Olivier Corcos

Tube Feeding Improves Intestinal Absorption in Short Bowel Syndrome Patients

BACKGROUND & AIMS Tube feeding, recommended for patients with short bowel syndrome in only the postoperative period, has not been compared with oral feeding for absorption. We studied whether tube feeding increased absorption in patients with short bowel syndrome following the postoperative period. METHODS A randomized crossover study compared absorption between isocaloric tube feeding and oral feeding in 15 short bowel syndrome patients more than 3 months after short bowel constitution. An oral feeding period combined with enriched (1000 kcal * day(-1)) tube feeding was also tested. We measured the net intestinal absorption rates of proteins, lipids, and total calories using elemental nitrogen, Van de Kamer, and bomb calorimetry methods, respectively. RESULTS Tube feeding increased the mean (+/-SD) percent absorption (P < .001) of proteins (72% +/- 13% vs 57% +/- 18%), lipids (69% +/- 25% vs 41% +/- 27%), and energy (82% +/- 12% vs 65% +/- 16%) compared with oral feeding. In the group given the combined feedings (n = 9), the total enteral intake and net percent absorption increased (P < .001) for proteins (67% +/- 10%), lipids (59% +/- 19%), and total energy (75% +/- 8%) compared with oral feeding. Absorption (kcal * day(-1)) was greater (P < .001) with tube (2225 +/- 457) and combined feedings (2323 +/- 491) than with oral feeding (1638 +/- 458). CONCLUSIONS In patients with short bowel syndrome, continuous tube feeding (exclusively or in conjunction with oral feeding) following the postoperative period significantly increased net absorption of lipids, proteins, and energy compared with oral feeding.

Chemotherapy for Gastro-Enteropancreatic Endocrine Tumours

Despite similar histological and morphological aspects, gastro-enteropancreatic (GEP) endocrine tumours represent a heterogeneous group of tumours with varying clinical expression depending on tumour type (functional or not), origin and extension, but also on histological differentiation and proliferative capacity. The natural history of well-differentiated tumours is often favourable without treatment and GEP endocrine tumours may remain indolent for many years. Chemotherapy may however be indicated in the presence of symptomatic non-progressive disease (progression evaluated over 3–6 months). In contrast, poorly differentiated GEP endocrine tumours are frequently aggressive and early treatment is required. Accurate staging is mandatory and where surgery is possible (even in the event of limited metastatic disease), this option should be re-evaluated in a multidisciplinary approach. Approximately 2/3 of malignant GEP tumours are metastatic at discovery and surgery is possible in a minority of patients; therefore, chemotherapy, with/without other strategies (e.g. local ablation), is frequently indicated in patients with symptomatic, bulky or progressive disease. For well-differentiated pancreatic tumours, the reference association is Adriamycin with streptozotocin yielding objective responses (OR) in 40–60% of patients. Prolonged treatment is limited due to potential cardiotoxicity of Adriamycin and standard 2nd-line regimens are not of proven efficacy; thus, other treatment modalities are usually additionally required (e.g. chemo-embolisation). A significant OR may render a small number of patients secondarily amenable to surgery. Published series evaluating chemotherapy for midgut endocrine tumours are outdated and disappointing. Objective response rates with combined associations (including either 5-fluorouracil and/or streptozotocin) rarely exceed 20% and where possible, chemo-embolisation for hepatic metastases combined with somatostatin analogues (± interferon) should be preferred. Poorly differentiated GEP tumours are generally aggressive tumours with metastases at diagnosis and tend to progress rapidly. Surgery is rarely possible and ineffective even in locally advanced disease due to a high risk of recurrence. Chemotherapy, using cisplatin and etoposide, is the reference treatment and frequently yields OR rates >50%. However, despite being chemosensitive, disease control is limited (8–10 months). Overall, advances in therapeutic chemotherapeutic options are required in the management of all types of advanced GEP endocrine tumours and evaluation of new drugs (e.g. irinotecan) and combination strategies (chemotherapy with local ablative therapies) are required in the future.

Endocrine pancreatic tumors in von Hippel-Lindau disease: clinical, histological, and genetic features.

