Cancer prevalence in United States, Nordic Countries, Italy, Australia, and France: an analysis of geographic variability.

BACKGROUND: The objectives of this study were to quantitatively assess the geographic heterogeneity of cancer prevalence in selected Western Countries and to explore the associations between its determinants. METHODS: For 20 cancer sites, 5-year cancer prevalence, incidence, and survival were observed and age standardised for the mid 2000s in the United States, Nordic European Countries, Italy, Australia, and France. RESULTS: In Italy, 5-year crude prevalence for all cancers was 1.9% in men and 1.7% in women, while it was ∼1.5% in all other countries and sexes. After adjustment for the different age distribution of the populations, cancer prevalence in the United States was higher (20% in men and 10% in women) than elsewhere. For all cancers combined, the geographic heterogeneities were limited, though relevant for specific cancers (e.g., prostate, showing >30% higher prevalence in the United States, or lung, showing >50% higher prevalence in USA women than in other countries). For all countries, the correlations between differences of prevalence and differences of incidence were >0.9, while prevalence and survival were less consistently correlated. CONCLUSION: Geographic differences and magnitude of crude cancer prevalence were more strongly associated with incidence rates, influenced by population ageing, than with survival rates. These estimates will be helpful in allocating appropriate resources.

Pituitary autoimmunity is associated with hypopituitarism in patients with primary empty sella.

OBJECTIVE: Some evidence suggests that late stage autoimmune hypophysitis (AH) may result in empty sella (ES). Aim of the study was to assess the prevalence of serum pituitary antibodies (PitAb) and their correlation with pituitary function in patients with ES. DESIGN: In this casecontrol study 85 patients with primary ES, 16 patients with ES secondary to head trauma, 214 healthy controls, and 16 AH were enrolled in a tertiary referral center. METHODS: PitAb were assessed in all cases and controls. Endocrine function was assessed by basal hormone measurement and dynamic testing in all ES cases. RESULTS: PitAb prevalence was higher in primary ES (6%) than in healthy subjects (0.5% p=0.003) and lower than in AH patients (50%, p<0.0001). PitAb were not found in patients with secondary ES. Hypopituitarism was found in 49% of primary ES and in 62% of secondary ES (p=0.34). A positive correlation between the presence of PitAb and hypopituitarism was found in primary ES (p=0.02). CONCLUSIONS: The significant association between pituitary autoimmunity and hypopituitarism suggests that ES, in selected cases, could be the final result of AH.

Diagnosis and treatment of autoimmune hypophysitis: a short review.

Medical therapy of autoimmune hypophysitis with immunosuppressive drugs can be effective to induce remission of the disease by treating both pituitary dysfunction and compression symptoms. We describe the case of a 41-yr-old man with autoimmune hypophysitis in whom prednisone therapy induced remission of the disease but was followed by a sudden relapse after withdrawal. A second trial of corticosteroid was started and succeeded in inducing remission of the disease. Eight months after the second withdrawal pituitary function was restored, pituitary mass had disappeared, only partial diabetes insipidus remained unchanged. Review of the literature identified 30 articles, among case reports and case series, reporting a total of 44 cases of autoimmune hypophysitis treated with glucocorticoids and/or azathioprine. Combining all the cases, medical therapy resulted to be effective in reducing the pituitary mass in 84%, in improving anterior pituitary function in 45%, and in restoring posterior pituitary function in 41%. Clinical aspects of autoimmune hypophysitis are discussed and a possible algorithm for the diagnosis and treatment of the disease is proposed.

Mycophenolate mofetil monotherapy for severe side effects of calcineurin inhibitors following liver transplantation.

