Adjuvant I-131 Lipiodol After Resection or Radiofrequency Ablation for Hepatocellular Carcinoma.

BACKGROUND AND OBJECTIVES: High rates of recurrence have been observed after curative treatment for hepatocellular carcinoma (HCC). The main aim of this study was to establish the influence of adjuvant transarterial radioembolization-based I-131 lipiodol on survival and recurrence. METHODS: Between 2004 and 2010, 38 patients were treated with adjuvant I-131 lipiodol therapy, at a dosage of 2220 MBq, within 4 months after surgery. This treated cohort was compared to a control cohort consisting of 42 consecutive patients operated prior to the time the I-131 lipiodol treatment became available. RESULTS: Recurrence-free survival in the control and in the I-131 lipiodol cohort was 12.6 and 18.7 months, respectively (HR = 1.871, p = 0.025). At 2 and 5 years, the cumulative incidence of a first recurrence or death was, respectively, 50 % and 61 % in the treated cohort versus 69 % and 74 % in the control cohort. Median overall survival was 55 and 29 months, respectively (p = 0.051). Among patients with a recurrence at 2 years, more patients had already experienced such recurrence at 1 year in the control cohort (70 % vs 33 %, p = 0.014). CONCLUSIONS: Adjuvant I-131 lipiodol improves disease-free survival in patients with HCC.

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group.

INTRODUCTION: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection. METHODS: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection. RESULTS: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis. CONCLUSION: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.

Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: a randomized clinical trial.

IMPORTANCE: Ninety percent of cases of acute calculous cholecystitis are of mild (grade I) or moderate (grade II) severity. Although the preoperative and intraoperative antibiotic management of acute calculous cholecystitis has been standardized, few data exist on the utility of postoperative antibiotic treatment. OBJECTIVE: To determine the effect of postoperative amoxicillin plus clavulanic acid on infection rates after cholecystectomy. DESIGN, SETTING, AND PATIENTS: A total of 414 patients treated at 17 medical centers for grade I or II acute calculous cholecystitis and who received 2 g of amoxicillin plus clavulanic acid 3 times a day while in the hospital before and once at the time of surgery were randomized after surgery to an open-label, noninferiority, randomized clinical trial between May 2010 and August 2012. INTERVENTIONS: After surgery, no antibiotics or continue with the preoperative antibiotic regimen 3 times daily for 5 days. MAIN OUTCOMES AND MEASURES: The proportion of postoperative surgical site or distant infections recorded before or at the 4-week follow-up visit. RESULTS: An imputed intention-to-treat analysis of 414 patients showed that the postoperative infection rates were 17% (35 of 207) in the nontreatment group and 15% (31 of 207) in the antibiotic group (absolute difference, 1.93%; 95% CI, -8.98% to 5.12%). In the per-protocol analysis, which involved 338 patients, the corresponding rates were both 13% (absolute difference, 0.3%; 95% CI, -5.0% to 6.3%). Based on a noninferiority margin of 11%, the lack of postoperative antibiotic treatment was not associated with worse outcomes than antibiotic treatment. Bile cultures showed that 60.9% were pathogen free. Both groups had similar Clavien complication severity outcomes: 195 patients (94.2%) in the nontreatment group had a score of 0 to I and 2 patients (0.97%) had a score of III to V, and 182 patients (87.8%) in the antibiotic group had a score of 0 to I and 4 patients (1.93%) had a score of III to V. CONCLUSIONS AND RELEVANCE: Among patients with mild or moderate calculous cholecystitis who received preoperative and intraoperative antibiotics, lack of postoperative treatment with amoxicillin plus clavulanic acid did not result in a greater incidence of postoperative infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01015417.

Complete pathological regression of hepatocellular carcinoma with portal vein thrombosis treated with sorafenib.

Sorafenib is a molecular-targeted therapy used in palliative treatment of advanced hepatocellular carcinoma (HCC) in Child-Pugh A patients. We describe the case of a patient who presented with a large HCC in the left liver associated with portal vein thrombosis (PVT). After 9 months of sorafenib treatment, reassessment showed that the tumors had decreased in size with recanalization of the portal vein. A lateral left hepatectomy was performed and pathology showed complete necrosis of the tumor. Sorafenib can downstage HCC in patients with cirrhosis allowing further surgical resection.

