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Background: Postoperative ascites (POA) is the most common complication after liver surgery for hepatocarcinoma (HCC), but its impact on survival is not reported. The aim of the study is to investigate its impact on overall survival (OS) and disease-free survival (DFS), and secondarily to identify the factors that may predict the occurrence. Method: Data were collected from 23 centers participating in the Italian Surgical HCC Register (HE.RC.O.LE.S. Group) between 2008 and 2018. POA was defined as ≥500 ml of ascites in the drainage after surgery. Survival analysis was conducted by the Kaplan Meier method. Risk adjustment analysis was conducted by Cox regression to investigate the risk factors for mortality and recurrence. Results: Among 2144 patients resected for HCC, 1871(88.5%) patients did not experience POA while 243(11.5%) had the complication. Median OS for NO-POA group was not reached, while it was 50 months (95%CI = 41–71) for those with POA (p < 0.001). POA independently increased the risk of mortality (HR = 1.696, 95%CI = 1.352–2.129, p < 0.001). Relapse risk after surgery was not predicted by the occurrence of POA. Presence of varices (OR = 2.562, 95%CI = 0.921–1.822, p < 0.001) and bilobar disease (OR = 1.940, 95%CI = 0.921–1.822, p: 0.004) were predictors of POA, while laparoscopic surgery was protective (OR = 0.445, 95%CI = 0.295–0.668, p < 0.001). Ninety-day mortality was higher in the POA group (9.1% vs 1.9% in NO-POA group, p < 0.001). Conclusion: The occurrence of POA after surgery for HCC strongly increases the risk of long-term mortality and its occurrence is relatively frequent. More efforts in surgical planning should be made to limit its occurrence.

A multicentre prospective survey on the use of artificial nutrition (AN) and its complications has been carried out on 1657 hospitalised patients including 7.8% in surgical departments, 7.1% in medical departments and 59.9% in intensive care units. Gastrointestinal diseases and cancer were the most frequent pathologies among patients requiring AN. Parenteral nutrition (PN) alone was employed in 1103 (66.5%) patients. In 267 (16.1%) PN was associated with enteral nutrition (EN). 287 (17.3%) patients were fed by the enteral route alone. The average daily energy intake was 35 kcal/kg for central PN, 26 kcal/kg for peripheral PN and 33 kcal/kg for EN. The mean daily nitrogen intake was 0.19 g/kg for central PN, 0.17 g/kg for peripheral PN and 0.20 g/kg for EN. In 10% of patients PN was electrolyte free and in only 50% all the main electrolytes were added. Trace elements were added in 48% of formulations, mainly as multiple combination. Insulin was added in 61% of PN patients, while albumin was given with PN in 20% of patients. Adverse reactions were observed in 10.9% of PN patients and in 11.5% of EN patients. The most frequent complications occurring in parenterally fed patients were infections of the central venous catheter and metabolic alterations (severe electrolyte abnormalities, liver or renal dysfunction, hypo or persistent hyperglycemia). In enterally fed patients the frequent complications were abdominal distension, cramps and diarrhoea. Adverse reactions were responsible for discontinuation of AN in 2.2% of parenterally supported patients and in 5.7% of enterally fed patients.

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable. Electronic supplementary material The online version of this article (10.1007/s13304-020-00815-5) contains supplementary material, which is available to authorized users.

Study Objective: The effect of the different types of vaginal cuff closures on posthysterectomy sexual function has not been investigated in depth. We evaluated if there is a difference between transvaginal versus a laparoscopic closure after total laparoscopic hysterectomy (TLH) on female sexual function, using a validated questionnaire. Design: Secondary analysis of a prospective randomized controlled trial. Setting: Three academic research centers. Patients: Women consenting to telephone interviews on their sexual life before and after undergoing TLH were included. Interventions: Patients were randomly assigned to a laparoscopic or transvaginal approach for vaginal cuff closure at the end of TLH for benign indications. Measurements and Main Results: A validated questionnaire (the Female Sexual Function Index [FSFI]) was used to explore sexuality before and after the operation. Of the 1408 patients enrolled in the primary study, 400 patients were asked to complete the questionnaire. Of them, 182 (41.4%) were eligible and accepted enrollment in the present analysis. No difference was found in terms of pre- and postoperative FSFI scores between groups. Patients with a low preoperative FSFI score (

Background and aims: We investigated the clinical impact of the newly defined metabolic-associated fatty liver disease (MAFLD) in patients undergoing hepatectomy for HCC (MAFLD-HCC) comparing the characteristics and outcomes of patients with MAFLD-HCC to viral- and alcoholic-related HCC (HCV-HCC, HBV-HCC, A-HCC). Methods: A retrospective analysis of patients included in the He.RC.O.Le.S. Group registry was performed. The characteristics, short- and long-term outcomes of 1315 patients included were compared according to the study group before and after an exact propensity score match (PSM). Results: Among the whole study population, 264 (20.1%) had MAFLD-HCC, 205 (15.6%) had HBV-HCC, 671 (51.0%) had HCV-HCC and 175 (13.3%) had A-HCC. MAFLD-HCC patients had higher BMI (p < 0.001), Charlson Comorbidities Index (p < 0.001), size of tumour (p < 0.001), and presence of cirrhosis (p < 0.001). After PSM, the 90-day mortality and severe morbidity rates were 5.9% and 7.1% in MAFLD-HCC, 2.3% and 7.1% in HBV-HCC, 3.5% and 11.7% in HCV-HCC, and 1.2% and 8.2% in A-HCC (p = 0.061 and p = 0.447, respectively). The 5-year OS and RFS rates were 54.4% and 37.1% in MAFLD-HCC, 64.9% and 32.2% in HBV-HCC, 53.4% and 24.7% in HCV-HCC and 62.0% and 37.8% in A-HCC (p = 0.345 and p = 0.389, respectively). Cirrhosis, multiple tumours, size and satellitosis seems to be the independent predictors of OS. Conclusion: Hepatectomy for MAFLD-HCC seems to have a higher but acceptable operative risk. However, long-term outcomes seems to be related to clinical and pathological factors rather than aetiological risk factors.

Background Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial. Methods This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage. Results Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality. Conclusion Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers’ experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma. Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication. Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201, 7.438) for CCI and 5.507 (4.152, 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896, 4.115) for CCI and 2.439 (1.666, 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set. Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.

