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1.
Ann Gastroenterol ; 37(3): 255-265, 2024.
Article in English | MEDLINE | ID: mdl-38779639

ABSTRACT

Cystic liver disease has been increasingly reported in the literature, with a prevalence as high as 15-18%. Hepatic cysts are usually discovered incidentally, while their characterization and classification rely on improved imaging modalities. Complex cystic liver lesions comprise a wide variety of novel, re-introduced, and re-classified clinical entities. This spectrum of disorders ranges from non-neoplastic conditions to benign and malignant tumors. Their clinicopathological features, prognostic factors, and oncogenic pathways are incompletely understood. Despite representing a heterogeneous group of disorders, they can have similar clinical and imaging characteristics. As a result, the diagnosis and management of complex liver cysts can become quite challenging. Furthermore, inappropriate diagnosis and management can lead to high morbidity and mortality. In this review, we aim to offer up-to-date insight into the diagnosis, classification, and management of the most common complex cystic liver lesions.

2.
Ann Vasc Surg ; 92: 188-194, 2023 May.
Article in English | MEDLINE | ID: mdl-36639096

ABSTRACT

BACKGROUND: The objective of this study was to assess the Altura endoprosthesis outcomes up to 12 months for patients affected by infrarenal abdominal aortic aneurysms (AAA) either in elective or emergent situations. METHODS: This was a single-center retrospective study identifying all patients undergoing endovascular aneurysm repair (EVAR) with the Altura endoprosthesis from January 2021 to August 2022. Outcomes evaluated included mortality, technical and clinical success (freedom from procedure-related death, endoleak, migration, thrombosis, and reintervention), and the freedom from reintervention rate. RESULTS: A total of 34 (25 elective and 8 emergent) patients who underwent AAA with Altura endoprosthesis were retrospectively reviewed. The technical success of the Altura endograft either in elective or emergent situations was 100%. There was no inhospital mortality, but 1 (3%) patient who underwent AAA repair emergently, died unexpectedly 7 days after the discharge due to massive pulmonary embolism. The clinical success and the freedom from reintervention during the median follow-up of 12 months (interquartile range [IQR] 12-18), were 97%. One patient presented with disabling intermittent claudication at third month postoperatively, and the computed tomographic angiography (CTA) revealed thrombosis of one of the iliac endografts (3%). The patient underwent femorofemoral bypass with an uneventful postoperative course and immediate relief of the symptoms. One type II endoleak was spontaneously resolved on the sixth month. Sac shrinkage (>3 mm) was registered in 12 patients (35%), but the sac size was stable in the remaining 22 (65%) patients. CONCLUSIONS: The preliminary outcomes of the Altura endograft seem to be promising, suggesting that the endograft could be safely used either in elective or emergent situations. Further studies with a major number of participants are needed to document its technical and clinical performance, especially in emergency situations that could be amenable to improvement.


Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Blood Vessel Prosthesis , Retrospective Studies , Blood Vessel Prosthesis Implantation/adverse effects , Endoleak/diagnostic imaging , Endoleak/etiology , Endoleak/surgery , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Treatment Outcome , Risk Factors , Endovascular Procedures/adverse effects , Prosthesis Design
3.
Clin Transplant ; 32(3): e13187, 2018 03.
Article in English | MEDLINE | ID: mdl-29314293

