OTSC Proctology clip as appropriate treatment for complicated anorectal fistula.

PURPOSE: Evaluation of the effectiveness and tolerability of the application of an OTSC (Ovesco Endoscopy AG Tuebingen, Germany) Proctology clip as an innovative strategy of anorectal fistulae closure when established treatment strategies had already failed or were not feasible. METHODS: Retrospective single-center study including consecutive patients treated between March 2014 and March 2016 with the OTSC Proctology system for anorectal fistula closure, including one rectovaginal and one rectourethral fistula. The primary outcome was the healing rate with a minimum follow up of 6 months. Healing was defined as closure of the internal fistula ostium and absence of secretion or local inflammation during follow up. RESULTS: A total of 66 fistula closures by the OTSC Proctology clip were investigated, including cryptoglandular fistulas (45/66 patients, 68%), fistulas associated with CED (19/66 patients, 29%), and other non-cryptoglandular fistulas (2/66 patients, 4%). 47% (31/66 patients) had a failed previous therapy. In that selected collective, a successful fistula closure was achieved in 29/66 cases (44%) after a median follow up time of 40 months (6-61 months). Suprasphincteric and high transsphincteric fistulas showed healing in 63% and 42% in CD associated fistulas. CONCLUSION: Fistula closure by the OTSC Proctology clip is an innovative, sphincter protecting treatment strategy in anorectal fistulas that can achieve long-term cure in complex anorecta.

[A Challenge: Colorectal Foreign Bodies]. / Kolorektale Fremdkörper ­ eine Herausforderung für Patient und Arzt.

BACKGROUND: Colorectal foreign bodies are commonly seen in the emergency department. A delayed consultation may be associated with a worse outcome. Despite a low-lying position, the extraction can be a challenge and has to be done under general anesthesia. Sharp or potentially dangerous foreign bodies should be excluded before extraction manoeuvres and complications have to be ruled out after the retrieval. METHOD: Data were retrospectively collected from 2002 to 2017. Overall 33 patients were included. In addition, a systematic search, employing the PRISMA criteria, was performed. The search was carried out on PubMed (1623), Cochrane Library (17) and Google Scholar (300). Case reports, papers not written in English and publications before 1980 were excluded. RESULTS: With an average delay of 33 h, patients admitted themselves to the emergency department. Attempts to remove foreign bodies in the emergency department were successful in 2 cases (6%). General anaesthesia was required in 31 (94%) patients. An emergency laparotomy was necessary in 3 cases (9%). No complications were noticed. CONCLUSION: A delayed consultation is not associated with a worse outcome. Complications should be ruled out by endoscopy. After a normal control, the patient can be discharged prematurely without further imaging.

Purse-string closure technique reduces the incidence of incisional hernias following the reversal of temporary ileostomy.

PURPOSE: The incidence of incisional hernia (IH) at ileostomy closure site has not been sufficiently evaluated. Temporary loop ileostomy is routinely used in patients after low anterior resection for rectal cancer. The goal of this study was to compare the IH rates of standard suture skin closure and purse-string skin closure techniques. PATIENTS AND METHODS: Patients undergoing ileostomy reversal and follow-up CT scan at the University Hospital Frankfurt between January 2009 and December 2015 were retrospectively analyzed regarding IH and associated risk factors. Patients received either direct stitch skin closure (group DC) or purse-string skin closure (group PS). RESULTS: In total, 111 patients underwent ileostomy reversal in the aforementioned period. In 88 patients, a CT scan was performed 12-24 months after ileostomy reversal for cancer follow-up. Median follow-up was 12 months. Median time interval between ileostoma formation and closure was 12 (± 4 SD) weeks. In 19 of 88 patients (21.5%), an IH was detected. The incidence of IH detected by CT scan was significantly lower in the PS group (n = 7, 12.9%) compared to the DC group (n = 12, 35.2%, p = 0.017). CONCLUSIONS: This retrospective study shows an advantage of the purse-string skin closure technique in ileostomy reversals. The use of this technique for skin closure following ileostomy reversals is recommended to reduce the IH rates. Randomized controlled trials are needed to confirm these findings.

Bad bacteria in acute appendicitis: rare but relevant.