Introduction: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI-versus open-ALPPS for HCC, with specific focus on PHLF. Methods: Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Results: Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%, P < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days, P < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05, P = .040) and partial parenchymal transection (OR = 0.04, P = .027) were protective against PHLF. Conclusion: This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.

Background: Posthepatectomy liver failure is one of the most feared complications in extended hepatic resections. In 2012, a novel two-stage liver resection was developed, able to induce rapid and extensive hypertrophy by portal vein ligation and in situ liver splitting - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). The technique became more widely employed but its use remained controversial due to reporting of high complication and mortality rates. Method: A national audit was performed to gather information about the safety of the procedure and to better understand the complications. The audit was offered to all high-volume hepatobiliary centers in Italy. Results: Of all Italian centers approached in January 2012, 12 centers with experience in ALPPS enrolled and participated in collection of data. Fifty patients underwent ALPPS between 2012 and 2014. In 48/50 patients completion of hepatectomy was performed successfully. Major morbidity occurred in 54% with a 20% 90-day mortality. Uni- and multivariate analysis showed that ALPPS for cholangiocarcinoma and a peak of bilirubin over 5 mg/dl between stages was associated with increase of 90 day mortality and worse survival. Discussion: It is proposed that a moratorium be introduced for classic ALPPS in cholangiocarcinoma and to abort ALPPS in patients who develop an interstage increase in bilirubin, due to the high risk of liver failure and mortality.

Strong evidences suggest that glutamine (GLN) plays a key role of in several metabolic pathways and it has been recognized as an essential substrate for the appropriate function of many organs and the principal metabolic fuel for different rapidly dividing cells. Moreover, GLN is essential for cell metabolism because it is able to modulate gluconeogenesis, lipogenesis, anabolic processes, to preserve mitocondrial ATP levels and attenuate the activation of inducible nitric oxide synthase following ischemia, trauma and sepsis, and to maintain gut integrity. GLN supplementation might be important in stress conditions to maintain a stable tissue and plasma pool and improve the above pathways. The randomized clinical trials published so far evaluating GLN supplementation in elective surgical patients and in subjects receiving intensive care treatment - with few exceptions - suffer several important methodological limitations such as lack of sample size calculation, blindness, a priori definition of complications, intention-to-treat analysis, subgroup and post-hoc analysis, statistical underpower, and heterogeneous cohort enrollment. The protective effect of GLN supplementation on primary outcome measures, such as morbidity and mortality is not persuasive. The most methodologically robust trials evaluating GLN supplementation showed no benefits or even a trend to harm in specific subgroups. Up to now the available data do not support the routine use of GLN in elective surgical and in critically ill patients. Others large randomized trials are needed to clarify if there is any role for GLN supplementation in specific subgroups.

The aim of the study was to evaluate perioperative outcomes and to evaluate factors influencing rative morbidity and adoption of minimally invasive technique in 1-team (1-T) versus two teams (2-T) management of synchronous colorectal liver metastases. Background: The aim of the study was to evaluate perioperative outcomes and to evaluate factors influencing rative morbidity and adoption of minimally invasive technique in 1-team (1-T) versus two teams (2-T) management of synchronous colorectal liver metastases. Methods: Within four referral centers, a group of 234 patients treated in 1-T centers was identified and compared with a group of 253 patients treated in 2-T. A nonparametric bootstrap process was applied to the original cohorts of 1-T group and 2-T group as a resampling method to obtain bootstrapped cohorts (155 patients per group). Results: 33.5% of patients in 1-T boot group and 38.1% in the 2-T boot group were operated by laparoscopic approach. Multivariate analysis revealed that approach to primary tumor (laparoscopic or open) and intraoperative blood loss were independent prognostic factors for morbidity. Team approach did not show any significant correlation with incidence of postoperative complications nor with choice for laparoscopic approach. Conclusion: The optimization of team strategy for patients with SCRLM is not solely based on the adoption of a 1-T or 2-T approach, but should instead be based on the implementation of a standard protocol for management of these patients.

Purpose The practical management of cavernous angioma located within eloquent brain area before, during and after surgical resection is poorly documented. We assessed the practical pre-operative, intra-operative, and post-operative management of cavernous angioma located within eloquent brain area. Method An online survey composed of 61 items was sent to 26 centers to establish a multicenter international retrospective cohort of adult patients who underwent a surgical resection as the first-line treatment of a supratentorial cavernous angioma located within or close to eloquent brain area. Results 272 patients from 19 centers (mean 13.6 ± 16.7 per center) from eight countries were included. The pre-operative management varied significantly between centers and countries regarding the pre-operative functional assessment, the pre-operative epileptological assessment, the first given antiepileptic drug, and the time to surgery. The intra-operative environment varied significantly between centers and countries regarding the use of imaging systems, the use of functional mapping with direct electrostimulations, the extent of resection of the hemosiderin rim, the realization of a post-operative functional assessment, and the time to post-operative functional assessment. The present survey found a post-operative improvement, as compared to pre-operative evaluations, of the functional status, the ability to work, and the seizure control. Conclusions We observed a variety of practice between centers and countries regarding the management of cavernous angioma located within eloquent regions. Multicentric prospective studies are required to solve relevant questions regarding the management of cavernous angioma-related seizures, the timing of surgery, and the optimal extent of hemosiderin rim resection.

Objective To describe the diagnosis and the management of hematometra in a patient with unicornuate uterus with noncommunicating functional horn (hemi uterus and rudimentary uterine hemicavity). Design Video case report. Setting Minimally invasive gynaecology unit. Patient(s) Sixteen-year-old nulliparous woman admitted to the gynaecologic emergency department with pelvic pain during menses. Intervention(s) Two-dimensional transvaginal ultrasound, magnetic resonance imaging, and laparoscopic rudimentary horn resection. Main Outcome Measure(s) Description of a case of anomaly of the female reproductive tract treated by laparoscopy. Result(s) After pain reduction and stabilization of clinical condition, ultrasound and magnetic resonance were performed, which detected a hemi uterus with a right rudimentary uterine hemicavity and a hematosalpinx. The removal of the right rudimentary uterine horn was successfully performed. The patient was in good health at the 3-month follow-up visit. Conclusion(s) Laparoscopic amputation of a functional rudimentary horn is considered the basic and traditional surgical option for women with hemiuterus. A detailed diagnostic evaluation should be performed to avoid misdiagnoses of other anomalies with blind hemicavity, which may be treated by hysteroscopy. Laparoscopic surgery with minimally invasive approach could be an essential tool to treat these cases, achieving optimal results with low postsurgical pain and a short hospital stay.