ABSTRACT

BACKGROUND: The utilization of extended criteria liver allografts (ECD) shortens time to transplantation. OBJECTIVE: To characterize the effect of liver allograft fibrosis on graft and patient survival after liver transplantation (LT), with particular attention to fibrosis progression. METHODS: Retrospective database search of donor and recipient liver allograft histology of liver transplants performed between 2007 and 2011. Donor and patient characteristics were analyzed. RESULTS: One hundred and one patients underwent LT with donor liver allografts with early-stage fibrosis (stage 1 fibrosis and stage 2 fibrosis). The level of liver fibrosis did not progress in 40% of the patients tested, and there was a regression of fibrosis in 30%. At a median follow-up of 71 months, of 101 patients transplanted with fibrotic livers, 63 patients (63%) were alive with functioning initial grafts, six patients (6%) were retransplanted, and 35 patients expired. The graft survival rates were 82% and 69% at 1 and 5 years, respectively. Graft survival differences were not found to be statistically significant between the degrees of liver allograft fibrosis: 5-year graft survival (73% for stage 1 fibrosis and 62% for stage 2 fibrosis, P = .24). The entire fibrosis group was further compared with a control group of 208 consecutive primary liver transplant patients with allografts having no fibrosis. The 5-year graft survival was not significantly different between the groups (69% for the fibrosis group vs 75% for the nonfibrosis group, P = .19). Survival was also not statistically different between the groups (5-year survival of 73% for the fibrosis group vs 79% for the nonfibrosis group, P = .2). In patients with HCV, graft survival differences were not found to be statistically significant with the use of early-stage fibrotic livers: 5-year graft survival of 60% for fibrosis group vs 70% for the nonfibrosis group, P = .22). CONCLUSION: This study demonstrates that allografts with early-stage fibrosis achieve acceptable long-term survival after liver transplantation. Given these preliminary results, the use of organs with early-stage fibrosis warrants further studies at a larger scale to validate these results.


Subject(s)
Liver Cirrhosis/physiopathology , Liver Diseases/mortality , Liver Transplantation/mortality , Tissue Donors , Allografts , Case-Control Studies , Female , Follow-Up Studies , Humans , Liver Diseases/pathology , Liver Diseases/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
4.
Dig Surg ; 33(3): 203-12, 2016.
Article in English | MEDLINE | ID: mdl-26918360

ABSTRACT

BACKGROUND: The optimal management approach to pancreatic serous cystic neoplasms (SCNs) is still evolving. METHODS: Consecutive patients with SCN managed at the Liverpool Pancreas Cancer Centre between 2000 and 2013 were retrospectively reviewed. RESULTS: There were 64 patients consisting of 39 women (60.9%) and 25 men (39.1%). Forty-seven patients (73.4%) had surgical removal and 17 (26.6%) were observed. The possibility of a non-SCN malignancy was the predominant indication for resection in 27 (57.4%) patients. Postoperative morbidity occurred in 26 (55.3%) patients with 2 (4.3%) deaths. An increased risk of resection was associated with patient's age (p = 0.011), diagnosis before 2009 (p < 0.001), pain (p = 0.043), possibility of cancer (p = 0.009) and a solid SCN component on imaging (p = 0.002). Independent factors associated with resection were a diagnosis before 2009 (p = 0.005) and a solid SCN component (p < 0.001). Independent factors associated with shorter time to surgical resection were persistent pain (p = 0.003) and a solid SCN component (p = 0.007). CONCLUSION: There was a reduction in the proportion of resections with the application of an observe-only policy for asymptomatic patients with more definite features of SCN. Improved criteria are still required in the remainder of patients with uncertain features of SCN in deciding for intervention or surveillance.


Subject(s)
Neoplasms, Cystic, Mucinous, and Serous/therapy , Pancreatectomy , Pancreatic Neoplasms/therapy , Watchful Waiting , Abdominal Pain/etiology , Abdominal Pain/surgery , Age Factors , Aged , Aged, 80 and over , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Male , Middle Aged , Neoplasms, Cystic, Mucinous, and Serous/diagnostic imaging , Neoplasms, Cystic, Mucinous, and Serous/pathology , Pancreatectomy/adverse effects , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/etiology , Retrospective Studies , Tomography, X-Ray Computed
5.
Ann Surg ; 263(5): 992-1001, 2016 May.
Article in English | MEDLINE | ID: mdl-26501713

