Pancreatectomies for pancreatic neoplasms in pediatric and adolescent age: A single institution experience.

BACKGROUND: There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth. METHODS: This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017. RESULTS: Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3-15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection. CONCLUSIONS: In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant.

A 10-year study of rendezvous intraoperative endoscopic retrograde cholangiography during cholecystectomy and the risk of post-ERCP pancreatitis.

BACKGROUND: Rendezvous intraoperative endoscopic retrograde cholangiography (RV-IOERC), also called guidewire-facilitated IOERC, is one of the single-stage options available for managing common bile duct stones (CBDS) during laparoscopic cholecystectomy. The objective of this study is to investigate procedure-related complications in IOERC patients and stone clearance. METHODS: All patients who underwent IOERC between January 2000 and December 2009 were identified from the local registry of Karolinska University Hospital in Huddinge. Medical charts and ERC reports were studied, and descriptive statistics were obtained. Outcomes were procedure-related complications, especially post-ERCP pancreatitis (PEP), stone clearance, and mortality. RESULTS: 307 patients were identified. In 264 of the patients, the rendezvous cannulation technique was successful (86 %); in the remaining 43 patients, conventional cannulation technique was necessary. In total, PEP occurred in seven patients (2.28 %). One of the PEP patients was in the rendezvous cannulated group (0.37 %), whereas six patients developed PEP in the nonrendezvous group (13.95 %, p < 0.001). The primary stone clearance rate was 88.27 % (271/307). There was no mortality within 90 days in the series. CONCLUSIONS: IOERC with RV cannulation technique for management of CBDS during laparoscopic cholecystectomy has a low PEP rate and a high stone clearance rate, making it a safe and feasible method for removing CBDS. However, the technique requires logistics to perform IOERC in the operating theater. The present data suggest that IOERC with RV cannulation is superior to conventional cannulation with respect to risk of PEP.

Food intake and meal pattern in IAPP knockout mice with and without infusion of exogenous IAPP.

OBJECTIVE: The current study used islet amyloid polypeptide (IAPP) knockout mice (KO mice) to investigate the physiological role of IAPP in the regulation of food intake (FI). MATERIAL AND METHODS: FI and body weight were measured in KO and wild-type (WT) mice for 27 weeks. In an additional short-term experiment, IAPP (25 pmol·kg(-1)min(-1)) was infused subcutaneously for 3 days in KO and WT mice, and FI, meal pattern, and body weight were analyzed. RESULTS: In the long-term experiment, no significant differences in body weight were seen between WT and KO mice at any point. FI, meal number, and meal size did not differ significantly between the groups in any of the five selected weeks that were studied. In the short-term experiment, FI decreased significantly during IAPP infusion in both WT and KO groups. FI was significantly lower in the KO mice compared with WT on days 1 and 2 (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: The data showing no differences in FI and body weight were seen between KO and WT mice, indicating that FI can be controlled in the absence of IAPP. The more marked anorectic effect seen in the KO mice during IAPP infusion suggests that IAPP receptors and/or IAPP post-receptor signaling pathways are up-regulated in mice lacking endogenous IAPP.

Management of alcohol use disorders in patients with chronic pancreatitis.

CONTEXT: The outcome of treatment for patients with chronic pancreatitis may be improved by multidisciplinary management. OBJECTIVE: To study patients with chronic pancreatitis, especially regarding alcohol use, within a multi disciplinary program. MAIN OUTCOME MEASURES: Prospective assessment at baseline and follow-up of alcohol use disorders using DSM-IV criteria, AUDIT score, interview-based quantification of alcohol intake and the biomarker for alcohol use s-CDT in patients referred because of chronic pancreatitis together with retrospective classification with the M-ANNHEIM risk factor analysis and severity scoring for chronic pancreatitis. RESULTS: Sixty patients (95%) of 63 consecutively included patients were classified as having chronic pancreatitis. Forty-four of these (73%) were available for follow-up evaluation, which took place after a minimum of 1 year (median 3 years). Alcohol consumption decreased at follow-up and no patients had ongoing alcohol dependence (P<0.001) as compared to 10 (23%) at initial evaluation. Patients with harmful alcohol use (AUDIT score ≥8 points) and pathological s-CDT had a reduction in both parameters (P=0.004 and P=0.060, respectively). Pain score according to M-ANNHEIM was unchanged, whereas use of analgesics decreased (P=0.005). CONCLUSIONS: This feasibility study of patients with chronic pancreatitis demonstrated that multidisciplinary management seems to give a positive and sustainable effect on alcohol abuse and may be a useful concept for optimal classification, selection and treatment of patients with chronic pancreatitis.

