Microvascular infiltration has limited clinical value for treatment and prognosis in hepatocellular carcinoma.

BACKGROUND: Microvascular infiltration (MVI) is considered a necessary step in the metastatic evolution of hepatocellular carcinoma (HCC), but its prognostic value after liver resection (LR) is uncertain. We studied the clinical value of MVI compared to the Milan criteria in a consecutive series of patients submitted to radical LR. METHODS: A total of 441 patients were retrospectively evaluated. MVI and the Milan criteria were analyzed and compared as prognostic factors for overall and disease-free survival (DFS). RESULTS: MVI was present in 189 patients (42.8 %). Grading, satellitosis, size of cancer, and alfa fetoprotein value were significantly related to MVI, which was present in 34.3 and 53.2 % of Milan+ and Milan- patients, respectively (p = 0.00001). Both MVI and the Milan criteria were associated with a lower overall and DFS, but only the Milan criteria were associated with the rate of early recurrence and the feasibility of a curative treatment of the recurrence. The application of MVI parameters to patients classified by the Milan criteria further selects the outcome in Milan+ patients (5-year survival rate of 54.1 and 67.9 %, respectively, in the presence or absence of MVI) but not in Milan- patients. CONCLUSIONS: MVI is related to survival after LR for HCC, but the clinical value of this information is limited. In Milan+ patients, the absence of MVI selects the cases with better prognosis. In the presence of a liver recurrence, the Milan criteria related to the primary HCC show a better prognostic accuracy and have clinical relevance in the decision-making process.

Impact on liver cancer treatment of a first erroneous diagnosis of hemangioma.

BACKGROUND: Most liver hemangioma (HA) diagnoses are presumptive and based on radiological features and growth trend. The goal of this study was to analyze the impact of a false diagnosis of hemangioma upon the overall therapeutic course and upon the prognosis of a liver malignancy. METHODS: Twenty-eight patients with liver cancer who were observed in the period 2001-2007 after an initial erroneous diagnosis of HA were retrospectively evaluated. We studied their radiological workup after blind revision of the images by two radiologists with specific expertise in liver imaging, analyzing the relationship between overall management and center volume, mean delay from the first test to the curative treatment, and clinical consequences of this diagnostic mistake. RESULTS: The diagnosis of false HA occurred in a low-volume center (LVC) in 75 % of cases. A specific risk for liver cancer was present in 71.4 % of patients. US gave a false diagnosis of HA in 25/27 patients, a CT scan in 18/25 patients, and MRI in 6/16 patients. The final diagnosis was reached with a mean delay of 22 months. Liver resection was possible in 22 patients; in the 17 hepatocellular carcinoma cases, the survival rate was 69.4 % at 5 years after the first observation. CONCLUSIONS: A false diagnosis of HA in the presence of malignancy is not rare nowadays and significantly reduces the chances of cure. In situations at risk of having the error occur (poor technical quality of imaging, low specific experience, doubtful diagnosis, and high-cancer-risk patient), the rationale approach is to discuss the case with a multidisciplinary team skilled in the field of liver cancer.

Multiple primary malignancies of the liver and the colon: a complex diagnostic and decisional process with a final unanswered question.

We herein present the case of a 78-year-old man with an incidental finding of a solid hepatic mass without symptoms and only a laparotomic cholecystectomy for acute cholecystitis in the past surgical history. A colonoscopy, a magnetic resonance imaging scan, a positron emission tomography scan, and a computed tomography scan completed the preoperative workup: a neoplastic lesion 4.3×3 cm in size was diagnosed at segments IV and V, associated with a neoplastic involvement of the splenic flexure without signs of colonic occlusion. After colonic resection, a frozen section on a granulomatous-like tissue at gastric border suggested a diagnosis of an adenocarcinoma of bilio-pancreatic type, changing the surgical strategy to include gastric resection and hepatic pedicle node dissection. The discussion turns around the idea that a final diagnosis of colon cancer with regional nodal involvement (pT3N1) and metastatic gallbladder cancer with multiple peritoneal seedings cannot be excluded.