Background Vaginal cuff dehiscence following hysterectomy is considered an infrequent but potentially devastating complication. Different possible techniques for cuff closure have been proposed to reduce this threatening adverse event. Objective The aim of the present randomized study was to compare laparoscopic and transvaginal suture of the vaginal vault at the end of a total laparoscopic hysterectomy, in terms of incidence of vaginal dehiscence and vaginal cuff complications. Factors associated with vaginal dehiscence were also analyzed. This article presents the results of the interim analysis of the trial. Study Design Patients undergoing total laparoscopic hysterectomy for benign indications were randomized at the time of colpotomy to receive vaginal closure through transvaginal vs laparoscopic approach using a 1:1 ratio. Allocation concealment was obtained using a password-protected randomization database. Monopolar energy for colpotomy was set at 60W. Vaginal closure was performed with a single-layer running braided and coated 0-polyglactin suture. In all cases an attempt was performed to include the posterior peritoneum in the suture. Laparoscopic knots were tied intracorporeally. All patients were scheduled for a postoperative follow-up visit 3 months after surgery, to detect possible vaginal cuff complications. Univariate and multivariable analyses were performed to identify independent predictors of vaginal cuff dehiscence after total laparoscopic hysterectomy. Results After enrollment of 1408 patients, a prespecified interim analysis was conducted. Thirteen (0.9%) women did not undergo the postoperative assessment and were excluded. Baseline characteristics of the 1395 patients included (695 in the transvaginal group and 700 in the laparoscopic group) were similar between groups. Patients in the transvaginal group had a significantly higher incidence of vaginal dehiscence (2.7% vs 1%; odds ratio, 2.78; 95% confidence interval, 1.16–6.63; P = .01) and of any cuff complication (9.8% vs 4.7%; odds ratio, 2.19; 95% confidence interval, 1.43–3.37; P = .0003). Based on these findings, the data monitoring committee recommended that the trial be terminated early. After multivariable analysis, transvaginal closure of the vault was independently associated with a higher incidence of vaginal dehiscence and any vaginal complication; premenopausal status and smoking habit were independently associated with a higher risk of dehiscence. Conclusion Laparoscopic closure of the vaginal cuff at the end of total laparoscopic hysterectomy is associated with a significant reduction of vaginal dehiscence, any cuff complication, vaginal bleeding, vaginal cuff hematoma, postoperative infection, need for vaginal resuture, and reintervention.

We implanted a VNS device after more than two months from SRSE onset and multiple therapeutic attempts in a patient with Lafora disease and recurrent SE. We performed a very rapid stimulation parameter titration, without apparent side effects. We managed to withdraw anaesthetics 24 hours after reaching an assumed therapeutic setting. Therefore, according to the proposed efficacy criteria in SE [6], we assumed that the VNS implant was responsible for the SRSE interruption. No further SE nor GTCS occurred over the following nine months. The outcome on consciousness, however, was dismal, probably due both to the long duration of the status and of anaesthetic treatment and to the severity of the underlying disease. This was the first and sole VNS implantation acutely performed in our Centre for a RSE. Although this is a single case, our results support considering VNS acute implantation soon in the course of this condition, with the dual purpose of interrupting the status and preventing its recurrence

Background: The primary endpoint of this study is to analyze short term benefit of laparoscopic approach (minimally invasive liver surgery [MILS]) over the open techniques in patients submitted to surgery for breast cancer liver metastases (BCLM) within a disease-specific perspective. Material and Methods: A group of 30 patients who underwent laparoscopic liver resection for BCLM constituted the Study group (MILS group) and was matched in a ratio of 1:2 with patients who underwent open surgery for BCLM (Open group, constituting the Control group). Results: MILS approach resulted in a statistically significant lower blood loss (150 vs 300 mL; P

Hormonal replacement therapy (HRT) is effective in treating the symptoms of menopause. Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity with a tendency towards invasion and infiltration. Being an estrogen-dependent disease, it tends to regress after menopause. Nevertheless, it affects up to 2.2% of postmenopausal women. Conclusive data are not available in the literature on the appropriateness of HRT in women with endometriosis or a past history of the disease. The hypothesis that exogenous estrogen stimulation could reactivate endometriotic foci has been proposed. The aim of this state-of-the-art review was to revise the current literature about endometriosis in perimenopause and menopause and to investigate the possible role of HRT in this setting of patients. An electronic databases search (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) was performed, with the date range of from each database’s inception until May 2019. All of the studies evaluating the impact of different HRT regimens in patients with a history of endometriosis were selected. 45 articles were found: one Cochrane systematic review, one systematic review, five narrative reviews, two clinical trials, two retrospective cohort studies, 34 case reports and case series. Some authors reported an increased risk of malignant transformation of endometriomas after menopause in patients assuming HRT with unopposed estrogen. Low-quality evidence suggests that HRT can be prescribed to symptomatic women with a history of endometriosis, especially in young patients with premature menopause. Continuous or cyclic combined preparations or tibolone are the best choices. HRT improves quality of life in symptomatic post-menopausal women, who should not be denied the replacement therapy only due to their history of endometriosis. Based on low-grade literature evidence, we recommend to prescribe combined HRT schemes; tibolone could be considered.

Background Borderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins, especially in the case of up-front resections, but it is important to know the limits of surgical therapy in this disease. This study aimed to investigate the impact of extent of pancreatic and venous resection on short- and long-term outcomes in patients with pancreatic adenocarcinoma (PDAC). Methods This was a retrospective study from a prospectively maintained database of pancreatic resections for PDAC. Short- and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy (TP) or pancreaticoduodenectomy (PD) with simultaneous portal vein (PV) and/or superior mesenteric vein (SMV) resection. Venous resections were carried out as tangential venous resection (TVR) or segmental venous resection (SVR). Patients were divided into 4 groups: (1) PD + TVR, (2) PD + SVR, (3) TP + TVR, (4) TP + SVR. Uni- and multivariate Cox regression analysis were performed to identify factors associated with survival. Results Ninety-nine patients were submitted to simultaneous pancreatic and venous resection for PDAC. Among them, 25 were submitted to PD + TVR (25.3%), 12 to PD + SVR (12.1%), 23 to TP + TVR (23.2%), and 39 to TP + SVR (39.4%). Overall, major morbidity (Clavien-Dindo grade ≥ IIIA) was 26.3%. Thirty- and 90-day mortality were 3% and 11.1%, respectively. There were no significant differences among groups in terms of short-term outcomes. Median overall survival of patients submitted to PD + TVR was significantly higher than those to TP+SVR (29.5 vs 7.9 months, P = 0.001). Multivariate analysis identified TP (HR = 2.11; 95% CI: 1.31–3.44; P = 0.002) and SVR (HR = 2.01; 95% CI: 1.27–3.15; P = 0.003) as the only independent prognostic factors for overall survival. Conclusions Up-front TP associated to SVR was predictive of worse survival in borderline resectable PDAC. Perioperative treatments in high-risk surgical groups may improve such poor outcomes.