Tensile strength of biological fibrin sealants: a comparative study.

BACKGROUND: Fibrin sealants are commonly used in liver surgery, although their effectiveness in routine clinical practice remains controversial. Individual sealant characteristics are based on hemostatic effects and adhesion properties that can be experimentally measured using the 'rat skin test' or the 'pig skin test'. This study used a more relevant and realistic experimental canine model to compare the differences in the adhesive properties of four fibrin sealants in hepatectomy: Tisseel/Tissucol, Tachosil, Quixil, and Beriplast. MATERIALS AND METHODS: A partial hepatectomy was performed in beagle dogs under general anesthesia to obtain liver cross-sections. Fibrin sealants were allocated to dog livers using a Youden square design. The tensile strength measurement was performed using a traction system to measure the rupture stress point of a small wooden cylinder bonded to the liver cross-section. RESULTS: Significantly greater adhesion properties were observed with Tisseel/Tissucol compared with Quixil or Beriplast (P = 0.002 and 0.001, respectively). Similarly, Tachosil demonstrated significantly greater adhesive properties compared with Beriplast (P = 0.009) or Quixil (P = 0.014). No significant differences were observed between Tisseel/Tissucol and Tachosil or between Beriplast and Quixil. CONCLUSIONS: The results of this comparative study demonstrate that different fibrin sealants exhibit different adhesive properties. Tisseel/Tissucol and Tachosil provided greatest adhesion to liver cross-section in our canine model of hepatectomy. These results may enable the optimal choice of fibrin sealants for this procedure in clinical practice.

Does an information leaflet about surgical site infection (SSI) improve recollection of information and satisfaction of patients? A randomized trial in patients scheduled for digestive surgery.

BACKGROUND: A previous study suggested that most surgical patients do not remember having received information about surgical site infection (SSI). In other fields, written information has been suggested to improve patient satisfaction and recollection of information. Our objective was to assess if providing patients with written information about SSI, in addition to oral information, could influence patient satisfaction, recall of information, and opinion regarding SSI. METHODS: A total of 207 patients scheduled for digestive surgery at a university hospital were randomized between usual oral information about SSI, plus an information leaflet about SSI (group O/L), or usual oral information alone (group O). Patients were interviewed 5 weeks after surgery to assess their recall and satisfaction regarding information, opinion regarding SSI, and declared intention of seeking legal action in case of SSI. Surgeons and interviewer were blinded to patients' group allocation. Recruitment occurred between October 2005 and August 2006. RESULTS: Of the original 207 patients, 161 patients (O/L=87, O=74) underwent operation and were interviewed as scheduled. Satisfaction was higher in group O/L (67% vs. O: 43%; P=0.003). The recall of having received information (O/L: 39% vs. O: 31%; P=0.29), was similar between the two groups. Judging SSI as always preventable was more frequent in group O/L (28% vs. O: 9%; P=0.004) with a trend toward a more frequent intention of seeking legal action (O/L: 10% vs. O: 3%; P=0.055). CONCLUSIONS: The leaflet did not improve patient recall of information about SSI, but it was associated with an increased level of satisfaction. The association between the leaflet and judging SSI as always preventable was unexpected.

Novel serum markers of fibrosis progression for the follow-up of hepatitis C virus-infected patients.

Liver biopsy is considered the gold-standard method for the assessment of liver fibrosis during follow-up of hepatitis C virus-infected patients, but this invasive procedure is not devoid of complications. The aim of the present study was to identify novel non-invasive markers of fibrosis progression. By microarray analysis, we compared transcript levels in two extreme stages of fibrosis from 16 patients. Informative transcripts were validated by real-time PCR and used for the assessment of fibrosis in 23 additional patients. Sixteen transcripts were found to be dysregulated during the fibrogenesis process. Among them, some were of great interest because their corresponding proteins could be serologically measured. Thus, the protein levels of inter-alpha inhibitor H1, serpin peptidase inhibitor clade F member 2, and transthyretin were all significantly different according to the four Metavir stages of fibrosis. In conclusion, we report here that dysregulation, at both the transcriptional and protein levels, exists during the fibrogenesis process. Our description of three novel serum markers and their potential use as serological tests for the non-invasive diagnosis of liver fibrosis open new opportunities for better follow-up of hepatitis C virus-infected patients.