Parietal and peritoneal localizations of hepatocellular carcinoma: is there a place for a curative surgery?

BACKGROUND: The clinical course of peritoneal and parietal recurrence of hepatocellular carcinoma (HCC-PPL) is not well known. METHODS: Twenty-eight patients with a histologically proven HCC-PPL were analyzed out of a series of 515 patients operated for HCC (group 1). The risk factors, histological features, growing dynamic and results of surgical treatment were analyzed and compared with patients having other extrahepatic localizations of HCC (group 2; 26 patients). Survival data were also compared with patients with intrahepatic-only recurrence (group 3; 211 patients). RESULTS: In group 1, a needle tract injury was present in 57.1% and a previous spontaneous rupture in 14.3% of cases. Parietal seeding was generally single, while peritoneal seeding was frequently multiple. Grading was poor in 84.7%, microvascular infiltration was observed in 57.1% and a rapid growth in 55.5% of cases. In Group 2, only 4 out of 26 patients underwent surgery. Survival was significantly better in group 3 than in group 1, and in group 1 than in group 2. CONCLUSIONS: Extrahepatic HCC recurrence is related to an aggressive biology of the cancer; many characteristics of high malignancy are usually present in these cases. After radical surgery for HCC-PPL, an acceptable survival may be obtained.

Lynch syndrome from a surgeon perspective: retrospective study of clinical impact of mismatch repair protein expression analysis in colorectal cancer patients less than 50 years old.

BACKGROUND: In clinical practice, unexpected diagnosis of colorectal cancer in young patients requires prompt surgery, thus genetic testing for Lynch Syndrome is frequently missed, and clinical management may result incorrect. METHODS: Patients younger than 50 years old undergoing colorectal resection for cancer in the period 1994-2007 were identified (Group A, 49 cases), and compared to a group of randomly selected patients more than 50 (Group B, 85 cases). In 31 group A patients, immunohistochemical expression analysis of MLH1, MSH2 and MSH6 was performed; personal and familial history of patients with defective MMR proteins expression was further investigated, searching for synchronous and metachronous tumors in probands and their families. RESULTS: Fifty-one percent of patients did not express one or more MMR proteins (MMR-) and should be considered Lynch Syndrome carriers (16 patients, group A1); while only 31.2% of them were positive for Amsterdam criteria, 50% had almost another tumor, 37.5% had another colorectal tumor and 68% had relatives with colorectal tumor. This group of patients, compared with A2 group (< 50 years old, MMR+) and B group, showed typical characteristics of HNPCC, such as proximal location, mucinous histotype, poor differentiation, high stage and shorter survival. CONCLUSIONS: The present study confirms that preoperative knowledge of MMR proteins expression in colorectal cancer patients would allow correct staging, more extended colonic resection, specific follow-up and familial screening.

Association between human parainfluenza virus type 1 and smoking history in patients with an abdominal aortic aneurysm.

Several studies have suggested that infectious agents may induce the development of abdominal aortic aneurysms and/or accelerate their progression. The aim of this study was to evaluate the presence of the respiratory-transmitted viruses such as influenza A and B and parainfluenza type 1 genomes in bioptic fragments of abdominal aortic aneurysms. Furthermore, the association between viral infection and traditional risk factors for aneurysms was investigated employing multivariate logistic regression models. The genome of parainfluenza 1 was detected in 11 out of 57 patients with abdominal aortic aneurysm, influenza A only in one, whereas none of the specimens analyzed resulted positive for influenza B. After adjustment of age, gender, and clinical diagnosis, being current smokers was associated independently with parainfluenza 1 detection in aneurysms. The identification of parainfluenza 1 in aortic aneurysm biopsies supports previous observations of a possible role of viruses in the lesion development. Smoking, by interfering with the respiratory tract's ability to defend itself and predisposing to upper and lower respiratory tract infections may accelerate the onset and progression of abdominal aortic aneurysms.

