Lessons learned about appendiceal neuroendocrine neoplasms from data analysis of the Belgian Cancer Registry 2010-2015.

BACKGROUND AND STUDY AIMS: Appendiceal neuroendocrine neo-plasms (aNENs) are a diverse group of malignant neoplasms of varying biological behavior for which information about manage-ment and outcome is sparse, with the majority of available studies being retrospective, including only a limited number of patients, and therefore not necessarily reflecting the reality in the community. In the present study clinical, epidemiological and pathological data of appendiceal neuroendocrine neoplasms in Belgium is provided and compared with current literature. METHODS: A population-based study was conducted by linking data of the Belgian Cancer Registry with medical procedures in the Belgian Health Insurance database for patients diagnosed with aNEN between 2010 and 2015. RESULTS: We found an aNEN incidence of 0.97/100.000 person years in Belgium. Neuroendocrine carcinoma of the appendix are rare. Most appendiceal neuroendocrine tumors (aNETs) are small G1 tumors. Positive lymph nodes are often found in tumors larger than 2cm, especially aNET G2. CONCLUSION: A rapid uptake of changing classifications was seen in the community. However, systematic reporting of risk factors for small aNEN can still be improved and should be stimulated. In 9% of cases, reclassifications had to be made, pointing out that in a retrospective analysis, original pathological reports should be checked for specific parameters, before reliable conclusions can be drawn.

Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

Surveillance recommendations for patients with Lynch syndrome and FAP : a monocentric study.

BACKGROUND AND STUDY AIMS: The most important causes of hereditary colorectal cancer are Lynch syndrome (LS) and the adenomatous polyposis syndromes (familial adenomatous poly- posis syndrome or FAP, attenuated FAP or AFAP and MUTYH associated polyposis syndrome or MAP). The aim of this study was to investigate whether all patients with a hereditary syndrome within one center receive uniform advice regarding surveillance and treatment. PATIENTS AND METHODS: A retrospective analysis was performed of all electronic patient health records of patients with LS, FAP, AFAP and MAP who received genetic counselling or were followed by a health care specialist at the University Hospital in Ghent. RESULTS: Data from 122 patients were collected. For all patients, recommendations from the medical genetics department were highly consistent. Adherence to their recommendations was good within the center for the management of colon polyps. There was a lack of consistency in the screening and surveillance advice for other tumors in departments other than gastroenterology. Only 33 patients had systematic follow-up consultations to check results and organize surveillance. CONCLUSION: Previously, small studies have suggested that patients with hereditary gastrointestinal cancer syndromes infrequently have surveillance as specified in the guidelines. This study shows almost uniform recommendations and good adherence for surveillance of the colon, but incomplete or contradictory advice for surveillance of other organs. The need for an integrated approach from a multidisciplinary team will only increase in the future, because more families with hereditary cancer are likely to be found due to the increased use of next generation sequencing in cancer diagnostics.

The clinical effectiveness of the COPDnet integrated care model.

RATIONALE: Integrated care models have the potential to improve outcomes for patients with COPD. We therefore designed the COPDnet integrated care model and implemented it in two hospitals and affiliated primary care regions in the Netherlands. The COPDnet model consists of a comprehensive diagnostic trajectory ran in secondary care followed by a non-pharmacological intervention program of both monodisciplinary and multidisciplinary components. OBJECTIVE: To assess the clinical effectiveness of the COPDnet integrated care model on health status change in patients with COPD. METHODS: A total of 402 patients with COPD were offered care according to the COPDnet model. At baseline and between 7- and 9-months later health status was measured with the Clinical COPD Questionnaire (CCQ). Primary analysis was carried out for the sample at large. In addition, subgroup analyses were performed after stratification for the type of non-pharmacological intervention where patients had been referred to. RESULTS: The CCQ total score improved statistically significantly from 1.94 ± 1.04 to 1.73 ± 0.96 (P < 0.01) in the 154 patients with valid follow-up measurements. Subgroup analyses revealed significant improvements in the patients receiving pulmonary rehabilitation only. No change in health status was found in patients receiving pharmacotherapy only, carried out self-treatment or who participated in mono-disciplinary primary care offered by allied healthcare professionals. CONCLUSIONS: An improved health status was found in patients with COPD who received care according to the COPDnet integrated care model. Subgroups participating in an interdisciplinary pulmonary rehabilitation program predominantly accounted for this effect.

Update on liver transplantation for cholangiocarcinoma : a review of the recent literature.