Withdrawal of calcineurin inhibitors (CNI) followed by mycophenolate mofetil (MMF) monotherapy after liver transplantation (LT) remains controversial due to the increased risk of acute rejection and graft loss. The aim of the present study, performed in a large cohort of liver-transplanted patients with severe CNI-induced side effects, was to assess renal function recovery, and safety in terms of liver function, of complete CNI withdrawal and replacement by MMF monotherapy. Fifty-two patients treated with MMF monotherapy for CNI-induced toxicity were analyzed. Mean estimated glomerular filtration rate (eGFR) increased significantly during the period of MMF monotherapy, from 37 +/- 10 to 44.7 +/- 15 mL/min/1.73 m(2) at 6 months (p = 0.001) corresponding to a benefit of +17.4% in renal function. eGFR stabilized or improved in 86.5%, 81% and 79% of cases, and chronic renal dysfunction worsened in 13.5%, 19% and 21% of cases, at 6, 12 and 24 months after CNI withdrawal, respectively. Only two patients experienced acute rejection. MMF monotherapy may be efficient at reversing/stabilizing CRD, and appears relatively safe in terms of liver graft function in long-term liver-transplanted patients. However, clinicians must bear in mind the potential risk of rejection and graft loss, and should be very cautious in the management of such 'difficult-to-treat patients'.

[Transvaginal repair of genital prolapse with Prolift: evaluation of safety and learning curve]. / Cure de prolapsus par voie vaginale selon la technique du Prolift: évaluation du caractère minimal invasif et de sa courbe d'apprentissage.

AIMS: Evaluation of the mini invasiveness and the learning curve of the Prolift technique. MATERIALS AND METHODS: Prospective study. All patients were operated on by the same surgeon. The mini-invasiveness of the procedure was estimated through the evaluation of the intraoperative and immediate postoperative complications. The learning curve was evaluated through the analysis of the operative time. RESULTS: Between January and December 2007. Forty-seven patients were included in the study. Mean follow-up was: 11,8 months. Two cases of bladder injury and two cases of intraoperative bleeding (>500 ml) were reported. One case of vaginal erosion and one case of recurrence of the prolapse occurred during the follow-up. The mean operative time was 62+/-18 min. The mean operative time of the posterior step of the Prolift was 24+/-min and remained stable after the 18th procedure. DISCUSSION: The learning cure of the posterior of the procedure is longer because of the passage of the needles through the ischiorectal foramens. The technique is mini-invasive considered the low rate of intra and immediate postoperative complication and the learning curve short. CONCLUSIONS: Longer follow-up is needed to evaluate the efficacy of the procedure in the long term.

Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome.

BACKGROUND: A subset of patients with irritable bowel syndrome (IBS) have an increased number of mast cells (MCs) in the colonic mucosa. Psychological factors are believed to contribute to the course of IBS. AIMS: To examine associations between fatigue, depression and MCs of the colonic mucosa in IBS. METHODS: Colonic biopsies were taken from 50 Rome II IBS patients, 21 healthy controls and 11 depressed/fatigued patients without IBS. The cellularity of the lamina propria was determined as the number of inflammatory cells per high power field (hpf) through a 400x microscope. The Fatigue Impact Scale (FIS) and the short form Beck Depression Inventory (BDI) evaluated the severity of fatigue and depression. RESULTS: IBS patients had a significant increase in the cellularity of the lamina propria compared with controls or with depressed patients (mean (SD) 94.5 (48-110) vs 68 (58-82) and 78 (87-90) cells per hpf, p = 0.005 and p = 0.05, respectively), in particular of MCs (9.3 (5.6-11.7) vs 4.0 (2.7-6.8) and 4.3 (2.8-7.8) cells per hpf, p = 0.001 and p = 0.005, respectively). Both the FIS and BDI scores were significantly higher in IBS or in depressed patients than in controls (p<0.001). In IBS, the FIS score correlated significantly with the cellularity of the lamina propria (r = 0.51, p<0.0001) and MCs (r = 0.64, p<0.0001). In IBS, the BDI score correlated significantly with MCs (r = 0.29, p = 0.03). CONCLUSIONS: Elevated MCs counts are a key feature of the low-grade inflammatory infiltrate in the caecal mucosa of IBS. Fatigue and depression are associated with mucosal cell counts, in particular MCs, suggesting that psychological factors are associated with the low-grade inflammatory infiltrate in IBS.

Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH.