PURPOSE: Bacterial infections are a factor for morbidity in patients with acute appendicitis (AA). The spreading of multidrug-resistant (MDR) bacteria is a significant problem in surgery, and the most relevant MDR pathogens are summarized as Enterobacteriaceae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci (ESKAPE) bacteria. Data regarding the species and distribution of bacteria in AA are available, but information about the resistances and their relevance is deficient. METHODS: In this retrospective study, we analyzed microbiological swabs of patients with AA. The outcome parameters of patients after laparoscopic appendectomy were analyzed against microbiological results, including antibiotic resistance testing. Positive swabs were compared with bacteria cultivated after alternative abdominal emergency surgery (AES). RESULTS: In total, 584 patients with AA were included and had a mean age of 35.5 years. In 216 patients (36.9%), a swab was taken, and in 128 (59.3%) swabs, bacteria could be cultivated. The most frequent organisms were Escherichia coli, Bacteroides species, and Pseudomonas. In 9.4% of the positive AA swabs, MDR germs were cultivated, and all of them were ESKAPE pathogens. Patients with MDR bacteria in AA suffered more infectious complications (p = 0.006) and needed longer hospitalizations (p < 0.009). In AES, aside from appendicitis, a different spectrum containing more MDR bacteria was cultivated (5.9 vs. 20.9%; p < 0.0001). CONCLUSIONS: Although they occur less frequently in appendectomy compared to emergency surgeries for other abdominal diseases, MDR bacteria are traceable in this common disease and contribute to additional morbidity.

Salvage abdominoperineal excisions in recurrent anal cancer--impact of different reconstruction techniques on outcome, morbidity, and complication rates.

BACKGROUND: Squamous cell cancer of the anus (SCCA) is a rare disease of the gastrointestinal tract. Even though chemoradiation therapy is the treatment of choice, a substantial number of patients develop recurrent cancers or present with persisting SCCA. Therefore, abdominoperineal excisions as a salvage therapy are the only chance of cure. PATIENTS AND METHODS: Hospital files of all patients with recurrent squamous cell carcinoma of the anus who underwent abdominoperineal excision performed at the Department of General and Visceral Surgery of the University Hospital Frankfurt between January 2003 and December 2013 were retrospectively reviewed. RESULTS: Fourteen (nine males, five females) patients underwent abdominoperineal resections for recurrent SCCA. In six patients, the pelvic floor was closed by direct suture, four patients underwent reconstruction using a vertical rectus abdominis myocutaneous (VRAM) flap, and four patients received a gluteal myocutaneous flap. Patients receiving flap-mediated closure revealed a median hospital stay of 26 days (range 13-60 days) compared to 11 days (range 9-30 days) in patients with direct closure (p = 0.01). Two patients (14%) suffered from wound infections (Dindo-Clavien II), whereas three patients (21%) underwent up to seven reoperations for breakdown of their wounds and/or laparotomies (Dindo-Clavien IIIb). The calculated 5-year survival rate was 86%. Patients with rpT0/T1 stage had a significantly longer survival compared to patients presenting with rpT2/T3/T4 tumors. CONCLUSION: Abdominoperineal excisions in patients with recurrent SCCA can provide long-term local control and survival. The complication rate is not associated with the closure technique employed, but patients undergoing flap-mediated closure revealed a significantly longer hospital stay.

Education in thyroid surgery: a matched-pair analysis comparing residents and board-certified surgeons.

PURPOSE: Resident participation in operative procedures is mandatory in educational residency programs but remains controversial, especially in the context of patient safety. This study compared the surgical quality and outcomes of thyroidectomies performed by surgical residents (RESs) and board-certified surgeons (BCSs). METHODS: This retrospective matched-pair study included patients undergoing thyroidectomies for multinodular goiter, Grave's disease and early-stage thyroid cancer that were performed by a RES with BCS supervision between 2006 and 2014. The intraoperative and postoperative course, complication rates and handling of the recurrent laryngeal nerve (RLN) and parathyroid glands were analyzed. RESULTS: In total, 112 thyroidectomies that were performed by a RES fulfilled the inclusion criteria and were matched 1:1 with BCS patients. We included 88 hemithyroidectomies, 80 subtotal thyroidectomies and 56 total thyroidectomies. No significant differences in the handling of the RLN or parathyroid glands, the rates of postoperative RLN palsies or the rates of hypocalcaemia were found. No intraoperative complications led to the replacement of the RES as the surgeon-in-charge. Three RES and two BCS patients experienced postoperative haemorrhages (p = 0.205), and three surgical site infections (p = 1.000) occurred in each group. The mean operative time and the length of stay did not differ significantly between the two groups. CONCLUSIONS: Major aspects of patient safety in thyroid surgery are not affected by resident participation. Thyroidectomies performed by RES are not significantly longer and reveal no differences in length of stay or complication rates. The economic burden of resident involvement is modest.

