The Histopathological Growth Pattern of Colorectal Liver Metastases Impacts Local Recurrence Risk and the Adequate Width of the Surgical Margin.

BACKGROUND: The histopathological growth pattern (HGP) of colorectal liver metastases (CLM) has been associated with prognosis. This study was designed to elucidate if the HGP is associated with local recurrence risk and impacts the adequate width of surgical margin. METHODS: All consecutive patients resected for CLM in 2018-2019 were considered. HGP was prospectively classified as follows: desmoplastic, pushing, and replacement. Surgical margin was classified as follows: R0 (margin ≥ 1 mm), R1vasc (0-mm margin, tumor detachment from intrahepatic vessels), and R1par (tumor exposure along transection plane). R0 resections were further distinguished in R0min (1-mm margin) and R0wide (> 1-mm margin). RESULTS: A total of 340 resection areas in 136 patients were analyzed (70 R0min, 143 R0wide, 31 R1vasc, 96 R1par). HGP was desmoplastic in 26 cases, pushing in 221, and replacement in 93. Thirty-six local recurrences occurred (11%, median follow-up 21 months): 1 after R0wide, 4 after R0min, 3 after R1vasc, and 28 after R1par resection. In R1par group, local recurrence rate was high independently of HGP (29%). In R1vasc and R0min groups, local recurrence risk was higher in the replacement group (R1vasc: 29% vs. 4% if pushing/desmoplastic; R0min: 11% vs. 4%). In R0wide group, local recurrence risk was low for all HGP ( < 1%). Independent predictors of local recurrence were replacement HGP (odds ratio = 1.654, P = 0.036), and R1par resection (odds ratio = 57.209, P < 0.001 vs. R0). CONCLUSIONS: Replacement HGP is associated with an increased risk of local recurrence. In these patients, a wide surgical margin should be pursued, because R1vasc and R0min resections could be insufficient. R1par resection is inadequate, independently of the HGP.

Multicentre evaluation of case volume in minimally invasive hepatectomy.

BACKGROUND: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. METHODS: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). RESULTS: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). CONCLUSION: A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.

ANTECEDENTES: Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimally­invasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes. RESULTADOS: Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumen­resultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.

Guillain-Barré syndrome associated with SARS-CoV-2 infection. A systematic review.

Guillain-Barré syndrome (GBS) incidence can increase during outbreaks of infectious illnesses. A few cases of GBS associated with coronavirus disease 2019 (COVID-19) infection have been reported. The aim was to identify specific clinical features of GBS associated with COVID-19. PubMed, Embase and Cochrane were searched from 1 November 2019 to 17 May 2020 and included all papers with full text in English, Spanish, French or Italian, reporting original data of patients with GBS and COVID-19. Data were extracted according to a predefined protocol. A total of 18 patients reported in 14 papers were included in this review. All the patients were symptomatic for COVID-19, with cough and fever as the most frequently reported symptoms. The interval between the onset of symptoms of COVID-19 and the first symptoms of GBS ranged from -8 to 24 days (mean 9 days; median 10 days). Most of the patients had a typical GBS clinical form predominantly with a demyelinating electrophysiological subtype. Mechanical ventilation was necessary in eight (44%) patients. Two (11%) patients died. Published cases of GBS associated with COVID-19 report a sensorimotor, predominantly demyelinating GBS with a typical clinical presentation. Clinical features and disease course seem similar to those observed in GBS related to other etiologies. These results should be interpreted with caution since only 18 cases have been heterogeneously reported so far.

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases.

BACKGROUND: The impact of chemotherapy-associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres. METHODS: PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords 'chemotherapy', 'liver resection', 'outcome' and 'colorectal metastases' to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo-Clavien grade III-V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery-specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery-specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001). CONCLUSION: An increase in postoperative major morbidity and liver surgery-specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.

Liver resection in patients with eight or more colorectal liver metastases.