BACKGROUND: The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. AIM: To develop a new blood test specifically dedicated for this new diagnostic target of interest. METHODS: Eight Hundred and forty-six biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets. RESULTS: The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%. CONCLUSION: The new blood test MACK-3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved.

Laparoscopic subtotal colectomy with cecorectal anastomosis for slow-transit constipation.

Subtotal colectomy with cecorectal anastomosis represents an interesting alternative to total colectomy with ileorectal anastomosis. Several technical variants to the methods for performing the anastomosis between the cecum and the rectal stump after subtotal colectomy have been reported. The mechanical, antiperistaltic, end-to-end cecorectal anastomosis is safe and easy to perform. The authors aimed to assess the safety and feasibility of this technique performed laparoscopically in a series of four patients. All the procedures were completed laparoscopically. The mean time for surgery was 200 min (range, 180-220 min). There was no mortality and no postoperative complications. The mean hospital stay was 4 days (range, 3-5 days). This technique can be performed laparoscopically with all the advantages inherent to the minimally invasive approach.

[A surprising reason for consulting: wires projecting from the anus, a rare complication of intra uterine device insertion]. / Un motif de consultation surprenant: la perception de fils sortant par l'anus. à propos d'une complication rare de la pose de DIU.

Rectal perforation by migration of an intrauterine device is a rare complication which gynecologists must be aware of. Treatment can associate endoscopic examinations and a surgical procedure.

Internal hernia after mini-gastric bypass: Myth or reality?

The mini-gastric bypass (MGBP) is becoming an increasingly popular procedure worldwide. It is based on an "omega" reconstruction, resulting in a single anastomosis and in potential shortening of operative time. Internal hernia represents a potentially life-threatening complication after laparoscopic Roux-en-Y gastric bypass, but it has not yet been reported after a mini-gastric bypass. We herein describe, for the first time, a case of internal hernia after this surgery.

Risk of Dumping Syndrome after Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: Early Results of a Multicentre Prospective Study.

Background. Bariatric surgery is an important field of surgery. An important complication of bariatric surgery is dumping syndrome (DS). Aims. To evaluate the incidence of DS in patients undergoing bariatric surgery. Methods. 541 patients included from 5 nutrition and bariatric centers in France underwent either LSG or LRYGB. They were evaluated at 1 month (M1) and 6 months (M6) postoperatively by an interview and completion of a dumping syndrome questionnaire. Results. 268 patients underwent LSG (Group A) and 273 underwent LRYGB. From the LRYGB patients 229 had mechanical gastrojejunoanal anastomosis with 30 mm linear stapler (Group B) and 44 had manual (hand sewn) 15 mm gastrojejunal anastomosis (Group C). Overall incidence of DS was 8.5% at M1 and M6. In LSG group (Group A), only 4 patients (1.49%) reported episodes of DS at M1 and 3 (1.12%) at M6. In Group B, 41 patients (17.90%) reported episodes of DS at M1 and 43 (18.78%) at M6. Group C experienced one case (2.27%) of DS at M1 and none (0%) at M6. Conclusions. Patients undergoing LRYGB, especially with larger gastrojejunal anastomosis, are more prone to developing DS following surgery than patients undergoing LSG or LRYGB with calibrated manual anastomosis.

Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.

Turcot's syndrome is a genetic disease characterized by the concurrence of primary brain tumors and colon cancers and/or multiple colorectal adenomas. We report a Turcot family with no parental consanguinity, in which two affected sisters, with no history of tumors in their parents, died of a brain tumor and of a colorectal tumor, respectively, at a very early age. The proband had a severe microsatellite instability (MIN) phenotype in both tumor and normal colon mucosa, and mutations in the TGFbeta-RII and APC genes in the colorectal tumor. We identified two germline mutations within the PMS2 gene: a G deletion (1221delG) in exon 11 and a four-base-pair deletion (2361delCTTC) in exon 14, both of which were inherited from the patient's unaffected parents. These results represent the first evidence that two germline frameshift mutations in PMS2, an MMR gene which is only rarely involved in HNPCC, are not pathogenic per se, but become so when occurring together in a compound heterozygote. The compound heterozygosity for two mutations in the PMS2 gene has implications for the role of protein PMS2 in the mismatch repair mechanism, as well as for the presymptomatic molecular diagnosis of at-risk family members. Furthermore, our data support and enlarge the notion that high DNA instability in normal tissues might trigger the development of cancer in this syndrome.

Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether the addition of gemcitabine (G) to vinorelbine (V) improves survival and quality of life (QoL) among elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC aged >/= 70 years with advanced disease were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1,200 mg/m(2) + V 30 mg/m(2) on days 1 and 8 every 3 weeks. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned based on the first 60 patients per arm. RESULTS: In May 1999, the survival data were analyzed of 120 eligible patients (V group = 60; G + V group = 60) who had been randomized from June 1997 to February 1999. Forty-nine patients had stage IIIB disease, and 71 had stage IV. At a median potential follow-up of 14 months (range, 3 to 22 months), 93 patients had died (G + V group = 41; V group = 52). In the G + V group, median survival time was 29 weeks and projected 1-year survival was 30%; these values were 18 weeks and 13% in the V group. According to multivariate Cox analysis, the risk of death in the G + V arm compared with the V arm was 0.48 (95% confidence interval, 0. 29 to 0.79; P <.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The overall response rates were 22% and 15% in the G + V and V groups, respectively. CONCLUSION: In elderly patients with NSCLC, G + V treatment is associated with significantly better survival than is V alone.

[Vaginal evisceration. Report of a new case]. / L'éviscération vaginale. A propos d'un nouveau cas.

Vaginal evisceration is rare and most commonly found in postmenopausal women. We report the case of a postmenopausal woman due to ruptured enterocele. Surgical treatment was done through a midline laparotomy and consisted of bowel resection with primary anastomosis and vaginal vault suture repair. Risk factors for this rare clinical entity are discussed along with the different therapeutic options.

[Bowel perforation as late complication of tension-free vaginal tape]. / Perforation intestinale tardive après une opération de TVT.

Tension-free vaginal tape (TVT) is considered as the treatment of choice for female stress urinary incontinence. Bowel erosion is a rare complication of TVT that generally occurs a few days after surgery with a clinical picture of peritonitis and/or intestinal obstruction. Herein is reported a case of a bowel erosion with a late clinical manifestation 3 months after hysterectomy and TVT placement for genital prolapse and urinary incontinence. Bowel erosion may complicate TVT operation several months after surgery and should be considered as differential diagnosis in patients presenting with a clinical picture of peritonitis and/or intestinal obstruction.

ER stress induces NLRP3 inflammasome activation and hepatocyte death.

The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1ß secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1ß secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases.

Heparin-urokinase treatment in aseptic dural sinus thrombosis.

Five patients affected by aseptic dural sinus thrombosis have been treated with a combination of heparin sodium and urokinase. In all of them, the therapy was followed by complete clinical recovery. Postoperative cerebral angiography showed patency of the involved sinuses in all.

Small bowel volvulus resulting from a congenital band treated laparoscopically.

In recent years, laparoscopy has dramatically changed the approach to the patient with acute abdominal pain. We report the case of a patient with small bowel volvulus caused by a congenital band binding the greater omentum to the mesentery, which was promptly diagnosed and treated using laparoscopy. Early intervention averted irreversible ischemic lesions of the intestine and the need for bowel resection. With the routine use of laparoscopy in the setting of acute abdominal pain, rare affections can be easily diagnosed and effectively treated.

Perforation of the ileum due to foreign body treated laparoscopically.

Laparoscopy has gained widespread acceptance in the setting of acute abdominal pain. We report the case of a patient with acute abdominal pain in the right lower quadrant that proved to be due to a fish bone perforation of the ileum at laparoscopy. The fish bone was retrieved and the perforation closed laparoscopically. Laparoscopy is a powerful diagnostic and therapeutic tool and should be used routinely in patients with acute abdominal affections.