The use of purse-string skin closure in loop ileostomy reversals leads to lower wound infection rates--a single high-volume centre experience.

PURPOSE: Wound infections affect not only the individual patient but lead to an increase in medical costs. After ileostomy reversal, surgical site infections are a common problem. The objective of the study was to compare the infection rates of purse-string and conventional skin closure techniques in a high volume setting. METHODS: Patients undergoing ileostomy reversal at the Goethe University Hospital between January 2009 and August 2012 were retrospectively analysed regarding surgical site infections and associated risk factors. Patients received either conventional skin closure (running, interrupted or stapled suturing; group C) or subcuticular purse-string suture (group PS). RESULTS: In total, 114 patients have been analysed. Conventional wound closure was performed in 81 patients and 33 patients received purse-string skin closure. The groups did not differ regarding age, gender, indication for ileostomy, previous chemotherapy, and operation time. Median hospital stay was 7 days (3-34) in group PS and 8 (3-53) in group C (p = 0.15). Wound infections only occurred in groups C (n = 10, 12 %) compared to group PS (n = 0; 0 %; p = 0.034), and the wound closure technique was the only significant factor associated with surgical site infection. Surgery performed by a resident under supervision was not a risk factor for complications compared to the procedure done by a senior surgeon (p = 0.73). CONCLUSION: This study reveals an advantage of the purse-string skin closure technique in ileostomy reversals analysing a large cohort of patients. Therefore, we recommend the use of the purse-string skin closure in ileostomy reversals as one way to lower wound infection rates.

Urapidil in the preoperative treatment of pheochromocytomas: a safe and cost-effective method.

BACKGROUND: Surgery for pheochromocytoma may lead to uncontrolled catecholamine secretion with severe hypertension and cardiac failure. Perioperative α1-receptor-blockade with orally administered phenoxybenzamine or intravenous urapidil therefore is a standard procedure in the treatment regime prior to surgery. METHODS: Medical records of 30 patients who underwent surgery for pheochromocytoma during the years 2002-2011 were retrospectively analyzed. We investigated the difference in the clinical course of patients undergoing surgery for pheochromocytoma with either phenoxybenzamine or urapidil pretreatment with special regard to the intraoperative course and length of hospital stay and costs. RESULTS: Nineteen (16 female, 3 male) patients (63 %) received a preoperative α-block with orally administered phenoxybenzamine. Eleven patients (6 female, 5 male) (37 %) were treated with intravenous urapidil for 3 days prior to surgery. Intraoperative episodes of hypertension or hypotension did not differ significantly. The median total hospital stay in phenoxybenzamine-treated patients was 17 days in contrast to 11 days in the urapidil group (p = 0.0087). Patients who received i.v. pretreatment spent significantly fewer days in the hospital prior to operation [median: 3 days (range: 3-7 days) versus 9 days (range: 3-21 days); p = 0.0001]. The reduction in the number of days in the hospital in the urapidil group led to a significantly elevated revenue per day (637.49/day versus 412.50/day; p = 0.001). CONCLUSIONS: Perioperative treatment with the selective α1 blocker urapidil remains a simple and cost effective method in the treatment regime of patients with pheochromocytoma.

Outcome of surgery for ileojejunal neuroendocrine tumors.

