Perineal hernia repair after abdominoperineal rectal excision with prosthetic mesh-a single surgeon experience.

AIM: Extralevator abdominoperineal excision for rectal cancer is associated with an increased incidence of perineal hernia. The purpose of this study was to determine clinical outcome following perineal hernia repair with prosthetic mesh by a perineal open approach. METHODS: We present a case series of 10 patients who underwent 12 repairs of their hernia using a prosthetic mesh placed by a perineal open technique. Patients were identified from a prospectively maintained database and their case records were retrieved along with their imaging and analysed retrospectively. RESULTS: Perineal hernia incidence in our series is 10%. The median age was 73 ± 5.9 years. No gender predilection was found. The median time interval between extralevator abdominoperineal excision and surgical repair of perineal hernia was 25.3 months. The surgical approach was perineal with the use of a double layer prosthetic mesh. The recurrence ratio was 30% (n = 3). Overall morbidity was also 30% with no major complications (Clavien-Dindo I-II). Recurrence following primary repair was diagnosed in a median time interval of 28.3 ± 16.57 months. Two patients had repeat surgery to treat their recurrence. CONCLUSIONS: Our small series supports the use of a prosthetic mesh repair of perineal hernias through a perineal approach. It is safe and effective with complication rates similar to those previously reported.

Results of pancreatic surgery in the elderly: is age a barrier?

BACKGROUND: By 2033, the number of people aged 85 years and over in the UK is projected to double, accounting for 5% of the total population. It is important to understand the surgical outcome after a pancreatic resection in the elderly to assist decision making. METHODS: Over a 9-year period (from January 2000 to August 2009), 428 consecutive patients who underwent a pancreatic resection were reviewed. Data were collected on mortality, complications, length of stay and survival. Patients were divided into two groups (younger than 70 and older than 70 years old) and outcomes were analysed. RESULTS: In all, 119 (27.8%) patients were ≥ 70 years and 309 (72.2%) patients were < 70 years. The median length of stay for the older and younger group was 15 days (range 3-91) and 14 days (range 3-144), respectively. The overall mortality was 3.4% in the older group and 2.6% in the younger group (P = 0.75). The older cohort had a cumulative median survival of 57.3 months (range 0-119), compared with 78.7 months (range 0-126) in the younger cohort (P < 0.0001). In patients undergoing a pancreatic resection for ductal adenocarcinoma and cholangiocarcinoma there was a significant difference in survival with P-values of 0.043 and 0.003, respectively. For ampullary adenocarcinoma, the older group had a median survival of 47.1 months compared with 68.3 months (P = 0.194). CONCLUSION: Results from this study suggest that while elderly patients can safely undergo a pancreatic resection and that age alone should not preclude a pancreatic resection, there is still significant morbidity and mortality in the octogenarian subgroup with poor long-term survival with the need for quality-of-life assessment.

Results of the Eighth Scientific Workshop of ECCO: Pathophysiology and Risk Factors of Postoperative Crohn's Disease Recurrence after an Ileocolonic Resection.

Postoperative recurrence [POR] after an ileocolonic resection with ileocolonic anastomosis is frequently encountered in patients with Crohn's disease. The 8th Scientific Workshop of ECCO reviewed the available evidence on the pathophysiology and risk factors for POR. In this paper, we discuss published data on the role of the microbiome, the mesentery, the immune system and the genetic background. In addition to investigating the causative mechanisms of POR, identification of risk factors is essential to tailor preventive strategies. Potential clinical, surgical and histological risk factors are presented along with their limitations. Emphasis is placed on unanswered research questions, guiding prevention of POR based on individual patient profiles.

Pancreatic carcinoma masquerading as groove pancreatitis: case report and review of literature.

CONTEXT: Groove pancreatitis is a distinct form of chronic pancreatitis affecting the space surrounded by the pancreatic head, duodenum and common bile duct. It is an uncommon pancreatic disease with challenging imaging diagnosis that can lead to surgical dilemmas. The purpose of this study is to report a case and review the current clinical, radiological and pathological characteristics of groove pancreatic carcinoma and groove pancreatitis. CASE REPORT: A 58-year-old man, with a history of alcohol excess, presented with a 4 month history of upper abdominal pain associated with weight loss and vomiting. Failed duodenal dilatation led to gastroenterostomy with biopsies showing chronic inflammation. Further presentation with jaundice and pancreatic groove mass led to a Whipple's pancreaticoduodenectomy. Histopathology report demonstrated cystic areas in both medial and lateral walls of his duodenum microscopically consistent with groove pancreatitis and a moderate to poorly differentiated adenocarcinoma. CONCLUSION: Several studies have been attempted to clarify the points of differentiation between carcinoma and pancreatitis in the groove area. This discrimination has been proved to be difficult; frequently the definitive diagnosis is only obtained after surgical intervention. This condition should be considered when making the differential diagnosis in pancreatic groove pathology and duodenal stenosis.

Late Complications After Endoscopic Sphincterotomy.