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Background A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. Methods A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. Results We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. Conclusion These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

Background The role of neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases is currently a matter of debate. The aim of the present study was to analyse life-expectancy, quality adjusted life-expectancy and cost-effectiveness of the two chemotherapeutic strategies. Methods A Markov decision model was developed, on the basis of parameters derived from an extensive literature search of the last ten years, to compare outcomes of peri-operative versus post-operative chemotherapy. Results Life-expectancy observed for peri-operative chemotherapy was 54.56 months and 52.62 months with post-operative chemotherapy only; the quality-adjusted life-expectancy with peri-operative chemotherapy was 39.33 quality-adjusted life-months (QALMs) and 37.84 QALMs with post-operative chemotherapy. Peri-operative chemotherapy results in an increase in total costs of 1180 € over ten years and in an incremental cost-effectiveness ratio (ICER) of 791.9 €/QALM. The model was more sensitive to the expected 3-year recurrence-free survival (RFS) and cost of hepatic resection: with respect to an expected 3-year RFS ⩽ 25% the peri-operative approach was more cost-effective than post-operative strategy but differences in average cost-effectiveness were small. The relationship between ICER and cost of hepatic resection was inverse because the higher the cost of hepatic resection, the higher the cost saving due to patients becoming unresectable during neo-adjuvant therapy. Conclusions In the treatment of resectable colorectal liver metastases, the addition of neo-adjuvant chemotherapy could be cost-effective because it makes it possible to avoid hepatic resection in patients who do not respond to the neo-adjuvant approach; however, the life-expectancy of the two strategies is very similar.

BACKGROUND:The impact of advanced donor age on hepatic artery thrombosis (HAT) after liver transplantation (LT) is controversial. METHODS: We analyzed the incidence of and risk factors for HAT in LT with donors aged 70 years or older. Eighty patients were transplanted between 1998 and 2002 (group A) and 132 between 2003 and 2008 (group B). RESULTS:In the more recent approach to hepatic artery (HA) reconstruction, the donor HA was systematically preferred to the Carrel patch/celiac trunk, the reconstruction of donor accessory right HA on the donor gastroduodenal artery significantly increased, and the use of interposition grafts was minimized. Group B showed higher Model for End-stage Liver Disease score, lower ischemia time, and lower use of the folding technique/mesenteric conduits. There were 10 cases of HAT (4.7%): 8 (10%) in group A and 2 (1.5%) in group B (P=0.007). Early HAT occurred in 7 (8.8%) patients in group A and in 2 (1.5%) in group B (P=0.02). Group A (P=0.01), anatomical variations of HA (P=0.005), and the use of interposition grafts (P=0.004) were all factors independently affecting HAT. CONCLUSIONS:A low incidence of late HAT was observed in single-center LTs with very old donors. Early HAT decreased over time to largely acceptable rates because of more appropriate technical management.

OBJECTIVE: To evaluate the evolution of liver transplantation (LT) in cases with partial and total portal vein thrombosis (PVT). BACKGROUND: Portal vein thrombosis and in particular total PVT are still surgically demanding conditions, which can exclude patients from LT or increase the postoperative complications after LT. METHODS: We reviewed our 10-year experience (first era 1998–2002 and second era 2003–2008), comparing the outcome of patients with PVT to a group without PVT. RESULTS: Among 889 LTs, we intraoperatively diagnosed 91 PVTs (10.2%):51 partial PVTs (56%) and 40 total PVTs (44%). The rate of complete PVTs increased from the first to the second era (2.2% vs. 6.7%, P < 0.005). Partial PVTs were mainly treated with thrombectomy while complete PVTs were managed with thrombectomy in 26 cases (63%), jumping graft in 6 (15%), portocaval hemitransposition in 6 (15%), and anastomosis to varix in 3 (7%). Among cases of PVT and no-PVT, the postoperative mortality was comparable (6.6% vs. 5.8%), as were the 1- and 5-year patient survival rates (85% and 68% PVT vs. 86% and 73% non-PVT). The postoperative outcome was similar in the PVT group between patients with partial and complete PVT, but in this last group, patient survival differed significantly between the 1st and 2nd era (57% vs. 89% at 1 year, P < 0.05). CONCLUSIONS: Liver transplantation offers good survival in patients with partial PVT but also in selected cases with total PVT, where surgical innovation has improved the results.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC. Liver Transpl 13:857–866, 2007. © 2007 AASLD.

Background: Two-stage hepatectomy (TSH) is well established for the treatment of patients who have colorectal cancer liver metastases (CRLM) with a small liver remnant. The technique of associating liver partitioning and portal vein occlusion for staged hepatectomy (ALPPS) has been advocated as a novel tool to increase resectability. Using a case-match design, this study aimed to compare TSH and ALPPS for patients with CRLM.Methods: All patients undergoing ALPPS for CRLM at three major hepatobiliary centers in Italy (ALPPS group) were compared in a case-match analysis with patients undergoing TSH (TSH group) at a single institution. The groups were matched with a 1:3 ratio using propensity scores based on covariates representing severity of metastatic disease. The main end points of the study were feasibility of complete resection and intra- and postoperative outcomes.Results: The two treatments did not differ significantly in feasibility. Two patients in the TSH group dropped out compared with no patients in the ALPPS group. A comparable volume gain in future liver remnant (FLR) was obtained in the ALPPS and TSH groups (47 vs. 41 %, nonsignificant difference) but during a shorter interval in ALPPS group. The overall and major complication rate was significantly higher after stage 2 in the ALPPS group (Clavien ≥ 3a: 41.7 vs. 17.6 % in TSH group; p = 0.025).Conclusion: The feasibility of resection using ALPPS compared with TSH for CRLM was not significantly greater, but perioperative complications were increased. Therefore, ALPPS should be proposed to patients with caution and warnings. Currently, TSH remains the standard approach for performing R0 resection in patients with advanced CRLM and inadequate FLR.