ABSTRACT

OBJECTIVE: To examine the outcomes from minimal access retroperitoneal pancreatic necrosectomy (MARPN) and open pancreatic necrosectomy (OPN) for severe necrotizing pancreatitis in a single center. BACKGROUND: The optimal management of severe pancreatic necrosis is evolving with a few large center single series. METHODS: Between 1997 and 2013, patients with necrotizing pancreatitis at the Liverpool Pancreas Center were reviewed. Outcome measures were retrospectively analyzed by intention to treat. RESULTS: There were 394 patients who had either MARPN (274, 69.5%) or OPN (120, 30.5%). Complications occurred in 174 MARPN patients (63.5%) and 98 (81.7%) OPN patients (P < 0.001). OPN was associated with increased postoperative multiorgan failure [42 (35%) vs 56 (20.4%), P = 0.001] and median (inter-quartile range) Acute Physiology and Chronic Health Evaluation II score 9 (6-11.5) vs 8 (5-11), P < 0.001] with intensive care required less frequently in MARPN patients [40.9% (112) vs 75% (90), P < 0.001]. The mortality rate was 42 (15.3%) in MARPNs and 28 (23.3%) in OPNs (P = 0.064). Both the mortality and the overall complication rates decreased between 1997-2008 and 2008-2013 [49 (23.8%) vs 21 (11.2%) P = 0.001, respectively; and 151 (73.3%) vs 121 (64.4%), P = 0.080, respectively). Increased mortality was independently associated with age (P < 0.001), preoperative intensive care stay (P = 0.014), and multiple organ failure (P < 0.001); operation before 2008 (P < 0.001) and conversion to OPN (P = 0.035). MARPN independently reduced mortality odds risk (odds ratio = 0.27; 95% confidence interval = 0.12-0.57; P < 0.001). CONCLUSIONS: Increasing experience and advances in perioperative care have led to improvement in outcomes. The role of MARPN in reducing complications and deaths within a multimodality approach remains substantial and should be used initially if feasible.


Subject(s)
Pancreatitis, Acute Necrotizing/surgery , APACHE , Adult , Aged , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures , Pancreatitis, Acute Necrotizing/mortality , Pancreatitis, Acute Necrotizing/pathology , Retroperitoneal Space/pathology , Retroperitoneal Space/surgery , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
6.
World J Gastroenterol ; 21(20): 6361-73, 2015 May 28.
Article in English | MEDLINE | ID: mdl-26034372

ABSTRACT

AIM: To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). METHODS: Major databases including PubMed (Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying (DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%CI) were calculated using either a fixed-effects or random-effects model. RESULTS: Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE (OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation (OR = 2.68; 95%CI: 0.77-4.58, P < 0.00001), with a tendency towards shorter time to liquid (WMD = 2.97, 95%CI: -0.46-7.83; P = 0.09) and solid diets (WMD = 3.69, 95%CI: -0.46-7.83; P = 0.08) as well as shorter inpatient stay (WMD = 3.92, 95%CI: -0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD = -217.70, 95%CI: -429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time (WMD = -5.30, 95%CI: -43.44-32.84; P = 0.79), pancreatic fistula (OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage (OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess (OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection (OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube (OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality (OR = 0.31; 95%CI: 0.05-2.01; P = 0.22). CONCLUSION: SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.


Subject(s)
Ampulla of Vater/surgery , Common Bile Duct Neoplasms/surgery , Organ Sparing Treatments/methods , Pancreaticoduodenectomy/methods , Pylorus/surgery , Ampulla of Vater/pathology , Chi-Square Distribution , Common Bile Duct Neoplasms/pathology , Gastric Emptying , Gastroparesis/etiology , Gastroparesis/physiopathology , Gastroparesis/prevention & control , Humans , Length of Stay , Odds Ratio , Organ Sparing Treatments/adverse effects , Pancreaticoduodenectomy/adverse effects , Pylorus/physiopathology , Recovery of Function , Risk Factors , Time Factors , Treatment Outcome
7.
Int Surg ; 100(4): 696-701, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25875553

