations. We reinvestigated the intestinal histology in a series of 48 patients (10 females, 38 males; mean age 56.5 years, standard deviation of the mean +/- 11.2 years). A total of 126 biopsy samples, obtained prior to, during, and after therapy, were evaluated by light microscopy. In 43 patients (90%), histology was consistent with common descriptions, while it was uncommon in 3 patients (6%), and non-diagnostic in 2 patients (4%). During treatment, several alterations occurred. Apart from a continuous decrease in PAS-positive macrophages, the pattern of mucosal infiltration changed from diffuse to patchy. Moreover, the cytological aspects of PAS-positive macrophages changed substantially, and this change was used to propose four different subtypes. Initially, subtype 1 macrophages predominated (74%), but showed a gradual decrease within a few months of therapy. After 15 months, subtype 3 and subtype 4 macrophages predominated (< 80%). In 7 of 9 patients followed over long periods some subtype 3 or subtype 4 macrophages persisted. It is concluded that at diagnosis and during treatment the intestinal histology of Whipple's disease is heterogeneous. A few PAS-positive macrophages commonly persist at long-term follow-up. This and other features suggest the presence of a persistent immune defect.

Role of apoptosis in gastric epithelial turnover.

Gastric epithelial turnover is a dynamic process. It is characterized by continuous cell proliferation, which is counterbalanced by cell loss. The biological principle that mediates the homeostasis of epithelium is programmed cell death, or apoptosis. Currently, several subtypes of apoptosis are distinguished, which are mediated by different mechanisms. Various subtypes of apoptosis also occur in the gastric epithelium under various conditions. In the normal stomach, apoptosis due to cell isolation (anoikis) mediates the physiological epithelial turnover. Albeit rarely seen in routine histology, approximately 2% of epithelial cells in the normal stomach are apoptotic. In Helicobacter pylori-induced gastritis, apoptosis and epithelial proliferation are moderately increased, with approximately 8% apoptotic epithelial cells. In gastritis, factors such as CD95 ligand or tumor necrosis factor (TNF) alpha act as death factors. They bind to specific receptors, CD95 and TNF-R, which are induced either by other cytokines, such as interferon gamma, or by Helicobacter pylori itself. In addition to CD95, H.pylorican also induce upregulation of CD95 ligand expression. Taken together, the upregulated expression of CD95, and the presence of CD95L in the close proximity to apoptotic gastric epithelial cells suggest a functional role of the CD95-CD95L system in the induction of apoptosis in H.pylori-gastritis. The role of other pathways to apoptosis is currently under study. Apart from being a biological phenomenon, apoptosis in the stomach may also have direct clinical consequences. An extreme example is given in gastric graft-vs.-host disease when epithelial denudement occurs.

Autonomic dysfunction in patients with achalasia of the oesophagus.

It has been suggested that achalasia is associated with extraoesophageal sympathetic and parasympathetic dysfunction. In a prospective study we applied conventional ultrasonography and duplex sonography to investigate basal and postprandial peak systolic velocity (PSV), pulsatility index (PI) and resistance index (RI) of superior mesenteric artery and PSV of portal vein in nine patients with achalasia and 10 healthy controls (study I). In addition, in eight of these patients autonomic nervous function was investigated by pupillary function tests as well as cardiovascular reflex tests and compared with eight age- and sex-matched controls (study II). The results indicated that postprandial increase of PSV in the superior mesenteric artery was significantly lower, and postprandial decrease of PI and RI significantly higher in achalasia compared to healthy controls. In contrast, postprandial increase of PSV in the portal vein was not significantly different between both groups. Autonomic function tests revealed significant lower maximal pupillary contraction and redilatation velocities, significantly lower heart rate variation during orthostasis, deep respiration test and Valsalva manoeuvre in achalasia compared to controls. It is concluded that achalasia is associated with extraoesophageal autonomic nervous dysfunction that involves cardiovascular and pupillary function as well as regulation of mesenteric arterial blood flow.

Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: a randomized, double-blind, placebo-controlled study.