Esophageal cancer in the elderly: an analysis of the factors associated with treatment decisions and outcomes.

BACKGROUND: Only limited data has been reported so far regarding oesophageal cancer (EC) in elderly patients. The aim of the study is to identify the baseline parameters that influenced therapeutic decision. METHODS: All consecutive patients 70 years or older being treated for EC were retrospectively analyzed. Patients without visceral metastasis were divided into two groups: treatment with curative intent (chemoradiotherapy, surgery, radiotherapy, mucosectomy or photodynamic therapy) or best supportive care (BSC). Patients with metastasis were divided into two groups: palliative treatment (chemotherapy, chemoradiotherapy or radiotherapy) or BSC. RESULTS: Two hundred and eighty-two patients were studied. Mean age was 76.5 ± 5.5 years and 22.4% of patients had visceral metastasis. In patients without visceral metastasis (n = 220) the majority had treatment with curative intent (n = 151) whereas in patients with metastasis (n = 62) the majority had BSC (n = 32). Severe adverse events (≥ grade 3) were observed in only 17% of the patients. Patients without specific carcinologic treatment were older, had more weight loss, worse WHO performance status and Charlson score in multivariate analysis. DISCUSSION: Our results suggest that elderly patients with an EC could benefit from cancer treatment without major toxicities. Weight loss, WHO performance status and the Charlson score could be used to select the appropriate treatment in an elderly patient.

Complications associated with two laparoscopic procedures used in the management of rectal endometriosis.

BACKGROUND: To evaluate intra- and postoperative complications associated with laparoscopic management of rectal endometriosis by either colorectal segmental resection or nodule excision. METHODS: During 39 consecutive months, 46 women underwent laparoscopic management of rectal endometriosis and were included in a retrospective comparative study. The distinguishing feature of the study is that the choice of the surgical procedure is not related to the characteristics of the nodule. RESULTS: Colorectal segmental resection with colorectal anastomosis was carried out in 15 patients (37%), while macroscopically complete rectal nodule excision was performed in 31 women (63%). No intraoperative complications were recorded. In the colorectal resection group, 3 women (18%) had a bladder atony (spontaneously regressive in 2 women), 4 women (24%) experienced chronic constipation, one had an anastomosis leakage (6%), while 2 women (13%) had acute compartment syndrome with peripheral sensory disturbance. In the nodule excision group, 1 woman (4%) developed transitory right obturator nerve motor palsy. Based on both postoperative pain and improvement in quality of life, all 29 women in the excision group (100%) and 14 women in the colorectal resection group (82%) would recommend the surgical procedure to a friend suffering from the same disease. CONCLUSION: Our study suggests that carrying out colorectal segmental resection in rectal endometriosis is associated with unfavourable postoperative outcomes, such as bladder and rectal dysfunction. These outcomes are less likely to occur when rectal nodules are managed by excision. Information about complications related to both surgical procedures should be provided to patients managed for rectal endometriosis and should be taken into account when a decision is being made about the most appropriate treatment of rectal endometriosis in each case.

Late supra-diaphragmatic lymph node recurrence following resection of a fibrolamellar hepatocarcinoma: an unusual case.

We report the case of a patient who presented with a supra-diaphragmatic lymph node recurrence 8 years after resection of a right liver fibrolamellar carcinoma. Treatment of this recurrence consisted of local excision by a right thoracotomy approach. Postoperative course was uneventful and the patient did not experience recurrence within 2 years. Based on this observation, we describe the major lymphatic vessels of the liver, in order to explain this unusual metastatic site occurrence.

Down-regulated expression of the TSAP6 protein in liver is associated with a transition from cirrhosis to hepatocellular carcinoma.