BACKGROUND: Patients with large numbers of colorectal liver metastases (CRLMs) are potential candidates for resection, but the benefit from surgery is unclear. METHODS: Patients undergoing resection for CRLMs between 1998 and 2012 in two high-volume liver surgery centres were categorized according to the number of CRLMs: between one and seven (group 1) and eight or more (group 2). Overall (OS) and recurrence-free (RFS) survival were compared between the groups. Multivariable analysis was performed to identify adverse prognostic factors. RESULTS: A total of 849 patients were analysed: 743 in group 1 and 106 in group 2. The perioperative mortality rate (90 days) was 0.4 per cent (all group 1). Median follow-up was 37.4 months. Group 1 had higher 5-year OS (44.2 versus 20.1 per cent; P < 0.001) and RFS (28.7 versus 13.6 per cent; P < 0.001) rates. OS and RFS in group 2 were similar for patients with eight to ten, 11-15 or more than 15 metastases (48, 40 and 18 patients respectively). In group 2, multivariable analysis identified three preoperative adverse prognostic factors: extrahepatic disease (P = 0.010), no response to chemotherapy (P = 0.023) and primary rectal cancer (P = 0.039). Patients with two or more risk factors had very poor outcomes (median OS and RFS 16.9 and 2.5 months; 5-year OS zero); patients in group 2 with no risk factors had similar survival to those in group 1 (5-year OS rate 44 versus 44.2 per cent). CONCLUSION: Liver resection is safe in selected patients with eight or more metastases, and offers reasonable 5-year survival independent of the number of metastases. However, eight or more metastases combined with at least two adverse prognostic factors is associated with very poor survival, and surgery may not be beneficial.

Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours.

BACKGROUND: Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221). METHODS: Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m(-2), day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)). RESULTS: Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation. CONCLUSIONS: Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m(-2)) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.

Locally advanced mid/low rectal cancer with synchronous resectable liver metastases: systematic review of the available strategies and outcome.

The management of patients with locally advanced mid/low rectal cancer with resectable liver metastases is complex because of the need to combine the optimal treatment of both tumors. This study aims to review the available treatment strategies and compare their outcome, focusing on radiotherapy (RT) and liver-first approach (LFA). A systematic review was performed in PubMed, Embase, and web sources including articles published between 2000 and 02/2023 and reporting mid-/long-term outcomes. Overall, twenty studies were included (n = 1837 patients). Three- and 5-year overall survival (OS) rates were 51-88% and 36-59%. Although several strategies were reported, most patients received RT (1448/1837, 79%; > 85% neoadjuvant). RT reduced the pelvic recurrence risk (5.8 vs. 13.5%, P = 0.005) but did not impact OS. Six studies analyzed LFA (n = 307 patients). LFA had a completion rate similar to the rectum-first approach (RFA, 81% vs. 79%) but the interval strategy-an LFA variant with liver surgery in the interval between radiotherapy and rectal surgery-had a better completion rate than standard LFA (liver surgery/radiotherapy/rectal surgery, 92% vs. 75%, P = 0.011) and RFA (79%, P = 0.048). Across all series, LFA achieved the best survival rates, and in one paper it led to a survival advantage in patients with multiple metastases. In conclusion, different strategies can be adopted, but RT should be included to decrease the pelvic recurrence risk. LFA should be considered, especially in patients with high hepatic tumor burden, and RT before liver surgery (interval strategy) could maximize its completion rate.

Comparison of laparoscopic and open intraoperative ultrasonography for staging liver tumours.

