Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs).

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

Alpha-fetoprotein and human chorionic gonadotrophin-beta as prognostic markers in neuroendocrine tumour patients.

Serum chromogranin A is the most useful general and prognostic tumour marker available for neuroendocrine tumour (NET) patients. The role of other tumour markers is less clear. In order to determine the diagnostic and prognostic value of serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin-beta (hCGbeta) in NETs, a database containing biochemical, histological, and survival data on 360 NET patients was constructed. This data was statistically assessed, using Statistical Package for the Social Sciences, to determine the utility of commonly measured tumour markers with particular emphasis on AFP and hCGbeta. Alpha-fetoprotein and hCGbeta were raised in 9.5 and 12.3% of patients respectively and jointly raised in 9.1% of patients in whom it was measured. Alpha-fetoprotein levels associated strongly and positively with tumour grade, serum CgA and hCGbeta levels, and worse survival. Human chorionic gonadotrophin-beta levels also associated strongly and positively with serum CgA and AFP levels, and worsening survival. Alpha-fetoprotein and hCGbeta are elevated in high-grade NETs, with a rapidly progressive course and poorer survival. They also correlate with chromogranin-A, which is known to be a marker of tumour burden and to have prognostic value. Thus AFP and hCGbeta are clinically important in NETs and when elevated are poor prognostic markers.

A review of thymic tumours.

Tumours of the thymus are uncommon and are generally regarded as being indolent. Whilst this is often true of thymomas; thymic adenocarcinoma and thymic neuroendocrine cancer can be aggressive and have a poor prognosis. Understanding the biology of these tumours is important for prognosis and management. The pathological features of these tumours are examined in detail. Imaging modalities for aiding in diagnosis and staging of these tumours are described; this includes CT and MRI, plus more recent advances including the use of FDG-PET and Indium-111 Octreotide scintigraphy. The treatment options available including curative surgery, debulking surgery, chemotherapy, somatostatin analogues and peptide receptor radionuclide therapy are discussed. The optimal chemotherapy regimens are still unclear, although promising results have been obtained with platinum-based chemotherapy. The role for adjuvant therapy in both thymic carcinoma and thymoma is unclear except, in patients with stage I thymomas. There is a high expression of somatostatin receptors in thymic tumours and anti-tumour benefit has been reported in patients treated with somatostatin analogues. A new development is the role of peptide receptor radionuclide therapy. This has become an established therapy in management of gastroenteropancreatic neuroendocrine tumours and its use has been recently described in case reports in both thymoma and thymic carcinoma.

Lung scintigraphy with nonspecific human immunoglobulin G ((99m)Tc-HIG) in the evaluation of pulmonary involvement in connective tissue diseases: correlation with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT).

PURPOSE: In patients with connective tissue diseases (CTD), the early detection and evaluation of the severity of the pulmonary involvement is mandatory. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are considered to be valuable noninvasive diagnostic modalities. Radiopharmaceuticals have also been used for this purpose. Our aim was the evaluation of technetium-labeled human polyclonal immunoglobulin G (HIG) lung scintigraphy in the early detection and assessment of the severity of the pulmonary involvement in CTD patients. METHODS: Fifty-two nonsmoking CTD patients were studied by PFTs, HRCT, and HIG. According to PFTs, patients were divided in group A (impaired PFTs-abnormal pulmonary function) and group B (normal pulmonary function). Semiquantitative analysis was done on HIG and HRCT and corresponding scores were obtained. RESULTS: Significant difference was found between HIG scores in the two groups (0.6 +/- 0.07 vs 0.51 +/- 0.08, P < 0.001). There was a statistically significant negative correlation between HIG scores and PFTs results and a positive correlation between HIG and HRCT scores. HIG demonstrated similar clinical performance to HRCT. At the best cut-off levels of their score (0.56 and 7, respectively), HIG had a superior sensitivity (77.5 vs 57.5%) with lower specificity (75 vs 91.7%). The combination of the two methods increased the sensitivity of abnormal findings at the expense of specificity. CONCLUSIONS: HIG scintigraphy can be used in the early detection and evaluation of the severity of the pulmonary involvement in CTD, whereas, when used in combination with HRCT, the detection of affected patients can be further improved.

Multimodality treatment of neuroendocrine tumors of the thymus.

BACKGROUND: Neuroendocrine tumors of the thymus are rare neoplasms. Four patients with this tumor who underwent multimodality treatment are presented and the literature is briefly reviewed. METHODS: The medical records of all patients treated for neuroendocrine tumors of the thymus from 1979 to 2002 were reviewed. Tumors were classified using a slight modification of the World Health Organization criteria. RESULTS: The patients' median age was 38 years. All patients underwent extensive excision of the tumor. Histological diagnosis was atypical carcinoid (2), typical carcinoid (1), and small cell carcinoma (1). All patients developed recurrence(s). One patient died 132 months after diagnosis. The remaining three patients are alive with no symptoms at 135, 99, and 35 months, respectively, after diagnosis. Two patients with recurrences have been on treatment with Octreotide LAR with satisfactory results. One patient is free of disease. CONCLUSIONS: Neuroendocrine tumors of the thymus are potentially aggressive tumors. Radical resection is the treatment of choice. The encouraging results obtained by administration of Octreotide LAR in two of our patients warrant further investigation.

Carcinoid tumors of the appendix. Prognostic factors and evaluation of indications for right hemicolectomy.