AIMS: Hepatocellular carcinoma (HCC) results from cirrhosis and, in Western Europe, hepatitis C virus and alcoholism are the predominant causes of this disease. We recently documented a global transcript repression in hepatocarcinoma nodules. The tumour suppressor activated pathway-6 (TSAP6) transcript codes for a transmembrane molecule that is an inducer of a caspase-3-dependent apoptotic pathway. The down-regulation of TSAP6 transcripts in HCC and perinodular cirrhosis, which contrasts with a sustained transcript level in HCC-free cirrhosis, has suggested that this hepatic protein level may provide a prognostic marker for HCC occurrence. METHODS AND RESULTS: This protein was quantified by semiquantitative assessment of immunohistochemistry on samples from 42 cases HCC-free cirrhosis, 49 cases cirrhosis with HCC, 43 HCC associated with healthy liver and 31 controls. TSAP6 expression was linked to the liver state, healthy or cirrhotic without or with an HCC and to tumour grade. CONCLUSIONS: With biopsies periodically performed for surveillance purposes, the decreased expression of TSAP6 in cirrhotic tissue could reflect a decrease in the apoptotic process and could be interpreted as a warning sign. This evaluation of the TSAP6 level in cirrhotic liver conveys predictive information for the development of HCC.

Ciliated hepatic foregut cyst discovered after kidney transplantation in a hepatitis C virus-infected patient: a report of one case and review of the literature.

Ciliated hepatic foregut cyst (CHFC) is a rare liver lesion derived from the embryonic foregut. In most cases, CHFC remains asymptomatic but some malignant transformations have been reported. Typical imaging features usually lead to diagnosis using ultrasonography, computed tomography scan examination or MRI. When the diagnosis remains uncertain, a fine needle aspiration with cytology is appropriate. The presence of ciliated epithelial cells with hepatocytes and mucous cells on aspiration cytology is enough to assess the diagnosis. Surgery is recommended when there is uncertain diagnosis or malignant lesion suspicion. We report herein, the case of a CHFC discovered in a hepatitis C virus-infected patient following a renal transplantation. To eliminate a lymphoma or a liver tumor arising because of patient's immunosuppression status, a surgical resection of the lesion was performed. The surgical outcome was uneventful. Regarding this case, embryogenesis, morphological characteristics and treatment of the lesions are discussed.

Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma.

AIM: To look at a comprehensive picture of etiology-dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS: With a liver-oriented microarray, transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism, 12; hepatitis C, 10) and 5 controls. Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set (12 + 10) and a test set (6 + 7). RESULTS: A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism) or -2 (hepatitis C) and ontology indicated a predominant inflammatory response (alcoholism) or changes in cell cycle regulation, transcription factors and interferon responsiveness (hepatitis C). A stringent selection of 23 transcripts whose differences between etiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis. These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION: Etiology-specific abnormalities (chromo-some preference; differences in transcriptomes and related functions) have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C. This may open novel avenues for differential therapies in this disease.

Excess Body Mass Index Loss at 3 Months: A Predictive Factor of Long-Term Result after Sleeve Gastrectomy.

Introduction. Laparoscopic Sleeve Gastrectomy (SG) is considered as successful if the percentage of Excess Body Mass Index Loss (% EBMIL) remains constant over 50% with long-term follow-up. The aim of this study was to evaluate whether early % EBMIL was predictive of success after SG. Methods. This retrospective study included patients who had SG with two years of follow-up. Patients had follow-up appointments at 3 (M3), 6, 12, and 24 months (M24). Data as weight and Body Mass Index (BMI) were collected systematically. We estimated the % EBMIL necessary to establish a correlation between M3 and M24 compared to % EBMIL speeds and calculated a limit value of % EBMIL predictive of success. Results. Data at operative time, M3, and M24 were available for 128 patients. Pearson test showed a correlation between % EBMIL at M3 and that at M24 (r = 0.74; p < 0.0001). % EBMIL speed between surgery and M3 (p = 0.0011) was significant but not between M3 and M24. A linear regression analysis proved that % EBMIL over 20.1% at M3 (p < 0.0001) predicted a final % EBMIL over 50%. Conclusions. % EBMIL at M3 after SG is correlated with % EBMIL in the long term. % EBMIL speed was significant in the first 3 months. % EBMIL over 20.1% at M3 leads to the success of SG.

Use of water-soluble contrast medium (gastrografin) does not decrease the need for operative intervention nor the duration of hospital stay in uncomplicated acute adhesive small bowel obstruction? A multicenter, randomized, clinical trial (Adhesive Small Bowel Obstruction Study) and systematic review.

