18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

PURPOSE: Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. METHODS: PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. RESULTS: Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUVmax ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUVmax cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. CONCLUSION: 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

Transcatheter arterial embolization is the first-line therapy of choice in peptic ulcer bleeding not responding to endoscopic therapy.

OBJECTIVE: In 5-10% of patients with peptic ulcer bleeding (PUB) it is impossible to achieve endoscopic hemostasis because of severe bleeding. These patients have traditionally been treated surgically. Transcatheter arterial embolization (TAE) may, however, be associated with a better outcome because of the less-invasive nature of the procedure. The aim of the present study was to identify the treatment of choice in endoscopy-refractory PUB. MATERIALS AND METHODS: A retrospective study. Consecutive patients treated with surgery or TAE for endoscopy-refractory PUB during a period of 16 years at a university hospital were included. Primary hemostasis, rebleeding rate, mortality, and complications were assessed. Mortality was compared between groups after adjustment for age, comorbidity, and anemia using logistic regression analyses. Comorbidity was quantified using the Charlson comorbidity index (CCI). RESULTS: One hundred and eighteen patients were included. Patients treated with TAE had a higher CCI (mean: 2.33 vs 1.42; p = .003), and more severe anemia (mean: 6.8 vs 7.9 g/dl; p = .007) compared with patients treated with surgery. Surgery was associated with a higher rate of primary hemostasis (100% vs 91%; p = .007), lower rate of rebleeding (15% vs 40%; p = .004) but also higher rate of complications (60% vs 38%; p = .02) than TAE. Surgery was associated with an increased mortality (Odds ratio: 3.05; p = .033) when adjusting for confounding factors and excluding patients (n = 3) who were not candidates for both interventions. CONCLUSIONS: We propose use of TAE as first-line therapy in these patients as it may be associated with lower mortality and lower rate of complications compared with surgery.

The effect of exogenous GLP-1 on food intake is lost in male truncally vagotomized subjects with pyloroplasty.

Rapid degradation of glucagon-like peptide-1 (GLP-1) by dipeptidyl peptidase-4 suggests that endogenous GLP-1 may act locally before being degraded. Signaling via the vagus nerve was investigated in 20 truncally vagotomized subjects with pyloroplasty and 10 matched healthy controls. Subjects received GLP-1 (7-36 amide) or saline infusions during and after a standardized liquid mixed meal and a subsequent ad libitum meal. Despite no effect on appetite sensations, GLP-1 significantly reduced ad libitum food intake in the control group but had no effect in the vagotomized group. Gastric emptying was accelerated in vagotomized subjects and was decreased by GLP-1 in controls but not in vagotomized subjects. Postprandial glucose levels were reduced by the same percentage by GLP-1 in both groups. Peak postprandial GLP-1 levels were approximately fivefold higher in the vagotomized subjects. Insulin secretion was unaffected by exogenous GLP-1 in vagotomized subjects but was suppressed in controls. GLP-1 significantly reduced glucagon secretion in both groups, but levels were approximately twofold higher and were nonsuppressible in the early phase of the meal in vagotomized subjects. Our results demonstrate that vagotomy with pyloroplasty impairs the effects of exogenous GLP-1 on food intake, gastric emptying, and insulin and glucagon secretion, suggesting that intact vagal innervation may be important for GLP-1's actions.

Combined pretherapeutic endoscopic and laparoscopic ultrasonography may predict survival of patients with upper gastrointestinal tract cancer.