BACKGROUND: Laparoscopic liver surgery must reproduce open surgical steps. Intraoperative ultrasonography (IOUS) is mandatory, but reliability of laparoscopic IOUS has been poorly evaluated. The aim of this study was to compare laparoscopic versus open IOUS in staging liver tumours. METHODS: All patients scheduled for liver resection between September 2009 and March 2011 were considered. Inclusion criteria were primary and metastatic tumours. Exclusion criteria were: hilar/gallbladder cholangiocarcinoma, ten or more lesions, repeat resection, laparoscopic hepatectomy, adhesions and unresectability. Following percutaneous ultrasonography and thoracoabdominal computed tomography (CT), and on indication contrast-enhanced (CE) liver magnetic resonance imaging (MRI) and/or positron emission tomography (PET)-CT, patients were scheduled for laparoscopy, laparoscopic IOUS, then laparotomy, open IOUS and Partial hepatectomy. Data were collected prospectively. Reference standards were final pathology and 6-month follow-up results. RESULTS: Sixty-five patients were included, who had a median of 3 preoperative imaging studies (ultrasonography/CT 100 per cent, CE-MRI 67 per cent, PET-CT 54 per cent). A total of 119 lesions were diagnosed. Laparoscopic IOUS detected 22 additional lesions (+18·5 per cent) in 14 patients. Open IOUS detected two additional lesions, but did not confirm four lesions; overall 20 additional lesions (+16·8 per cent) were detected in ten patients. Pathology confirmed 14 newly detected malignant nodules (+11·8 per cent) in eight patients. After 6 months ten new nodules were identified in six patients. The sensitivity of preoperative imaging, laparoscopic IOUS and open IOUS was 83·1, 92·3 and 93·0 per cent respectively; accuracy was 79, 82 and 88 per cent. In comparison with open IOUS, the sensitivity and accuracy of laparoscopic IOUS were 98·6 and 94 per cent. CONCLUSION: Laparoscopic IOUS is a reliable tool for staging liver tumours with a performance similar to that of open IOUS in detecting new nodules.

In vivo lymph node mapping and pattern of metastasis spread in locally advanced mid/low rectal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: The lymph node status is one of the strongest prognostic determinants in rectal cancers. After chemoradiotherapy (CRT), lymph nodes are difficult to detect. This study aims to evaluate the feasibility of lymph node mapping in the mesorectum after CRT to analyze the pattern of metastasis spread and to assess the reliability of blue dye injection in sentinel lymph node detection. METHOD: Ten patients with cN+ mid/low RCs after CRT were prospectively enrolled. The protocol scheduled intraoperative blue dye injection, surgery, and specimen examination with fat clearance technique. The mesorectum was divided into three equal "levels" (upper, middle, and lower); each level was divided into three equal "sectors" (right anterolateral, posterior, and left anterolateral). Lymph nodes were defined "small" if ≤5 mm. RESULTS: Two hundred seventy-six lymph nodes were retrieved in ten patients; 76.5 % were small lymph nodes. Six patients were pN+ (33 metastatic lymph nodes, 76 % small); small lymph node analysis upstaged one patient from N0 to N1 and four patients from N1 to N2. Metastasis distribution across sectors was continuous, without "skip sectors." The blue dye detected the sentinel lymph node in all patients; in half of the cases, it was out of the tumor sector. Blue dye identified 69.7 % of metastatic lymph nodes; its sensitivity decreased together with the metastatic deposit size (84 % macrometastases, 28.6 % micrometastases, 0 % occult tumor cells; p = 0.004). CONCLUSION: The fat clearance technique should be the standard pathological examination in patients with RCs after CRT; N staging was improved by small lymph node identification. Lymph node metastases have a continuous spread through mesorectal sectors. Blue dye injection is effective in sentinel lymph node detection.

Distant supervision for imaging-based cancer sub-typing in Intrahepatic Cholangiocarcinoma.

Finding effective ways to perform cancer sub-typing is currently a trending research topic for therapy opti-mization and personalized medicine. Stemming from genomic field, several algorithms have been proposed. In the context of texture analysis, limited efforts have been attempted, yet imaging information is known to entail useful knowledge for clinical practice. We propose a distant supervision model for imaging-based cancer sub-typing in Intrahepatic Cholangiocar-cinoma patients. A clinically informed stratification of patients is built and homogeneous groups of patients are characterized in terms of survival probabilities, qualitative cancer variables and radiomic feature description. Moreover, the contributions of the information derived from the ICC area and from the peri tumoral area are evaluated. The findings suggest the reliability of the proposed model in the context of cancer research and testify the importance of accounting for data coming from both the tumour and the tumour-tissue interface. Clinical relevance - In order to accurately predict cancer prognosis for patients affected by ICC, radiomic variables of both core cancer and surrounding area should be exploited and employed in a model able to manage complex information.