BACKGROUND: Our primary objective was to establish a cutoff value for the soluble fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured using the Elecsys assay to predict late-onset preeclampsia in low-risk pregnancies. Our secondary objective was to evaluate the ability of combination models using Elecsys data, second trimester uterine artery (UtA) Doppler ultrasonography measurements, and the serum fetoplacental protein levels used for Down's syndrome screening, to predict preeclampsia. METHODS: This prospective cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation. RESULTS: Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver operating characteristic curve analysis showed that the third trimester sFlt-1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used to determine the five best combination models for early detection of late-onset preeclampsia. The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed FPR of 10%, the combination of body mass index and the second trimester sFlt-1 level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded a DR of 62.5% at a fixed FPR of 10%. CONCLUSIONS: The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio, and the combination of the second trimester sFlt-1 level with body mass index, were better predictors of late-onset preeclampsia than any individual marker.

OBJECTIVE: To derive a birth weight predictive equation and to compare its diagnostic value with that of ultrasound. METHODS: A longitudinal observational cohort study, including singleton pregnancies at term, was performed at St. Orsola-Malpighi Hospital, University of Bologna (Italy). A birth weight prediction formula, including symphysis-fundal height (SFH), BMI, maternal abdominal circumference (mAC) and parity was derived from a general linear model (GLM) (retrospective study). Moreover, on a new series of patients, the fetal weight was estimated by using both GLM and ultrasound using Hadlock formula (prospective study). The residual analysis and the intraclass correlation coefficient (ICC) were used to test the accuracy of methods in predicting birth weight. RESULTS: Between January and November 2012, 1034 patients were included in the retrospective study and 44 in the prospective one. The following GLM was derived: estimated birth weight (g) = 1485.61 + (SFH (cm) × 23.37) + (11.62 (cm) × mAC) + [BMI × (-6.81)] + (parity (0 = nulliparous, 1 = multiparous) × 72.25). When prospectively applied, the GLM and ultrasound provided a percentage of prediction within ±10% of the actual weight of 73% and 84%, respectively. Ultrasound estimation, as opposite of GLM one, was significantly associated with neonatal weight (R(2 )= 0.388, F = 26.607, p value

Objective: To develop a model for prediction of late preeclampsia (PE; which develops at or after 34 weeks' gestation) based on maternal history and characteristics, mean arterial pressure (MAP), and circulating levels of mRNA for the placenta-specific 1 (PLAC1) gene in maternal plasma at 14-18 weeks' gestation. Method: This was a screening study of singleton pregnancies at 14-18 weeks' gestation including 43 women that subsequently developed PE and 200 that were unaffected by PE. A Gaussian model was fitted to the log distribution of the multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1 gene were used to combine the a priori risk from maternal characteristics with MAP to produce patient-specific risks for each case. Results: Screening by maternal characteristics (including BMI, woman's mother's history of PE, previous PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at a fixed false-positive rate (FPR) of 10%. The addition of PLAC1 yielded a detection rate (DR) of 62.8% at the same level of FPR. PLAC1 alone yielded a DR of 30.2%. Conclusion: In late PE, molecular markers can be used to improve the DR of screening and can be a valid option for the biochemical approach.

BACKGROUND: The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS: We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS: HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION: LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

Study Objective To show a new laparoscopic technique of hysteropexy for uterine retrodisplacement (retroversion and/or retroflexion). Design Narrated step-by-step explanation of the Bologna hysteropexy technique using descriptive text and an educational video. Setting Tertiary referred center of minimally invasive gynecology, Sant'Orsola Hospital, Bologna University. Interventions The Bologna hysteropexy is proposed as an additional procedure after surgical laparoscopic interventions for benign gynecologic disease. The technique consists of 2 semicontinuous absorbable sutures (Biosyn monofilament no. 1 [Covidien, Mansfield, MA] with 2/3 inch diameter needle, 36 mm) suspending the uterus to the anterior abdominal wall, through the plication and shortening of round ligaments. A knot is tied intracorporeally between the 2 free ends of the semicontinuous sutures, drawing a V shape figure and resulting in uterine ventrosuspension. Conclusion The Bologna technique hysteropexy is simple and quick to perform. It is effective in suspending the uterus in anteverted and anteflexed positions at 6-month ultrasound follow-up. No perioperative complications were recorded. It can be done with a standard surgical suture-passer and does not add additional cost to surgery. Furthermore, an absorbable suture is desirable for fertile women.

Purpose: Survival estimates are commonly reported as actuarial survival after the first observation, but future survival probabilities can change over time. Conditional survival is a measure of prognosis for patients who have sometimes already survived several years since diagnosis; however, data on conditional survival for cirrhotic patients, resected for hepatocellular carcinoma (HCC), are lacking. Experimental Design: Clinical data from 300 consecutive cirrhotic patients who underwent HCC resection were reviewed and the actuarial survival estimated. The 5-year conditional survival was calculated as CS = S(x + 5)/S(x) and represents the probability of surviving an additional 5 years, given that the patient has already survived x years. Results: The 3-, 5-, and 10-year survival rates were, respectively, 69.0%, 57.7%, and 25.3% and were lower in cases of portal hypertension, Model for End-stage Liver Disease (MELD) score ≥9, United Network for Organ-Sharing T3 tumor, GIII–GIV tumors, and microscopic vascular invasion. However, the 5-year conditional survival calculation showed that patients resected for more advanced (T3) tumors or with adverse histologic features will experience the same survival probabilities as patients with less advanced tumors or favorable histology from the third year after surgery onward, as they had probably escaped recurrence from intrahepatic metastases. Patients who underwent repeated hepatectomy for recurrence presented higher conditional survival. Conclusions: Conditional survival showed that the impact of different variables influencing survival is not linear over time after hepatic resection. Information derived from conditional survival can be used to better manage patients with HCCs, including the potential future setting of adjuvant therapies and the choice of listing, or not, for transplantation resected patients not recurring within 2 years. Clin Cancer Res; 18(16); 4397–405. ©2012 AACR.

