Biliopancreatic diversion for severe obesity: long-term weight maintenance and occurrence of nutritional complications are two facets of the same coin.

BACKGROUND: Despite the widespread clinical use of hypoabsorptive metabolic bariatric surgery, very long-term outcomes are still lacking. The aim of the study was to assess the long-term safety and efficacy of biliopancreatic diversion at 30 years in patients with class 3 obesity (BMI over 40 kg/m2). METHODS: This retrospective single-centre study used data from a prospectively collected database on a sample of consecutive patients submitted to biliopancreatic diversion with a minimum follow-up of 30 years. Outcomes assessed included overall survival, long-term weight loss and weight maintenance, remission of obesity-related co-morbidities, and short- and long-term surgical and/or nutritional or metabolic complications. RESULTS: Among 199 consecutive patients (136 female, 63 male) who had surgery between November 1992 and April 1994, the mean age at operation was 38 (range 14-69) years and mean preoperative BMI was 48.7 (32.0-74.3) kg/m2. At baseline, 91 of 199 patients (45.7%) had type 2 diabetes. At 20 and 30 years, 122 (61%) and 38 (19%) of the 199 patients respectively were available for follow-up. At 30 years, the overall mortality rate was 12% (23 of 199). Surgical complications were concentrated in the short-term follow-up, whereas nutritional or metabolic complications increased progressively over time. A nutritional complication was diagnosed in 73 of 122 patients (60%) at 20 years and 28 of 38 (74%) at 30 years. Weight loss and glycaemic control were maintained throughout the follow-up; mean % total weight loss was 32.8 (range 14.1-50.0) at 1 year and 37.7 (range 16.7-64.8) at 30 years. One patient presented with recurrence of type 2 diabetes at 20 and 30 years; there were no patients with new-onset type 2 diabetes. CONCLUSION: Biliopancreatic diversion leads to good and sustained weight maintenance up to 30 years with low perioperative risk, but at the cost of a high long-term prevalence of nutritional complications.

Mechanisms of Enhanced Osteoclastogenesis in Alkaptonuria.

Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation, which leads to progressive and severe osteoarthopathy starting from the second decade of life. Thus, in AKU patients, bone involvement represents an important clinical issue, which we investigated. Serum levels of receptor activator of NF-κB ligand (RANKL), osteoprotegerin, sclerostin, Dickkopf-1, and bone remodeling markers were measured in nine AKU patients (two children and seven adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD) and femoral-BMD. In the two AKU children, the average of LS-BMD and femoral-BMD Z-scores were within the normal range, but reduced with respect to the controls. Otherwise, in the adult AKU patients, LS-BMD T-score was inside the normal range, but femoral-BMD T-score reached osteopenic levels. Consistently, in AKU adults, higher RANKL and C-terminal telopeptide of collagen type 1 and lower osteoprotegerin levels were observed than in controls. Otherwise, spontaneous osteoclastogenesis was already evident in peripheral blood mononuclear cell cultures from AKU children, together with a high percentage of circulating osteoclast precursors. Osteoclastogenesis was sustained by the high levels of tumor necrosis factor-α, RANK, RANKL, and LIGHT. In conclusion, the altered osteoclastogenesis was observed already in AKU children, despite the absence of evident injury. Thus, a preventive approach in young patients, targeting osteoclast activity, may prevent the macroscopic bone disease that appears in adult AKU.

Long-Term Follow-Up Study of Liver-Related Outcome After Bilio-Pancreatic Diversion in Patients with Initial, Significant Liver Damage.

BACKGROUND: Obesity is associated with NAFLD, and bariatric surgery has significant impact on this liver disease, with reported improvement in hepatic fibrosis. AIMS: To investigate the effects of bariatric surgery on long-term liver disease-related outcome in obese patients with nonalcoholic fatty liver disease (NAFLD) and significant liver damage. METHODS: This study included 56 NAFLD patients who underwent bilio-pancreatic diversion for morbid obesity and who had significant fibrosis at intraoperative liver biopsy. Data were analyzed at 1, 3, and 5 years of follow-up, and at the latest available visit in patients who had longer follow-up. We assessed the incidence of clinically relevant liver events (ascites, hepatic encephalopathy, portal hypertension-related bleeding, and jaundice) as well as modifications of a validated biochemical index such as the NAFLD score. RESULTS: During a median follow-up of 78 months, median weight decreased from 119 to 78 kg (P < 0.0001), and median body mass index decreased from 45.2 to 29.0 kg/m2 (P < 0.0001). None of the patients developed clinical complications of liver disease, and none died due to liver-related causes. Median NAFLD score significantly decreased (P = 0.0005) during follow-up from - 0.929 (- 1.543 to - 0.561) to - 1.609 (- 2.056 to - 1.102). The NAFLD score category was unchanged in 32 patients (57%), improved in 18 (32%), and worsened in 6 (11%). CONCLUSIONS: Patients with NAFLD and proven histological liver damage at surgery do not develop complications of liver disease in long term after bilio-pancreatic diversion. Moreover, noninvasive parameters of liver damage improve. Thus, preexisting liver damage does not seem to be a contraindication to bilio-pancreatic diversion.