ABSTRACT

Laparoscopic surgery results in decreased immune and metabolic stress response compared to open surgery. Our aim was to evaluate the suspension of host immune defense in terms of apoptosis, necrosis, and survival of peripheral T-lymphocytes in patients undergoing laparoscopic versus open cholecystectomy. Apoptosis, necrosis and viability of peripheral T-lymphocytes were measured preoperatively and postoperatively by means of flow cytometry in 27 patients undergoing laparoscopic cholecystectomy and 25 undergoing open cholecystectomy. White cell count, CRP, and serum glucose levels were also measured. Viable peripheral T-lymphocytes were significantly decreased in open cholecystectomy (P = 0.02), while their late apoptotic as well as the overall necrotic rate were significantly increased (P = 0.01 and P < 0.01, respectively). Open cholecystectomy was also associated with lower levels of surviving circulating T-lymphocytes (P = 0.01) and higher percentage of necrotic T lymphocytes (P = 0.03) 24 hours postoperatively compared to laparoscopic cholecystectomy. Serum CRP was increased 24 hours after open cholecystectomy (P = 0.04). All differences failed to sustain more than 48 hours postoperatively. Increased viability and decreased necrosis of circulating T-lymphocytes were observed in laparoscopic cholecystectomy. Necrosis (and not apoptosis) seems to be the predominant pathway of T-lymphocyte death in open cholecystectomy, in a process reaching its peak at 24 hours and further attenuating 48 hours postoperatively.


Subject(s)
Cholecystectomy/methods , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Apoptosis , Blood Glucose/analysis , C-Reactive Protein/analysis , Cholecystectomy, Laparoscopic , Female , Flow Cytometry , Humans , Lymphocyte Count , Male , Middle Aged , Necrosis
8.
World J Gastroenterol ; 21(8): 2510-21, 2015 Feb 28.
Article in English | MEDLINE | ID: mdl-25741162

ABSTRACT

AIM: To conduct a meta-analysis comparing outcomes after pancreaticoduodenectomy (PD) with or without prophylactic drainage. METHODS: Relevant comparative randomized and non-randomized studies were systemically searched based on specific inclusion and exclusion criteria. Postoperative outcomes were compared between patients with and those without routine drainage. Pooled odds ratios (OR) with 95%CI were calculated using either fixed effects or random effects models. RESULTS: One randomized controlled trial and four non-randomized comparative studies recruiting 1728 patients were analyzed. Patients without prophylactic drainage after PD had significantly higher mortality (OR=2.32, 95%CI: 1.11-4.85; P=0.02), despite the fact that they were associated with fewer overall complications (OR=0.62, 95%CI: 0.48-0.82; P=0.00), major complications (OR=0.75, 95%CI: 0.60-0.93; P=0.01) and readmissions (OR=0.77, 95%CI: 0.60-0.98; P=0.04). There were no significant differences in the rates of pancreatic fistula, intra-abdominal abscesses, postpancreatectomy hemorrhage, biliary fistula, delayed gastric emptying, reoperation or radiologic-guided drains between the two groups. CONCLUSION: Indiscriminate abandonment of intra-abdominal drainage following PD is associated with greater mortality, but lower complication rates. Future randomized trials should compare routine vs selective drainage.


Subject(s)
Drainage/methods , Pancreaticoduodenectomy , Adult , Aged , Chi-Square Distribution , Drainage/adverse effects , Drainage/instrumentation , Drainage/mortality , Female , Humans , Male , Middle Aged , Odds Ratio , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/mortality , Patient Readmission , Postoperative Complications/mortality , Postoperative Complications/therapy , Risk Factors , Time Factors , Treatment Outcome
9.
Dig Surg ; 31(4-5): 312-7, 2014.
Article in English | MEDLINE | ID: mdl-25401989

ABSTRACT

AIM: We hereby present and evaluate a technique for hepatic parenchymal transection based on the application of Metzenbaum scissors and clips during liver ischemia. METHODS: Our technique was retrospectively evaluated in 32 noncirrhotic, noncholestatic patients with intrahepatic cholangiocarcinoma and 32 patients with hepatocellular carcinoma (23 of whom cirrhotic, 71.9%). Patient data were retrieved from our Hepatobiliary Surgery Database. Type and duration of vascular clamping, blood transfusion requirements, marginal status and immediate postoperative complications were analyzed. RESULTS: Twenty-seven extended (>4 liver segments; 42.2%) and 37 nonextended (≤4 liver segments; 57.8%) liver resections were analyzed. Warm liver ischemia duration was 14 (interquartile range: 11-17.8) min. Thirty-three patients (51.6%) were transfused with a median of 2 (1.5-3) units of packed red blood cells. Tumor-free margins were achieved in 90.6% of cases (n = 58). The overall morbidity rate was 18.8% with a 4.7% mortality rate. Our technique allowed for excellent identification and safe dissection and preservation, or ligation of major liver vessels. CONCLUSIONS: The proposed technique is simple, fast, safe and with low cost. It is associated with limited postoperative complications while from an oncologic standpoint it enables the surgeon to achieve a high percentage of tumor-free margins while protecting major vascular structures.