Phase Ib study of weekly mammalian target of rapamycin inhibitor ridaforolimus (AP23573; MK-8669) with weekly paclitaxel.

BACKGROUND: The additive cytotoxicity in vitro prompted a clinical study evaluating the non-prodrug rapamycin analogue ridaforolimus (AP23573; MK-8669; formerly deforolimus) administered i.v. combined with paclitaxel (PTX; Taxol). MATERIALS AND METHODS: Patients with taxane-sensitive solid tumors were eligible. The main dose escalation foresaw 50% ridaforolimus increments from 25 mg with a fixed PTX dose of 80 mg/m(2), both given weekly 3 weeks in a 4-week cycle. Collateral levels with a lower dose of either drug were planned upon achievement of the maximum tolerated dose in the main escalation. Pharmacodynamic studies in plasma, peripheral blood mononuclear cells (PBMCs) and skin biopsies and pharmacokinetic (PK) interaction studies at cycles 1 and 2 were carried out. RESULTS: Two recommended doses were determined: 37.5 mg ridaforolimus/60 mg/m(2) PTX and 12.5 mg/80 mg/m(2). Most frequent toxic effects were mouth sores (79%), anemia (79%), fatigue (59%), neutropenia (55%) and dermatitis (48%). Two partial responses were observed in pharyngeal squamous cell and pancreatic carcinoma. Eight patients achieved stable disease > or =4 months. No drug interaction emerged from PK studies. Decrease of eukaryotic initiation factor 4E-binding protein1 (4E-BP1) phosphorylation was shown in PBMCs. Similar inhibition of phosphorylation of 4E-BP1 and mitogen-activated protein kinase was present in reparative epidermis and vascular tissues, respectively. CONCLUSION: Potential antiangiogenic effects and encouraging antitumor activity justify further development of the combination.

Combined first-stage hepatectomy and colorectal resection in a two-stage hepatectomy strategy for bilobar synchronous liver metastases.

BACKGROUND: This study assessed the feasibility and outcomes of combined colorectal and hepatic resection as the first step of two-stage hepatectomy in patients with bilobar synchronous colorectal liver metastases. METHODS: All patients with bilobar synchronous colorectal liver metastases who were considered for two-stage hepatectomy, combining resection of the primary tumour with the first stage of hepatectomy, between 2000 and 2008 were selected from a prospectively collected database at two institutions. Data were analysed retrospectively on an intention-to-treat basis. RESULTS: Thirty-three patients were studied. Twenty patients received neoadjuvant chemotherapy. Combined colorectal resection and clearance of left-sided liver metastases was the first-stage procedure in all but one patient, in whom right clearance was performed. In 17 patients right portal vein ligation was undertaken at the same time. No patient died. Two patients had anastomotic leakage. Interval chemotherapy was given to 25 patients, five of whom also had percutaneous portal vein embolization. Twenty-five patients had the second-stage hepatectomy, but not eight patients with disease progression. There was one postoperative death after the second stage, and eight patients experienced morbidity. Median follow-up from the first stage was 28.7 months. Overall and disease-free survival rates for patients who completed the procedure were 80 and 44 per cent respectively at 3 years, and 48 and 22 per cent at 5 years. CONCLUSION: In patients with bilobar synchronous colorectal liver metastases who are candidates for two-stage hepatectomy, combined resection of the primary tumour and first-stage hepatectomy reduces the number of procedures, optimizes chemotherapy administration and may improve outcome.

Liver dysfunction and sepsis determine operative mortality after liver resection.