Clinical and molecular characterization of a second family with the 12q14 microdeletion syndrome and review of the literature.

The 12q14 microdeletion syndrome is a rare condition characterized by low birth weight, failure to thrive, short stature, learning disabilities, and osteopoikilosis. To date, 20 cases of 12q14 deletion have been reported in the literature, displaying both phenotypic than genetic variability. We report on three familial cases, a mother and two brothers, with severe short stature. The mother and elder brother presented with osteopoikilosis while the younger brother had severe short stature and developmental delay. SNP array analysis revealed a 1.9 Mb heterozygous 12q14.2q14.3 deletion in all three patients encompassing 14 genes and 3 miRNAs. In addition, the younger brother carried a paternal 11q13.4 duplication including the SHANK2 gene. This latter patient was investigated for developmental delay and did not show osteopoikilosis, confirming the role of age in the clinical presentation of this condition. To the best of our knowledge, this is the second family described with the syndrome. Comparing the clinical and molecular data of our patients with those previously reported we performed a detailed genotype-phenotype correlation confirming the association between growth retardation and osteopoikilosis when the rearrangement includes both LEMD3 and HMGA2 genes. In addition, we suggest the XPOT, TBK1, WIF1 genes as candidates for the clinical features observed in our patients and discuss for the first time the possible involvement of some microRNAs, when deleted, in the etiology of the phenotypes in 12q14 microdeletion syndrome patients. We expect the interpretation of our findings to be useful both from a molecular point of view and for genetic counseling.

Short-term survival of hyperammonemic neonates treated with dialysis.

BACKGROUND: In severe neonatal hyperammonemia, extracorporeal dialysis (ECD) provides higher ammonium clearance than peritoneal dialysis (PD). However, there are limited outcome data in relation to dialysis modality. METHODS: Data from infants with hyperammonemia secondary to inborn errors of metabolism (IEM) treated with dialysis were collected in six Italian centers and retrospectively analyzed. RESULTS: Forty-five neonates born between 1990 and 2011 were enrolled in the study. Of these, 23 were treated with PD and 22 with ECD (14 with continuous venovenous hemodialysis [CVVHD], 5 with continuous arteriovenous hemodialysis [CAVHD], 3 with hemodialysis [HD]). Patients treated with PD experienced a shorter duration of predialysis coma, while those treated with HD had a shorter ammonium decay time compared with all the other patients (p < 0.05). No difference in ammonium reduction rate was observed between patients treated with PD, CAVHD or CVVHD. Carbamoyl phosphate synthetase deficiency (CPS) was significantly associated with increased risk of death (OR: 9.37 [1.52-57.6], p = 0.016). Predialysis ammonium levels were significantly associated with a composite end-point of death or neurological sequelae (adjusted OR: 1.13 [1.02-1.27] per 100 µmol/l, p = 0.026). No association was found between outcome and dialysis modality. CONCLUSIONS: In this study, a delayed ECD treatment was not superior to PD in improving the short-term outcome of neonates with hyperammonemia secondary to IEM.

Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma.

BACKGROUND: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. METHODS: Seven and 10 patients received 325 µg and 650 µg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. RESULTS: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 µg that was durable at 12 months in four patients. No CR was seen at 325 µg of L19-TNF. CONCLUSIONS: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 µg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.

Successful early management of a female patient with a metabolic stroke due to ornithine transcarbamylase deficiency.

