A Duplicated Gallbladder in a Patient Presenting with Acute Cholangitis. A Case Study and a Literature Review.

Gallbladder duplication can present a clinical challenge primarily due to difficulties with diagnosis and identification. Recognition of this anomaly and its various types is important since it can complicate a gallbladder disease or a simple hepatobiliary surgical procedure. The case report of a 63-year-old woman who presented with cholangitis and underwent a successful laparoscopic management of symptomatic gallbladder duplication is described, emphasizing several important considerations. Using ERCP, MRCP and 3D reconstructions the two cystic ducts with one common bile duct were identified. A review of the literature in referral of this variant, its anatomical classifications and significance to clinical and surgical practice is included. In conclusion, gallbladder anomalies should be anticipated in the presence of a cystic lesion reported around the gallbladder when evaluating radiologic studies. In case of surgery, preoperative diagnosis is essential to prevent possible biliary injuries or reoperation if accessory gallbladder has been overlooked during initial surgery. Laparoscopic cholecystectomy remains feasible for intervention can be safely done and awareness is necessary to avoid complications or multiple procedures.

Immune-related intestinal pseudo-obstruction associated with nivolumab treatment in a lung cancer patient.

Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management.

Parecoxib's effects on anastomotic and abdominal wound healing: a randomized Controlled trial.

BACKGROUND: Current evidence regarding the effects of selective cyclooxygenase inhibitors on gastrointestinal anastomoses is controversial. An experimental randomized control study was conducted in our institution to histopathologically evaluate the consequences of parecoxib, on intestinal and abdominal wound healing. METHODS: Twenty-four adult Wistar rats underwent laparotomy, ascending colon transection, and hand-sewn anastomosis. They were randomized to receive either parecoxib (0.5 mg/kg twice daily) or 0.9% normal saline by intraperitoneal injection postoperatively. Animals were euthanatized either on the third or the seventh postoperative day. Semiquantitative methods were used to evaluate both intestinal and abdominal wounds for inflammatory cell composition, angiogenesis, fibroblasts, granular tissue, collagen deposition, epithelization, and presence of necrosis, exudate, and abscess formation. Results are presented as (parecoxib: median [IQR] versus control: median [IQR], P-value). RESULTS: No macroscopic anastomotic leakage or wound dehiscence was observed. Intestinal anastomoses in the parecoxib group, showed significantly decreased epithelization (2 [1] versus 3 [1], [P = 0.004]) and collagen deposition (2 [0] versus 3 [1], [P = 0.041]). No difference was observed in angiogenesis (3 [1] versus 2.5 [1], [P = 0.158]). Abdominal wall specimens appeared to demonstrate decreased epithelization (2 [2] versus 4 [0.5], [P = 0.0004]) in the treatment group. No difference between the two groups was identified regarding collagen deposition (2.5 [1] versus 2 [0.5], [P = 0.280]) and angiogenesis (2.5 [1] versus 2 [1], [P = 0.633]). Necrosis was significantly more present in the parecoxib group in both specimen types, (3.5 [1] versus 2.5 [1], [P = 0.017]) and (3 [1] versus 1 [0.5], [P < 0.0001]). CONCLUSIONS: The present study shows that despite the absence of clinical adverse effects, parecoxib can impair anastomotic and abdominal wound healing on a histopathological level.

Clinical presentation and management of gastro-intestinal and pancreatic secondary metastatic tumors.

PURPOSE: As progress regarding the treatment has occurred over recent years in oncology, more patients with metastatic disease are presented for diagnosis and further management. The purpose of this study was to reveal the incidence, location and to describe the clinical characteristics and outcome in a series of patients diagnosed with pancreatic, small and large bowel metastatic tumors that underwent metastasectomy. METHODS: A total of 12 patients (7 male and 5 female) diagnosed with extrahepatic gastrointestinal (GI) and pancreatic metastases from 2001 to 2013 were operated for resection of secondary metastatic tumors to the small and large bowel and the pancreas. Four out of 12 patients were asymptomatic and a secondary tumor was detected during follow up. RESULTS: The median interval revealing the metastatic tumor since the management of the primary tumor was 6.5 years (range 1-27). Primary tumors were malignant melanoma (4 patients), renal cell carcinoma (RCC; 2 patients), leiomyosarcoma of the uterus (2 patients), lobular breast cancer, mesenchymal chondrosarcoma of the skull, endometrial adenocarcinoma and a non-Hodgkin lymphoma (one case each). The median follow-up was 15 months (range 4-120). CONCLUSIONS: Metastatic secondary tumors have to be considered especially when the patient's medical history includes a previous malignancy. They may also occasionally present as the initial manifestation of an occult primary lesion leading to diagnostic difficulty. Although radical surgery is the most effective approach, treatment and survival grossly depend on histological type and the stage of the primary disease. Hence, management of these patients should be individualized by a multidisciplinary team.