Subject(s)
Blood Loss, Surgical/prevention & control , Hepatectomy/instrumentation , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Surgical Instruments , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Bile Ducts, Intrahepatic/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Cholangiocarcinoma/surgery , Cohort Studies , Female , Follow-Up Studies , Hepatectomy/methods , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Operative Time , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Rate , Treatment Outcome
10.
Clin Exp Metastasis ; 31(5): 511-20, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24590865

ABSTRACT

DNA methylation is the best characterised epigenetic change so far. However, its role in breast cancer metastasis has not as yet been elucidated. The aim of this study was to investigate the differences between the methylation profiles characterising primary tumours and their corresponding positive or negative for metastasis lymph nodes (LN) and correlate these with tumour metastatic potential. Methylation signatures of Caveolin-1, CXCR4, RAR-ß, Cyclin D2 and Twist gene promoters were studied in 30 breast cancer primary lesions and their corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry. Tumours were typified by methylation of RAR-ß and hypermethylation of Cyclin-D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour-infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated between node-negative and metastatic tumours. Nodal metastasis was associated with tumour and lymph node profiles of extended methylation of Caveolin-1 and lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1 expression in stromal cells associated with tumour aggressiveness while strong Caveolin-1 expression in tumour cells correlated with decreased 7-year disease-free survival. Methylation-mediated activation of CXCR4 and inactivation of Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1 expression heterogeneity correlated with disease progression. This evidence contributes to the better understanding and, thereby, therapeutic management of breast cancer metastasis process.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Caveolin 1/genetics , Lymph Nodes/pathology , Receptors, CXCR4/genetics , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Caveolin 1/metabolism , DNA Methylation , Female , Gene Expression Profiling , Humans , Immunophenotyping , Lymph Nodes/metabolism , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Staging , Promoter Regions, Genetic , Receptors, CXCR4/metabolism , Risk Factors
11.
Expert Rev Mol Diagn ; 14(3): 333-46, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24649820

ABSTRACT

Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.


Subject(s)
Molecular Diagnostic Techniques/methods , Pancreatitis, Acute Necrotizing/diagnosis , Biomarkers/blood , Humans , Pancreatitis, Acute Necrotizing/metabolism , Prognosis , Proteome/metabolism , Severity of Illness Index
12.
BMC Gastroenterol ; 13: 17, 2013 Jan 18.
Article in English | MEDLINE | ID: mdl-23331458