BACKGROUND/AIMS: Carcinoid tumors of the appendix are thought to be the most common type of appendiceal neoplasms. Although the vast majority of appendiceal carcinoids behave in a benign fashion, they are considered malignant because they all have the potential for invasion, metastasis and production of physiologically active substances. The aim of our study is to evaluate the gravity of the prognostic factors and the indications for extended surgical treatment. METHODOLOGY: Twenty-four patients, six male (aged from 18 to 59 years) and eighteen female (aged from 16 to 27 years) are included in our study. All these patients were managed and followed-up in our section during the last 17 years (follow-up range 10-17 years). Following confirmation of the diagnosis, secretion of 5-HLAA (5-Hydroxy-Inndole-Acetic Acid) was measured after a 24-hour collection of urine. Moreover, ultrasound (US) examination of the liver and computerized tomography (CT) scanning of the upper abdomen were performed after the operation in all patients. Also, patients with tumor size more than 1cm underwent a Somatostatin Receptor Scintigraphy (Octreoscan). The follow-up data of all patients included measurement of 5-HLAA and US examination every six months. RESULTS: The most common site for the tumors was the tip of the appendix (18/22). In the rest of the cases, the neoplasms were located in the base (4/22) and in the body (2/22), while in one patient the mesoappendix was invaded. In sixteen patients the tumor size was less than 1cm, in seven patients the tumor diameter was measured to be 1 to 2cm and in one patient the tumor was 3cm. Most of our patients (16/22) underwent only an appendicectomy, while in the rest of them (in the patients with tumor size between 1-2cm and in the patient with invasion of mesoappendix) a right hemicolectomy was performed. No patient was found to have metastatic disease during the operation, while the patient with invasion of the mesoappendix developed metastases in the lung, two years after the operation. CONCLUSIONS: Carcinoid tumors of the appendix, in most cases, are found incidentally during appendicectomies, especially in young females and usually are less than 1cm in size, which is probably the reason of the absence of metastases in all cases. Histological examination and size of the tumor are important factors that contribute to the selection of the surgical treatment and both must be estimated by the surgeons to make the final choice.

Replacement of the pyloric sphincter with the ileocecal valve: an experimental study.

BACKGROUND: Several surgical methods have been devised and applied to overcome the complications associated with the loss of the pyloric sphincter after distal gastrectomy. However, none of these methods creates an efficient sphincteric mechanism at the anastomotic site. The purpose of this experimental study in dogs was to replace the pylorus with the ileocecal valve and determine whether its sphincteric function would be preserved in its new location without affecting gastrointestinal motility and the health of the animals. METHODS: Thirteen dogs underwent surgical removal of the pyloric sphincter and a partial distal gastrectomy. The ileocecal valve, with a short segment of ileum, was then relocated so that the ileal segment was anastomosed to the stomach while the cecal segment was anastomosed to the duodenum. Intestinal continuity was reestablished by anastomosing the distal ileum with the ascending colon. Intraileal and intracolic pressures were measured in all animals prior to and following transposition of the ileocecal valve. In 3 of these animals, pre-pyloric (intragastric) and post-pyloric (intraduodenal) pressures were also measured before the pylorus was removed. Pressure measurements on both sides of the transposed ileocecal valve were performed again 4-6 months later. All pressure measurements were made directly with a water manometer. Radiographic and fluoroscopic studies were carried out on all animals to assess gastrointestinal motility, gastric emptying times, and the sphincteric competence of the transposed ileocecal valve. Hematological and biochemical studies intended to assess the nutritional status of all animals were carried out. Also, postoperative measurements were made of gastric basic acid output. RESULTS: All animals were alive and well 4-6 months after the initial operative procedure. Hematological studies and biochemical tests and studies of liver function remained normal. There was a slight reduction in serum B12 levels and, as expected, a significant postoperative reduction in gastric basic acid output. The intraluminal pressure measurements and the radiographic and fluoroscopic studies all showed that the sphincteric mechanism of the ileocecal valve was preserved in its new location, that gastrointestinal motility was not impaired, and that the healthy condition of the animals was maintained. Gross and histological examination of the transposed segments of the intestinal tract did not reveal any abnormalities. CONCLUSION: Because the anatomy and physiology of the human alimentary tract are similar to those of the dog, this technique may be applicable clinically, when indicated, to avoid and/or relieve complications resulting from gastrectomy, when those complications do not respond or have not responded to conservative management.

Use of the pylorus for preventing ileostomy complications. An experimental canine study.

PURPOSE: Conventional ileostomy, as it is well known, presents with persistent watery diarrhea, among other complications. The present-day modified methods of conventional ileostomy cannot effectively prevent these unpleasant consequences. The purpose of this study was to try to use the sphincter mechanism of the pylorus in ileostomy in dogs experimentally to prevent the above symptoms. METHOD: Following a highly selective vagotomy, the antrum with the pylorus and a 3-cm segment of the duodenum were separated from the gastrointestinal tract along with its vasculature and innervation, and the distal duodenal end was closed. Then, the terminal loop of ileum (before an ileostomy was performed) was dissected, and the distal segment was anastomosed with the proximal end of duodenum; the proximal segment of this loop was anastomosed with the stump of the antrum. The gastrointestinal continuity was established by anastomosis of the gastric stump to the first loop of the jejunum. RESULTS: After the procedure, the sphincter mechanism of the pylorus was preserved, and bowel movements became solid and infrequent, so a colostomy bag could be applied consistently. CONCLUSIONS: Similarity of anatomy and physiology of the alimentary tract in dogs and human favors possible application of this procedure to humans, with better results than with conventional ileostomy.