Complex cystic liver lesions: classification, diagnosis, and management.

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.

Low-Profile Altura Endograft System for Endovascular Abdominal Aorta Aneurysm Repair. Preliminary Results in Elective and Emergent Situations.

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.

Management and Outcome of 64 Patients with Pancreatic Serous Cystic Neoplasms.

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.

Outcomes From Minimal Access Retroperitoneal and Open Pancreatic Necrosectomy in 394 Patients With Necrotizing Pancreatitis.

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.

Changes in T-lymphocytes' viability after laparoscopic versus open cholecystectomy.

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.

Metzenbaum-assisted liver resection: a safe and effective liver resection technique.

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.

Prognostic markers in acute pancreatitis.

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.

Co-culture of primary human tumor hepatocytes from patients with hepatocellular carcinoma with autologous peripheral blood mononuclear cells: study of their in vitro immunological interactions.

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.

Review of the molecular profile and modern prognostic markers for gastric lymphoma: how do they affect clinical practice?

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.

Apoptotic and proliferative status in HPV (+) and HPV (-) inverted papilloma patients. Correlation with local recurrence and clinicopathological variables.

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.

Clinical implications of sleeve gastrectomy as a source of spleen infarction or ischemia.

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.

Bax, cytochrome c, and caspase-8 staining in parotid cancer patients: markers of susceptibility in radiotherapy?

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.

Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas.

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.

Prospective appraisal of a 2-day training course on laparoscopic sleeve gastrectomy: the ELTC experience.

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.

Surgical resection for advanced gallbladder carcinoma. The Mount Sinai experience.

BACKGROUND/AIMS: Advanced gallbladder cancer (GC) carries dismal prognosis, due to its extent at diagnosis and the low R0 resection performance rate. METHODOLOGY: Thirty-two GC patients referred to our Department with an intention to treat between 1993 and 2005. All patients had advanced T stage (> or = T3). Pathological findings, surgical procedures and survival data were analyzed. RESULTS: Seventeen radical procedures (16 hepatectomies and 1 cholecystectomy with common bile duct resection), 4 palliative procedures (12.5%) and 11 surgical explorations (34.4%) were performed (53.1%, resectability rate). Hepatectomies were performed with 0% mortality, 11.8% morbidity and 94.1% resectability rate. The respective 1-, 3- and 5- year survival rates were 71.4%, 28.6% and 14.3%. Radical lymph node dissection (p = 0.03), absence of perineural tumor invasion (p = 0.03) and patients' age <70 years (p < 0.01) were non-independently associated with favorable prognosis in the hepatectomy-treated group of GC patients. CONCLUSIONS: GC patients with stage > or = IIA should be treated with hepatectomy combined with radical lymphadenectomy in order to achieve better staging and disease control. Incorporating the caudate lobe, more than 4 liver segments, or part of the extrahepatic biliary tree in the resection specimen in selected patients, might help eliminate perineural metastatic spread and achieve improved overall survival.

Use of rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin's lymphoma of the head and neck.

BACKGROUND: Rituximab, an anti-CD20 chimeric monoclonal antibody that specifically depletes mature B cells, is an effective single agent in the treatment of relapsed or refractory indolent lymphomas, and has been shown to improve the survival rate of elderly patients with diffuse large-B-cell lymphoma when used in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). PATIENTS AND METHODS: The combined effect of rituximab and CHOP has been comparatively studied against CHOP alone in 18 elderly patients with non-Hodgkin's lymphoma of the head or neck treated in the 1st Department of Otolaryngology at Hippokration Hospital between January 1998 and January 2004. RESULTS: Response rates were 91% and 100% in patients treated with rituximab plus CHOP and with CHOP alone, respectively. Overall survival and disease-free survival rates were 91% in the rituximab plus CHOP group, compared with 83% and 60%, respectively, in the CHOP alone group (p=0.75 and p=0.24 for the differences between the groups, respectively). The rituximab plus CHOP therapy was generally well tolerated, with few adverse events reported. CONCLUSION: The results of this small case series, although not statistically significant, suggest that rituximab in combination with CHOP may represent an effective treatment option for elderly patients with non-Hodgkin's lymphoma of the head and neck.

BCL-2, p53 and HLA-DR antigen expression in surgically treated parotid cancer patients.

Our objective was to investigate the prognostic significance of bcl-2 protein, p53 protein and HLA-DR antigen expression in a group of surgically treated parotid cancer patients. We studied bcl-2, p53 and HLA-DR immunohistochemical expression in paraffin-embedded surgically removed tissue specimens derived from 26 patients with parotid cancer and 9 patients with Warthin parotid tumors operated between 2000 and 2006 at the Hippokration Hospital of Athens. The staining results were correlated with the patients' clinicopathological characteristics and clinical outcome. Bcl-2 expression was associated with a significantly decreased survival in patients with advanced tumor stage (P = 0.04), high grade lesions (P = 0.02), or cervical node involvement (P = 0.03). Radiotherapy was associated with a significantly improved recurrence-free survival among patients with negative tumor staining for either bcl-2, or both HLA-DR and bcl-2 [HLA-DR(-)/Bcl-2(-)] (P = 0.04 for both comparisons). Classical clinicopathologic factors failed to show prognostic value both in the univariate and the multivariate analyses performed. Our results suggest that bcl-2 can be used to identify locally advanced or histologically aggressive tumors with a lower survival probability following the application of standard treatment modalities. Furthermore, bcl-2(+) patients should be considered for more aggressive adjuvant treatment protocols, since conventional radiotherapy often fails to decrease relapse rates in this setting of patients.