Objectives: Endocrine pancreatic tumors (EPTs) in von Hippel-Lindau (VHL) disease pose difficult management problems. We aimed to assess (1) the accuracy of somatostatin receptor scintigraphy, (2) histological features with focus on malignancy and genotype-phenotype correlations, and (3) prognosis of VHL-EPT. Methods: Thirty-five patients with EPT-VHL (20 women; median age, 37 years) from 29 families were studied. Histological diagnosis was available in 29 patients. Endocrine pancreatic tumor patients were treated surgically (n = 22), medically (n = 8), or followed (n = 5). Somatostatin receptor scintigraphy was performed in 27 patients. Germinal alterations of the VHL gene were determined. Results: Tumors were malignant in 58% of patients. Somatostatin receptor scintigraphy was positive in 60% of cases, and weak expression of the somatostatin receptor type 2A was found in 47% of tumors. In operated patients, there was no mortality or tumor relapse (median follow-up, 5 [1-10] years). Mortality rate due to EPT was 6%. Germinal mutations were mainly located in exons 3 and 1, and a specific mutation (P86S) was identified. Conclusions: Most EPTs in VHL patients are somatostatin receptor scintigraphy-positive and malignant, without correlation with the VHL genotype. Surgical resection is often required, but prognosis of these EPTs seems to be fairly good.Abbreviations: CNS - central nervous system, CT scan - computed tomography, EPT - endocrine pancreatic tumors, EUS - endoscopic ultrasonography, SRS - somatostatin receptor scintigraphy, VHL - von Hippel-Lindau disease

Prevalence of Extrapancreatic Cancers in Patients With Histologically Proven Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Case–Control Study

BACKGROUND: Some studies have suggested that intraductal papillary mucinous neoplasms (IPMN) of the pancreas could be associated with extrapancreatic cancers (EPC)—especially from gastric and colorectal origin. The aim of this case–control study was to examine the association of EPC in patients with histologically proven IPMN.PATIENTS: A case–control study comparing 178 patients with resected IPMN (hyperplasia/low-grade dysplasiaAND METHODS: N = 91, high-grade dysplasia/invasive cancer N = 87) with 356 age- and gender-matched controls. EPC were searched for in patients with IPMN and controls, as well as familial histories of cancer and alcohol and tobacco intake. The prevalence and odds ratio were calculated.RESULTS: No difference was observed between alcohol and tobacco intake in IPMN patients and controls. EPC was found in 30 of 178 (16.8%) patients with IPMN (70% of which preceding IPMN) and in 30 of 356 (8.4%) controls (P = 0.003). The most frequent cancers in patients with IPMN and controls were: breast (30% in each group), prostate (10% and 13%, respectively, not significant [NS]), and colon/rectum (10 and 6%, respectively, NS). No correlation was found between the occurrence of EPC and the grade of IPMN.CONCLUSIONS: The prevalence of EPC in patients with IPMN is higher as compared with controls. The type and age at onset of EPC do not differ from the general population. Most of the EPCs precede the diagnosis of IPMN. A systematic screening of EPC should be performed only after the age of 50 yr or in case of a familial history of cancer, as yet recommended.

Faecal D/L lactate ratio is a metabolic signature of microbiota imbalance in patients with short bowel syndrome.

Our objective was to understand the functional link between the composition of faecal microbiota and the clinical characteristics of adults with short bowel syndrome (SBS). Sixteen patients suffering from type II SBS were included in the study. They displayed a total oral intake of 2661±1005 Kcal/day with superior sugar absorption (83±12%) than protein (42±13%) or fat (39±26%). These patients displayed a marked dysbiosis in faecal microbiota, with a predominance of Lactobacillus/Leuconostoc group, while Clostridium and Bacteroides were under-represented. Each patient exhibited a diverse lactic acid bacteria composition (L. delbrueckii subsp. bulgaricus, L. crispatus, L. gasseri, L. johnsonii, L. reuteri, L. mucosae), displaying specific D and L-lactate production profiles in vitro. Of 16 patients, 9/16 (56%) accumulated lactates in their faecal samples, from 2 to 110 mM of D-lactate and from 2 to 80 mM of L-lactate. The presence of lactates in faeces (56% patients) was used to define the Lactate-accumulator group (LA), while absence of faecal lactates (44% patients) defines the Non lactate-accumulator group (NLA). The LA group had a lower plasma HCO3− concentration (17.1±2.8 mM) than the NLA group (22.8±4.6 mM), indicating that LA and NLA groups are clinically relevant sub–types. Two patients, belonging to the LA group and who particularly accumulated faecal D-lactate, were at risk of D-encephalopathic reactions. Furthermore, all patients of the NLA group and those accumulating preferentially L isoform in the LA group had never developed D-acidosis. The D/L faecal lactate ratio seems to be the most relevant index for a higher D- encephalopathy risk, rather than D- and L-lactate faecal concentrations per se. Testing criteria that take into account HCO3− value, total faecal lactate and the faecal D/L lactate ratio may become useful tools for identifying SBS patients at risk for D-encephalopathy.