The introduction of endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (ES) has changed the treatment of choledocholithiasis. An increasing number of young patients are requiring ES, and this raises concern regarding any potential long-term complications arising from irreversibly altering the anatomy of the sphincter of Oddi. In particular, concern has been raised regarding the risk of late cholangiocarcioma. A review was performed evaluating the relationship between ES for benign disease and the subsequent development of late complications, including biliary tract malignancy, the formation of primary duct stones, and recurring cholangitis. A systematic review of articles published between 1970 and 2013 was undertaken. Current evidence shows that ES is a safe and effective treatment for common bile duct stones. The long-term risk of subsequent cholangiocarcinoma has not been convincingly proven although in many of these studies the follow-up period was inadequate. There does appear to be an associated increased incidence of cholangiocarcinomas following sphincterotomy although this is not proven to be causative. If there is an increased risk of cholangiocarcinoma following ES, it is likely to be small in western populations. However, until longer follow-up studies are published, it may be prudent to avoid ES in the very young.

EGFR and KRAS mutational analysis and their correlation to survival in pancreatic and periampullary cancer.

OBJECTIVES: Pancreatic and periampullary cancers have a high incidence of activating KRAS mutations. The aim of this study was to determine the incidence of KRAS and EGFR mutations in pancreatic and periampullary cancers and their relationship with survival. METHODS: One hundred patients undergoing pancreaticoduodenectomy or pancreatic biopsy for cancer were recruited. Samples of formalin-fixed paraffin-embedded or fresh pancreatic tissue were obtained. EGFR was analyzed by DNA sequencing of exons 18 to 21. KRAS was analyzed by pyrosequencing of codons 12, 13, and 61. RESULTS: EGFR mutations were found in 2 (2.3%) of 88 assessable cases. One in exon 18 (c.1966C>T, p.Q710X) and 1 in exon 19 (c.2066A>G, p.E734G). A synonymous single-nucleotide polymorphism in exon 20 (c.2361G>A, p.Q787) was identified in 57 (67.8%) of 84 patients studied. Twenty-eight (41.2%) of 68 cases harbored a point mutation in KRAS codon 12 (26 cases) and codon 61 (2 cases). The overall median survival was 308 days (range, 7-2623 days). The presence of KRAS point mutations did not significantly alter median survival time (22.8 vs 28.1 months, P = 0.88). CONCLUSIONS: EGFR somatic mutations are rare in pancreatobiliary malignancies. KRAS mutations are less common than previous reports and do not correlate with survival.

Epidermal growth factor receptor in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

Poly(A) cDNA real-time PCR for indicator gene measurement in cancer.

Microarray gene expression profiling has identified gene signatures or "Indicator" genes predictive of outcome in many cancer types including lymphoma, and more recently pancreatic cancer. This has identified novel and powerful diagnostic and prognostic and generically applicable markers, promising more specific diagnosis and treatment, together with improved understanding of pathobiology. There is now an urgent need to translate these signatures to clinical use. However, gene microarrays rely on relatively large amounts of fresh starting tissue obviating measurement of Indicator genes in routine practice, and there is a need for development of another, simple, robust, relatively inexpensive and sensitive method for their translation to clinical use. We have piloted the use of real-time PCR measurement of specific prognostic genes, so called "Indicator" genes, in globally amplified polyA cDNA for this purpose. Poly(A) PCR coordinately amplifies cDNA copies of all polyadenylated mRNAs, thereby generating a PCR product (polyA cDNA) whose composition reflects the relative abundance of all expressed genes in the starting sample. Poly(A) PCR enables global mRNA amplification from picogram amounts of RNA and has been routinely used to analyse expression in small samples including single cells. The poly(A) cDNA pool generated is also indefinitely renewable and as such represents a "molecular block". Real-time PCR measurement, using gene-specific primers and probes, of the expression levels of specific Indicator genes then allows gene signatures to be detected within the poly(A) cDNA, thereby enabling expression profiling of very small amounts of starting material. This chapter details this method as applied to fresh and paraffin embedded tissue and to pancreatic juice. In this chapter, we have concentrated on application of the method to pancreatic cancer, but the generic nature of the method renders it applicable to any cancer type, thereby representing a novel platform for cancer diagnosis across all tumour types.

Poly(adenylic acid) complementary DNA real-time polymerase chain reaction in pancreatic ductal juice in patients undergoing pancreaticoduodenectomy.

OBJECTIVES: There is a need to develop methods of early diagnosis for pancreatic cancer. Pancreatic juice is easily collected by endoscopic retrograde cholangiopancreatography and may facilitate diagnosis using molecular markers. The aim of this work was to explore the feasibility of measurement of gene expression in RNA isolated from ductal juice. METHODS: Intraoperative sampling of pancreatic juice was undertaken in 27 patients undergoing pancreaticoduodenectomy for suspected tumor. Total RNA was extracted and used as template for poly(adenylic acid) (poly[A]) polymerase chain reaction (PCR) to generate a globally amplified complementary DNA pool representative of all expressed messenger RNAs. Real-time PCR was performed for trefoil factor 2 (TFF2), carboxypeptidase B1 (CPB1), and kallikrein-related peptidase 3 (KLK3) in a subset of samples; all samples were normalized for 3 reference genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH], PSMB6, and beta-2-microglobulin [B2M]). RESULTS: The median volume of the pancreatic juice obtained was 1245 microL (range, 50-5000 microL). The RNA integrity number ranged from 1.9 to 10. Reverse transcriptase PCR was positive for pancreas-specific genes (TFF2 and CPB1) and negative for prostatic-specific antigen in all samples. CONCLUSIONS: These results demonstrate that RNA analysis of pancreatic juice is feasible using a combination of poly(A) PCR and real-time PCR. In addition, the poly(A) complementary DNA generated can be probed for multiple genes and is indefinitely renewable, thereby representing a molecular block of importance for future research.