Delaying surgery to perform CT scans for suspected appendicitis decreases the rate of negative appendectomies without increasing the rate of perforation nor postoperative complications.

PURPOSE: Negative appendectomies are costly and are embedded with unnecessary risks for the patients. A careful indication for surgery seems mandatory even more so, since conservative therapy emerges as a potential alternative to surgery. The aims of this population-based study were to analyze whether radiological examinations for suspected appendicitis decreased the rate of negative appendectomies without increasing the rate of perforation or worsening postoperative outcomes. METHOD: This study is a retrospective analysis of a prospective population-based database. The data collection included preoperative investigations and intraoperative and postoperative outcomes. RESULTS: Based on 2559 patients, the rate of negative appendectomies decreased significantly with the use of CT scan as compared to clinical evaluation only (9.3 vs 5 %, p = 0.019), whereas ultrasonography alone was not able to decrease this rate (9.3 vs 6.2 %, p = 0.074). Delaying surgery for radiological investigation did not increase the rate of perforation (18.1 vs 19.2 %; adjusted odds ratio (OR) 1.01; 0.8-1.3; p = 0.899). Postoperative complications (surgical reintervention, postoperative wound infection, postoperative hematoma, postoperative intra-abdominal abscess, postoperative ileus) were all comparable. CONCLUSION: In this population-based study, CT scan was the only radiological modality that significantly reduced the rate of negative appendectomy. The delay induced by such additional imaging did not increase perforation nor complication rates. Abdominal CT scans for suspected appendicitis should therefore be more frequently used if clinical findings are unconclusive.

Colorectal polypectomy during insertion and withdrawal or only during withdrawal? A randomized controlled trial.

BACKGROUND AND STUDY AIMS: Removal of colorectal polyps is routinely performed during withdrawal of the endoscope. However, polyps detected during insertion of the colonoscope may be missed at withdrawal. We aimed to evaluate whether polypectomy during both insertion and withdrawal increases polyp detection and removal rates compared with polypectomy at withdrawal only, and to assess the duration of both approaches. PATIENTS AND METHODS: Patients were included into the study when the first polyp was detected, and randomized into two groups; in group A, polyps ≤ 10 mm in diameter were removed during insertion and withdrawal of the colonoscope, while in group B, these polyps were removed at withdrawal only. Main outcome measures were duration of colonoscopy, number of polyps detected during insertion but not recovered during withdrawal, technical ease, patient discomfort, and complications. RESULTS: 150 patients were randomized to group A and 151 to group B. Mean (± standard deviation [SD]) duration of colonoscopy did not differ between the groups (30.8 ± 15.6 min [A] vs. 28.5 ± 13.8 min [B], P = 0.176). In group A 387 polyps (mean 2.58 per colonoscopy) were detected and removed compared with 389 polyps detected (mean 2.58 per colonoscopy) in group B of which 376 were removed (13 polyps were missed, mean size [SD] 3.2 [1.3] mm; 7.3 % of patients). Patient tolerance was similar in the two groups. CONCLUSIONS: Removal of polyps ≤ 10 mm during withdrawal only is associated with a considerable polyp miss rate. We therefore recommend that these polyps are removed during both insertion and withdrawal.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite.

BACKGROUND AND STUDY AIMS: Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination. PATIENTS AND METHODS: This was a prospective single-blinded trial involving 50 patients who were undergoing elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the biopsy forceps first without and then with suctioning following contact with the sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds at 30-cm distance from the biopsy channel valve of the colonoscope, with time starting at forceps removal. Airborne bacteria were collected by an impactor air sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy room air. RESULTS: At the beginning and end of the daily colonoscopy program, the median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air suctioning during removal of the biopsy forceps reduced the bioaerosol burden from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 - 16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates. CONCLUSION: The bacterial aerosol burden during handling of biopsy forceps can be reduced by applying air suction while removing the forceps. This simple method may reduce transmission of infectious agents during gastrointestinal endoscopies.