Background: Mortality is high among patients with hematologic malignancies admitted to intensive care units for acute respiratory failure. Early noninvasive mechanical ventilation seems to improve outcomes. Objective: To characterize noninvasive mechanical ventilation use in Italian intensive care units for acute respiratory failure patients with hematologic malignancies and its impact on outcomes vs. invasive mechanical ventilation. Design, Setting, Participants: Retrospective analysis of observational data prospectively collected in 2002–2006 on 1,302 patients with hematologic malignancies admitted with acute respiratory failure to 158 Italian intensive care units. Measurements: Mortality (intensive care unit and hospital) was assessed in patients treated initially with noninvasive mechanical ventilation vs. invasive mechanical ventilation and in those treated with invasive mechanical ventilation ab initio vs. after noninvasive mechanical ventilation failure. Findings were adjusted for propensity scores reflecting the probability of initial treatment with noninvasive mechanical ventilation. Results: Few patients (21%) initially received noninvasive mechanical ventilation; 46% of these later required invasive mechanical ventilation. Better outcomes were associated with successful noninvasive mechanical ventilation (vs. invasive mechanical ventilation ab initio and vs. invasive mechanical ventilation after noninvasive mechanical ventilation failure), particularly in patients with acute lung injury/adult respiratory distress syndrome (mortality: 42% vs. 69% and 77%, respectively). Delayed vs. immediate invasive mechanical ventilation was associated with slightly but not significantly higher hospital mortality (65% vs. 58%, p .12). After propensity-score adjustment, noninvasive mechanical ventilation was associated with significantly lower mortality than invasive mechanical ventilation. Limitations: The population could not be stratified according to specific hematologic diagnoses. Furthermore, the study was observational, and treatment groups may have included unaccounted for differences in covariates although the risk of this bias was minimized with propensity score regression adjustment. Conclusions: In patients with hematologic malignancies, acute respiratory failure should probably be managed initially with noninvasive mechanical ventilation. Further study is needed to determine whether immediate invasive mechanical ventilation might offer some benefits for those with acute lung injury/adult respiratory distress syndrome. (Crit Care Med 2011; 39:2232–2239)

Accurate knowledge of biliary anatomy and its variants is essential to ensure successful hepatic surgery; however, data from European countries are lacking. Two hundred cholangiograms obtained from patients submitted to whole liver transplantation were reviewed; donors’ characteristics were related to the prevalence of typical biliary anatomy and its variants. A comprehensive literature search was performed with MEDLINE and EMBASE from 1980 to 2010 to investigate whether geographical origin could be related to biliary abnormalities. Typical biliary anatomy was observed in 64.5% of cases, but female donors more frequently presented an anatomic variation; typical anatomy was present in 55.0% of females and in 74.0% of males (P = 0.005). Twenty-two reports were identified by the literature search with a total of 7,559 cases, including the present series; heterogeneity was low (Q = 14.60; I2

BACKGROUND: With substantial improvements in perioperative care and surgical technique, both mortality and morbidity after liver resection have progressively decreased; however, long-term prognosis is greatly affected by tumor recurrence, which represents the most frequent cause of death. The aim of this study is to analyze the outcome after hepatic resection in the present clinical scenario, where great improvements in diagnostic techniques, surveillance schedules, in other active treatments will potentially have a positive impact on survival. METHODS: Data from 300 consecutive hepatic resections performed on cirrhotic patients in a tertiary-care referral hospital from 1997 and 2008 were reviewed, and survival was calculated for the two periods considered. The first group of patients underwent hepatectomy between 1997 and 2002 (n = 126) and the second group of patients between 2003 and 2008 (n = 174). RESULTS: In the more recent period, tumor selection criteria for resectability included more patients with multinodular tumors so that solitary tumors decreased from 89.7 to 78.7% (P = 0.019); however, the tumor, node, metastasis (TNM) system stage remained unaffected. The 5-year recurrence rate remained similar (67.4 vs. 65.8%; P = 0.836). Despite these features, the 5-year patient survival increased from 52.6 to 65.8% (P = 0.023). This end result was related to a larger proportion of patients with tumor recurrence undergoing repeat resection or salvage transplantation that increased from 22.2 to 36.9% (P = 0.039). CONCLUSIONS: The increased survival is most likely the result of more stringent follow-up as well as increased accuracy in detecting recurrence at earlier stages, and consequently of more chances for potential cure when treating recurrent tumor.

AIM: To assess the safety and effectiveness of prophylaxis for venous thromboembolism (VTE) in a large population of patients with hepatocellular carcinoma (HCC) on cirrhosis. METHODS: Two hundred and twenty nine consecutive cirrhotic patients with HCC who underwent hepatic resection were retrospectively evaluated to assess whether there was any difference in the incidence of thrombotic or hemorrhagic complications between those who received and those who did not receive prophylaxis with low-molecular weight heparin. Differences and possible effects of the following parameters were investigated: age, sex, Child-Pugh and model for end-stage liver disease (MELD) score, platelet count, presence of esophageal varices, type of hepatic resection, duration of surgery, intraoperative transfusion of blood and fresh frozen plasma (FFP), body mass index, diabetes and previous cardiovascular disease. RESULTS: One hundred and fifty seven of 229 (68.5%) patients received antithromboembolic prophylaxis (group A) while the remaining 72 (31.5%) patients did not (group B). Patients in group B had higher Child-Pugh and MELD scores, lower platelet counts, a higher prevalence of esophageal varices and higher requirements for intraoperative transfusion of FFP. The incidence of VTE and postoperative hemorrhage was 0.63% and 3.18% in group A and 1.38% and 1.38% in group B, respectively; these differences were not significant. None of the variables analyzed including prophylaxis proved to be risk factors for VTE, and only the presence of esophageal varices was associated with an increased risk of bleeding. CONCLUSION: Prophylaxis is safe in cirrhotic patients without esophageal varices; the real need for prophylaxis should be better assessed.

Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.