ABSTRACT

BACKGROUND: Many studies have suggested that the immune response may play a crucial role in the progression of hepatocellular carcinoma (HCC). Therefore, our aim was to establish a (i) functional culture of primary human tumor hepatocytes and non-tumor from patients with hepatocellular carcinoma (HCC) and (ii) a co-culture system of HCC and non-HCC hepatocytes with autologous peripheral blood mononuclear cells (PBMCs) in order to study in vitro cell-to-cell interactions. METHODS: Tumor (HCC) and non-tumor (non-HCC) hepatocytes were isolated from the liver resection specimens of 11 patients operated for HCC, while PBMCs were retrieved immediately prior to surgery. Four biopsies were obtained from patients with no liver disease who had surgery for non malignant tumor (normal hepatocytes). Hepatocytes were either cultured alone (monoculture) or co-cultured with PBMCs. Flow cytometry measurements for MHC class II expression, apoptosis, necrosis and viability (7AAD) were performed 24 h, 48 h and 72 h in co-culture and monocultures. RESULTS: HCC and non-HCC hepatocytes exhibited increased MHC-II expression at 48h and 72h in co-culture with PBMCs as compared to monoculture, with MHC II-expressing HCC hepatocytes showing increased viability at 72 h. PBMCs showed increased MHC-II expression (activation) in co-culture with HCC as compared to non-HCC hepatocytes at all time points. Moreover, CD8+ T cells had significantly increased apoptosis and necrosis at 48h in co-culture with HCC hepatocytes as compared to monocultures. Interestingly, MHC-II expression on both HCC and non-HCC hepatocytes in co-culture was positively correlated with the respective activated CD8+ T cells. CONCLUSIONS: We have established an in vitro co-culture model to study interactions between autologous PBMCs and primary HCC and non-HCC hepatocytes. This direct interaction leads to increased antigen presenting ability of HCC hepatocytes, activation of PBMCs with a concomitant apoptosis of activated CD8+ T cells. Although, a partially effective immune response against HCC exists, still tumor hepatocytes manage to escape.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cell Communication/physiology , Hepatocytes/pathology , Leukocytes, Mononuclear/pathology , Liver Neoplasms/pathology , Aged , Apoptosis/physiology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Hepatocellular/metabolism , Cell Survival/physiology , Coculture Techniques , Female , Hepatocytes/metabolism , Histocompatibility Antigens Class II/metabolism , Humans , Leukocytes, Mononuclear/metabolism , Liver Neoplasms/metabolism , Male , Middle Aged , Necrosis/physiopathology , Time Factors
14.
Can J Surg ; 55(2): 117-24, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22564515

ABSTRACT

Primary gastric lymphoma is a rare cancer of the stomach with an indeterminate prognosis. Recently, a series of molecular prognostic markers has been introduced to better describe this clinical entity. This review describes the clinical importance of several oncogenes, apoptotic genes and chromosomal mutations in the initiation and progress of primary non-Hodgkin gastric lymphoma and their effect on patient survival. We also outline the prognostic clinical importance of certain cellular adhesion molecules, such as ICAM and PECAM-1, in patients with gastric lymphoma, and we analyze the correlation of these molecules with apoptosis, angiogenesis, tumour growth and metastatic potential. We also focus on the host-immune response and the impact of Helicobacter pylori infection on gastric lymphoma development and progression. Finally, we explore the therapeutic methods currently available for gastric lymphoma, comparing the traditional invasive approach with more recent conservative options, and we stress the importance of the application of novel molecular markers in clinical practice.


Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Lymphoma, Non-Hodgkin/genetics , Lymphoma, Non-Hodgkin/mortality , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Antigens, CD/genetics , Antigens, CD/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Disease-Free Survival , Female , Genes, p16 , Genes, p53 , Humans , Lymphoma, Non-Hodgkin/therapy , Male , Molecular Biology , Neoplasm Invasiveness/pathology , Neoplasm Staging , Prognosis , Risk Assessment , Sensitivity and Specificity , Stomach Neoplasms/therapy , Survival Rate , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism
15.
Pathol Res Pract ; 208(6): 338-43, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-22560505

ABSTRACT

Inverted papilloma (IP) is a rare sinonasal benign lesion characterized by aggressive biological behavior. Our aim was to evaluate the expression of various proliferation and apoptotic markers and the presence of HPV genotypes in paraffin sections gathered from surgically treated IP patients. Immunohistochemistry for PCNA, bax, cytochrome c and caspase-8 and flow cytometry for the detection of apoptosis, necrosis and ki67 expression were performed. The identification of various HPV subtypes was achieved by nested PCR amplification. Nasal polyps (NP) and specimens from normal nasal epithelium (NE) were used as controls. PCNA was more frequently expressed in IP compared to NE (p=0.04) and caspase-8 and bax staining were less frequently observed in IP compared to NP (p=0.004 and p=0.01 respectively) and NE (p=0.003 and p=0.01, respectively). IP and NP presented significantly higher Ki67 flow cytometry values compared to NE (p<0.001 and p=0.02 respectively). Cytochrome c was more frequently expressed in IP specimens with more prominent inflammation (p=0.02). A low HPV DNA detection rate was observed. Neither HPV status nor any of the apoptotic or proliferative markers studied was associated with the patients' clinicopathological characteristics. Increased Ki67 appeared to correlate with disease recurrence (p=0.01). Increased PCNA and Ki67 and decreased bax and caspase-8 expression indicate that cell proliferation is increased while apoptosis is inhibited in IP, explaining its biological behavior.


