Clinical relevance and effect of surgical wound classification in appendicitis: Retrospective evaluation of wound classification discrepancies between surgeons, Swissnoso-trained infection control nurse, and histology as well as surgical site infection rates by wound class.

BACKGROUND: Surgical wound classification (SWC) is used for risk stratification of surgical site infection (SSI) and serves as the basis for measuring quality of care. The objective was to examine the accuracy and reliability of SWC. This study was purposed to evaluate the discrepancies in SWC as assessed by three groups: surgeons, an infection control nurse, and histopathologic evaluation. The secondary aim was to compare the risk-stratified SSI rates using the different SWC methods for 30 d postoperatively. METHODS: An analysis was performed of the appendectomies from January 2013 to June 2014 in the Cantonal Hospital of Schaffhausen. SWC was assigned by the operating surgeon at the end of the procedure and retrospectively reviewed by a Swissnoso-trained infection control nurse after reading the operative and pathology report. The level of agreement among the three different SWC assessment groups was determined using kappa statistic. SSI rates were analyzed using a chi-square test. RESULTS: In 246 evaluated cases, the kappa scores for interrater reliability among the SWC assessments across the three groups ranged from 0.05 to 0.2 signifying slight agreement between the groups. SSIs were more frequently associated with trained infection control nurse-assigned SWC than with surgeons based SWC. CONCLUSIONS: Our study demonstrated a considerable discordance in the SWC assessments performed by the three groups. Unfortunately, the currently practiced SWC system suffers from ambiguity in definition and/or implementation of these definitions is not clearly stated. This lack of reliability is problematic and may lead to inappropriate comparisons within and between hospitals and surgeons.

Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of ß-adrenergic signaling induced similar effects to chronic stress, and pharmacological ß-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural ß-adrenergic signaling regulates pancreatic cancer progression and suggest ß-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

Efficient and safe small-bowel adhesiolysis.

Small-intestine adhesiolysis can be very time consuming and may be associated with bowel wall damage. The risk for injuries to the small or large bowel resulting in increased morbidity and costs is considerable. Both efficient and gentle dissection of adhesions is important in order to avoid intraoperative perforation or, worse, postoperative intestinal leaks. We present a technique using drops of body-warm isotonic saline solution to create an edematous swelling of the adhesions. This procedure not only protects the bowel from cooling and drying, but also simplifies the dissection and, thus, lowers the risk of intestinal lesions.

The silencing of N-myc downstream-regulated gene-1 in an orthotopic pancreatic cancer model leads to more aggressive tumor growth and metastases.

BACKGROUND: The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence. METHODS: Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis. RESULTS: The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015). CONCLUSION: NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.

Lymphotoxin ß receptor signaling promotes development of autoimmune pancreatitis.

BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic pancreatitis. Current treatment options are limited and disease relapse is frequent. We investigated factors that contribute to the development of AIP and new therapeutic strategies. METHODS: We used quantitative polymerase chain reaction, immunohistochemical, and enzyme-linked immunosorbent analyses to measure the expression of cytokines and chemokines in tissue and serum samples from patients with and without AIP. We created a mouse model of human AIP by overexpressing lymphotoxin (LT)α and ß specifically in acinar cells (Ela1-LTab mice). RESULTS: Messenger RNA levels of LTα and ß were increased in pancreatic tissues from patients with AIP, compared with controls, and expression of chemokines (CXCL13, CCL19, CCL21, CCL1, and B-cell-activating factor) was increased in pancreatic and serum samples from patients. Up-regulation of these factors was not affected by corticosteroid treatment. Acinar-specific overexpression of LTαß (Ela1-LTαß) in mice led to an autoimmune disorder with various features of AIP. Chronic inflammation developed only in the pancreas but was sufficient to cause systemic autoimmunity. Acinar-specific overexpression of LTαß did not cause autoimmunity in mice without lymphocytes (Ela1-LTab/Rag1(-/-)); moreover, lack of proinflammatory monocytes (Ela1-LTab/Ccr2(-/-)) failed to prevent AIP but prevented early pancreatic tissue damage. Administration of corticosteroids reduced pancreatitis but did not affect production of autoantibodies, such as antipancreatic secretory trypsin inhibitor in Ela1-LTab mice. In contrast, inhibition of LTßR signaling reduced chemokine expression, renal immune-complex deposition, and features of AIP in Ela1-LTab mice. CONCLUSIONS: Overexpression of LTαß specifically in acinar cells of mice causes features of AIP. Reagents that neutralize LTßR ligands might be used to treat patients with AIP.

Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells.

Scutellaria baicalensis (SB) and SB-derived polyphenols possess anti-proliferative activities in several cancers, including pancreatic cancer (PaCa). However, the precise molecular mechanisms have not been fully defined. SB extract and SB-derived polyphenols (wogonin, baicalin, and baicalein) were used to determine their anti-proliferative mechanisms. Baicalein significantly inhibited the proliferation of PaCa cell lines in a dose-dependent manner, whereas wogonin and baicalin exhibited a much less robust effect. Treatment with baicalein induced apoptosis with release of cytochrome c from mitochondria, and activation of caspase-3 and -7 and PARP. The general caspase inhibitor zVAD-fmk reversed baicalein-induced apoptosis, indicating a caspase-dependent mechanism. Baicalein decreased expression of Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, presumably through a transcriptional mechanism. Genetic knockdown of Mcl-1 resulted in marked induction of apoptosis. The effect of baicalein on apoptosis was significantly attenuated by Mcl-1 over-expression, suggesting a critical role of Mcl-1 in this process. Our results provide evidence that baicalein induces apoptosis in pancreatic cancer cells through down-regulation of the anti-apoptotic Mcl-1 protein.

How do we apply video-assisted retroperitoneal necrosectomy with minimal access?

BACKGROUND: The conservative treatment of acute necrotizing pancreatitis has greatly improved due to broad antibiotic treatment and improved organ support in intensive care units. Nevertheless, infected necrosis or persistent multi-organ dysfunction are predictors of poor outcome. In these patients, there is still a need to perform necrosectomy. Open surgery results in extensive operative trauma and is associated with high morbidity and mortality. Therefore, several minimally invasive techniques have been developed recently. Retroperitoneal necrosectomy has been shown to be safe and to reduce morbidity and mortality compared to the open procedure. METHODS AND RESULTS: In an instructive video, we show the technique of video-assisted retroperitoneal necrosectomy with minimal access, including the preoperative percutaneous drainage and several accesses to the necrosis. We discuss the indication for retroperitoneal necrosectomy as well as the optimal time point of the intervention. CONCLUSION: In the management of acute necrotizing pancreatitis, the multidisciplinary approach is crucial. The initial treatment by the intensive care units should be extended to intervention or surgery in case of infected necrosis or persistent multi-organ dysfunction. We show here a minimal access solution with the placement of a percutaneous drain followed by video-assisted retroperitoneal necrosectomy.

[Abdominal pain in the general doctor's practice]. / Abdominalschmerzen in der Hausarztpraxis.

Abdominal pain is a frequent symptom and in the majority of cases the underlying disease is not life threatening. The general practitioner's first task is to differentiate between inflammatory and other diseases. The patient's history, the clinical examination and laboratory tests form the basis for the differential diagnosis. A sonography is the first additional examination in the vast majority of the cases. Accidentally found gallstones usually do not require surgical intervention. Surgery in asymptomatic patients should be limited to gallbladder polyps and patients with calcifications in their gallbladder wall.

Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma.