Randomized clinical trial comparing venous cutdown with the Seldinger technique for placement of implantable venous access ports.

BACKGROUND: The aim of this randomized controlled study was to compare the primary success rate between venous cutdown and the Seldinger technique for placement of the totally implantable venous access port (TIVAP). METHODS: A total of 152 patients were randomized to receive TIVAP placement by either venous cutdown or the Seldinger technique. The main endpoint was the primary success rate. Secondary endpoints included overall success rate, procedure time and perioperative complication rates. Multiple logistic regression analysis was undertaken to assess the influence of different variables on primary success. RESULTS: The primary success rate was 71 per cent for venous cutdown and 90 per cent for the Seldinger technique (P = 0.007). The mean procedure time was significantly shorter for the Seldinger technique (48.9 versus 64.8 min; P < 0.001). The overall success rate was 97.4 per cent. The rate of perioperative complications was similar for the two approaches (5 per cent), but was higher when a procedure was converted. The variables sex, body mass index, implantation side and surgeon experience had no impact on the primary success rate. CONCLUSION: The Seldinger technique was more effective and quicker than venous cutdown, and should be regarded as the method of choice for TIVAP placement. REGISTRATION NUMBER: NCT00272623 (http://www.clinicaltrials.gov).

Long-term follow-up of proximal versus distal laparoscopic gastric bypass for morbid obesity.

BACKGROUND: Laparoscopic gastric bypass is the 'gold standard' for treatment of morbidly obese patients in many centres. There is debate regarding the optimal length for small bowel limbs. This study aimed to determine whether the proximal or distal approach is better. METHODS: Twenty-five patients undergoing primary distal gastric bypass in 2000-2002 were randomly matched for age, sex and preoperative body mass index (BMI) with 25 patients having a primary proximal bypass. All distal operations were performed laparoscopically; one proximal procedure was converted to open surgery. RESULTS: Mean operating time was 170 min for proximal and 242 min for distal bypasses (P = 0.004); median hospital stay was similar in the two groups. There were no deaths and the overall complication rate was similar, as was weight loss at 4 years: BMI decreased from 45.9 to 31.7 kg/m2 for the proximal and from 45.8 to 33.1 kg/m2 for the distal approach. Co-morbidities decreased after surgery in both groups; the prevalence of diabetes, arterial hypertension and dyslipidaemia at all time points was similar in the two groups. CONCLUSION: Proximal and distal laparoscopic gastric bypass operations are feasible and safe, with no differences in weight loss or reduction of co-morbidity in unselected morbidly obese patients.

High secondary failure rate of rebanding after failed gastric banding.

BACKGROUND: Over the last decade, more than 130,000 laparoscopic adjustable gastric bandings (LAGB) have been performed for the treatment of morbid obesity. Nowadays, longer follow-up data are available in the literature and increasing numbers of late complications and treatment failures of gastric banding have been reported. The aim of the present study was the long-term evaluation of two different rescue operations after failed LAGB: conversion to laparoscopic Roux-en-Y bypass (LRYGB) versus laparoscopic gastric rebanding. METHODS: Between January 1997 and November 2002, 74 consecutive patients underwent either laparoscopic gastric rebanding (n = 44) or LRYGB (n = 30) after failed LAGB. There were 14 men and 60 women, with a median age of 42 (23-60) years. The indication for reoperation was an increasing body mass index (BMI) and band-related complications such as pouch dilatation, band slippage, and penetration after LAGB. Rebandings were done by preference during the initial period of the study and LRYGB was the treatment of choice during the latter period. The success of the rescue operation was assessed by postoperative changes in the BMI, improvements of co-morbidities, and the need for further reoperations (secondary failure). The median follow-up was 36 months (range, 24-60 months). RESULTS: Patients who underwent LRYGB had a significantly better weight loss than patients with a rebanding operation (mean -6.1 versus +1.5 BMI points). In addition, the LRYGB patients showed a significantly better control of serum cholesterol during the long term follow-up (-0.6 versus +0.1 mmol/l). Almost half of the patients (45%) in the rebanding group needed a further operative revision, whereas only 20% underwent reoperation after rescue LRYGB. Thus, the secondary failure rate in the rebanding group was significantly higher compared to the bypass group (p = 0.028). CONCLUSIONS: The present long-term study confirms our previous finding that LRYGB is a better treatment than rebanding after failed laparoscopic gastric banding regarding weight loss and treatment of co-morbidities. During the long-term follow-up the reoperation rate due to secondary failure became significantly higher in the rebanding group. We therefore recommend that LRYGB should be preferred as rescue procedure after failed laparoscopic adjustable gastric banding.