Significance of serum and bile tumor markers in the diagnostic approach of patients with malignant pancreatobiliary disease.

PURPOSE: Serum and bile tumor markers are under intense scrutiny for the diagnosis of malignant disease. The purpose of our study was to report the usefulness of serum and bile tumor markers for the discrimination between benign and malignant pancreatobiliary diseases. METHODS: Between March 2010 and May 2013, 95 patients with obstructive jaundice or history of biliary obstruction, were included in the study. During ERCP, bile samples were obtained for measurement of tumor markers CEA, CA19- 9, CA125, CA72-4 and CA242. Serum samples were taken before ERCP for the same measurements. The patients were divided into two groups: patients with malignant disease and patients with benign disease. RESULTS: Serum tumor marker levels were significantly higher in patients with malignant disease. Serum CA242 and CA19-9 exhibited the highest diagnostic accuracy (76.8% and 73.7%, respectively). CA125 and CA72-4 levels in bile samples were significantly higher in patients with malignant disease. Bile CA125, CEA and CA72-4 achieved the best diagnostic accuracy (69, 65 and 65), respectively). The combined detection of CA19-9, CA242 in serum and CA125, CA72-4 in bile along with total bilirubin levels, showed the best diagnostic accuracy (81%). CONCLUSIONS: Serum and bile tumor markers, when studied alone, lack the diagnostic yield to discriminate benign from malignant pancreatobiliary diseases. In cases of diagnostic dilemmas the combination of serum and bile markers might be helpful.

Neuroendocrine differentiation in embryonal type hepatoblastoma.

Hepatoblastoma, a malignant tumor which arises occasionally in older children but very rarely in adults, exhibits divergent differentiation with embryonal cells, fetal hepatocytes and immature elements. This report describes an embryonal type hepatoblastoma with neuroendocrine differentiation in a 16-year-old patient, which was diagnosed postoperatively. Clinical and radiologic work-up failed to reveal a primary gastrointestinal malignancy and no primary lesions were detected in any other organ. This feature of hepatoblastoma is considered to be a multidirectional differentiation of the small epithelial or stem cells of the liver. At 2-year follow up, the patient remains symptom-free, with normal laboratory and diagnostic imaging studies, and no recurrent or metastatic disease identified.

Obstructive jaundice due to ampullary metastasis of renal cell carcinoma.

Renal cell carcinoma is often characterized by the presence of metachronous metastases in unusual sites. The presence of isolated metastases is treated with surgical excision with good anticipated results. On the other hand, systemic chemotherapy is administered in the context of metastatic spread, usually sunitib or sorafenib. In such cases, however, the presence of symptomatic foci calls for minimal intervention.We present a case of a 77-year-old patient who presented with obstructive jaundice due to an ampullary mass. Endoscopic excision and biopsy set the diagnosis of metastatic renal cell carcinoma. Consequently, imaging studies revealed the presence of multiple foci in the lungs and bone. Therefore, pancreatoduodenectomy was excluded and the patient underwent endoscopic ampullectomy and was set to oral sunitinib. Interestingly, despite generalized spread, local control was achieved until the patient succumbed to carcinomatosis.Painless obstructive jaundice in a patient with history of renal cancer and negative computed tomography scanning for pancreatic or other causes of obstruction should alert for prompt investigation for an ampullary metastasis.

Retroperitoneal ganglioneuroma presenting as lower back pain.

Retroperitoneal ganglioneuroma (RGN) is a rare benign tumor that arises from the retroperitoneal sympathetic ganglia composed of mature Schwann cells, ganglion cells and nerve fibers. These tumors can occur anywhere along the paravertebral sympathetic plexus and occasionally from adrenal medulla. Although they grow in excessive size, they may cause compression to adjacent organ or structures thus giving rise to symptoms. Resecting RGN's is a challenging endeavor, as they tend to encase neighboring vessels to their site of origin. The reported case is a 43-year-old male who presented with lumbar pain that increased progressively in intensity over the last 6 months. Preoperative investigations revealed a large tumor with encasement of the origins of the superior mesenteric artery and bilateral renal arteries. The tumor was completely resected and the final pathology confirmed the diagnosis of RGN.