NDRG1 is a hypoxia-inducible protein, whose modulated expression is associated with the progression of human cancers. Here, we reveal that NDRG1 is markedly upregulated in the cytoplasm and on the membrane in human hepatocellular carcinoma (HCC). We demonstrate further that hypoxic stress increases the cytoplasmic expression of NDRG1 in vitro, but does not result in its localization on the plasma membrane. However, grown within an HCC-xenograft in vivo, cells express NDRG1 in the cytoplasm and on the plasma membrane. In conclusion, hypoxia is a potent inducer of NDRG1 in HCCs, albeit requiring additional stimuli within the tumour microenvironment for its recruitment to the membrane.

Acute Abdomen: A Rare Case of Ruptured Hepatocellular Carcinoma.

Spontaneous ruptures of hepatocellular carcinoma (HCC) are rare. Nevertheless they may lead to difficult decisions in the emergency situation. The acute therapies include conservative treatment, transarterial embolization and surgery. Curative treatment of HCC can be achieved by liver resection solely. The decision-making depends on prognostic patient's factors, such as hepatic viral infection status, Child-Pugh grade, liver cirrhosis and number of tumors. In this case transarterial embolization was preferable as a bridging therapy prior to further diagnostics and therapy, to lower the perioperative morbidity and mortality. The therapy of these cases needs an interdisciplinary approach to choose the best possible procedure in each case.

Acute Cytomegalovirus Hepatitis in an Immunocompetent Host as a Reason for Upper Right Abdominal Pain.

Cytomegalovirus infections are widely distributed with a seroprevalence of up to 100%. The majority of the cases take a silent course or deal with unspecific clinical symptoms. Complications in immunocompetent patients are rare but may affect the liver and lead up to an acute organ failure. In this case report, we describe a 35-year-old immunocompetent female with an acute cytomegalovirus infection presenting as acute hepatitis with ongoing upper right abdominal pain after cholecystectomy. Upper right abdominal pain is a common symptom with a wide range of differential diagnoses. If common reasons can be excluded, we want to sensitize for cytomegalovirus infection as a minor differential diagnosis even in immunocompetent patients.

The diagnostic challenges of autoimmune pancreatitis.

Autoimmune pancreatitis is a rare but important differential diagnosis from pancreatic cancer. This autoimmune disease can mimic pancreatic cancer by its clinical symptoms, including weight loss and jaundice. Furthermore imaging findings may include a mass of the pancreas. Here we present the case of a 67-year-old male patient diagnosed with autoimmune pancreatitis but showing the well-known symptoms of pancreatic cancer. This emphasizes the difficulties of histological findings and the importance of the correct diagnostic process.

Bioluminescent orthotopic model of pancreatic cancer progression.

Pancreatic cancer has an extremely poor five-year survival rate of 4-6%. New therapeutic options are critically needed and depend on improved understanding of pancreatic cancer biology. To better understand the interaction of cancer cells with the pancreatic microenvironment, we demonstrate an orthotopic model of pancreatic cancer that permits non-invasive monitoring of cancer progression. Luciferase-tagged pancreatic cancer cells are resuspended in Matrigel and delivered into the pancreatic tail during laparotomy. Matrigel solidifies at body temperature to prevent leakage of cancer cells during injection. Primary tumor growth and metastasis to distant organs are monitored following injection of the luciferase substrate luciferin, using in vivo imaging of bioluminescence emission from the cancer cells. In vivo imaging also may be used to track primary tumor recurrence after resection. This orthotopic model is suited to both syngeneic and xenograft models and may be used in pre-clinical trials to investigate the impact of novel anti-cancer therapeutics on the growth of the primary pancreatic tumor and metastasis.

A retroperitoneal bronchogenic cyst mimicking a pancreatic or adrenal mass.

