Gerardo Sarno

New-onset diabetes after kidney transplantation: prevalence, risk factors, and management.

New-Onset Diabetes After Transplantation (NODAT) is an increasingly recognized severe metabolic complication of kidney transplantation causing lower graft function and survival and reduced long-term patient survival mainly due to cardiovascular events. The real incidence of NODAT after kidney transplantation is difficult to establish, because different classification systems and definitions have been employed over the years. Several risk factors, already present before or arising after transplantation, in particular the employed immunosuppressive regimens, have been related to the development of NODAT. However the responsible pathogenic mechanisms are still far to be perfectly known. Awareness of NODAT and of the NODAT-related factors is of paramount importance for the clinicians in order to individuate higher risk patients and arrange screening strategies. The risk of NODAT can be reduced by planning preventive measures and by tailoring immunosuppressive regimens according to the patient characteristics. Once NODAT has been diagnosed, the administration of specific anti-hyperglycemic therapy is mandatory to reach a tight glycemic control, which contributes to significantly reduce posttransplant mortality and morbidity.

Liver Resection for Primary Intrahepatic Stones: A Single-Center Experience

HYPOTHESIS Primary intrahepatic lithiasis occurs frequently in East Asia but is rare in Western countries. Biliary pain and episodes of cholangitis are the most common presenting symptoms, whereas intrahepatic cholangiocarcinoma represents a long-term unfavorable complication of the disease. When a single liver lobe or segment is involved, partial hepatectomy may be regarded today as an effective method of treatment. DESIGN Retrospective study. SETTING Hepatobiliary unit in a tertiary care hospital. PATIENTS The clinical records of 35 patients treated for primary intrahepatic lithiasis between January 1, 1992, and December 31, 2005, were reviewed and clinical data, cholangiograms, operative procedures, and early and late results were examined. INTERVENTIONS Thirty-four patients underwent liver resection; left hepatectomy (18 patients) and left lateral segmentectomy (10 patients) were the most frequently performed procedures. A cholangiocarcinoma was found in 3 patients (8.6%): 2 underwent liver resection and 1, who was found unresectable at surgery, underwent only explorative laparotomy. MAIN OUTCOME MEASURES Survival, quality of life, laboratory data, and need for further treatments. RESULTS There was no postoperative mortality. Morbidity was 20.0% with a prevalence of infectious complications related to bile leakage. Long-term results, assessed in 26 patients with follow-up longer than 12 months (range, 12-170 months; mean, 63 months), were good or fair in 24 patients (92.3%), including 3 patients who needed subsequent endoscopic removal of biliary stones. CONCLUSIONS Primary intrahepatic lithiasis more commonly involves 1 single liver segment or lobe. Partial hepatectomy is a safe and effective procedure, allowing definitive treatment of the disease and prevention of cancer.

Liver Resection for Hepatocellular Carcinoma ≤3 cm: Results of an Italian Multicenter Study on 588 Patients

BACKGROUND The best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm. STUDY DESIGN Retrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method. RESULTS Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS. CONCLUSIONS Liver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.

New-onset Diabetes Mellitus: Predictive Factors and Impact on the Outcome of Patients Undergoing Liver Transplantation

Liver transplantation (LT) for hepatocellular carcinoma (HCC) is the treatment of choice for patients with tumor characteristics within the Milan criteria associated with Child B or C cirrhosis. LT provides the best cure for both the tumor and the cirrhosis. There have been several emerging reports that new-onset diabetes mellitus (NODM) after transplantation (NODAT) is one of the most negative predictive factors for low survival rate and related co-morbidities. Little is known about the onset of NODM in post-transplant patients and, overall, whether the pathogenesis of NODM differs from that known for the general population. Principally, it is still unknown whether NODAT is related to the primary hepatic disease, the surgical procedures, immunosuppressive treatments, or is it due to the donor liver. This review will focus on the identification of factors, in the setting of LT, which may lead to the development of NODM. Early prevention of these factors may abate the incidence of NODM and positively impact survival rate, and thus ameliorate the worsening of cardiovascular risk factors which usually occur after LT.

The good and bad effects of statins on insulin sensitivity and secretion

Abstract Aims: Statins are the main lipid-lowering treatment in both primary and secondary prevention populations. Whether statins deteriorates glycemic control, predisposing to the onset of diabetes mellitus has been a matter of recent concern. Statins may accelerate progression to diabetes via molecular mechanisms that impact insulin sensitivity and secretion. In this review, we debate the relative effect of statins in driving insulin resistance and the impairment of insulin secretion. Methods: Narrative overview of the literature synthesizing the findings of literature was retrieved from searches of computerized databases, hand searches, and authoritative texts employing the key words “Statins”, “Randomized Clinical Trial”, “Insulin sensitivity”, “Insulin resistance”, “Insulin Secretion”, “Diabetes Mellitus” alone and/or in combination. Results: The weight of clinical evidence suggests a worsening effect of statins on insulin resistance and secretion, anyway basic science studies did not find a clear molecular explanation, providing conflicting evidence regarding both the beneficial and the adverse effects of statin therapy on insulin sensitivity. Conclusions: Although most of the clinical studies suggest a worsening of insulin resistance and secretion, the cardiovascular benefits of statin therapy outweigh the risk of developing insulin resistance, thus the data suggest the need to treat dyslipidemia and to make patients aware of the possible risk of developing type 2 diabetes or, if they already are diabetic, of worsening their metabolic control.