A network-based computational and experimental framework for repurposing compounds toward the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is among the most common liver pathologies, however, none approved condition-specific therapy yet exists. The present study introduces a drug repositioning (DR) approach that combines in vitro steatosis models with a network-based computational platform, constructed upon genomic data from diseased liver biopsies and compound-treated cell lines, to propose effectively repositioned therapeutic compounds. The introduced in silico approach screened 20'000 compounds, while complementary in vitro and proteomic assays were developed to test the efficacy of the 46 in silico predictions. This approach successfully identified six compounds, including the known anti-steatogenic drugs resveratrol and sirolimus. In short, gallamine triethiotide, diflorasone, fenoterol, and pralidoxime ameliorate steatosis similarly to resveratrol/sirolimus. The implementation holds great potential in reducing screening time in the early drug discovery stages and in delivering promising compounds for in vivo testing.

Gastric glomus tumor: a case report.

Gastric glomus tumors are rare mesenchymal tumors of the gastrointestinal tract. We describe a 72-year-old patient who presented with episodes of melena and was subsequently investigated for a tumor of the antrum of the stomach. Surgical resection revealed a 2 x 2 x 1.7 cm well circumscribed submucosal tumor, extending into the muscularis propria. The histopathologic examination of the specimen demonstrated a glomus tumor of the stomach. We discuss the preoperative investigation, the diagnostic problems and the surgical treatment of the patient with this rare submucosal lesion.

Isolated jejunal perforation following blunt abdominal trauma.

Isolated jejunal perforation caused by blunt abdominal trauma is uncommon and most often seen after motor vehicle accidents. We present a case of "blowout" perforation of the jejunum in a young male who was admitted to our hospital with intense abdominal pain following a physical assault. The Injury Severity Score was 0. Although the erect chest radiograph was negative for free air, abdominal computed tomography scan revealed a large amount of free intraperitoneal air. The exploratory laparotomy that followed revealed only a 3 cm-long perforation of the jejunum, 20 cm from the ligament of Treitz. Although our experience as a trauma center is limited, clinical suspicion and timely exploration in this case led to prompt surgical intervention and a successful outcome.

Serous Microcystic Cystadenocarcinoma of the Pancreas with Synchronous Liver Metastases: Clinical Characteristics and Management.

Serous cystadenocarcinoma of the pancreas is a rare but well-established entity. The origin and evolution of this disorder remain unclear, but even metastatic cases have an excellent prognosis. These tumors are very similar to benign serous cystic neoplasms (SCNs) of the pancreas, except that they tend to be larger, are locally invasive, and present distant metastasis. The most frequent local invasion is adjacent vessels, spleen, stomach, and duodenum. The most common site of distant metastasis is the liver. Diagnosis via imaging as well as pathology examination may be misguided due to atypical characteristics of the tumor. In fact, in some, the diagnosis of malignancy was established only after metastases were detected. We present a 60-year-old female patient with malignant serous microcystic cystadenocarcinoma of the pancreas and liver metastasis that was initially misdiagnosed as a metastatic renal cell carcinoma. The patient underwent tumor resection and liver metastasectomy and she is currently doing well after three years of follow-up, with no tumor recurrence or new metastatic liver nodules based on imaging findings.

The Carotenoid Compound of Saffron Crocetin Alleviates Effects of Ischemia Reperfusion Injury via a Mechanism Possibly Involving MiR-127.

Renal impairment is associated with high mortality rates in severely ill patients. The need to prevent and treat renal damage underlines the importance of understanding the pathophysiological mechanisms that characterize it. This could also enable early diagnosis and the design of alternative therapeutic approaches. The aim of this study is to investigate the effect of crocetin, a known antioxidant, on the prevention of renal damage due to ischemia-reperfusion injury and the investigation of the mechanisms involved. The present study was performed on C57BL/6 mice aged 10-12 weeks. The animals had access to water and food ad libitum. The experiment, as described in materials and methods, was completed at 24 h, in which case the kidneys were removed for further study, both at tissue morphology (with immunohistochemistry) and changes in the level of miRs' expression by qRT-PCR. Accordingly, using the automatic precision analyzer, the serum levels of the basic parameters currently used clinically for the monitoring of renal function were determined. The administration of crocetin, despite the short presence of the substance in the body, affects all the biochemical parameters analyzed (urea, creatinine, uric acid, and ions of Na, K, Cl, P, Mg and Ca), ​​causing significant decrease of their measured values. Crocetin also resulted in a significant limitation of the inflammation elements and the degree of epithelial damage. Furthermore, the administration of crocetin appears to restore levels of expression of miR21, miR127 and miR132.