Disseminated invasive aspergillosis with cerebral involvement successfully treated with caspofungin and voriconazole.

We describe a case of cerebral aspergillosis which was successfully treated with a combination of caspofungin and voriconazole. The patient remains in remission 18 months after stopping antifungal treatment. We discuss primary and salvage therapy of invasive aspergillosis with focus on cerebral involvement. Since historical data showed a fatal outcome in most cases, amphotericin B does not cross the blood brain barrier while voriconazole does, we chose a combination of voriconazole plus caspofungin as primary therapy.

Bedside sonographic control for positioning enteral feeding tubes: a controlled study in intensive care unit patients.

BACKGROUND AND STUDY AIM: The correct placement of an enteral feeding tube in the duodenum in critically ill patients is usually controlled radiographically. However, a direct bedside method that obviates the need for exposure to radiation would be preferable. The aim of this study was to demonstrate the usefulness of bedside sonographic position control for placing enteral feeding tubes in critically ill patients. PATIENTS AND METHODS: After placement of the enteral feeding tube, the position of the tip was determined using bedside transabdominal ultrasound. Native ultrasound was enhanced by injection of air bubbles into the feeding tube. The tube was regarded as being correctly positioned when the tube was visualized within the second or third parts of the duodenum. Plain abdominal radiographs with contrast served as the gold standard test. RESULTS: A total of 76 consecutive examinations were analyzed. In 12 patients, access to the upper abdominal wall was not possible because of open wounds; in another 13 patients who had undergone extensive abdominal surgery, the duodenum could not be identified and so no conclusion could be reached regarding the position of the tube. In 51/76 patients (67 %) ultrasound identified the duodenum and it was possible to determine the position of the tube (46 true positives and 2 true negatives); the position was incorrectly diagnosed in three patients. The sensitivity was 96 % (95 %CI 87 % - 98 %) and the specificity was 50 % (95 %CI 36 % - 65 %), with a positive predictive value of 94 %. CONCLUSIONS: Bedside sonographic control of the positioning of enteral feeding tubes is very sensitive and can be a valuable alternative to radiological control, especially in patients without open abdominal wounds, external installations, or extensive abdominal surgery.

[Evidential basis in bariatric surgery]. / Was ist "evidence based" in der Adipositaschirurgie?

Bariatric surgery is currently considered the best treatment option for morbid obesity. With the rapid development of laparoscopic techniques, a significant increase in the number bariatric procedures in recent years can be observed. Various surgical techniques to treat morbid obesity have been described, but only few prospective studies compare the different procedures, leading to a lack of evidence for their use. However, from the available literature some general recommendations can be given: (a) preoperative workup in an interdisciplinary team is mandatory, (b) primary bariatric procedures should be performed laparoscopically, and (c) the combination of restrictive and malabsorptive techniques is more efficient than a purely restrictive method, which is also true for the treatment of comorbid diabetes and arterial hypertension. In this paper, we present recent developments in bariatric surgery, with special emphasis on the available evidence for the best treatment of morbidly obese patients.

Is endosonography guided fine needle aspiration (EUS-FNA) for sarcoidosis as good as we think?