Cholangiocarcinoma (CC) represent 3% of all gastrointestinal tumours and can be classified anatomically in 3 types: intrahepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinomas. Resection is the treatment of choice but is only achieved in a few cases (<20%) because of invasion of the biliary tract and/or vascular structures. The outcome of advanced CC is poor with an overall survival (OS) of maximum 15 months with chemotherapy. In the 1990s, CC was regarded as a contraindication for liver transplantation (LT). LT has recently been proposed as potentially curative option for ICC and PCC. Careful patient selection has changed OS. This article provides an update on current status of LT for patients with unresectable CC.

Pooled analysis of the surgical treatment for colorectal cancer liver metastases.

Liver metastases in colorectal cancer patients decreases the expected 5 year survival rates by a factor close to nine. It is generally accepted that resection of liver metastases should be attempted whenever feasible. This manuscript addresses the optimal therapeutic plan regarding timing of resection of synchronous liver metastases and the use of chemotherapy in combination with resection of synchronous metachronous liver metastases. The aim is to pool all published results in order to attribute a level of evidence to outcomes and identify lacking evidence areas. A systematic search of guidelines, reviews, randomised controlled, observational studies and updating a meta-analysis was performed. Data were extracted and analysed. Data failed to demonstrate an effect of timing of surgery or use of chemotherapy on overall survival. Concomitant resection of liver metastases and the primary tumour may result in lower postoperative morbidity. Systemic peri-operative chemotherapy may improve progression free survival compared to surgery alone.

Flow cytometric immunobead assay for fast and easy detection of PML-RARA fusion proteins for the diagnosis of acute promyelocytic leukemia.

The PML-RARA fusion protein is found in approximately 97% of patients with acute promyelocytic leukemia (APL). APL can be associated with life-threatening bleeding complications when undiagnosed and not treated expeditiously. The PML-RARA fusion protein arrests maturation of myeloid cells at the promyelocytic stage, leading to the accumulation of neoplastic promyelocytes. Complete remission can be obtained by treatment with all-trans-retinoic acid (ATRA) in combination with chemotherapy. Diagnosis of APL is based on the detection of t(15;17) by karyotyping, fluorescence in situ hybridization or PCR. These techniques are laborious and demand specialized laboratories. We developed a fast (performed within 4-5 h) and sensitive (detection of at least 10% malignant cells in normal background) flow cytometric immunobead assay for the detection of PML-RARA fusion proteins in cell lysates using a bead-bound anti-RARA capture antibody and a phycoerythrin-conjugated anti-PML detection antibody. Testing of 163 newly diagnosed patients (including 46 APL cases) with the PML-RARA immunobead assay showed full concordance with the PML-RARA PCR results. As the applied antibodies recognize outer domains of the fusion protein, the assay appeared to work independently of the PML gene break point region. Importantly, the assay can be used in parallel with routine immunophenotyping for fast and easy diagnosis of APL.

Second primary malignancies in patients with a gastrointestinal neuroendocrine tumour: a case report and review of the literature.

A second primary malignancy (SPM) is frequently reported in patients with a gastrointestinal neuroendocrine tumour (NET). The majority of SPM are located in the gastrointestinal tract, but malignancies at other sites are described as well. This phenomenon might just be coincidental due to high incidence rates of asymptomatic NET lesions in patients who are operated or who undergo autopsy for another primary malignancy. However, other theories have been developed since the observed incidences rates seem to be double as high as expected. Some authors suggest a common genetic predisposition, while others report tumourigenic properties of various neuroendocrine peptides, including secretin, gastrin and cholecystokinin. This review is illustrated by a case report of a patient in whom the radiological diagnosis of a diffuse liver metastasized adenocarcinoma of the rectum changed dramatically after positron emission tomography and explorative laparoscopy to a curable adenocarcinoma of the rectum with a simultaneous well-differentiated neuroendocrine carcinoma.

Endoscopic treatment of a perforated duodenal diverticulum.

We describe a case of a perforated duodenal diverticulum, which was managed by a combined percutaneous and endoscopic approach. In combination with conservative treatment, this technique can be a challenging alternative to surgery.

Aortic pressure pain: clinical significance. Any relationship to the irritable bowel syndrome?