BACKGROUND: Ornithine transcarbamylase deficiency (OTC-D) is a urea cycle disorder caused by dysfunction of ornithine transcarbamylase, which frequently leads to hyperammonemia. Hyperammonemia represents a medical emergency requiring prompt treatment to reduce plasma ammonia levels and prevent severe neurological damage, coma, and death, particularly in patients with acute decompensation-related coma. The clinical symptoms of OTC-D can manifest themselves either at an early stage, which is often associated with severe symptoms, or in later life (late-onset OTC-D), when symptoms may be less severe. There is currently little agreement over diagnostic signs of the condition or the most appropriate therapeutic approach. Hyperammonemia is usually treated with ammonia scavengers, continuous venovenous hemodialysis, and dietary changes. N-carbamylglutamate is approved for the treatment of hyperammonemia in N-acetylglutamate synthetase deficiency and may have efficacy in other urea cycle disorders. METHODS/RESULTS: Here, we report a 13-year-old girl who was diagnosed with OTC-D at the age of 3 years. On this occasion, the patient presented with vomiting, lethargy, and mental confusion. Despite biochemical parameters being within normal ranges, she was comatose within a few hours. She was promptly treated with a combined therapy of continuous venovenous hemodialysis and N-carbamylglutamate, resulting in a gradual normalization of clinical symptoms within 30 hours. No neurological damage was apparent at 18 months after treatment. CONCLUSIONS: This case demonstrates that clinical benefits can be obtained by beginning aggressive treatment of OTC-D within a few hours of the onset of severe neurological symptoms even in the absence of altered biochemical markers.

Pyrrhic victory? Long-term results of biliopancreatic diversion on patients with type 2 diabetes and severe obesity.

BACKGROUND: The long-term results after biliopancreatic diversion (BPD) in patients with type 2 diabetes (T2D) and severe obesity is still being debated. OBJECTIVE: Retrospective evaluation of the long-term metabolic and clinical conditions of patients with T2D following BPD. SETTING: University hospital. METHODS: A total of 173 patients with T2D and severe obesity were investigated prior to and at 3-5 and 10-20 years after BPD. Anthropometric, biochemical, and clinical findings preoperatively and throughout follow-up were considered. The long-term data were compared with those of a cohort of 173 T2D patients with obesity treated with conventional therapy. RESULTS: T2D resolved within the first postoperative phases in most patients, and in the long and very long term, the fasting blood glucose level remained above the normal range in only 8% of patients. Likewise, a stable improvement of blood lipid pattern was observed (follow-up rate 63%). In contrast, in nonsurgical patients in the long term, the glucose and lipid metabolic parameters remained in the pathologic range in all cases. In the BPD group, a very high number of severe BPD-related complications was recorded, and 27% of the BPD patients died, whereas in the control group, 87% of patients were still alive at the end of the follow-up period (P < .02). CONCLUSION: Despite the high T2D stable resolution rate and the normalization of most metabolic data at 10-20 years following surgery, these results indicate that BPD should be indicated with caution in the surgical treatment of T2D in patients with severe obesity.

Diabetes Resolution at 10 Years After Biliopancreatic Diversion in Overweight and Class 1 Obese Patients with Type 2 Diabetes.

BACKGROUND: Long-term anti-diabetic effects of BPD in overweight or class 1 obese T2DM patients were investigated reporting the results at 10 years after BPD performed in severely non-obese T2DM patients. MATERIAL AND METHODS: Thirty T2DM patients with BMI lower than 35 kg/m2 were investigated at 1, 5, and 10 years after BPD, and the results are compared with those of 30 T2DM patients followed for 10 years on pharmacological and/or behavioral conventional therapy. RESULTS: Mean levels of fasting blood glucose (FBG) and serum glycated hemoglobin (HbA1C) showed a marked reduction 1 year after BPD, values remaining slightly above the diabetic range throughout the entire follow-up. T2DM remission was observed in about 50% of the cases at 5 and 10 years after the operation. In 16 patients (53%), severe BPD-related complications developed, in ten cases requiring a surgical revision of the operation. In the BPD group, one patient died for malignant lymphoma and two patients after surgical revision. Within the control group, during the 10-year follow-up, no changes in the diabetic status were observed, being the FBG and HbA1C mean values higher than those recorded in the BPD patients at any follow-up time. All T2DM subjects of the control group were alive at the end of the 10-year follow-up. CONCLUSION: Despite satisfactory long-term metabolic outcomes, these data indicate that BPD should be used with caution as a metabolic procedure in the treatment of T2DM in overweight or class 1obese patients.

Effects of biliopanceratic diversion on type 2 diabetes in patients with BMI 25 to 35.