BACKGROUND: This study evaluated the association between oral gastrografin administration and the need for operative intervention in patients with presumed adhesive small bowel obstruction. METHODS: Between October 2006 and August 2009, 242 patients with uncomplicated acute adhesive small bowel obstruction were included in a randomized, controlled trial (the Adhesive Small Bowel Obstruction Study, NCT00389116) and allocated to a gastrografin arm or a saline solution arm. The primary end point was the need for operative intervention within 48 hours of randomization. The secondary end points were the resection rate, the time interval between the initial computed tomography and operative intervention, the time interval between oral refeeding and discharge, risk factors for the failure of nonoperative management, in-hospital mortality, duration of stay, and recurrence or death after discharge. We performed a systematic review of the literature in order to evaluate the relationship between use of gastrografin as a diagnostic/therapeutic measure, the need for operative intervention, and the duration of stay. RESULTS: In the gastrografin and saline solution arms, the rate of operative intervention was 24% and 20%, respectively, the bowel resection rate was 8% and 4%, the time interval between the initial computed tomography and operative intervention, and the time interval between oral refeeding and discharge were similar in the 2 arms. Only age was identified as a potential risk factor for the failure of nonoperative management. The in-hospital mortality was 2.5%, the duration of stay was 3.8 days for patients in the gastrografin arm and 3.5 days for those in the saline solution arm (P = .19), and the recurrence rate of adhesive small bowel obstruction was 7%. These results and those of 10 published studies suggest that gastrografin did not decrease either the rate of operative intervention (21% in the saline solution arm vs 26% in the gastrografin arm) or the number of days from the initial computed tomography to discharge (3.5 vs 3.5; P = NS for both). CONCLUSION: The results of the present study and those of our systematic review suggest that gastrografin administration is of no benefit in patients with adhesive small bowel obstruction.

[Intraperitoneal hyperthermic chemotherapy in the management of recurrent peritoneal carcinomatosis. Preliminary results in 5 patients]. / Faisabilité d'une chimiohyperthermie intra-péritonéale itérative après chirurgie de cytoréduction pour récidive de carcinose péritonéale. A propos de 5 cas.

Peritoneal carcinomatosis has been treated by extensive cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). We report here our experience of 5 patients treated twice or three times by recurrent procedure of HIPEC and cytoreduction. The mortality rate was 0% and morbidity one 30%. Three patients have died at 6, 10, 18 months respectively after the second cytoreduction surgery and HIPEC, and two patients are still alive at 40 and 67 months. Our results might suggest that recurrent peritoneal carcinomatosis after cytoreduction and HIPEC, could be usefully treated by another cytoreduction and HIPEC procedure in a curative approach superior to more conventional treatments.

The role of Kupffer cells after major liver surgery.

BACKGROUND: Kupffer cells (KCs) are the resident macrophages of the liver. KCs have an enormous endotoxin eliminating capacity. Endotoxins play an important role in the development of systemic complications after partial hepatectomy by activating KCs. The role of KCs and endotoxins after partial hepatectomy is investigated. METHODS: Wistar rats (n = 16, 250-275 g) were randomly assigned to have 1 mL dichloromethylene-diphosphonate (CL2MDP) or 1 mL NaCl 0.9% i.v. Forty-eight hours later, all rats received a two-thirds liver resection. Twenty-four hours later, rats received at random 50 microg/kg endotoxin (LPS) in 1 mL or 1 mL of NaCl 0.9% IV. The rats were killed 4 hours after LPS or SAL infusion. RESULTS: CL2MDP infusion resulted in a complete KC elimination. KC-depleted rats had the lowest mean arterial pressure, the highest heart and ventilatory rate after endotoxemia. All rats were able to maintain pH in normal ranges. The KC-depleted rats after partial hepatectomy had the lowest CO2 levels and the highest levels of lactate during endotoxemia. Oxygen levels were similar in all groups. Hepatic, pulmonary, and renal mRNA expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta were decreased in KC-depleted rats. Plasma levels of TNF-alpha were significantly decreased in KC-depleted rats. Furthermore, the highest influx of macrophages and polymorphonuclear cells in the lung and kidney were measured in KC-depleted rats during endotoxemia. CONCLUSIONS: Partial hepatectomy in KC-depleted rats result in a more pronounced endotoxin-mediated systemic inflammation and decreased synthesis of cytokines.