Subject(s)
Nose Neoplasms/pathology , Papilloma, Inverted/pathology , Papillomaviridae/isolation & purification , Tumor Virus Infections/pathology , Adult , Aged , Aged, 80 and over , Apoptosis , Base Sequence , Biomarkers, Tumor/metabolism , Cell Proliferation , DNA, Viral/analysis , Female , Flow Cytometry , Genotype , Humans , Male , Middle Aged , Molecular Sequence Data , Neoplasm Recurrence, Local , Nose Neoplasms/surgery , Nose Neoplasms/virology , Papilloma, Inverted/surgery , Papilloma, Inverted/virology , Papillomaviridae/genetics , Paranasal Sinuses/pathology , Paranasal Sinuses/virology , Proliferating Cell Nuclear Antigen/metabolism , Retrospective Studies , Tumor Virus Infections/complications
17.
Obes Surg ; 21(10): 1490-3, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21086063

ABSTRACT

Splenic arterial demarcation has been observed during laparoscopic sleeve gastrectomy (LSG). The present study aims to detect its actual incidence during LSG and clarify its clinical significance. This is a prospective observational study of 287 consecutive patients that underwent LSG by the same surgical team over 3 years. In all patients, the gastric fundus was mobilized using a standard technique. Before withdrawal of the pneumoperitoneum, the spleen was exposed and carefully inspected for evidence of arterial demarcation. Patients with a clear demarcation were followed with Doppler ultrasound. Computed tomography scan with oral contrast was performed to rule out septic complications. Median preoperative body mass index was 46 kg/m(2) (range 35.1-78). Median operative time was 58 min (range 42-185), median hospital stay was 3 days (range 3-45), and overall morbidity rate was 8.6%. Intraoperative demarcation of the upper splenic pole was evident in 12 patients (4.1%). Eleven patients had uneventful postoperative course. One patient raised temperature of 38.5°C at the 7th postoperative day and was readmitted for further treatment. Once afebrile, the patient was discharged on the 10th postoperative day and continued on prophylactic low molecular weight heparin (tinzaparin, 7,500 U sc.) for 20 days. Splenic discoloration following LSG is an uncommon complication with minimal clinical significance, which could be related to hematoma, venous congestion, or ischemia. The possibility of a late splenic abscess cannot be ruled out. No risk factors can be identified preoperatively.


Subject(s)
Bariatric Surgery/adverse effects , Gastrectomy/adverse effects , Ischemia/epidemiology , Obesity, Morbid/surgery , Spleen/blood supply , Splenic Infarction/epidemiology , Adolescent , Adult , Algorithms , Female , Humans , Incidence , Ischemia/etiology , Ischemia/therapy , Male , Middle Aged , Prospective Studies , Risk Factors , Splenic Infarction/etiology , Splenic Infarction/therapy , Young Adult
18.
Otolaryngol Head Neck Surg ; 142(4): 605-11, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20304286