INTRODUCTION: Surgical approaches to complicated benign intestinal failure are accepted worldwide, especially in the pediatric population. Intestinal transplant surgery is thought to rescue patients in whom complications of total parenteral nutrition (TPN) develop. OBJECTIVE: To report our experience with surgical intestinal rescue in an adult population with intestinal failure. PATIENTS AND METHODS: An intestinal rehabilitation program initiated at our institution included comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. From 2000 to 2009, of 81 adult patients referred by our gastroenterologists for bowel rehabilitation, 42 (51,8%) underwent 43 transplantations (32 isolated intestinal grafts and 11 multivisceral grafts). Underlying diseases were primarily short-bowel syndrome, Gardner syndrome, and intestinal pseudo-obstruction. Thirty-nine patients (48,2%) underwent surgical rescue (40 cases) consisting of bowel resection, adhesiolysis, stricturoplasty, liver transplantation with portocaval hemitransposition (6 cases in 5 patients). Underlying diseases were primarily intestinal fistulas, stenosis, or perforations, short-bowel syndrome, cocoon syndrome, and complete portal thrombosis. RESULTS: After a mean (SD) follow-up of 1043 (1016) days, in the transplantation population, 21 patients (50%) are alive, with a 1-, 3-, 5-year patient survival of 76%, 59%, and 52%, respectively, and graft survival of 66%, 54%, and 48%, respectively. After 901 (404) days in the rescue population, 32 patients (82%) are alive (2 died, and 5 were lost to follow-up); in 75%, TPN 25% was discontinued, and are receiving oral feeding with TPN support. The 1- and 3-year survival rate was 100% and 83%, respectively. CONCLUSIONS: Deaths occurred primarily in the transplantation population. Intestinal surgical rescue, when possible, is optimal.

BACKGROUND: Few studies have measured cadaveric kidney weight to investigate its relation to recipient kidney function related to it. The aim of this study was to evaluate kidney weight (cadaveric donor) and its relationship to creatinine clearance (CrCl) after 12 months posttransplantation. METHODS: We evaluated 81 renal transplantation recipients from cadaveric donors. We collected donor and recipient demographic, clinical and anthropometric data. Data about kidney weight were obtained through kidney measurement using an electronic machine at the moment of transplantation. RESULTS: The mean kidney weight was 201.4 +/- 10.2 g (200.5 +/- 11.6 g in women and 210.3 +/- 14.1 g in men). Kidney weight correlated with CrCl at 12 months (0.001). The CrCl at 12 months showed a significant correlation of graft weight/recipient weight ratio (P < .01). CONCLUSION: The cadaveric donor kidney weight significantly influenced the CrCl at 12 months after transplantation.

Background Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors. Methods We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus. Results Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5-13.5) in comparison with those of group A (median, 4.6; range, 1.8-9.1) (P=0.0001). Conclusions By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.

Sirolimus (SRL) is a newer immunosuppressant whose possible benefits and side effects in comparison to calcineurin inhibitors (CNIs) still have to be addressed in the liver transplantation setting. We report the results of the use of SRL in 86 liver transplant recipients, 38 of whom received SRL as the main immunosuppressant in a CNI-sparing regimen. Indications for the use of SRL were: impaired renal function (n = 32), CNI neurotoxicity (n = 16), hepatocellular carcinoma (HCC) at high risk of recurrence (n = 21), recurrence of HCC (n = 6), de novo malignancies (n = 4), cholangiocarcinoma (n = 1), and the need to reinforce immunosuppression (n = 6). Among patients on SRL-based treatment, four episodes of acute rejection were observed, three of which occurred during the first postoperative month. Renal function significantly improved when sirolimus was introduced within the third postoperative month, while no change was observed when it was introduced later. Neurological symptoms resolved completely in 14/16 patients. The 3-year recurrence-free survival of patients with HCC on SRL was 84%. Sixty-two patients developed side effects that required drug withdrawal in seven cases. There was a reduced prevalence of hypertension and new-onset diabetes among patients under SRL. In conclusion, SRL was an effective immunosuppressant even when used in a CNI-sparing regimen. It was beneficial for patients with recently developed renal dysfunction or neurological disorders.

Liver resection is the only potential curative treatment for hilar cholangiocarcinoma. In this article, we evaluate mortality, survival, prognostic factors, and changes in surgical approach during the last two decades at a Western hepato-biliary center. METHODS: Fifty-one patients undergoing liver resections constitute the study population. Patients undergoing palliative procedures were considered as a control group for comparison to the resected group. After 1997, a more aggressive surgical approach was applied that is based on the experience of Japanese surgeons. RESULTS: Curative resections were achieved in 37 (72.5%) patients, and R1 resections were performed in 14 (27.5%). The overall 3- and 5-year survival rates were 47.3 and 34.1%, respectively. The 3- and 5-year survival rates were 38 and 19% in the R1 resection group, and 15% and 0 in the non-resected group, respectively. Univariate analysis revealed that lymph node and perineural invasion, R1 resection, and a bilirubin level >10 mg/dl affected long-term survival. Multivariate analysis showed that only perineural invasion was significant in affecting long-term survival. Univariate analysis showed that the mean preoperative bilirubin levels and mean blood transfusion were related to the mortality rate. The resectability rate significantly increased from 25 to 75.6% after 1997 following implementation of the new surgical approach. CONCLUSIONS: An aggressive surgical approach increases the resectability rate and may improve long-term survival even after R1 resection. Severe hyperbilirubinemia should be preoperatively drained, possibly by the percutaneous approach.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) prognosis strongly depends upon nuclear grade and the presence of microscopic vascular invasion (MVI). The aim of this study was to develop an artificial neural network (ANN) that is able to predict tumour grade and MVI on the basis of non-invasive variables. METHODS: Clinical, radiological, and histological data from 250 cirrhotic patients resected (n=200) or transplanted (n=50) for HCC were analyzed. ANN and logistic regression models were built on a training group of 175 randomly chosen patients and tested on the remaining testing group of 75. Receiver operating characteristics curve (ROC) and k-statistics were used to analyze model accuracy in the prediction of the final histological assessment of tumour grade (G1-G2 vs. G3-G4) and MVI (absent vs. present). RESULTS: Pathologic examination showed G3-G4 in 69.6% of cases and MVI in 74.4%. Preoperative serum alpha-fetoprotein (AFP), tumour number, size, and volume were related to tumour grade and MVI (p

Malignant mixed tumors of the liver in adults are extremely rare. To our knowledge, only a few cases have been reported in the literature. Nested stromal-epithelial tumors (NSET) of the liver are characterized by non-hepatocytic, non-biliary tumors with nests of epithelial and spindle cells, an associated myofibroblastic stroma, as well as variable calcifications and ossifications. We report a case of NSET of the liver affecting a young woman and provide detailed histological and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature.