Surgical techniques for the management of enteroatmospheric fistulae.

BACKGROUND: An intestinal fistula in the "open abdomen" is called "enteroatmospheric" and is a great challenge for the surgeon because of the high mortality and morbidity rates associated with it. This report is a study of the surgical strategy for treating patients with enteroatmospheric fistulae. METHODS: During a 3-year period (2005-2007), two males and one female patient with a mean age of 63 years were referred to our surgical department for management of enteroatmospheric fistulae that developed after operations carried out for severe peritonitis, which was a consequence of sigmoid diverticulum rupture in two cases and disruption of an entero-enteric Roux-en-Y anastomosis after total gastrectomy for cancer in one. RESULTS: All patients were appropriately supported in a surgical intensive care unit, with administration of total parenteral nutrition and appropriate antibiotics to eliminate secondary infections. Several re-operations were necessary to treat the enteroatmospheric fistulae. Eventually, all patients were discharged after a lengthy hospital stay (45-145 days). CONCLUSIONS: The essential principles of our operative strategy are: (1) early intervention; (2) a lateral surgical approach via the circumference of the open abdomen to avoid further damage to the exposed viscera; (3) excision of the involved bowel loop with an end-to-end anastomosis; (4) temporary abdominal closure and coverage of the open abdomen with an absorbable mesh, promoting tissue granulation; (5) skin grafting attempts; and (6) selective use of vacuum-assisted closure.

Esophagopericardial fistula as a rare complication after total gastrectomy for cancer.

BACKGROUND: Esophagopericardial fistula is a rare but life-threatening complication of benign, malignant or traumatic esophageal disease. It is most commonly associated with benign etiology and carries a high mortality rate which increases with delay in diagnosis. CASE PRESENTATION: We present a case of an esophagopericardial fistula as a rare complication in a 53-year-old male patient, 7 months after total gastrectomy for an adenocarcinoma of the esophagogastric junction. CONCLUSION: The prognosis of esophagopericardial fistula is poor, especially when it is associated with malignancy.

Ischemic postconditioning decreases iNOS gene expression but ischemic preconditioning ameliorates histological injury in a swine model of extended liver resection.

BACKGROUND: Both pre- and postconditioning have been shown to protect the liver parenchyma from ischemia/reperfusion (I/R) injury during hepatectomy by altering the production of NO. However, to date there is no study to compare their effect on the inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) gene expression, who are the main modulators in the pathway of NO during the acute phase of I/R injury. METHODS: We designed a prospective experimental cohort comprising of three groups (sham group-SG, preconditioning-PrG and postconditioning group-PoG) and consisting of 10 animals per group. All animals underwent extended hepatectomy (70%) under prolonged warm ischemia either after preconditioning or followed by postconditioning or without any protective maneuver (SG). Following reperfusion blood samples and liver biopsies were obtained at the start of reperfusion (0 hours), at 6 and 12 hours post reperfusion. iNOS and eNOS gene expression was assessed on liver tissue by polymerase chain reaction (PCR); in addition, the extent of hepatocellular injury was histologically assessed. RESULTS: At the beginning of reperfusion iNOS expression was significantly reduced in the PoG in comparison to the SG (Kruskal-Wallis test, P=0.012; Mann-Whitney U test, P<0.0005 Bonferroni correction) and continued to remain at low levels until 6 hours post reperfusion (Kruskal-Wallis test, P=0.01; Mann-Whitney U test, P<0.0005-Bonferroni correction) This difference was eliminated by 12 hours. No significant differences were found in the expression of eNOS between groups and within time measurements. Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were found increased at the start of reperfusion; their levels continued to increase by 6 hours in all groups, however only in the PoG the increase attended statistical significance at 12 hours after reperfusion. ALT levels presented only minor alterations during the course of reperfusion. The PrG was found to have more intense hepatocellular injury at the start of reperfusion than the PoG however, that appeared to gradually settle by 12 hours in contrast to PoG where the hepatocellular injury continued to deteriorate. CONCLUSIONS: PoG appeared to decrease iNOS overexpression more effectively than PrG in comparison to animals who have undergone no protective maneuver (SG). However, PrG was more effective than PoG in ameliorating the hepatocellular injury observed at 12 hours after the ischemic insult.