BACKGROUND: Preliminary data show that endosonography guided fine needle aspiration (EUS-FNA) may be an accurate method for diagnosing sarcoidosis. However, these data were obtained in a small selected group of patients with a very high pretest probability of sarcoidosis. This retrospective study reports on the use of EUS-FNA in an unselected group of patients with mediastinal lymphadenopathy of unknown origin. METHODS: The EUS database of a single tertiary referral centre was reviewed for patients who underwent EUS-FNA for mediastinal lymphadenopathy of unknown origin. Clinical presentation and imaging studies of each case were carefully reviewed and the diagnosis "sarcoidosis" or "no sarcoidosis" attributed if possible. The diagnoses were compared with the result of EUS-FNA. RESULTS: One hundred and twenty four patients were investigated. In 35 cases EUS-FNA identified granulomas (group 1); in the other 89 cases (group 2) no granulomas were detected. The definite diagnoses in group 1 were sarcoidosis (n = 25), indefinite (n = 7), no sarcoidosis (n = 3). The definite diagnoses in group 2 were sarcoidosis (n = 3), indefinite (n = 9), no sarcoidosis (n = 77). Of the 77 cases with no sarcoidosis, 44 were diagnosed with other diseases. The other 33 showed non-specific changes in the FNA and sarcoidosis was excluded by negative non-EUS pathology (n = 17) and clinical presentation. The sensitivity and specificity for EUS-FNA were 89% (95% CI 82 to 94) and 96% (95% CI 91 to 98), respectively, after exclusion of the indefinite cases in both groups. CONCLUSIONS: EUS-FNA is an accurate method for diagnosing sarcoidosis in an unselected group of patients with mediastinal lymphadenopathy. The reported sensitivity and specificity must be appreciated in the context of the difficult and often incomplete clinical diagnosis of sarcoidosis.

Endoscopic ultrasonography in the diagnosis and staging of neoplasms of the head and neck.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive and highly accurate method of detecting mediastinal lymph-node metastases in gastrointestinal and lung cancer. Little information is available regarding the use of EUS-FNA to stage tumors in the head and neck region. This study reports experience with EUS in the diagnosis and staging of these tumors and their mediastinal spread. PATIENTS AND METHODS: The records of patients who underwent EUS for diagnosis and/or staging of head and neck tumors were reviewed. Referral criteria were suspected invasion of the esophagus by a lower-neck mass on cervical computed tomography (CT) or magnetic resonance imaging (MRI), or mediastinal lymphadenopathy > 10 mm on a chest CT. RESULTS: Thirty-two patients (23 men, nine women; mean age 65 years, range 44 - 80) were referred and underwent 35 EUS examinations. In one patient, EUS was not possible due to a benign esophageal stricture. In 17 patients with suspected esophageal invasion on CT scans, EUS demonstrated invasion of the esophagus in four cases and of the pleura in one; 12 tumors showed no visible invasion of adjacent structures. The other 17 examinations were carried out for suspected mediastinal metastatic disease. In eight cases, EUS-FNA confirmed metastatic disease, whereas only benign changes were shown in the other nine cases. EUS-FNA also provided the first tissue diagnosis in two primary tumors and identified malignancy in one patient with no CT suspicion of positive mediastinal lymph nodes. EUS avoided the need for more invasive investigations in all patients with mediastinal lymphadenopathy, and it changed the management in 12 of the 17 patients (71 %) with suspected esophageal invasion and in eight of the 17 patients (47 %) with suspected mediastinal disease. CONCLUSIONS: EUS with FNA provides a viable approach to the diagnosis and staging of tumors in the head and neck region when there is a suggestion of esophageal invasion on CT or MRI, or enlarged mediastinal lymph nodes. EUS with FNA may avoid the need for mediastinoscopy or other more invasive techniques for staging of these neoplasms.

Comparison of EUS-guided 19-gauge Trucut needle biopsy with EUS-guided fine-needle aspiration.