Effects of a Multimodal Management Strategy for Acute Mesenteric Ischemia on Survival and Intestinal Failure

BACKGROUND & AIMS Acute mesenteric ischemia (AMI) is an emergency with a high mortality rate; survivors have high rates of intestinal failure. We performed a prospective study to assess a multidisciplinary and multimodal management approach, focused on intestinal viability. METHODS In an Intestinal Stroke Center, we developed a multimodal management strategy involving gastroenterologists, vascular and abdominal surgeons, radiologists, and intensive care specialists; it was tested in a pilot study on 18 consecutive patients with occlusive AMI, admitted to a tertiary center from July 2009 to November 2011. Patients with left ischemic colitis, nonocclusive AMI, chronic mesenteric ischemia, and other emergencies were excluded. Patients received specific medical management: revascularization of viable small bowel and/or resection of nonviable small bowel; 12 patients received arterial revascularization. We evaluated the percentages of patients who survived for 30 days or 2 years, the number with permanent intestinal failure, and morbidity. Lengths and rates of intestinal resection were compared with or without revascularization, and in patients with early or late-stage disease. RESULTS Patients were followed up for a mean of 497 days (range, 7-2085 d); 95% survived for 30 days, 89% survived for 2 years, and 28% had morbidities within 30 days. Intestinal resection was necessary for 7 cases (39%), with mean lengths of intestinal resection of 30 cm and 207 cm, with or without revascularization, respectively (P = .03). Among patients with early or late-stage AMI, rates of resection were 18% and 71%, respectively (P = .049). Patients with early stage disease had shorter lengths of intestinal resection than those with late-stage disease (7 vs 94 cm; P = .02), and spent less time in intensive care (2.5 vs 49.8; P = .02). CONCLUSIONS A multidisciplinary and multimodal management approach might increase survival of patients with AMI and prevent intestinal failure.

Pancreatic Endocrine Microadenomatosis in Patients With von Hippel-lindau Disease: Characterization by Vhl/hif Pathway Proteins Expression

Introduction Von Hippel-Lindau (VHL) disease is an inherited syndrome caused by germline mutation in the VHL tumor suppressor gene predisposing to pancreatic endocrine tumors (PET). Whether these tumors derive from preexisting endocrine microadenomatosis as in multiple endocrine neoplasia type 1 (MEN1) is yet unknown. pVHL regulates hypoxia-inducible factor (HIF) that causes transcription activity of target genes like carbonic anhydrase 9 (CA9), vascular endothelial growth factor (VEGF), and cyclin D1. Our aim was to look for overexpression of these molecules to identify precursor endocrine lesions in the pancreas of VHL patients. Methods Nontumoral pancreas of 18 VHL patients operated on for PET, was examined for microadenomatosis (≤5 mm) and compared with pancreatic specimen obtained from non-VHL patients or MEN1 patients. The immunohistochemical expression of chromogranin, insulin, glucagon, HIF-1α, HIF-2α, VEGF, CA9, cyclin D1, and CD34 was assessed. Results In addition to 39 macrotumors (1 to 5/patient), chromogranin-positive endocrine microadenomas were found in 13 (72%) patients located within acini or close to ducts or islets. Strong coexpression of HIF-1α, cyclin D1, CA9, and VEGF and lack of expression of insulin and glucagon allowed distinction with normal or hyperplastic islets. CD34 identified a high microvessel density in these nodules. Expression of HIF-1α and CA9 was not found in islets of controls and in MEN1 microadenomas. Conclusions Pancreatic endocrine microadenomas are present in >70% of VHL patients operated on for PET. These results demonstrate that the pVHL/HIF pathway is involved very early in pancreatic endocrine tumorigenesis in this disease.