Retroperitoneal location of bronchogenic cysts is extremely rare. Most commonly they are encountered in the posterior mediastinum. Bronchogenic cysts arise from developmental aberrations of the tracheobronchial tree in the early embryologic period. We report a 42-year-old female patient with a retroperitoneal bronchogenic cyst in the left adrenal region. She was admitted to our hospital with epigastric pain and subsequently underwent CT of the abdomen. The examination revealed a mass related to the left adrenal gland. Endocrine tests for adrenal hypersecretion were negative. Because of the uncertain entity, laparoscopic adrenalectomy was performed. Pathological examination revealed a bronchogenic cyst in proximity to an inconspicuous left adrenal gland. Although very rare, bronchogenic cysts should be considered in the differential diagnosis of retroperitoneal cystic lesions and surgical resection pursued for symptom resolution and to establish a definitive histology.

The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo.

OBJECTIVES: The flavonoid quercetin holds promise as an antitumor agent in several preclinical animal models. However, the efficacy of oral administration of quercetin in a pancreatic cancer mouse model is unknown. METHODS: The antiproliferative effects of quercetin alone or in combination with gemcitabine were tested in 2 human pancreatic cancer cell lines using cell count and MTT assays. Apoptosis was evaluated by flow cytometry. Tumor growth in vivo was investigated in an orthotopic pancreatic cancer animal model using bioluminescence. Quercetin was administered orally in the diet. RESULTS: Quercetin inhibited the growth of pancreatic cancer cell lines, which was caused by an induction of apoptosis. In addition, dietary supplementation of quercetin attenuated the growth of orthotopically transplanted pancreatic xenografts. The combination of gemcitabine and quercetin had no additional effect compared with quercetin alone. In vivo quercetin caused significant apoptosis and reduced tumor cell proliferation. CONCLUSIONS: Our data provide evidence that oral administration of quercetin was capable of inhibiting growth of orthotopic pancreatic tumors in a nude mouse model. These data suggest a possible benefit of quercetin in patients with pancreatic cancer.

How to counter the problem of R1 resection in duodenopancreatectomy for pancreatic cancer?

OBJECTIVE: Although duodenopancreatectomy has been standardized for many years, the pathological examination of the specimen was re-described in the last years. In methodical pathological studies up to 85% had an R1 margin.1,2 These mainly involved the posterior und medial resection margin.3 As a consequence we need to optimize and standardize the pathological workup of the specimen and to extend the surgical resection, where possible without risk for the patient. METHOD AND RESULT: In an instructive video we show the technique of duodenopancreatectomy with emphasis on the dorsal and medial resection margin. Furthermore we show the standardized pathological workup of the specimen, involving the reporting of all the resection margins. CONCLUSION: To accurately determine R1 status at the posterior and medial resection margin, a close collaboration between pathologist and surgeon is crucial. Pathologists do a standardized workup of the resected specimen with staining of the surfaces and systematic analysis of all the resection margins. Surgeons need to extend the resection of the pancreatic head to the superior mesenteric artery by dorsal dissection.

Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study.

The CIAO Study ("Complicated Intra-Abdominal infection Observational" Study) is a multicenter investigation performed in 68 medical institutions throughout Europe over the course of a 6-month observational period (January-June 2012).Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.2,152 patients with a mean age of 53.8 years (range: 4-98 years) were enrolled in the study. 46.3% of the patients were women and 53.7% were men. Intraperitoneal specimens were collected from 62.2% of the enrolled patients, and from these samples, a variety of microorganisms were collectively identified.The overall mortality rate was 7.5% (163/2.152).According to multivariate analysis of the compiled data, several criteria were found to be independent variables predictive of patient mortality, including patient age, the presence of an intestinal non-appendicular source of infection (colonic non-diverticular perforation, complicated diverticulitis, small bowel perforation), a delayed initial intervention (a delay exceeding 24 hours), sepsis and septic shock in the immediate post-operative period, and ICU admission.Given the sweeping geographical distribution of the participating medical centers, the CIAO Study gives an accurate description of the epidemiological, clinical, microbiological, and treatment profiles of complicated intra-abdominal infections (IAIs) throughout Europe.