BACKGROUND AND STUDY AIMS: The accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) depends on immediate specimen review by a cytopathologist. Stromal tumors, lymphoma, and well-differentiated pancreatic cancer are difficult to diagnose on the basis of cytology alone. To overcome these limitations, a 19-gauge Trucut needle has been developed to obtain histological samples at EUS. This pilot study compares the specimen adequacy and diagnostic accuracy of EUS-guided Trucut needle biopsy (EUS-TNB) with EUS-FNA. PATIENTS AND METHODS: A total of 18 patients underwent EUS-TNB and EUS-FNA. The specimen adequacy and diagnostic accuracy of the two techniques was compared. The technical performance and safety profile of the Trucut needle were also evaluated. RESULTS: The EUS-TNB specimen was adequate for evaluation in 15/18 patients compared with 18/18 with EUS-FNA (83 % vs. 100 %, not significant). The diagnostic accuracy of EUS-TNB was not significantly different from EUS-FNA (78 % vs. 89 %). Two complications were encountered: one patient developed mediastinitis and required surgery; another had immediate bleeding that was managed conservatively. One technical problem was encountered: the Trucut needle failed to deploy after two passes when a gastric stromal cell tumor was being biopsied. CONCLUSION: The diagnostic accuracy of the new EUS-TNB is comparable to that of EUS-FNA. In our experience, the overall efficacy and safety profile of the Trucut needle appears modest.

Critical evaluation of the different staging systems for hepatocellular carcinoma.

BACKGROUND: Diagnostic and therapeutic options for hepatocellular carcinoma (HCC) have improved substantially in recent years. A number of new palliative and potentially curative treatment strategies are now available. However, evaluation of the therapeutic modalities and assessment of the prognosis of HCC remain difficult owing to the lack of consensus on a single staging system and the availability of a number of new staging systems, each claiming to be the most appropriate. METHODS: The most frequently used staging systems for HCC are presented here. Their ability to stratify patients into different treatment groups and to define prognosis are discussed. In addition, the advantages and disadvantages of each system are analysed. RESULTS AND CONCLUSION: None of the currently used staging systems fulfils all the requirements for stratification of patients with HCC into groups of different prognosis and therapeutic recommendations. An international agreement on a single staging system is urgently needed in order to permit comparable randomized clinical trials. Only in this way will the outcome for those with HCC be improved.

[New modalities and concepts in the treatment of hemorrhoids]. / Neues in der differenzierten Behandlung des Hämorrhoidalleidens.

The surgical treatment of haemorrhoids has significantly changed by introducing new techniques in the last years. Nowadays, low grade haemorrhoids, grade II and III, are easily and painfree treatable by a minimal invasive, Doppler transducer guided ligation of the haemorrhoidal arteries. In cases of circular protruding haemorrhoids, grade III and IV; the stapled mucosectomy described by Longo is also a new effective treatment. Both procedures can be performed for an outpatient or with short hospital stay and allows patients to return to work earlier compared to conventional techniques. Additionally, due to the new techniques the treatment of haemorrhoids is less painful and has increased patients' satisfaction. Therefore, the traditional haemorrhoidectomy, the Milligan-Morgan or the Ferguson procedure, has become less common and is only performed in a few special indications.

Influence of naloxone on gastric emptying of solid meals, myoelectrical gastric activity and blood hormone levels in young healthy volunteers.