OBJECTIVE: Biliopancreatic diversion (BPD) resolves type 2 diabetes in near totality of morbidly obeses [BMI (body mass index) ≥35 kg/m]. However, studies of BPD effect in BMI range 25.0 to 34.9 kg/m, including about 90% of diabetic patients, are lacking. MATERIALS AND METHODS: If BPD effects are independent of weight changes, they should be maintained in patients who, being mildly obese or overweight, will lose little or no weight after operation. Thirty type 2 diabetic patients with BMI 25 to 34.9 were submitted to BPD and monitored 12 months. Thirty-eight diabetic patients selected from a large database, kept 1 year on medical therapy, served as controls. RESULTS: Nineteen male and 11 female. Mean age 56.4 ± 7.4 years, weight 84.8 ± 11.1 kg, BMI 30.6 ± 2.9 kg/m, waist circumference 104 ± 9.4 cm, diabetes duration 11.2 ± 6.9 years, HbA1c 9.3±1.5. Twelve patients on insulin. Fifteen (2 F) with BMI < 30 (mean: 28.1). No mortality or major adverse events occurred. BMI progressively decreased, stabilizing around 25 since the fourth month, without excessive weight loss. One year after BPD, mean HbA1c was 6.3%±0.8, with 25 patients (83%) controlled (HbA1c≤7%) on free diet, without antidiabetics, and the remaining improved. Acute insulin response to intravenous glucose had increased from 1.2 ± 2.9 to 4.2 ± 4.4 µIU/mL. Diabetes resolution correlated positively with BMI. HbA1c decreased at 1 year in the control group, along with an overall increased amount of antidiabetic therapy. CONCLUSIONS: BPD improves or resolves diabetes in BMI 25 to 35 without causing excessive weight loss, its action being on insulin sensitivity and beta-cell function. The strikingly different response between morbidly obese and low BMI patients might depend on different beta-cell defect. ClinicalTrials.gov Identifier: NCT00996294.

Single-Port vs. Conventional Multi-Port Laparoscopic Lymph Node Biopsy.

BACKGROUND AND OBJECTIVES: The purpose of the investigation was to compare clinical results and diagnostic accuracy for conventional multiport laparoscopic lymph node biopsy (MPLB) and single-port laparoscopic lymph node biopsy (SPLB) operations at a single institution. METHODS: A set of 20 SPLB patients operated on from October 2016 to May 2019 were compared to an historical series of 35 MPLB patients. Primary endpoints were the time of surgery, estimated blood loss, surgical conversion, length of stay and morbidity. The secondary endpoint was the diagnostic accuracy of the technique. RESULTS: SPLB was completed laparoscopically in all cases. Two MPLB patients (5.7%) experienced a surgical conversion due to intraoperative difficulties. Duration of surgery was similar in SPLB and MPLB groups respectively (84 ± 31.7 min vs. 81.1 ± 22.2; P = .455). A shorter duration of hospital stay was shown for patients operated on by SPLB compared to the MPLB group (1.7 ± 0.9 days vs. 2.1 ± 1.2 days; P = .133). The postoperative course was uneventful in both groups. In 95% of the SPLB and 97.1% of the MPLB cases respectively, LLB achieved the necessary information for the diagnosis. CONCLUSION: SPLB has shown good procedural and postoperative outcomes as well as a high diagnostic yield, comparable to traditional MPLB. Therefore, our results show that this approach is safe and effective and can be an equally valid option to MPLB to obtain a diagnosis or to follow the progression of a lymphoproliferative disease. Further studies are necessary to support these results before its widespread adoption.

Type 2 Diabetes Remission and Control in Overweight and in Mildly Obese Diabetic Patients at Long-Term Follow-Up After Biliopancreatic Diversion.

BACKGROUND: In severely obese patients with type 2 diabetes (T2DM), the metabolic benefits after biliopancreatic diversion (BPD) are due to mechanisms independent of weight loss. Therefore, the anti-diabetic effect of BPD in overweight or mildly obese T2DM patients was investigated. METHODS: Ninety T2DM patients with BMI 25-35 underwent BPD and were evaluated 1 and 5 years after the operation (follow-up rate 100 and 83%, respectively). RESULTS: T2DM control (Hb1Ac < 7%) and remission (Hb1Ac < 6 without antidiabetics) was observed in 86.6 and 65% of cases at 1 year and 64.0% and 26.5% at 5 years, respectively. The long-term T2DM remission was predicted by baseline BMI value. Both before BPD and throughout the follow-up period, HOMA values were similar in the metabolically successful and unsuccessful subjects, while C-peptide normalized for FBG value as a marker of beta cell mass and insulin secretion increased progressively only in the former from 1.06 ± 0.64 to 1.44 ± 1.08 mcg/l ml/dl-1 * 100 (p < 0.002). CONCLUSIONS: In T2DM patients with BMI of 25-35, a positive metabolic outcome is less frequent than in their counterparts with morbid obesity. In T2DM overweight patients, in spite of a short-term normalization of FBG and HbA1c levels and a well-sustained increase of insulin sensitivity, a long-term T2DM relapse occurs in the majority of the cases. While the surgically obtained decrease in insulin resistance leads to T2DM control in half of the patients, the increase in insulin secretion is mandatory for T2DM stable remission.