BACKGROUND: Liver failure is the principal cause of death after hepatectomy. Its progression towards death and its relationship with sepsis are unclear. This study analysed predictors of mortality in patients with liver dysfunction and the role of sepsis in the death of these patients. METHODS: The study focused on patients with liver dysfunction, excluding those with vascular thrombosis, after liver resection at one of two centres between 1998 and 2006. RESULTS: Liver dysfunction occurred after 57 (4.5 per cent) of 1271 hepatectomies. Fifty-three patients without vascular thrombosis were included in the analysis, with a mortality rate of 23 per cent. Independent predictors of death were age (odds ratio (OR) 1.18 per year increase; P = 0.017), cirrhosis (OR 54.09; P = 0.004) and postoperative sepsis (OR 37.58; P = 0.005). Sepsis occurred in 15 patients (28 per cent), seven of whom died. Intestinal pathogens were isolated in 12 patients with sepsis. The risk of sepsis was significantly increased in those with surgical complications (11 of 16 versus four of 37; P < 0.001). CONCLUSION: Sepsis plays a key role in the death of patients with liver dysfunction after hepatectomy. Early recognition and aggressive treatment of sepsis may reduce mortality.

Barrett's oesophagus: long-term follow-up after complete ablation with argon plasma coagulation and the factors that determine its recurrence.

BACKGROUND: Argon plasma coagulation seems to be a promising technique for ablation of Barrett's oesophagus, yet few long-term efficacy data are available. AIM: To report on a long-term follow-up and the factors that determine the recurrence of intestinal metaplasia in a cohort of patients with non dysplastic, intestinal type Barrett's oesophagus, after complete ablation of the metaplastic mucosa with argon plasma coagulation. METHODS: Ninety-six patients underwent endoscopic argon plasma coagulation with adequate acid suppression obtained through a continuous omeprazole therapy (50 patients) or through laparoscopic fundoplication (46 patients). Complete ablation was achieved in 94 patients who underwent follow-up. Endoscopic and histological examinations were performed every 12 months. RESULTS: The median follow-up of the patients was 36 months (range 18-98). A recurrence of intestinal metaplasia was found in 17 patients (18%), with an annual recurrence rate of 6.1%. Neither dysplasia, nor adenocarcinoma were found during the follow-up. Through the use of logistic regression analysis, previous laparoscopic fundoplication was associated with a reduced recurrence rate of intestinal metaplasia (odds ratio 0.30, 95% confidence interval 0.10-0.93). CONCLUSIONS: The long-term recurrence of intestinal type Barrett's oesophagus was low after complete ablation with argon plasma coagulation. The control of oesophageal acidity acid exposure with laparoscopic fundoplication seems to reduce the recurrence rate.

Prevention of intrahepatic recurrence by adjuvant (131)iodine-labeled lipiodol after resection for hepatocellular carcinoma in HCV-related cirrhosis.

AIM: To evaluate the impact of postoperative injection into the hepatic artery of 131-iodine-labeled lipiodol on disease-free and overall survival rates in patients who underwent liver surgical resection for hepatocellular carcinoma. METHODS: Ten consecutive patients with HCV (hepatitis C virus)-related cirrhosis who underwent liver surgical resection for hepatocellular carcinoma were treated with adjuvant injection of 131-iodine-labeled lipiodol. They were matched with 20 HCV-positive cirrhotic controls who underwent liver resection alone; patients were paired in terms of age, Child-Pugh class, tumor size, microscopic vascular invasion, tumor histological pattern, presence of satellite nodules and type of surgical resection. Recurrence was defined as the development of a new hypervascularizated nodule in the liver. RESULTS: No significant differences were found between the two groups in clinical, biologic and histologic characteristics, except a lower platelet count in the control group. None of the treated patients developed an intrahepatic recurrence until the 15th month from liver resection, whereas recurrences occurred in nine of the 20 patients in the control group (p=0.01). From 18 months onwards, recurrences appeared also in the treated patients, and after 36 months of follow-up both recurrence rate and overall survival were not significantly different between the two groups. CONCLUSIONS: Intrahepatic injection of 131-iodine-labeled lipiodol improves the disease-free survival rate following liver resection of hepatocellular carcinoma in the short term up to 15 months; this advantage fades, however, away after 36 months.