UNLABELLED: Vitamin E has been shown to protect against liver damage induced by oxidative stress in animal experiments. Based on our previous findings of diminished vitamin E levels in patients suffering from viral hepatitis, we treated 23 hepatitis C patients refractory to alpha-interferon therapy with high doses of vitamin E (2 x 400 IU RRR-alpha-tocopherol/day) for 12 weeks. STUDY DESIGN: pro-spective randomized double-blind crossover design. Clinical parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined for monitoring the disease state, in parallel vitamin E plasma levels and plasma lipids were determined. The plasma levels of the alpha-tocopherol were increased about 2-fold in all 23 patients. In 11 of 23 patients the clinical parameters indicative of liver damage were improved during the phase of vitamin E treatment (48% responders). ALT levels in responders were lowered by 46% and AST levels were lowered by 35% after 12 weeks of vitamin E treatment. Cessation of vitamin E treatment was followed by a rapid relapse of ALT and AST elevation, whereas retreatment led to a reproducible ALT decrease by 45% and AST decrease of 37% after a 6 months followup. Since vitamin E is non-toxic even at elevated doses ingested over extended periods, we suggest the treatment of patients refractory to alpha-interferon therapy suffering from hepatitis C with vitamin E as a supportive therapy.

Diminished plasma levels of vitamin E in patients with severe viral hepatitis.

RRR-alpha-Tocopherol (Vitamin E) was assayed in plasma of 48 patients with viral hepatitis and of 32 healthy controls. In patients with highly elevated serum transaminases (ALT > 100 U/L) vitamin E plasma levels were significantly lower (17.5 +/- 4.8 mumol/L) than in controls (22.7 +/- 4.2 mumol/L, p < 0.01). The vitamin E/lipid ratios (3.12 +/- 0.63 mumol/g) in these patients were 33% lower than those of the controls (4.68 +/- 0.54 mumol/g). The lowered vitamin E levels in patients with acute or chronic viral hepatitis with high activity of disease may be due to free radical-mediated liver injury.

Ischemic small bowel strictures in a case of incomplete Kawasaki disease.

The authors describe an atypical case of Kawasaki disease in a 9-month-old girl who presented with fever, coronary artery aneurysms, and acquired ischemic stricture of the proximal jejunum. Histology of the surgical specimen was consistent with mesenteric vasculitis. The infant had only some of the typical clinical signs of Kawasaki disease, suggesting that an atypical or incomplete form of the disease was present. To the best of the authors' knowledge this is only the third case to be reported of incomplete Kawasaki disease associated with ischemic bowel stricture. J Pediatr Surg 36:648-650.

Preoperative diagnostics and surgical management of tertiary hyperparathyroidism after chronic renal failure in a child.

Although hyperparathyroidism if a rare condition in young children, the pediatric surgeon is asked occasionally to participate in the management of a child with parathyroid disease. In this paper we report on a girl with global glomerulosclerosis, an unsuccessful renal transplantation and a long-term peritoneal dialysis, who developed an autonomous hyperparathyroidism. Emphasis is placed on the preoperative diagnosis and surgical management in children.

[Klippel-Trénaunay syndrome with involvement of the rectum. Surgical therapy after interventional-radiologic preparation]. / Klippel-Trénaunay-Syndrom mit Beteiligung des Rectums. Chirurgische Therapie nach interventionell-radiologischer Vorbereitung.

Abdominal organs such as the rectum and urinary bladder are rarely involved in Klippel-Trénaunay syndrome, but may occasionally be the source of severe blood loss. Since frequently no isolated source of bleeding is identified, severe blood loss can result in a critical condition. This article describes an unusual multimodal treatment concept for a patient with Klippel-Trénaunay syndrome associated with severe recurrent rectal bleeding. We present the case of a 39-year-old patient with Klippel-Trénaunay syndrome and a history of rectal bleeding since childhood requiring multiple blood transfusions over the years. He was referred to our department in a state of continuous rectal bleeding. Preoperative work-up revealed a complete alteration of the rectum and the distal parts of the sigmoid/colon by hemangiomas, with diffuse bleeding from the destroyed rectal mucosa. Preoperatively the superior rectal artery was embolized. After a 48-h interval, sphincter-preserving complete rectal excision including the sigmoid/colon was performed followed by a colon pouch anal anastomosis and protective loop ileostomy.

[Kasabach-Merritt syndrome in giant hemangioma of the liver. A case report]. / Kasabach-Merritt-Syndrom bei Riesenhämangiom der Leber. Ein Fallbericht.

Kasabach-Merritt-syndrome is rare coagulation disorder with consumption coagulopathy caused by vascular malformations. We report the case of a 44-year-old woman with repeated severe bleeding complications after small and medium sized operations with normal results in the tests of plasmatic coagulation. After discovery of a giant hemangioma of the liver the diagnosis was established. Activation of coagulation was stopped preoperatively by i.v.-heparinization and curative treatment by right-sided hemihepatectomy followed.