Single-Port Versus Conventional Laparoscopic Cholecystectomy: Better Cosmesis at the Price of an Increased Incisional Hernia Rate?

Background: The incidence of trocar site hernia (TSH) in single-port laparoscopic cholecystectomy (SPC) is still a debated issue. Aim of this retrospective study was to compare the incidence of postoperative hernia and cosmetic results among patients undergoing SPC and multiport laparoscopic cholecystectomy (MPC) performed at a single institution. Methods: A series of 60 SPC and 60 MPC patients operated on between July 2016 and May 2018 were compared. Primary endpoint was to assess the incidence of TSH at long term. All the patients were admitted as outpatients for physical examination and scar measurement. Secondary endpoints were the cosmetic results assessed by a cosmesis score (CS) and the body image questionnaire (BIQ). Results: After a median 18-month follow-up (range: 6-29 months), a hernia in umbilical trocar site was detected in 4 (7.1%) SPC patients and 1 (2%) MPC patient, the difference not being statistically significant (P = .216). BIQ was almost equivalent in SPC and MPC groups (5.15 versus 5.27; P = .518), respectively. Statistically significant differences in favor of SPC were found in CS (22.3 versus 19.72; P = .001) and in total length of scars (1.2 cm versus 4 cm; P < .001). Conclusions: SPC technique has proved to be safe and effective in experienced hands. Superior cosmesis of SPC over MPC is confirmed, but close attention to fascial closure is a vital component of SPC, and surgeons performing single-site surgery need to be aware of this increased potential for hernia formation.

Baseline neutrophil-to-lymphocyte ratio is associated with long-term T2D remission after metabolic surgery.

AIMS: Metabolic surgery is considered as a therapeutic option for obese patients with type 2 diabetes (T2D). In order to identify novel laboratory variables that could improve the selection of patients who might greatly benefit from a surgical approach, we focused on the neutrophil-to-lymphocyte ratio (NLR) as a predictor of long-term T2D remission following metabolic surgery. METHODS: Thirty-one obese patients with T2D included in this pilot study underwent Roux-en-Y gastric bypass or biliopancreatic diversion (BPD) at the Surgical Department of Genoa University, IRCCS Ospedale Policlinico San Martino in Genoa (Italy). Before surgery, serum samples were collected to evaluate blood count, glycemic profile, and circulating neutrophil degranulation products. RESULTS: The median age was 56 years, median body mass index (BMI) was 32.37 kg/m2, and median glycated hemoglobin was 8.4%. White blood cell count was in a range of normality, with a median NLR of 1.97. By a receiver operating characteristic curve analysis, NLR has been found to be significantly associated with T2D remission at 1, 3, and 5 years and the best cutoff of ≤ 1.97 has been identified by Youden index. When comparing study groups according to NLR cutoff, those with NLR ≤ 1.97 were older and underwent more often BPD. By a logistic regression analysis, NLR ≤ 1.97 has been found to predict T2D remission across 5 years, irrespective of baseline BMI. CONCLUSIONS: A baseline low NLR is associated with long-term T2D remission in obese patients undergoing metabolic surgery, suggesting that circulating inflammatory cells (i.e., neutrophils) might negatively impact on T2D remission.