PURPOSE: Neuroendocrine tumors (NET) of the ileum/jejunum are rare and may require different treatment options to provide long-term survival. The purpose of the study was to evaluate the outcome of surgery for ileojejunal NET. METHODS: A database of patients that underwent surgery for ileojejunal NETs between 1999 and 2010 was retrospectively analyzed regarding the clinical characteristics, surgical therapy, survival and prognostic factors. RESULTS: Only six of 97 patients with ileojejunal NET who underwent surgery had localized tumors (stage I/II), 29 had lymph node involvement (stage III) and 62 had distant metastases (stage IV) at the initial presentation. All stage I/II tumors were cured, in comparison to 69% of stage III and 0% of stage IV tumors (p = 0.01). Palliative surgery in combination with sequential multimodal treatment regimens resulted in a 5-year survival rate of 63% in patients with stage IV tumors. A multivariate analysis showed that incomplete resection (HR 2.87; CI 1.18-6.98; p = 0.04) and distant metastases (HR 5.39; 95% CI 1.23-23.57; p = 0.02) were associated with worse disease-specific survival. CONCLUSIONS: Localized and regionally restricted ileojejunal NETs have an excellent prognosis after surgical treatment. Although stage IV tumors cannot be cured, an aggressive surgical approach in combination with medical or interventional treatment can provide long-term survival.

Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice.

Pancreatic ductal adenocarcinoma (PDAC) is believed to arise through a multistep model comprised of putative precursor lesions known as pancreatic intraepithelial neoplasia (PanIN). Recent genetically engineered mouse models of PDAC demonstrate a comparable morphologic spectrum of murine PanIN (mPanIN) lesions. The histogenesis of PanIN and PDAC in both mice and men remains controversial. The most faithful genetic models activate an oncogenic Kras(G12D) knockin allele within the pdx1- or ptf1a/p48-expression domain of the entire pancreatic anlage during development, thus obscuring the putative cell(s)-of-origin from which subsequent mPanIN lesions arise. In our study, activation of this knockin Kras(G12D) allele in the Elastase- and Mist1-expressing mature acinar compartment of adult mice resulted in the spontaneous induction of mPanIN lesions of all histological grades, although invasive carcinomas per se were not seen. We observed no requirement for concomitant chronic exocrine injury in the induction of mPanIN lesions from the mature acinar cell compartment. The acinar cell derivation of the mPanINs was established through lineage tracing in reporter mice, and by microdissection of lesional tissue demonstrating Cre-mediated recombination events. In contrast to the uniformly penetrant mPanIN phenotype observed following developmental activation of Kras(G12D) in the Pdx1-expressing progenitor cells, the Pdx1-expressing population in the mature pancreas (predominantly islet beta cells) appears to be relatively resistant to the effects of oncogenic Kras. We conclude that in the appropriate genetic context, the differentiated acinar cell compartment in adult mice retains its susceptibility for spontaneous transformation into mPanIN lesions, a finding with potential relevance vis-à-vis the origins of PDAC.

Hedgehog signaling is required for effective regeneration of exocrine pancreas.

Although both endocrine and the exocrine pancreas display a significant capacity for tissue regeneration and renewal, the existence of progenitor cells in the adult pancreas remains uncertain. Using a model of cerulein-mediated injury and repair, we demonstrate that mature exocrine cells, defined by expression of an Elastase1 promoter, actively contribute to regenerating pancreatic epithelium through formation of metaplastic ductal intermediates. Acinar cell regeneration is associated with activation of Hedgehog (Hh) signaling, as assessed by up-regulated expression of multiple pathway components, as well as activation of a Ptch-lacZ reporter allele. Using both pharmacologic and genetic techniques, we also show that the ability of mature exocrine cells to accomplish pancreatic regeneration is impaired by blockade of Hh signaling. Specifically, attenuated regeneration in the absence of an intact Hh pathway is characterized by persistence of metaplastic epithelium expressing markers of pancreatic progenitor cells, suggesting an inhibition of redifferentiation into mature exocrine cells. Given the known role of Hh signaling in exocrine pancreatic cancer, these findings may provide a mechanistic link between injury-induced activation of pancreatic progenitors and subsequent pancreatic neoplasia.

Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer.