BACKGROUND: The combination of endoscopic and laparoscopic ultrasonography (EUS-LUS) is accurate for resectability assessment of patients with upper gastrointestinal cancer (UGIC). But neither the ability of EUS/LUS to predict long-term prognosis nor the potential impact on patient survival using this selection strategy has been investigated. This prospective, single-center study evaluated whether pretherapeutic EUS-LUS stratification related to the prognosis in UGIC patients and whether patient selection by this strategy provided a prognostic outcome comparable with survival data from the literature. METHODS: Each patient had a pretherapeutic tumor node metastasis (TNM) stage and a resectability assessment assigned based on EUS-LUS findings. Survival curves were constructed and compared for each of the EUS-LUS TNM stage and resectability groups at the end of the observation period. Finally, the R0 resection rate, median, and 5-year survival rates were compared with the literature. RESULTS: This study enrolled 936 consecutive patients with esophageal (n = 256), gastric (n = 273), or pancreatic (n = 407) cancer. A statistically significant survival difference (p < 0.01) between the different TNM stages and resectability groups predicted by EUS-LUS was observed regardless of the cancer type. The poor prognosis for the patients with irresectable or disseminated UGIC was accurately predicted by EUS and LUS. The R0 resection rate as well as the median and 5-year survival rates were comparable with data from the literature. CONCLUSION: The pretherapeutic EUS-LUS patient stratification related significantly to the final prognosis for UGIC patients. An EUS-LUS-based patient selection strategy seemed to provide a prognostic outcome similar to data from computed tomography (CT)-based populations.

Laparoscopic ultrasound-guided biopsy in upper gastrointestinal tract cancer patients.

BACKGROUND: Noninvasive pretherapeutic staging may be supplemented with laparoscopy and laparoscopic ultrasonography (LUS) in order to detect minute liver metastases, carcinosis or other signs of nonresectable or disseminated disease in patients with upper gastrointestinal tract cancer (UGIC). The aim of this study was to evaluate the use, potential clinical gain, and safety profile of LUS-guided biopsy in patients with UGIC. METHODS: A prospective consecutive study on LUS-guided biopsy in patients referred with UGIC between May 2007 and May 2008 was carried out. Previous noninvasive imaging methods had found no signs of disseminated disease. Laparoscopic or LUS-guided biopsies were only performed if a malignant result would change patient management. RESULTS: Two hundred and nine patients entered the study and, based on predefined biopsy indications, laparoscopy and LUS-guided biopsies changed patient management in a total of 27.3% (54/198) of the patients with a final malignant diagnosis. There were no complications. Liver and pancreas were the main target areas for LUS-guided biopsies, and more than half of the biopsies (55%) were taken from the primary tumor where other modalities had failed to obtain proof of malignancy. Twenty-six percent of biopsies were taken from a suspected metastatic lesion not seen before, whereas 19% were taken from previously suspected metastases where other imaging modalities had failed to obtain proof of malignancy. CONCLUSION: LUS-guided biopsy is a safe procedure which in combination with laparoscopic biopsies had an impact on patient management in one-quarter of UGIC patients.

Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty.

OBJECTIVE: Glucagon-like peptide 1 (GLP1) is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), but may interact with vagal neurons at its site of secretion. We investigated the role of vagal innervation for handling of oral and i.v. glucose. DESIGN AND METHODS: Truncally vagotomised subjects (n=16) and matched controls (n=10) underwent 50 g-oral glucose tolerance test (OGTT)±vildagliptin, a DPP4 inhibitor (DPP4i) and isoglycaemic i.v. glucose infusion (IIGI), copying the OGTT without DPP4i. RESULTS: Isoglycaemia was obtained with 25±2 g glucose in vagotomised subjects and 18±2 g in controls (P<0.03); thus, gastrointestinal-mediated glucose disposal (GIGD) - a measure of glucose handling (100%×(glucoseOGTT-glucoseIIGI/glucoseOGTT)) - was reduced in the vagotomised compared with the control group. Peak intact GLP1 concentrations were higher in the vagotomised group. Gastric emptying was faster in vagotomised subjects after OGTT and was unaffected by DPP4i. The early glucose-dependent insulinotropic polypeptide response was higher in vagotomised subjects. Despite this, the incretin effect was equal in both groups. DPP4i enhanced insulin secretion in controls, but had no effect in the vagotomised subjects. Controls suppressed glucagon concentrations similarly, irrespective of the route of glucose administration, whereas vagotomised subjects showed suppression only during IIGI and exhibited hyperglucagonaemia following OGTT. DPP4i further suppressed glucagon secretion in controls and tended to normalise glucagon responses in vagotomised subjects. CONCLUSIONS: GIGD is diminished, but the incretin effect is unaffected in vagotomised subjects despite higher GLP1 levels. This, together with the small effect of DPP4i, is compatible with the notion that part of the physiological effects of GLP1 involves vagal transmission.