Factors influencing outcomes in laparoscopic adrenal surgery.

PURPOSE: This study aims to recognize factors affecting operative and postoperative outcomes in patients undergoing unilateral laparoscopic adrenalectomy performed by using the transabdominal approach. METHODS: From a prospectively collected adrenal database, we performed a retrospective analysis of all patients undergoing unilateral adrenalectomy from July 2002 to December 2011. The outcome measures considered were the following: conversion rate, intra- and postoperative complications, duration of surgery, length of hospital stay, and return-to-work time. Demographic data, American Society of Anesthesiologists score, characteristics of adrenal tumor, and operative and postoperative variables were analyzed to assess their influence on the outcome variables. RESULTS: A total of 163 laparoscopic adrenalectomies were included. Intraoperative complications, conversion to laparotomy, and postoperative complications were observed in 6.7, 6.1, and 1.8 % of cases, respectively. Conversion to open surgery, intraoperative complications, metastasis, and pheochromocytoma were found to be predictive factors for operative time of >140 min. An operative duration of >140 min was associated with intraoperative complications. Tumor size, intraoperative complications, and adrenalectomy for metastasis significantly increased conversion rate. Hospital stay was extended by operative time of >140 min, conversion to laparotomy, and postoperative complications. CONCLUSION: Our study highlights that simple clinical variables, long procedures, and operative complications have a negative impact on procedural outcomes. Based on this, it may be possible to predict cases requiring collaboration with experienced surgeons in order to minimize perioperative morbidity.

A drastic complex atheromatous aorta. A case report.

Aortic atherosclerosis is the most common disease of the aorta. More than 50% of the plaques thicker than 4 mm are located along the descending aorta. The complex morphology of the plaque, such as ulceration or the presence of thrombi, is associated with increased embolic risk. The increasing use of transesophageal echocardiogram has enhanced the recognition of aortic atheromas. We describe a case of a male patient with complex atherosclerotic disease involving the coronary vessels and descending aortic tract with some embolic complications.

Heterogeneous expression of toll-like receptors in lymphatic endothelial cells derived from different tissues.

As lymphatic endothelial cells (LECs) express different lymphatic and vascular markers depending on the organ they are derived from, we analysed whether they also show a heterogeneity of response against pathogens. To this end we analysed, for the presence of mRNA encoding for all human toll-like receptor (TLR), LECs isolated from lymph nodes and thymuses. RNA for TLR1-6 and 9 was identified in thymus-derived cells, whereas cells derived from lymph nodes contained mRNA for TLR1-4, 6 and 9, but failed to express mRNA specific for TLR5. The differential expression of TLRs was confirmed by the phosphorylation of nuclear factor-κB p65 only when the two types of LECs were incubated with the appropriate TLR agonists. The stimulation with specific agonists gives rise to a heterogeneous pattern of cytokine and chemokine secretion: thymus-derived LECs produced preferentially interleukin-6, interferon-inducible protein (IP)-10 and tumour necrosis factor-α, whereas cells prepared from lymph nodes mainly released interleukin-8, monocyte chemotactic protein-1, RANTES and (IP)-10. Finally, cells purified from lymph nodes expressed a higher level of intercellular adhesion molecule-1 than did cells prepared from the thymus when stimulated with several TLR agonists. The expression of a large set of TLRs and the responsiveness to specific agonists suggest that LECs are able to respond to pathogens, and the observed differences reflect specialized functions, redundancy and/or roles of LECs of different origin.

Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma.