Continuous assessment of intrahepatic metabolism by microdialysis during and after portal triad clamping.

BACKGROUND: Ischemia-reperfusion injury is a major concern with portal triad clamping (PTC) in liver surgery. Microdialysis allows continuous intraoperative monitoring of tissue metabolism in the liver. Our aim was to evaluate the feasibility of microdialysis as a tool to assess the intrahepatic metabolic effects of PTC in patients undergoing liver resection. METHODS: Eleven patients who underwent liver resection were subjected to intrahepatic microdialysis. Dialysis fluid samples were collected before, during, and after a 20-min period of PTC. Glucose, lactate, pyruvate (markers of ischemia), and glycerol (marker of cell membrane damage) were analyzed and the lactate/pyruvate ratio was calculated. RESULTS: During PTC, intrahepatic glucose, lactate, and glycerol increased from 9.1±2.2 to 14.5±2.4 mM, from 2.2±0.3 to 5.8±0.5 mM, and from 63±14 to 142±28 µM, respectively. Pyruvate was unchanged, resulting in an increased lactate/pyruvate ratio (from 39±10 to 104±32). During initial reperfusion, glucose further increased to 16.4±2.9 mM. Pyruvate increased after reperfusion (from 93±18 to 138±23 µM), while lactate was stable, resulting in a normalized lactate/pyruvate ratio. Glycerol continued to increase during initial reperfusion. CONCLUSIONS: PTC was associated with considerable intrahepatic metabolic alterations with anaerobic metabolism, increased glycogenolysis, and cellular membrane damage resulting in increased levels of glucose, lactate, glycerol, and lactate/pyruvate ratio. Microdialysis is easy to use and allows continuous monitoring of intrahepatic metabolism during liver surgery.

PP56 improves energy homeostasis in a mouse model of pancreatic cancer.

In this study, we investigated whether the anti-inflammatory drug PP56 (alpha-trinositol) may improve cancer-induced metabolic disorders. We implanted human MiaPaCa2 pancreatic cancer cells in the pancreas of 14 athymic mice for 12 weeks, using six intact littermates as normal controls. During the 12 weeks, seven tumor-cell recipients were treated with PP56 by daily injection (PPT mice). The tumor-cell recipients that were otherwise untreated were used as tumor controls (TC mice). Impaired glucose tolerance and decreased body weight gain were seen in TC but not PPT mice. When an enzyme for fatty acid beta-oxidation namely medium-chain acyl-CoA dehydrogenase (MCAD) was determined in tumor grafts; tumors from PPT mice showed more MCAD than those from TC mice. This suggests that PP56 stimulated fatty acid beta-oxidation in MiaPaCa2 cells in vivo. In keeping with this notion, PPT mice had decreased plasma free fatty acids. In vitro, we demonstrated that MiaPaCa2 cells consumed more fatty acids in the presence of PP56. In another experiment, we infused PP56 or vehicle in normal mice and found that PP56 decreased circulating glucose in the animals. We also showed that PP56 increased glucose transport in L6 skeletal muscle cells in vitro. In conclusion, PP56 increases the turnover of circulating nutrients such as glucose and helps maintain energy homeostasis in mice with pancreatic cancer.

Pancreatic duct changes are not associated with early signs of chronic pancreatitis at magnetic resonance imaging (MRI) in patients with primary sclerosing cholangitis.

OBJECTIVE: The association between chronic pancreatitis (CP) and primary sclerosing cholangitis (PSC) has been reported previously. The aims of the present study were to evaluate the presence of early pancreatic abnormalities and duct changes, using MRCP/MRI in PSC and to evaluate possible risk factors for these changes and their clinical importance. MATERIALS AND METHODS: One hundred and three patients with PSC were identified among all MRI liver/pancreas referrals in 2001-2005. MRCP was used to grade pancreatic duct changes in three groups: grade 0 (normal), grade 1 (mild) and grade 2 (severe). For detection of early MRI signs of CP, the pancreas-spleen signal intensity ratio (SIR), the arterial and early venous phase ratio (A/PV ratio) and the age-related size of the pancreas were evaluated. RESULTS: Pancreatic duct changes were found in 24% of the PSC patients. The pancreatic duct changes were associated with extrahepatic biliary involvement and long duration of PSC but not associated with pancreas-spleen SIR, A/PV ratio, pancreas size, previous post-ERCP or acute pancreatitis. Severe pancreatic duct changes were significantly associated to abdominal pain. Clinically significant CP was seen in one PSC patient (1%). CONCLUSIONS: Pancreatic duct changes are associated with extrahepatic bile duct strictures and not with the early MRI signs of CP. Therefore, pancreatic duct changes seem to be part of the spectrum of PSC and should not be defined as CP. Pancreatic duct changes are of limited clinical importance but may contribute to abdominal pain in PSC.