ABSTRACT

OBJECTIVE: Negative bcl-2 and HLA-DR protein expression have been associated with responsiveness to adjuvant radiotherapy in surgically treated parotid cancer patients. The aim of this study was to investigate the prognostic significance of bax, cytochrome c, and caspase-8 protein expression in a group of surgically treated patients to determine whether they also suggest markers of responsiveness to adjuvant radiotherapy. STUDY DESIGN: Historical cohort study. SETTING: Otolaryngology department in a university hospital. SUBJECTS AND METHODS: The immunohistochemical expression of bax, cytochrome c, and caspase-8 were studied in paraffin-embedded tissue specimens originating from 27 surgically treated parotid cancer patients and nine patients with Warthin parotid tumors (control group) and correlated with the patients' clinicopathological characteristics and clinical outcome. RESULTS: Caspase-8 negative staining was more frequently observed in higher TNM stages and in tumors measuring more than 4 cm (P = 0.009 and P = 0.018, respectively). Caspase-8 (-)/cytochrome c (-) patients carried low-grade lesions without nodal involvement (P = 0.01 and P = 0.05, respectively). Caspase-8 (-) patients who received postoperative radiotherapy presented a significantly increased disease-free survival compared to those who did not (P = 0.04). Patients bearing bax (-) tumors who received postoperative radiotherapy presented an improved four-year disease-free survival compared to bax (-) patients who did not receive any type of adjuvant radiotherapy (P = 0.017). CONCLUSION: Bax, cytochrome c, and caspase-8 protein expression failed to independently predict survival in parotid cancer patients. However, patients with bax (-) or caspase-8 (-) tumors should be considered as candidates for adjuvant radiotherapy in order to achieve better local disease control.


Subject(s)
Biomarkers/analysis , Caspase 8/analysis , Cytochromes c/analysis , Parotid Neoplasms/chemistry , Parotid Neoplasms/radiotherapy , Radiotherapy, Adjuvant , bcl-2-Associated X Protein/analysis , Adenolymphoma/chemistry , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Middle Aged , Parotid Neoplasms/mortality , Parotid Neoplasms/surgery , Survival Rate
19.
Liver Int ; 30(7): 996-1002, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20141593

ABSTRACT

OBJECTIVE: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). PATIENTS: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. RESULTS: Gender (P=0.0086), UICC stage (P=0.0140) and R-class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19-9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I-II):UICC (III-IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19-9 (<100 U/ml):CA 19-9 (> or =100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3-4, 5 and 6 points (P=0.000001) and clinical groups with 3-4 and 5-6 points (P=0.0103) achieved statistically significant difference. CONCLUSIONS: We propose a clinical and prognostic scoring system predictive of long-term survival after surgical resections for ICC.


Subject(s)
Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/surgery , Health Status Indicators , Hepatectomy , Bile Duct Neoplasms/blood , Bile Duct Neoplasms/pathology , Biomarkers/blood , CA-19-9 Antigen/blood , Cholangiocarcinoma/blood , Cholangiocarcinoma/pathology , Europe , Female , Hepatectomy/mortality , Humans , Japan , Kaplan-Meier Estimate , Male , Monte Carlo Method , Neoplasm Invasiveness , Neoplasm Staging , New York , Predictive Value of Tests , Proportional Hazards Models , Reproducibility of Results , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome
20.
Surg Endosc ; 24(9): 2140-4, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20174940

ABSTRACT

BACKGROUND: The increasing role of laparoscopic sleeve gastrectomy (LSG) in the treatment of morbid obesity dictates the need for greater acquaintance with this type of surgery. This study was designed to evaluate the impact of a 2-day LSG course and a 4-day laparoscopic bariatric mini-training program on the knowledge and training gained by participating surgeons. METHODS: A total of 73 trainees (31 residents and 42 surgeons) completed a question survey immediately after completion of the respective courses. Questions probed demographic data, training experience before and after course completion, evaluation of course content, and operative experience. RESULTS: All residents and four of the general surgeons found the laparoscopic bariatric mini-training program to be of value with respect to future professional orientations. Seven surgeons started performing LSGs, while another five surgeons decided to occupy themselves with various types of laparoscopic bariatric procedures. The most useful parts of the course included the identification and treatment of complications, the use of new instrumentation, and surgical demonstrations (video or live), as decided by more than 80% of the participants. On a 1-5 scale, the presentation of novel knowledge was evaluated to be ≥ 3 by all participants. CONCLUSION: The 2-day LSG course offered participants high-quality novel knowledge and excellent training quality, and exerted impact on their personal career.


Subject(s)
Education, Medical, Continuing , Education, Medical, Graduate , Gastrectomy/education , Gastrectomy/methods , Laparoscopy/education , Obesity, Morbid/surgery , Clinical Competence , Educational Measurement , Female , Greece , Humans , Male , Prospective Studies , Surveys and Questionnaires
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