Pressure pain over the abdominal aorta is a clinical sign of undetermined significance. Ultrasonographic criteria were used to define and further evaluate this variety of epigastric tenderness. The incidence of aortic pressure pain, aortic characteristics, and gastrointestinal symptoms were scored in 250 consecutive patients. The incidence was approximately 7%. All the patients with aortic pressure pain had gastrointestinal symptoms, with a significantly higher mean symptom score. The occurrence of pressure pain was independent of any of the examined aortic characteristics, age, or body mass index. We further compared the incidence of aortic pressure pain between 25 patients with irritable bowel syndrome and 25 patients without apparent functional gastrointestinal disease. It was present in approximately 50% of the patients with irritable bowel syndrome. We found pressure pain over the abdominal aorta to be associated with significant gastrointestinal discomfort. A causal relationship is possible but not proven. Aortic pressure pain can be provoked in a significant subgroup of patients with the irritable bowel syndrome.

A case of Peutz-Jeghers syndrome with nasal polyposis, extreme iron deficiency anemia, and hamartoma-adenoma transformation: management by combined surgical and endoscopic approach.

We report a rare variant of Peutz-Jeghers syndrome identified by the presence of nasal polyposis and extreme anemia. Multiple hamartomatous polyps were found throughout the upper and lower gastrointestinal tract. We conducted a combined surgical-endoscopic approach to prevent the development of a short-bowel syndrome. The polyps removed by snare and surgical polypectomy showed features typical of harmartomas. Three colonic polyps and two nasal polyps showed histological evidence of adenomatous change. This adenomatous change seems to fit into the pathogenic sequence of hamartoma-adenoma.

Infectious gastroenteritis: are they all the same?

Campylobacter jejuni and Salmonella spp are the most frequently cultured micro-organisms in infectious gastroenteritis among patients hospitalized at the departments of gastroenterology and geriatrics. As a whole, the hospitalized patient population with Campylobacter gastroenteritis is a younger one, compared to the Salmonella-infected group. Both pathogens can be associated with a biochemical pancreatitis, which is usually without clinical importance. However, serious complications can occur, with a predominance of visceritis for C. jejuni, and renal function impairment for Salmonella spp. Finally, an asymptomatic carrier state is well known in the Salmonella infection spectrum, whereas C. jejuni might cause a recurrent disease in some patients.

Combined percutaneous balloon dilation and extracorporeal shock wave lithotripsy for treatment of biliary stricture and common bile duct stones.

We report a case of cholangitis, liver abscess, and common bile duct stones in a patient with a benign stricture at a choledochojejunal anastomosis, 3 yr after a complicated duodenohemipancreatectomy. Because surgical reintervention seemed inappropriate, a percutaneous transhepatic balloon dilation was performed after temporary internal-external biliary drainage. Extracorporeal shockwave lithotripsy (ESWL) was successfully applied to fragment all common bile duct stones, with subsequent spontaneous evacuation of all stone fragments through the dilated bilioenteric anastomosis. Only one similar case report has been published before (1), though with a different sequence of therapeutic modalities. Moreover, according to our literature review, this is the first report of ESWL of common bile duct stones by means of the Dornier Compact Lithotriptor (Dornier, Germany) with electromagnetic shockwave source.

Endoscopic drainage of pancreatic pseudocysts.

Endoscopic drainage is a recent method in the management of pancreatic pseudocysts. It has been developed as an alternative to surgical treatment in high risk patients. Our experience with this technique is illustrated by a well documented case report which is followed by a brief review of the literature.

Endoscopic sclerotherapy: the value of balloon tamponade and the importance of disinfection.

Endoscopic sclerotherapy in active variceal bleeding stopped bleeding in 48 out of 67 patients (72%). Survival of the acute bleeding episode was related to liver function: 6% mortality in Child A patients vs. 48% mortality in Child C. Comparing two treatment modalities: 24 h Linton balloon tamponade followed by sclerotherapy vs. sclerotherapy alone, our results in comparable groups slightly, although not significantly, favor tamponade-sclerotherapy treatment: 75% survival vs. 71%. As this treatment modality is more convenient and helps to avoid dangerous aspiration pneumonia, we advocate balloon tamponade prior to sclerotherapy in acute variceal bleeding. In maintenance treatment 65 patients were treated until eradication of varices. The rebleeding risk was 0.034% per patient per month, with 64% of the rebleeding within the 2 first months before complete eradication of the varices. The long-term survival depends largely on liver function: one year survival of 88% in Child A vs. 30% in Child C. Using Aethoxysklerol 1% in intravariceal injection, no stricture occurred. Using a sterile injection needle and a glutaraldehyde-disinfected endoscope, no infectious complications directly related to the procedure occurred, and all hemocultures remained negative.