BACKGROUND: The seventh TNM edition introduced a new, specific staging structure for intrahepatic cholangiocarcinoma (IHC). OBJECTIVE: To compare the accuracy of the sixth and the new seventh edition to predict survival after hepatectomy for IHC. METHODS: In all, 434 consecutive patients who underwent hepatectomy at 16 tertiary-care centres (1990-2008) were identified. End points were overall (OS) and recurrence-free survival (RFS) for both T cohorts and stage strata. RESULTS: After a median follow-up of 32.4 months, 3- and 5-year OS and RFS estimates were 47.1% and 32.9%, and 26.5% and 19.1%, respectively. Overall, both the editions were statistically significant discriminators of OS and RFS (P < 0.05). However, the survival curves of the new T2a and T2b cohorts appear superimposed. Conversely, the old T2 and T3 cohorts accurately stratify patients into distinct prognostic groups (P < 0.01). The seventh edition does not show monotonicity of gradients (the T4 category demonstrates significantly better OS and RFS compared with T2 patients). The seventh edition stage I and II are significantly different whereas the old stage I and II were not. CONCLUSIONS: The new seventh edition of the AJCC/UICC Staging System proved to be adequate although further studies are need to confirm its superiority compared with the previous edition.

Sequential multidisciplinary treatment of hepatocellular carcinoma: the role of surgery as rescue therapy for failure of percutaneous ablation therapies.

BACKGROUND AND OBJECTIVES: The recurrence of hepatocellular carcinoma (HCC) after percutaneous ablation is poorly evaluated. METHODS: Thirty-six cases of recurrence after percutaneous ablation (PA) (Group 1) are compared to those after surgery, treated with re-resection (26 patients, Group 2) and PA (31 patients, Group 3). RESULTS: Recurrence was usually local after PA and distant after resection. Compared to Groups 2 and 3, local recurrences after PA were larger (4.2 vs. 2.3 cm) and more often invasive (43% vs. 10%). No different clinical/pathological aspects were noted in distant recurrences among the groups. After treatment the survival rate (1, 2, 3 and 5 years) was no different between the groups; in an intention-to-treat analysis of survival for local recurrences, survival was significantly lower in Group 1 (78%, 78%, 67% and 28%) than in Groups 2 and 3 (100%, 88%, 75% and 45%) (P < 0.05). CONCLUSIONS: PA and surgery can be sequentially employed for HCC. The type of primary treatment does not influence the features of distant liver recurrence, while local recurrence after PA often requires more extensive liver resection.

Post-traumatic lesions of the aortic isthmus.

Lesions of the isthmus are the most frequent among post-traumatic lesions of the thoracic aorta (LTA): almost always secondary to closed thoracic traumas (road accidents, falls, crushing, and explosions), they are rarely iatrogenic (operatory catheterisms) or caused by penetrating wounds. In the review of the literature concerned in the report, from the analysis of 89 bibliographic sources, we note that the etiopathogenesis and the pathophysiology of the LTA still entail a very high immediate mortality, but we also note that, in recent years, remarkable improvements have been made not only in prevention, first-aid, diagnostic definition and in the understanding of the development of the LTA, but above all in therapeutic results. The correct use of the conservative approach, particularly in the immediately post-traumatic phases, the increasingly wide-spread use of endovascular exclusion (T-EVAR), even if not without numerous technical difficulties, and the further improvement of open surgery, currently make it possible to guarantee the individual patient the treatment that can offer the best probabilities of success, at least immediately. Final development, and a more complete and rigorous assessment of the medium and long term results of TEVAR will allow the formulation of therapeutic strategies that are even better defined and increasingly simple to implement, on the basis of algorithms, such as the one proposed by the Authors.

Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an unusual tumour. METHODS: The clinicopathological data of 67 patients with ICC and combined hepatocellular-cholangiocarcinoma (HCC-ICC) are presented. RESULTS: HCV-HBV infection was present in 37.3% and chronic liver disease in 38.7% of cases, a rate higher than in the normal population; in these patients the cancer was small, often asymptomatic and of combined type. Liver resection was performed in 51 patients; at 1, 3 and 5 years, overall survival was 87.9%, 59.0%, and disease-free survival was 47.7% and 78.8%, 51.4%, and 46.7%, respectively. The better results were in the group of cirrhotic patients in whom ICC was diagnosed by a screening program for HCC (5-year survival 76.6%). Nodal metastasis showed negative prognostic value for both overall and disease-free survival; in N+ patients mean survival was 14.7 months after liver resection and lymph node dissection. CONCLUSION: Viral infection and cirrhosis may be considered risk conditions for ICC and combined HCC-ICC; in resected patients survival was good. Nodal metastases must not be considered a contraindication for liver resection.