Diffusion-weighted magnetic resonance imaging of pancreas tumours.

The purpose of this study was to evaluate the accuracy of diffusion-weighted imaging (DWI) in diagnosis of pancreas cancer, to compare DWI with a conventional comprehensive MRI (MRI-c) and to analyse apparent diffusion coefficient (ADC) values of lesions. Thirty-six patients with pancreatic lesions (12 malignant and 24 benign) and 39 patients without lesions were included. MRI-c and DWI (free breathing, b values 0 and 500 s/mm(2)) were performed prospectively and consecutively in a 1.5-T system. The analysis was retrospectively performed blinded by two radiologists in consensus. The sensitivity, specificity, accuracy, and positive and negative predictive values of DWI and MRI-c were 92, 97, 96, 85, 98% and 100, 97, 97, 86, 100%, respectively. Mean ADC values of malignant lesions were significantly lower than those of benign lesions. DWI has a similar accuracy to MRI-c in diagnosis of pancreas cancer.

An experimental model of intestinal resection and compensated non-hypotensive blood loss.

BACKGROUND: Massive hemorrhage results in hypovolemia and hypotension that activate the sympathetic-adrenal-system, the hypothalamic-pituitary-adrenal axis, and induce metabolic changes such as hyperglycemia. Blood loss during surgery, however, is rapidly compensated by intravenous fluids to minimize negative impact on circulation. The aim of this study was to develop an experimental model for studies of the stress response and metabolic alterations seen after major abdominal surgery by combining intestinal resection with compensated non-hypotensive blood loss. MATERIAL AND METHODS: Intestinal resection in the rat was combined blood loss (7% and 16% of total blood volume) with subsequent fluid replacement (2 x volume of saline + hydroxyethyl starch, 50:50) to investigate the effects on blood pressure, plasma adrenaline, noradrenaline (0-2 h postoperatively), glucose, insulin, corticosterone, and hematocrit (0-24 h postoperatively). RESULTS: Surgical trauma alone or in combination with blood loss and fluid replacement did not decrease mean arterial blood pressure (MAP) compared with anesthetized controls. Plasma levels of catecholamines were unchanged during the period of blood loss. After surgery and blood loss, plasma glucose showed a blood loss volume-dependent increase up to 12 h postoperatively compared to surgery alone (P < 0.001-0.05). Plasma corticosterone increased after surgery alone and in combination with blood loss but the changes were not dependent on the magnitude of blood loss. CONCLUSIONS: Surgical trauma combined with compensated non-hypotensive blood loss induced persistent volume-dependent hyperglycemia that did not depend on changes in plasma corticosterone and, in the early postoperative phase, MAP and catecholamines. Our data indicate that blood loss per se, without causing hypotension or acute elevations in catecholamines, can induce marked postoperative hyperglycemia. The experimental model presented in this report will be a useful tool to further elucidate mechanisms underlying the changes in glucose metabolism seen after surgical injury.

Mechanism of increased lipolysis in cancer cachexia.

Loss of fat mass is a key feature of cancer cachexia and has been attributed to increased adipocyte lipolysis. The mechanism behind this alteration is unknown and was presently investigated. We studied mature s.c. fat cells and differentiated preadipocytes from 26 cancer patients with and without cachexia. Hormone-induced lipolysis and expression of lipolysis-regulating genes were determined together with body composition and in vivo lipolytic activity (fasting plasma glycerol or fatty acids related to body fat). Body fat was reduced by 40% and in vivo lipolytic activity was 2-fold increased in cachexia (P = 0.001). In mature adipocytes, the lipolytic effects of catecholamines and natriuretic peptide were 2- to 3-fold increased in cachexia (P < 0.001). This was completely counteracted by inhibiting the rate-limiting lipolysis enzyme hormone-sensitive lipase (HSL). In cachexia, the expression levels of HSL mRNA and protein were increased by 50% and 100%, respectively (P = 0.005-0.03), which strongly correlated with in vitro lipolytic stimulation (r = 0.7-0.9). The antilipolytic effect of insulin in mature fat cells and the stimulated lipolytic effect in differentiated preadipocytes were unaltered in cachexia. Patients who lost weight due to other factors than cancer cachexia had no change in adipocyte lipolysis. In conclusion, adipocyte lipolysis is increased in cancer cachexia not due to nonepigenic factors or to weight loss per se, but most probably because of enhanced expression and function of adipocyte HSL. The selective inhibition of this enzyme may prevent fat loss in cancer patients.