Aberrant expression of microRNAs (miRNAs) has emerged as an important hallmark of cancer. However, the putative mechanisms regulating miRNAs per se are only partially known. It is well established that many tumor suppressor genes in human cancers are silenced by chromatin alterations, including promoter methylation and histone deacetylation. We postulated that miRNAs undergo similar epigenetic inactivation in pancreatic cancer. Two human pancreatic cancer cell lines - MiaPACA-2 and PANC-1 - were treated with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC) or the histone deacetylase inhibitor, trichostatin A, as well as the combination of the two. Expression of miRNAs in control and treated cell lines was assessed using a custom microarray platform. Fourteen miRNAs were upregulated two-fold or greater in each of the cell lines following exposure to both chromatin-modifying agents, including 5 that were in common (miR-107, miR-103, miR-29a, miR-29b, and miR-320) to both MiaPACA-2 and PANC-1. The differential overexpression of miR-107 in the treated cancer cell lines was confirmed by Northern blot assays. Methylation-specific PCR assays for assessment of CpG island methylation status in the 5' promoter region of the miR-107 primary transcript demonstrated complete loss of methylation upon exposure to 5-Aza-dC. Enforced expression of miR-107 in MiaPACA-2 and PANC-1 cells downregulated in vitro growth, and this was associated with repression of the putative miR-107 target, cyclin-dependent kinase 6, thereby providing a functional basis for the epigenetic inactivation of this miRNA in pancreatic cancer.

Screening of patients with multiple endocrine neoplasia type 1 (MEN-1): a critical analysis of its value.

BACKGROUND: Screening of multiple endocrine neoplasia type 1 (MEN-1) patients is widely recommended because one-fifth succumb to malignant neoplasms. However, recommendations for screening modalities and intervals are based mostly on nonprospective data. METHODS: Thirty-five of 48 MEN-1 patients were evaluated at least twice by an annual screening program in a single-center, prospective, nonrandomized study between 1997 and 2006. The screening program comprised anamnesis, clinical examination, imaging procedures, and extensive biochemical evaluations. Prospectively diagnosed lesions were evaluated separately from nonprospectively diagnosed lesions at first evaluation. RESULTS: The median age of the patients was 45 years (range = 15-70) at initial assessment. They were followed for a median of 72 months (range = 24-108) by a median of 6 (range = 2-10) evaluations. The vast majority of lesions were nonprospectively diagnosed at initial evaluation: 13 of 17 patients had primary hyperparathyroidism (pHPT), 24 of 29 had pancreatic endocrine tumors (PETs), and 4 of 4 had carcinoids. Vice versa adrenal lesions were mostly prospectively detected (18/23). Malignancy was observed in 10 patients (28%) in the initial assessment and without symptoms in 5 patients (9 PETs, 3 carcinoids). Endoscopic ultrasound (EUS) of 29 patients detected 88 PETs which were followed for 157 patient years. The mean annual growing rate was 13.28 +/- 28.23 mm with respect to the baseline tumor diameter of 9 mm. In 35 patients the mean incidence of newly diagnosed PETs was 0.52/year. Adrenal lesions were invariably nonfunctional. A mean change in diameter of 6.7 +/- 23.44% was monitored and malignant transformation was absent. CONCLUSIONS: Most lesions are detected at initial screening, particularly malignant tumors. Computed tomography of the abdomen and chest did not identify additional lesions. The interval between screenings could be extended to 3 years based on annually calculated growth rates and the incidence of MEN-1-associated lesions. The assessment of calcium, gastrin, and prolactin is sufficient for biochemical screening in MEN-1.

An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer.