Vitamin D and pancreas: the role of sunshine vitamin in the pathogenesis of Diabetes Mellitus and Pancreatic Cancer

ABSTRACT Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin Ds immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation—all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin Ds role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hills criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

The impact of vitamin D deficiency on patients undergoing kidney transplantation: focus on cardiovascular, metabolic, and endocrine outcomes

Vitamin D deficiency is common among kidney transplant (KT) recipients because of reduced sunlight exposure, low intake of vitamin D, the immunosuppressive drug regimen administered, and steroid therapy. Glucocorticoids regulate expression of genes coding for enzymes that catabolize vitamin D, further reducing its level in serum. Although vitamin D primarily regulates calcium homeostasis, vitamin D deficiency is associated with the risk of several diseases, such as diabetes mellitus and tuberculosis. Aim of this review is to highlight endocrine and metabolic alterations due to the vitamin D deficiency by evaluating the mechanisms involved in the development of KT-related disease (cardiovascular, bone mineral density, and new-onset diabetes after transplantation). Next, we review evidence to support a link between low vitamin D status and KT-related diseases. Finally, we briefly highlight strategies for restoring vitamin D status in KT patients.

External lymphatic fistula after intra-abdominal lymphadenectomy for cancer. Treatment with total parenteral nutrition and somatostatin.

OBJECTIVE External lymphatic fistula or chyloperitoneum after intra-abdominal lymphadenectomy may present challenging problems. In the absence of definite guidelines the choice of treatment is often empirical, with unpredictable effectiveness, and the reporting of new cases may broaden the available experience. METHODS We describe two cases. One patient had high-output external fistula (1300 mL/d) after para-aortic lymphadenectomy for metastatic lymph nodes. The fistula became fully evident at postoperative day 4, with resumption of an oral diet, on the basis of a 1300-mL/d output of white milky fluid from an abdominal drainage. Oral feeding was interrupted and total parenteral nutrition was started; this was transiently associated with octreotide administration, subsequently replaced by somatostatin. The second patient had a low-output fistula (350 mL/d) after liver resection and lymphadenectomy for cholangiocarcinoma and underwent treatment with total parenteral nutrition and somatostatin. RESULTS In the first case the lymphatic fistula healed in just less than 3 wk, with the patient constantly remaining in very good condition, without secondary complications. In the second case the low-output fistula healed more rapidly. CONCLUSION Interruption of oral feeding with total parenteral nutrition and continuous somatostatin infusion was an effective treatment in both patients with an intra-abdominal lymphatic leak.

Removal of Duodenum Elicits GLP-1 Secretion

OBJECTIVE To evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects. RESEARCH DESIGN AND METHODS For evaluation of hormonal secretion and insulin sensitivity, 10 overweight patients without type 2 diabetes (age 61 ± 19.3 years and BMI 27.9 ± 5.3 kg/m2) underwent a mixed-meal test and a hyperinsulinemic-euglycemic clamp before and after pylorus-preserving pancreatoduodenectomy for ampulloma. RESULTS All patients experienced a reduction in insulin (P = 0.002), C-peptide (P = 0.0002), and gastric inhibitory peptide (GIP) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R2 = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R2 = 0.46; P = 0.03) and C-peptide (R2 = 0.37; P = 0.04). Given that the remaining pancreas presumably has preserved intraislet anatomy, insulin secretory capacity, and α- and β-cell interplay, our data suggest that the increased glucagon secretion is related to decreased systemic insulin. CONCLUSIONS Pylorus-preserving pancreatoduodenectomy was associated with a decrease in GIP and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion.

Primary hepatic leiomyosarcoma in a young man after Hodgkin’s disease: diagnostic pitfalls and therapeutic challenge

BACKGROUND Primary leiomyosarcoma of the liver is a rare tumor whose development patterns are unsatisfactorily known. PATIENT CASE A 26-year-old male patient with a previous history of radiochemotherapy treatment for Hodgkins lymphoma was referred to our unit with a histological and radiological diagnosis of primary hepatic leiomyosarcoma. Six months before referral, in a workup for hypertension, a CT scan of the abdomen had shown a 2.5-cm lesion in liver segment VII, which was interpreted as an angioma. Shortly before referral the lesion had grown to 7.8 cm, associated with two smaller lesions in segments VIII and III, and a diagnosis of hepatic leiomyosarcoma was made at biopsy. After referral he underwent a right hepatectomy with wedge resection of segment III. This was followed by rapid progression of the disease, in spite of transient stabilization under gemcitabine treatment. Octreotide was also administered after the detection of elevated chromogranin A in serum. The patient died 25 months after liver resection. CONCLUSIONS The challenges and peculiarities of this case are related to the rarity of the tumor, its accidental discovery without immediate suspicion of its nature, its very aggressive behavior that was only partly controlled by chemotherapy, and the unusual expression of a neuroendocrine phenotypic feature with high serum chromogranin A levels.