Managing injuries of hepatic duct confluence variants after major hepatobiliary surgery: an algorithmic approach.

AIM: To investigate injuries of anatomy variants of hepatic duct confluence during hepatobiliary surgery and their impact on morbidity and mortality of these procedures. An algorithmic approach for the management of these injuries is proposed. METHODS: During a 6-year period 234 patients who had undergone major hepatobiliary surgery were retrospectively reviewed in order to study postoperative bile leakage. Diagnostic workup included endoscopic and magnetic retrograde cholangiopancreatography (E/MRCP), scintigraphy and fistulography. RESULTS: Thirty (12.8%) patients who developed postoperative bile leaks were identified. Endoscopic stenting and percutaneous drainage were successful in 23 patients with bile leaks from the liver cut surface. In the rest seven patients with injuries of hepatic duct confluence, biliary variations were recognized and a stepwise therapeutic approach was considered. Conservative management was successful only in 2 patients. Volume of the liver remnant and functional liver reserve as well as local sepsis were used as criteria for either resection of the corresponding liver segment or construction of a biliary-enteric anastomosis. Two deaths occurred in this group of patients with hepatic duct confluence variants (mortality rate 28.5%). CONCLUSION: Management of major biliary fistulae that are disconnected from the mainstream of the biliary tree and related to injury of variants of the hepatic duct confluence is extremely challenging. These patients have a grave prognosis and an early surgical procedure has to be considered.

Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome.

BACKGROUND: CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias) syndrome has been rarely associated with other malignancies (lung, esophagus). This is the first report of a primary adenocarcinoma of the third portion of the duodenum in a patient with CREST syndrome. CASE PRESENTATION: A 54-year-old male patient with CREST syndrome presented with colicky postprandial pain of the upper abdomen, diminished food uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative lesion in the third portion of the duodenum was revealed during duodenoscopy, with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and follow-up is negative for local recurrence or metastases 21 months postoperatively. CONCLUSION: CREST syndrome has been associated with colon cancer, gastric polyps, familial adenomatous polyposis (FAP) syndrome and Crohn's disease; however, this is the first report of a primary adenocarcinoma of the duodenum in a patient with CREST syndrome. However, any etiologic relationship remains to be further investigated.

Pseudomyxoma Peritonei: Presentation of Two Cases and Challenging Issues in the Literature.

Pseudomyxoma peritonei (PMP) is a rather uncommon syndrome in oncology with a unique biological behavior and an estimated incidence of one to two cases per million per year. Clinically, it usually presents with a variety of unspecific signs and symptoms including abdominal pain and distention, ascites, or even bowel obstruction. Despite its intimidating clinical manifestation, PMP is characterized by satisfactory survival rates when treated with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). We present two interesting cases of PMP deriving from the appendix with a rather atypical presentation, which was successfully treated with cytoreduction and HIPEC. In addition, we intend to raise clinical suspicion on the diagnosis of PMP and comment on several challenging issues concerning the origin and classification of PMP.

Safety and efficacy of extending a previous endoscopic sphincterotomy for the treatment of retained or recurrent common bile duct stones.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of extending a previous endoscopic sphincterotomy (ES) in patients with retained or recurrent common bile duct (CBD) stones. METHODS: Between 2001 and 2013, extension of a previous ES, for known or suspected CBD stones, was performed in 118 patients (m/f, 53/65) with a median age of 74 (range: 31-91) years (group A). During the same period, ES was performed in 1064 patients with suspected or known choledocholithiasis (group B). The efficacy and complications of the extension (group A) were analyzed and a comparison was made between groups regarding complications. RESULTS: Bile duct cannulation was straightforward in all patients in group A, while it was considered difficult in 49% of patients in group B. Complete clearance was achieved in 76/97 patients (78%) with CBD stones, after a mean of 1.18 attempts per patient. Mechanical lithotripsy was required in 10% of patients. After extension, immediate bleeding occurred in 24 patients (20%), which stopped spontaneously in 9 (37%) and endoscopic hemostasis was required in the remainder. Complications were more frequent in group B (5.3% vs. 0.8%, P=0.031), but there was no significant difference for any individual complication. Immediate bleeding was more common in group B (29% vs. 20%, P=0.035), but there was no difference in clinical bleeding. CONCLUSION: Extension of a previous ES seems to be a simple, effective and safe technique, allowing stone clearance in nearly 80% of patients; it is thus recommended in patients with CBD stones after ES.