Recent evidence suggests that blockade of aberrant Hedgehog signaling can be exploited as a therapeutic strategy for pancreatic cancer. Our previous studies using the prototype Hedgehog small-molecule antagonist cyclopamine had shown the striking inhibition of systemic metastases on Hedgehog blockade in spontaneously metastatic orthotopic xenograft models. Cyclopamine is a natural compound with suboptimal pharmacokinetics, which impedes clinical translation. In the present study, a novel, orally bioavailable small-molecule Hedgehog inhibitor, IPI-269609, was tested using in vitro and in vivo model systems. In vitro treatment of pancreatic cancer cell lines with IPI-269609 resembled effects observed using cyclopamine (i.e., Gli-responsive reporter knockdown, down-regulation of the Hedgehog target genes Gli1 and Ptch, as well as abrogation of cell migration and colony formation in soft agar). Single-agent IPI-269609 profoundly inhibited systemic metastases in orthotopic xenografts established from human pancreatic cancer cell lines, although Hedgehog blockade had minimal effect on primary tumor volume. The only discernible phenotype observed within the treated primary tumor was a significant reduction in the population of aldehyde dehydrogenase-bright cells, which we have previously identified as a clonogenic tumor-initiating population in pancreatic cancer. Selective ex vivo depletion of aldehyde dehydrogenase-bright cells with IPI-269609 was accompanied by significant reduction in tumor engraftment rates in athymic mice. Pharmacologic blockade of aberrant Hedgehog signaling might prove to be an effective therapeutic strategy for inhibition of systemic metastases in pancreatic cancer, likely through targeting subsets of cancer cells with tumor-initiating ("cancer stem cell") properties.

The Safety Level of Total Central Venous Access Port Implantation Performed by Residents.

OBJECTIVE: The implantation of totally implantable venous access ports (TIVAPs) is one of the first procedures surgical residents learn. Complications after implantation procedures have a major impact on patient outcomes, as it may lead to a delay of chemotherapy regimens or of parenteral nutrition. The aim of this study was to compare the outcomes after totally implantable venous access ports implantations done by resident and attending surgeons. DESIGN: The study was performed as a retrospective analysis. SETTING: The study took place in primary care at the Department of General and Visceral Surgery at Frankfurt University Hospital. PARTICIPANTS: A total of 760 primary totally implantable venous access ports implantations performed between March 2008 and December 2016 were included in a database. Three groups of surgeons doing the implantations were defined: Group A (residents alone), Group B (resident with help), and Group C (attending surgeons). RESULTS: There was a significant difference between the surgeon groups in operation time (p < 0.001). The groups differed between Group A (mean, 49; SD, 22) and Group C (mean, 39; SD, 20); p < 0.001) and Group B (mean, 53; SD, 23) and Group C (mean, 39; SD, 20; p < 0.001). The incidence of surgical site infections between Groups A and C (3.6% vs. 0.3%; p = 0.003) and Groups B and C (2.5% vs. 0.3%; p = 0.027) differed also significantly. Based on multivariable logistic regression analysis operation time in minutes (OR, 1.04; 95%CI, 1.03-1.06; p < 0.001) was an independent risk factor for any intraoperative complications. For any postoperative complications younger age of the patient (OR, 0.98; 95%CI, 0.97-0.99; p = 0.004) and benign primary disease (OR, 3.25; 95%CI, 1.55-6.64; p = 0.002) were independent risk factors based on multivariable regression analysis. Based on multivariable regression analysis a lower body mass index of the patient (OR, 0.93; 95%CI, 0.86-0.99; p = 0.044), benign primary disease (OR, 2.89; 95%CI, 1.07-7.79; p = 0.036), and no chemotherapy (OR, 3.55; 95%CI, 1.50-8.39; p = 0.004) were independent risk factors for postoperative catheter infections. Surgeon group was no risk factor, neither for intraoperative and postoperative complications, nor for catheter explantation due to complications. CONCLUSION: Residents performing alone or residents performing with help can safely handle a central venous access port implantation. In patients with several risk factors, however, an attending should assist.

Characteristics and management of penetrating abdominal injuries in a German level I trauma center.

PURPOSE: Penetrating abdominal injuries caused by stabbing or firearms are rare in Germany, thus there is lack of descriptive studies. The management of hemodynamically stable patients is still under dispute. The aim of this study is to review and improve our management of penetrating abdominal injuries. METHODS: We retrospectively reviewed a 10-year period from the Trauma Registry of our level I trauma center. The data of all patients regarding demographics, clinical and outcome parameters were examined. Further, charts were reviewed for FAST and CT results and correlated with intraoperative findings. RESULTS: A total of 115 patients with penetrating abdominal trauma (87.8% men) were analyzed. In 69 patients, the injuries were caused by interpersonal violence and included 88 stab and 4 firearm wounds. 8 patients (6.9%) were in a state of shock at presentation. 52 patients (44.8%) suffered additional extraabdominal injuries. 38 patients were managed non-operatively, while almost two-thirds of all patients underwent surgical treatment. Hereof, 20 laparoscopies and 3 laparotomies were nontherapeutic. There were two missed injuries, but no patient experienced morbidity or mortality related to delay in treatment. 106 (92.2%) FAST and 91 (79.3%) CT scans were performed. Sensitivity and specificity of FAST were 59.4 and 94.2%, while those of CT were 93.2 and 85.1%, respectively. CONCLUSION: In hemodynamically stable patients presenting with penetrating abdominal trauma, CT is indicated and the majority of injuries can be managed conservatively. If surgical treatment is required, diagnostic laparoscopy for stable patients is feasible to avoid nontherapeutic laparotomy.

Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors.

BACKGROUND: Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset of invasive cancer. Biomarker discovery in precursor lesions has been hampered by the ready availability of fresh specimens, and limited yields of proteins suitable for large scale screening. METHODS: We utilized Liquid Tissue, a novel technique for protein extraction from archival formalin-fixed material, and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. RESULTS: The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed their overexpression in IPMNs. CONCLUSION: Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer.

Morphogenesis of pancreatic cancer: role of pancreatic intraepithelial neoplasia (PanINs).

INTRODUCTION: Pancreatic ductal adenocarcinoma (i.e., pancreatic cancer) is an almost universally lethal disease. The identification of precursor lesions of pancreatic cancer provides an opportunity for early detection and potential therapeutic intervention before the development of invasive cancer. DISCUSSION: It is now established that pancreatic cancers do not arise de novo but rather exhibit a sequential histological and genetic progression of precursor lesions culminating in frank, invasive neoplasia. Pancreatic intraepithelial neoplasia (PanIN) is the most common non-invasive precursor lesion of pancreatic cancer. The development of a consensus nomenclature scheme for PanINs has facilitated research into pancreatic cancer precursors and enabled standardization of results across institutions. CONCLUSION: PanINs harbor many of the molecular alterations observed in invasive pancreatic cancer, confirming their status as true non-invasive precursor lesions. Recently developed genetically engineered mouse models of pancreatic cancer also demonstrate the stepwise PanIN progression model, underscoring the commonalities in pancreatic neoplasia between mouse and man.

PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells.

The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent Apc Min/+ mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.

Identification of methylation-associated gene expression in neuroendocrine pancreatic tumor cells.

BACKGROUND: CpG islands methylation is the main epigenetic modification found in human tumors leading to transcriptional silencing of certain tumor suppressor genes. Reacquisition of p16/CDKN2A tumor suppressor gene expression by 5-aza-2'-deoxycytidine results in concurrent growth inhibition of neuroendocrine pancreatic tumor cells. However, the growth suppressive effects of 5-aza-2'-deoxycytidine is unlikely to be solely attributable to the restored p16/CDKN2A function, but rather a consequence of re-expression of additional genes silenced by de novo methylation. In an effort to validate DNA methylation as an important mechanism in neuroendocrine tumorigenesis and metastatic spread, we attempted to isolate methylation-specific transcripts in neuroendocrine pancreatic tumor cells. METHODS: Differentially expressed methylation-associated genes were identified by cDNA-representational difference analysis (cDNA-RDA). Differential expression was confirmed by semiquantitative RT-PCR using insert specific primers. RESULTS: We identified 48 differently expressed gene fragments and methylation-associated expression was confirmed by semi-quantitative RT-PCR. 52,3% (25 of 48) showed elevated expression levels after 5-aza-2'-deoxycytidine treatment, whereas 47.7% revealed lower expression levels. 7 fragments showed homology to genes with unknown function. Interestingly, 5-aza-2'-deoxycytidine treatment led to re-expression of cofillin whereas matriptase expression levels were significantly lower. Both genes have been associated with metastatic spread and tissue invasion. The other differentially expressed genes play an unknown role in the course of neuroendocrine tumorigenesis. CONCLUSION: DNA methylation appears to be an important molecular mechanism in the process of neuroendocrine pancreatic tumorigenesis and metastatic spread. The definition of DNA methylation patterns associated with neuroendocrine pancreatic tumors might open up the potential for a new sensitive diagnostic tool and might serve as a new antitumor target.