There is considerable evidence that opioid mechanisms are involved in the mediation of pyloric motor responses that in turn regulate gastric emptying. The purpose of this randomized, placebo-controlled crossover study was to investigate the effect of naloxone on gastric emptying of a solid meal, gastric myoelectrical activity and the postprandial release of gastrointestinal peptides and neuropeptides in 20 healthy volunteers. Naloxone was administered as an intravenous bolus, followed by continuous infusion according to an intravenous dosing nomogram. Gastric emptying time was evaluated by scintigraphy and gastric myoelectrical activity was evaluated by cutaneous electrogastrography. Naloxone did not significantly alter gastric half-emptying time and postprandial dominant gastric electrical frequency compared with placebo. It also did not significantly change the plasma levels of several peptide hormones with the exception of neuropeptide Y, which was significantly increased (P = 0.001). In conclusion, in doses that influence human intestinal motility, naloxone had no effect on gastric motility and release of several peptide hormones in healthy male volunteers. The importance of the isolated increased neuropeptide Y plasma level needs further investigation.

Neoadjuvant and adjuvant therapies for resectable hepatocellular carcinoma (HCC) and palliation strategies.

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver worldwide. The incidence of the tumor varies geographically. Thus, in the eastern area (China, Taiwan, and Japan) there are more than 20 cases per year per 100'000 population compared to less than 5 cases per 100'000 in most western countries [1]. The etiology of HCC is multifactorial. The two most important factors are the presence of cirrhosis and chronic hepatitis [2]. Early detection of HCC still remains a challenge. At the time of diagnosis, only 20-30% of all patients have tumors that are surgically resectable. Survival after curative resection is 30%-50% at five years. The poor outcome of the disease led to the development of different adjuvant and neoadjuvant therapies. There are numerous studies dealing with the treatment of HCC. Unfortunately, only few randomized controlled trials exist. In addition, there is no consensus on staging of HCC and no standardization of the outcome in the literature, which makes it difficult to compare the different procedures. This paper summarizes the current strategies in the treatment of HCC.

[Acute fatty liver in pregnancy: clinical and histopathological course. Case report]. / Akute Schwangerschaftsfettleber: Klinischer und histopathologischer Verlauf. Kasuistik

Acute fatty liver of pregnancy is a rare disease which may be letal if diagnosis is missed. The pathogenesis is not completely clear, but there is some evidence that some cases have been associated with a genetic deficiency of fatty acid beta-oxidation. Other predisposing factors include primiparity, multiple pregnancy, male fetal sex and pre-eclampsia. Clinical presentation and laboratory findings are often unspecific. Increasing serum aminotransferases are characteristic in the early stage of the disease. Liver biopsy establishes the diagnosis and typically shows microvesicular, centrilobular fatty changes of hepatocytes. Differential diagnosis includes the HELLP-Syndrome, cholestasis of pregnancy, pre-eclampsia and viral or drug induced hepatitis. Without adequate treatment liver failure with coagulopathy and encephalopathy may develop. Two cases of acute fatty liver in pregnancy in an early stage are presented. Clinical and histopathological findings as well as diagnostic and therapeutic procedures are discussed.

Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?

BACKGROUND: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.

Overexpression of activin A in stage IV colorectal cancer.

BACKGROUND AND AIMS: Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-beta) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and actRII). METHODS: Expression of inhibin subunits and activin receptors was analysed by northern blot analysis. Inhibin betaA and activin receptor expression were also assessed by use of polymerase chain reaction (PCR). In addition, activin A/inhibin betaA localisation in human colon samples was assessed by immunohistochemistry and in situ hybridisation. RESULTS: Inhibin betaA mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells whereas inhibin betaB and inhibin alpha were below the level of detection. In contrast, all four activin receptors were present in the three cell lines. Colon cancers overexpressed inhibin betaA mRNA in comparison with normal colon, and this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were slightly higher in the normal colon than in cancer tissues. By immunohistochemistry and in situ hybridisation, activin A and inhibin betaA mRNA were present in the mucosal epithelial cells in normal tissues from patients with stage I disease but were either absent or weakly present in normal tissues from patients with stage IV disease. Conversely, they were present at weak to moderate levels in stage I cancers but at high levels in stage IV cancers. CONCLUSIONS: Our findings indicate that activin A is overexpressed in human colorectal tumours, especially in stage IV disease, raising the possibility that activin A may have a role in advanced colorectal cancer.