[Congenital hyperinsulinism--diagnosis and treatment]. / Kongenit hyperinsulinisme--diagnostik og behandling.

Congenital hyperinsulinism (CHI) is a rare and heterogeneous disease with a challenging diagnostic process and a need of individualised treatment of each patient. In severe, neonatal or infant CHI, differentiation between the focal and diffuse form by rapid genetics, 18F-fluoro-L-dihydroxyphenylalanine positron emission tomography/computed tomography and peroperative microscopy of frozen section allows surgeons to resect the focal lesion instead of performing subtotal pancreatectomy. Milder CHI, sometimes difficult to diagnose, is treated conservatively. In spite of all improvements, cerebral complications are still frequently seen.

[Surgical treatment for locally advanced pancreatic cancer]. / Kirurgisk behandling ved lokalavanceret pancreascancer.

Treatment of patients with locally advanced pancreatic cancer remains a challenge, and the exact role of surgery with vascular resection remains unclear. Several studies on selected patient populations have addressed the problem, but with varying results. Although venous resection may be performed without increased morbidity and mortality, the majority of studies found no improved long-term survival when compared to oncological treatment.

[Prognosis following curative resection of the upper gastrointestinal tract cancer]. / Prognosen efter kurativ resektion af øvre gastrointestinal cancer.

INTRODUCTION: Cancer in the upper gastrointestinal tract has a poor prognosis and the best results are obtained by the few resectable patients. Earlier studies indicated that Danish survival might be inferior to that of other Scandinavian countries. The aim of this study was to evaluate the long-term survival after curative resections for these patients. MATERIAL AND METHODS: All patients referred for treatment of cancer of the oesophagus, stomach or pancreas were prospectively included. Data were registered with regard to pre-therapeutic examination and operative results. Deceased patients were found by comparison with the Danish Central Personal Register in January 2007. RESULTS: A total of 398 patients were included, of whom 164 were found to be possibly resectable. In total 118 (30%) patients underwent complete surgical resection. The median survival period for patients with oesophageal cancer, stomach cancer and pancreatic cancer was: 22.7 months (18.7-39.4), above 36 months and 31.4 months (19.2-) respectively. The observed 3-year survival was 40% (26-53), 56% (38-71) and 47% (31-62). The estimated 5-year survival was 35% (22-48), 56% (39-72), 43% (27-59). CONCLUSION: The observed long-term survival was comparable to international results. However, only one third of the patients were eligible for complete surgical resection. It is therefore important to establish a close cooperation between surgeons and oncologist to improve the overall survival for this group of patients.

Rapid genetic analysis in congenital hyperinsulinism.

BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.

[Tumor-induced colocolonic invagination in an adult]. / Tumorinduceret kolokolisk invagination hos en voksen.

A case of colocolonic invagination is presented. The mass was palpated preoperatively and diagnosed by barium enema X-ray and ultrasound. Operation confirmed the diagnosis and demonstrated a coecum tumor. The patient was treated successfully with a right hemicolectomy.

[Gallstones in children]. / Galdesten hos børn.

Children of all ages may develop gallstones. Ultrasonography is the diagnostic method of choice if gallstones are suspected. In children having gallstones diagnosed as a result of ultrasonography carried out due to different indication expectant treatment is recommended. Children presenting with typical clinical signs of gallstone colic need an operation. Laparoscopic cholecystectomy is the recommended choice, as data are lacking on the risk of recurrence of gallstones after cholecystolithotomy. Postoperative complications are few in otherwise healthy children.