Increased intestinal absorption by segmental reversal of the small bowel in adult patients with short-bowel syndrome: a case-control study

BACKGROUND Segmental reversal of the small bowel (SRSB) is proposed in patients with short-bowel syndrome (SBS) as a rehabilitative therapy, but its effects on absorption have not been studied. OBJECTIVE We aimed to determine intestinal macronutrient absorption and home parenteral nutrition (HPN) dependence in SBS patients with intestinal failure. DESIGN We included in a retrospective study all consecutive patients who had an SRSB between 1985 and 2010 and underwent a study of macronutrient absorption. Patients were matched to SBS controls with the same digestive characteristics. Energy and macronutrient absorption were measured. The dependence on HPN was expressed by the number of infusions per week and by the calories infused daily divided by the basal energy expenditure multiplied by 1.5. RESULTS Seventeen patients who had an SRSB were matched to 17 control patients. Intestinal absorption was higher in the SRSB group for total calories (69.5% compared with 58.0%), fat (48.4% compared with 33.2%), and protein (62.7% compared with 53.4%) (P < 0.05). Median oral autonomy was 100% ± 38.4% in the SRSB group, whereas it was 79% ± 39.6% in the control group (P < 0.05). The number of calories infused was lower in the SRSB group (500 ± 283 compared with 684 ± 541; P < 0.05), as was HPN dependence (33% ± 20% compared with 48% ± 38%; P < 0.05) at the time of the study. CONCLUSION SRSB allows a gain in macronutrient absorption, which is associated with a lower HPN dependence. To our view, SRSB should be integrated in intestinal rehabilitative adult programs.

Segmental reversal of the small bowel can end permanent parenteral nutrition dependency: an experience of 38 adults with short bowel syndrome.

Objective:This study aimed to assess the results of segmental reversal of the small bowel (SRSB) in patients with short bowel syndrome (SBS) who were “permanently” dependent on parenteral nutrition (PN) and to identify possible prognostic factors for weaning. Summary Background Data:SRSB is a nontransplant surgical option for patients with SBS who require long-term PN. Few studies have reported outcomes in humans. Methods:All patients who were permanently dependent on PN and underwent a SRSB between 1985 and 2010 for SBS were included. The data were retrospectively retrieved. Results:Thirty-eight patients underwent SRSB. The median age was 55.5 years (range, 18–76). The median length of the small bowel remnant was 49 cm (20–140), including a reversed segment of 10 cm (6–15). The median follow-up was 57.7 months (1–304). At the 5-year follow-up, 17 patients had been weaned from PN (45%). In the remaining patients, PN dependency had decreased from 7 ± 1 to 4 ± 1 days per week. The survival rate was 84%. The prognostic factors for weaning were a short time between subtotal enterectomy and SRSB (P = 0.036), a longer than typical stay in the nutrition unit (P = 0.035), and an SRSB longer than 10 cm (P = 0.024). Conclusions:SRSB has a role as a conservative alternative to small bowel transplantation in patients with SBS permanently dependent on PN. With a segmental reversal of 10 to 12 cm, almost half of the patients can be expected to be weaned from PN.

Gastro-Intestinal Vascular Emergencies

Gastro-Intestinal Vascular Emergencies include all digestive ischaemic injuries related to acute or chronic vascular and/or haemodynamic diseases. Gastro-intestinal ischaemic injuries can be occlusive or non-occlusive, arterial or venous, localized or generalized, superficial or transmural and share the risks of infarction, organ failure and death. The diagnosis must be suspected, at the initial presentation of any sudden, continuous and unusual abdominal pain, contrasting with normal physical examination. Risk factors are often unknown at presentation and no biomarker is currently available. The diagnosis is confirmed by abdominal computed tomography angiography identifying intestinal ischaemic injury, either with vascular occlusion or in a context of low flow. Recent knowledge in the pathophysiology of acute mesenteric ischaemia, clinical experience and existing recommendations have generated a multimodal and multidisciplinary management strategy. Based on the gastro-intestinal viability around a simple algorithm, and coordinated by gastroenterologists, the dual aim is to avoid large intestinal resections and death.