Pancreatic transection from blunt trauma associated with vascular and biliary lesions: a case report.

Major injuries of the pancreas may result in considerable morbidity and mortality when associated with vascular and visceral injuries. In such cases, a right diagnosis and a prompt surgical intervention are necessary to give a chance to the patient. We herein describe a case of blunt abdominal trauma in a 29-year-old man whose pancreatic rupture was associated with hepatic artery, splenic vein and extrahepatic bile duct damage. Immediate surgery was performed after computer tomograghy (CT), the haemorrhagic lesions dictat the emergency transfer to the operating room. Spleno-pancreatic resection was done with reconstruction of the hepatic artery, ligation of the splenic vein and a Roux-en-Y bilio-jejunal diversion. The early post-operative course was complicated by stenosis of the arterial reconstruction, which was treated by endovascular angioplasty followed by percutaneous drainage of symptomatic pseudocyst, rest and antibiotics. Finally, the patient was discharged and was alive without clinical problems at the time when we wrote this case report. The present case underlines the clinical relevance of vascular and visceral injuries associated with pancreatic trauma and the problems arising in the diagnostic evaluation and the surgical strategy of complex multiple visceral and vascular lesions in blunt abdominal trauma.

Evaluation of the healing time of non-operatively managed liver injuries.

BACKGROUND/AIMS: Post discharge prescriptions and follow-up protocols after non-operative treatment of blunt liver injuries are still controversial. The aim of this study was to detail the evolution of the hepatic injuries considering their different patterns and severity grades, stated by the Liver Injury Scale. METHODOLOGY: Analysis of a database concerning 79 consecutive patients submitted to ultrasound follow-up until complete recovery of liver injury. RESULTS: All patients had an uncomplicated course and the liver restoration was demonstrated between 3 and 300 days after the trauma. The median healing time of hematomas increased with the grading (p<0.001): 6 days (IQR=6.75), 45.5 days (IQR=91) and 108 days (IQR=89) for I, II and III grade lesions, respectively. Similarly behaved the lacerations and 29 days (IQR=14.25), 34 days (IQR=43.5) and 77.5 days (IQR=83.5) was the median healing time of II, III and IV grade lesions, statistical significance emerging only comparing II to IV grade lacerations (p<0.035). Considering the different lesion patterns within the same severity grade, the liver restoration was more prompt after lacerations (p<0.001). CONCLUSIONS: These data suggest that medical prescriptions and follow-up protocols can be tailored considering the lesion characteristics.

In vitro c-met inhibition by antisense RNA and plasmid-based RNAi down-modulates migration and invasion of hepatocellular carcinoma cells.

The receptor tyrosine kinase c-met is over-expressed in several types of human tumours. In hepatocellular carcinoma (HCC), its expression is inversely correlated to patient survival. To determine the role of c-met in the malignant properties of HCC cells, we tested the effectiveness of two ablative strategies to down-modulate c-met expression in SKHep1C3, an HCC-derived cell line, i.e. stable expression of antisense RNA c-met and RNA interference. A plasmid coding a 965-nt fragment complementary to 5' portion of c-met mRNA was constructed for the antisense strategy. RNA interference methodology was applied for transient silencing, achieved by small interfering RNAs, and for stable silencing using an RNA polymerase III promoter carrying plasmid coding small hairpin RNAs (shRNAs) that targeted c-met. The transfected cells showed consistently lower levels of c-met mRNA and protein. The results showed that the antisense and RNAi sequences chosen to target c-met mRNA reduced c-met expression efficiently and inhibited malignant properties of SKHep1C3 cells. These data indicate that c-met is an essential factor in the processes of migration and invasion of hepatocarcinoma cells; and c-met down-regulation may be included in a therapeutic strategy for HCC in experimental animal models.