A comparison of a personal series of biliopancreatic diversion and literature data on gastric bypass help to explain the mechanisms of resolution of type 2 diabetes by the two operations.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) are highly beneficial operations for type 2 diabetes mellitus (T2DM) in obese patients, leading to complete T2DM resolution in 75-90 and 97-99% of cases, respectively. In both RYGBP and BPD, the foregut is excluded from the food stream and the distal small bowel receives the food stimulation, while following BPD fat intestinal absorption is also extremely limited. This study was carried out to identify clinical features that could give insight on the different mechanisms of action on diabetes resolution. METHODS: The files of 443 severely obese patients with T2DM undergoing BPD from May 1976 to May 2007 were examined, and the presence of T2DM (fasting serum glucose >125 mg/ml) at 1-2 months, at 1 year, at 10 years, and at > or =20 years following the operation was recorded. RESULTS: The percentage of patients cured (fasting serum glucose reduced to < or =110 mg/dl, on free diet and with no therapy) was 74% at 1 month, 97% at 1 and 10 years, and 91% at > or =20 years, the 26% of uncured patients at 1 month being those with most severe preoperative T2DM. CONCLUSIONS: As the early results after BPD resemble those reported after RYGBP, it can be hypothesized that the duodenal exclusion and the distal small bowel stimulation are the first mechanisms acting in BPD, immediately after the operation, that only subsequently the myocellular fat depletion, which cannot be immediate, takes over, and that the minimal fat absorption is the mechanism accounting for the long-term results of BPD.

Does biliopancreatic diversion carry increased risk for colorectal cancer? A cohort study.

BACKGROUND: Because of the rearrangement of the gastrointestinal tract, biliopancreatic diversion (BPD) could lead to an increased risk of colorectal cancer caused by possible carcinogenetic action of the unabsorbed food and bile acid on colonic mucosa. METHODS: The incidence of colorectal cancer in 1,898 obese subjects submitted to BPD from May 76 to July 2002 with a minimum follow-up of 5 years was retrospectively evaluated. RESULTS: Among 28,811 person-years, seven cases of colorectal cancer were detected, for an overall incidence of 29.4 per 100,000, which is not different from that observed in the general Italian population, and lower than that reported for obese and type 2 diabetes patients. Logistic regression model suggests that occurrence of colorectal cancer is positively related to the time elapsed from BPD. CONCLUSION: This study indicates that BPD does not carry any increased risk for colorectal cancer. The complete postoperative restoration of insulin sensibility could exert a valuable protective action.

Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a congenital disorder characterised by growth retardation, facial dysmorphisms, skeletal abnormalities and mental retardation. Broad thumbs and halluces are the hallmarks of the syndrome. RSTS is associated with chromosomal rearrangements and mutations in the CREB-binding protein gene (CREBBP), also termed CBP, encoding the CREB-binding protein. Recently, it was shown that mutations in EP300, coding for the p300 protein, also cause RSTS. CBP and EP300 are highly homologous genes, which play important roles as global transcriptional coactivators. OBJECTIVE: To report the phenotype of the presently known patients with RSTS (n = 4) carrying germline mutations of EP300. RESULTS: The patients with EP300 mutations displayed the typical facial gestalt and malformation pattern compatible with the diagnosis of RSTS. However, three patients exhibited much milder skeletal findings on the hands and feet than typically observed in patients with RSTS. CONCLUSIONS: Part of the clinical variability in RSTS is explained by genetic heterogeneity. The diagnosis of RSTS must be expanded to include patients without broad thumbs or halluces.

Management of malabsorptive bariatric surgery after cancer surgery for malignancies of the digestive apparatus.

BACKGROUND: Data regarding management of former bariatric operations after onset of a malignancy are still lacking and there is no consensus whether bariatric surgery negatively influences the oncologic management of patients. OBJECTIVES: To investigate the strategy by which patients previously submitted to bariatric surgery were managed after diagnosis of malignancy of the digestive apparatus, whether a revision was performed or not, to assess the incidence of nutritional complications, and the effect of revision versus no revision of bariatric surgery on the outcome of cancer treatment. SETTING: University Hospital, Italy. METHODS: Occurrence of a malignancy of the digestive apparatus in patients submitted to biliopancreatic diversion was investigated retrospectively. Patients' data were collected preoperatively, at 2 and 3 years after the operation, at oncologic diagnosis, and at the longest available postoncologic follow-up. RESULTS: From May 1976 to January 2017, 3341 morbidly obese patients were submitted to biliopancreatic diversion. Sixteen patients were diagnosed with a malignancy involving the digestive apparatus 5 to 28 years after bariatric surgery. Of 10 patients diagnosed with colorectal cancer, 6 were revised. At 2 years after biliopancreatic diversion, body mass index, hemoglobin, and iron levels were significantly lower than preoperatively. Serum transferrin and total protein were unchanged. There was no difference between body mass index, hemoglobin, transferrin, and total protein levels at 2 years and at oncologic diagnosis, or between revised and unrevised patients. CONCLUSION: Revision of a preexisting bariatric operation after digestive cancer surgery is common, although selected, unrevised cases do not seem to be associated with worse outcome.