Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Predictive performance of factors associated with malignancy in intraductal papillary mucinous neoplasia of the pancreas.

BACKGROUND: Estimation of the risk of malignancy in intraductal papillary mucinous neoplasia (IPMN) of the pancreas is a clinical challenge. Several routinely used clinical factors form the basis of the current consensus guidelines. This study aimed to determine the predictive values of the most commonly assessed risk factors. METHODS: A meta-analysis of individual risk factors of malignancy in IPMN was performed. Contingency tables were derived from these data, and sensitivity, specificity, negative and positive predictive values, and diagnostic odds ratios (DOR) were determined. Hierarchical summary receiver operating characteristic (HSROC) curves for each factor were calculated and the respective area under the curve (AUC) was assessed. RESULTS: A total of 3443 studies were screened initially. Analysis of recent literature revealed 60 studies with 13 relevant risk factors including clinical, serological and radiological parameters. The largest area under the HSROC curve was found for weight loss (0·84) and jaundice/raised bilirubin level (0·80), followed by increased carcinoembryonic antigen (CEA) (0·79) or carbohydrate antigen (CA) 19-9 (0·78) levels. The most sensitive factors were patient age (71 per cent) and mural nodules (65 per cent), and jaundice/raised bilirubin level (97 per cent) and increased CEA level (95 per cent) were most specific. None of the analysed factors reached a positive or negative level of prediction beyond 90 per cent. CONCLUSION: None of the established criteria safely distinguishes malignant from non-malignant lesions.

Incidence, risk factors and clinical implications of chyle leak after pancreatic surgery.

BACKGROUND: Chyle leak is a well known but poorly characterized complication after pancreatic surgery. Available data on incidence, risk factors and clinical significance of chyle leak are highly heterogeneous. METHODS: For this cohort study all patients who underwent pancreatic surgery between January 2008 and December 2012 were identified from a prospective database. Chyle leak was defined as any drainage output with triglyceride content of 110 mg/dl or more. Risk factors for chyle leak were assessed by univariable and multivariable analyses. The clinical relevance of chyle leak was evaluated using hospital stay and resolution by 14 days for short-term outcome and overall survival for long-term outcome. RESULTS: Chyle leak developed in 346 (10·4 per cent) of 3324 patients. Pre-existing diabetes, resection for malignancy, distal pancreatectomy, duration of surgery 180 min or longer, and concomitant pancreatic fistula or abscess were independent risk factors for chyle leak. Both isolated chyle leak and coincidental chyle leak (with other intra-abdominal complications) were associated with prolonged hospital stay. Some 178 (87·7 per cent) of 203 isolated chyle leaks and 90 (70·3 per cent) of 128 coincidental chyle leaks resolved with conservative management within 14 days. Initial and maximum drainage volumes were associated with duration of hospital stay and success of therapy by 14 days. Impact on survival was restricted to chyle leaks that persisted at 14 days in patients with cancer undergoing palliative surgery. CONCLUSION: Chyle leak is a relevant complication, with an incidence of more than 10 per cent after pancreatic surgery, and has a major impact on hospital stay. Drainage volume is associated with hospital stay and success of therapy.

[Reconstruction of the distal radioulnar joint using the Herbert ulnar head prosthesis]. / Rekonstruktion des distalen Radioulnargelenks mit der Herbert-Ulnakopfprothese.

OBJECTIVE: To provide painfree forearm rotation in patients with degenerative changes of the distal radioulnar joint (DRUJ). The primary goal is to stabilize the DRUJ in patients with an unstable stump of the distal ulna following resection arthroplasty with the secondary effect of restoring painfree forearm rotation. INDICATIONS: Instability of the distal ulna following various types of resection arthroplasties. Primary or secondary osteoarthritis of the DRUJ. Replacement of an ulnar head destroyed by tumor or trauma. CONTRAINDICATIONS: Longitudinal instability of the forearm (e.g., following an Essex-Lopresti-type of injury, resection of the radial head). Inadequate soft tissue with severe ulnocarpal ligamentous insufficiency. Radial deformity (must be corrected before replacement of the ulnar head). SURGICAL TECHNIQUE: In cases of osteoarthritis of the DRUJ, dorsal exposure of the distal radioulnar joint to the depth of the 5th extensor compartment. Raising of an ulnar-based capsuloretinacular flap by sharp dissection off the ulnar neck proximally and off the dorsal part of the triangular fibrocartilage complex (TFCC) distally. Osteotomy of the distal ulna corresponding to the preoperatively planned size of the prosthesis and removal of the ulnar head, while preserving the attachment of the TFCC within the capsuloretinacular flap. Reaming of the ulnar medullary canal. Insertion of a trial prosthesis. The trial prosthesis has to fit accurately into the shaft with a fluoroscopically documented ulna minus situation of minus 1-2 mm at the wrist joint level. After implanting the definite stem and ulnar head of the Herbert ulnar head prothesis (Martin Medizintechnik®, Tuttlingen, Germany), the capsuloretinacular flap is reattached to the dorsal rim of the sigmoid notch through drilling holes and under advanced tension. In patients with an unstable distal ulnar stump, the operative procedure is technically more demanding as it is more difficult to raise a sufficient capsuloretinacular flap and due to the loss of the ulnar head as an anatomic landmark. POSTOPERATIVE MANAGEMENT: Long arm cast with 70° elbow flexion, 40° forearm supination, and 20° wrist extension for 2 weeks. Subsequently forearm rotation is limited at 40° in a removable ulnar gutter splint. Six weeks postoperatively unlimited active range of motion is allowed and normal activities are gradually commenced. Return to maximum stress 12 weeks postoperatively. RESULTS: Patient satisfaction is high due to an increased forearm rotation, stronger grip force, and remarkable pain relief. In most patients with an unstable distal ulnar stump following resection arthroplasty of the DRUJ, stability can be restored.

[Costal osteoid osteoma]. / Kostales Osteoidosteom.

We report about a rare case of osteoid osteoma of the 9th rib in a 32 year old woman. A search of medical literature yielded only 16 reports about costal osteoid osteoma. This tumor should be considered in cases of painful rib without anamnestic trauma.