Interleukin-6 sustains hepatic regeneration in cirrhotic rat.

BACKGROUND/AIMS: In the liver IL-6 displays growth-inducing and pro-survival activities. We studied the pro-proliferative and protective mechanisms of IL-6 treatment in a model of liver cirrhosis in wild type rat, investigating the theoretical basis for a potential pharmacologic role of IL-6 in cirrhosis. METHODOLOGY: We analyzed IL-6 receptors levels in cirrhotic liver. We also studied the activation of signaling pathways downstream IL-6 receptors by analyzing the DNA-binding activity of transcription factors STAT3, AP-1, HNF-1 and NF-kappaB and the phosphorylation status of AKT and eNOS. We also analyzed hepato-cell proliferation, by determining BrdU incorporation into DNA, and liver mass expansion. RESULTS: We show that liver cells from cirrhotic animals have increased expression of the IL-6 receptor alpha/gp80. In addition, we show that in cirrhosis the main molecular pathways downstream the receptors are intact and that IL-6 activates STAT3, AP-1 and NF-kappaB transcription factors, induces AKT and eNOS phosphorylation and increases hepato-cell proliferation and liver mass expansion in a dose-dependent manner. CONCLUSIONS: Our data demonstrate that the theoretical basis exists for the therapeutic employment of IL-6 in liver cirrhosis.

Metachronous occurrence of gastric carcinoma after gastric stromal tumor. Considerations on therapeutic strategy.

INTRODUCTION: To our knowledge, the metachronous occurrence of a stromal and epithelial gastric tumour has not been previously reported in the Literature. CASE REPORT: A 73-year-old man underwent open resection of a gastric stromal tumour located in the posterior antrum wall. The maximum size of the tumour was 5 cm, and final histological examination diagnosed it as a primary gastrointestinal autonomic nerve tumour (the so-called GAN tumour); mitotic index was intermediate (10 x 50 HPF). Twelve months later, during endoscopic follow-up, a small ulcerated adenocarcinoma was found at the gastric angulus and subtotal gastrectomy with D2 lymphadenectomy was performed. Final pathological stadiation was T1smN0. The patient is alive and disease free 50 months later. Since he has had two tumours, it would appear that this patient has a tendency to develop neoplasia. However, no risk factor was found being consistent with an aetiological role in both tumours, if we exclude the presence of chronic atrophic gastritis with intestinal metaplasia in the gastric mucosa around both tumours. CONCLUSIONS: In those cases of gastric stromal tumours, of intermediate size and mitotic index, in whom a wedge gastric resection may be proposed, a radical gastrectomy should be considered as a valid alternative, especially when, as in the described patient, chronic atrophic gastritis with intestinal metaplasia is associated.

[The Boerhaave syndrome. Personal experience]. / La sindrome di boerhaave: esperienza personale orientata al trattamento chirurgico.

Boerhaave syndrome is a rare disease with a mortality rate that varies from 10 to 40%. The typical clinical presentation (vomiting, pain, subcutaneuous emphysema) is relatively infrequent. In the case of atypical clinical presentation CT scan with contrast medium administered per os is fundamental for diagnosis. Though there is no general consensus on therapeutic strategies, prognosis is dependent on time interval between onset and diagnosis. We observed four patients with Boerhaave syndrome with an atypical presentation. The time lapse between acute event and diagnosis was less than 6 hours in two cases, 24 hours in one case and 72 hours in the last. All patients presented abdominal pain at admission, preceeded by vomiting in two cases. In all cases diagnosis was carried out by CT scan. All patients were treated surgically: in one case raffia alone was performed, in two cases raffia was associated with temporal bipolar oesophageal exclusion, one case went through oesophageal resection with delayed reconstruction of digestive continuity. One patient with severe COBP died from post-surgical sepsis. One fistula after cervical recanalisation and another after raffia of the oesophageal lesion were successfully treated with endoscopy. We suggest that an aggressive surgical approach is the best treatment for this rare and often severe disease.