Sensitivity of autopsy and radiological examination in detecting bone fractures in an animal model: implications for the assessment of fatal child physical abuse.

Skeletal injuries are often strong indicators of child abuse and their detection is therefore crucial. The aim of this study was to compare the sensitivity of three diagnostic approaches, namely autopsy, traditional (conventional) radiology, and computed tomography on "battered" piglets, in order to verify the sensitivity of each method, with respect to the true number of bone fractures assessed once the piglet was skeletonised (osteological control). Four newborn cadaver piglets who had died from natural causes were severely beaten post-mortem in every district of the body. Traditional radiography, computed tomography (CT) and autopsy were performed. The piglet was then macerated until skeletonised and the number of all fractures present recorded (osteological control). On the cranium, traditional radiology revealed only 35% circa of actual fractures, autopsy detected only 31% (P<0.01 for both comparisons versus osteological control), whereas CT imaging detected all fractures actually present. For ribs, radiology detected only 47% of all fractures present, and autopsy 65% circa (P>0.05 for both comparisons versus osteological control), while CT scans detected 34% (P<0.01). In suspected cases of fatal child abuse, we suggest that the bones of specific districts be directly analysed either at autopsy or by collecting specific diagnostic sites, such as parts of the rib cage, and subjecting them to maceration. The removed areas could be replaced with artificial material for cosmetic purposes. The authors stress the importance of combined radiological, CT scan, autopsy and osteological survey in the detection of perimortem bone fractures.

Role of daunosamine and hydroxyacetyl side chain in reaction with iron and lipid peroxidation by anthracyclines.

Doxorubicin (Adr), daunorubicin (Dnr), and analogs of Adr modified in daunosamine (4'-epi-Adr and 3'-N-acetyl-Adr) were investigated with respect to their reaction with Fe(III) and analyzed for the ability of the corresponding iron complexes to sustain lipid peroxidation of isolated human platelet membranes. When the proportion of iron [25 microM Fe(III)] to Adr was 1:4, almost 50% of the metal was reduced following 1 hour of anaerobic reaction, while only approximately equal to 14% of the bound iron could be extracted as Fe(II) in the reactions of the Dnr complexes. The reaction of Adr was associated with formation of two main novel anthracyclines. One of the products had lost the C14 atom of the C9 chain and displayed chromatographic features and visible UV light spectra identical to those of authentic 9-dehydroxyacetyl-9-carboxyl-Adr. In complexes of iron and Dnr, no significant anthracycline degradation was observed. Reduction of anthracycline-bound Fe(III) by 4'-epi-Adr (38%) and 3'-N-acetyl-Adr (21.2%) was consistently less than that by Adr. Complexes of the anthracyclines investigated had different abilities to sustain lipid peroxidation, which was blocked (a) by the iron chelators deferoxamine and bathophenanthroline, indicating that Fe(III) and Fe(II) were needed for the reaction, and (b) by ICRF-198, the chelating product that forms intracellularly by hydrolysis of razoxane, which can prevent Adr cardiotoxicity. Peroxidation was not affected by scavengers of reduced oxygen radicals (superoxide dismutase, catalase, and mannitol). The isolated membranes contributed to the reduction of anthracycline-bound Fe(III) and probably represented the main determinant of lipid peroxidation by iron-Dnr. Lipid peroxidation was significantly less for complexes of iron with 4'-epi-Adr or 3'-N-acetyl-Adr than for complexes of iron with Adr. The observed differences may be relevant to the different biologic properties of Adr and its analogs, in particular their different degrees of cardiotoxicity.