Background Allograft rejection in intestinal transplantation occurs frequently, and bacterial, fungal, and viral infections related to strong immunosuppression regimens remain an important complication posttransplantation. Induction therapy has enabled improvement in graft and patient survival rates. Objectives In analyze the effects of daclizumab and alemtuzumab as induction therapies on inflections complications and incidence of acute cellular rejection (ACR) during the early posttransplantation period. Patients and Methods Between December 2000 and August 2009, we performed 43 intestinal transplantation procedures in 42 adult recipients (median [SD] age, 34.8 [9.5] years; male-female ratio, 22:20; isolated or multivisceral graft, 32/11), and compared findings during the first 30 days posttransplantation in 40 recipients. Patients were divided into 2 groups: 12 treated with daclizumab (Zenapax; Hoffman-La Roche Ltd, Basel, Switzerland): 8 isolated intestinal grafts and 4 multivisceral grafts) and 28 treated with alemtuzumab (Campath-1H: 22 isolated intestinal grafts and 6 multivisceral grafts). Maintenance immunosuppression was based on tacrolimus and steroids in the first group and low-dose tacrolimus in the second group. Results During the first month posttransplantation, 8 daclizumab recipients (66.6%) experienced 9 episodes of mild ACR, which were successfully treated with steroid therapy, and 8 patients (66.6%) developed a bacterial infection requiring treatment. Fourteen episodes of ACR occurred in 12 alemtuzumab recipients (42.8%): 11 mild, 1 mild to moderate, and 2 moderate; 16 patients (57.1%) required treatment for infections. Five-year patient cumulative survival was 66% in daclizumab recipients and 43% in alemtuzumab recipients. Five-year graft survivals was 66% in daclizumab recipients and 41% in alemtuzumab recipients. In both groups, P was not statistically significative. Conclusions The infection rate is considerably high with both protocols. Alemtuzumab seems to offer better immunosuppression against ACRs during the first month posttransplantation.

BACKGROUND: Split liver transplantation (SLT) for two adult recipients is still considered a challenging procedure, especially when subjected to model for end-stage liver disease (MELD)-based allocation criteria. METHODS: Twenty-two SLTs were performed in adult recipients in a European center operating within a MELD-oriented system. Thirteen right-sided grafts and nine left-sided grafts were used. Right-sided grafts included 11 extended right grafts and two full right grafts. Left-sided grafts included six left lateral segment grafts and three full left grafts. Ninety-three percent of donors were allocated based on MELD score. Median graft-to-recipient body weight ratio was 1.53 (range 1.07-2.11) with right-sided grafts and 0.81 (range 0.67-1.11) with left-sided grafts. Liver cirrhosis (46%) and metabolic/genetic disorders (56%) were the main indications for transplant in recipients of right and left grafts, respectively. RESULTS: Overall patient and graft survival were 90% and 86%. Patient survival was 84% in recipients of right grafts and 100% in recipients of left grafts. Graft survival was 84% and 89%, respectively. Vascular and biliary complications occurred in 14% and 4% of cases. Postoperative serum levels of total bilirubin were significantly higher in recipients of left-sided grafts versus right-sided grafts on postoperative days 7 and 14. Prothrombin activity was significantly lower in recipients of left-sided grafts versus right-sided grafts on postoperative days 3 and 7. CONCLUSIONS: SLT for two adult recipients can be successfully performed even using left lateral segments by assigning one graft according to MELD score, and with a more liberal allocation of the second graft.

According to transplant registries, grafts from elderly donors have lower survival rates. During 1999-2005, we evaluated the outcomes of 89 patients who received a liver from a donor aged > or = 60 years and managed with the low liver-damage strategy (LLDS), based on the preoperative donor liver biopsy and the shortest possible ischemia time (group D > or = 60-LLDS). Group D > or = 60-LLDS was compared with 198 matched recipients, whose grafts were not managed with this strategy (89 donors < 60 years, group D < 60-no-LLDS and 89 donors aged > or =60 years, group D > or = 60-no-LLDS). In the donors proposed from the age group of > or =60 years, the number of donors rejected decreased during the study period and the LLDS was found to be responsible for this in a significant manner (47% vs. 60%, respectively P < 0.01). Among the recipients transplanted, the clinical features (age, gender, viral infection, child and model for end-stage liver disease score) were comparable among groups, but group D > or = 60-LLDS had a lower mean ischemia time: 415 +/- 106 min vs. 465 +/- 111 (D < 60-no-LLDS), P < 0.05 and vs. 476 +/- 94 (D > or = 60-no-LLDS), P < 0.05. After a median follow-up of 3 years, the 1- and 3-year graft survival rates of group D > or = 60-LLDS (84% and 76%) were comparable with group D < 60-no-LLDS (89% and 76%) and were significantly higher than group D > or = 60-no-LLDS (71% and 54%), P < 0.005. In conclusion, the LLDS optimized the use of livers from elderly donors.

HYPOTHESIS: The role of hepatitis B virus (HBV) infection in determining the prognosis after hepatectomy for hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. DESIGN: Retrospective study based on multicenter prospectively updated databases. SETTING: Two tertiary referral centers specializing in hepatobiliary surgery. PATIENTS: Two hundred four consecutive patients with cirrhosis undergoing hepatectomy for single nodules of HCC of 5 cm or smaller from January 1, 1997, through September 30, 2006. INTERVENTIONS: Patients were divided into the following groups according to their preoperative viral status: HBV positive and hepatitis C virus (HCV) negative (group 1); HBV negative and HCV positive (group 2); HBV negative and HCV negative (group 3); and HBV positive and HCV positive (group 4). MAIN OUTCOME MEASURES: A multivariate analysis was performed to determine factors associated with recurrence-free survival (RFS) among demographic, clinical, pathological, and surgical variables. RESULTS: The 2 centers had comparable RFS and early and late recurrence rates. Five-year RFS was significantly higher in groups 2 and 3 compared with group 1 (38%, 34%, and 9%, respectively; P = .007 and P = .05). Factors independently associated with RFS were HBV infection (P = .009; odds ratio, 1.79; 95% confidence interval, 1.15-2.78) and poor tumor differentiation (P < .001; odds ratio, 2.01; 95% confidence interval, 1.36-2.96). The concomitance of 0, 1, or 2 risk factors led to 5-year RFS rates of 49%, 20%, and 8%, respectively (P < .001). CONCLUSIONS: Infection with HBV is a strong predictive factor for lower RFS after hepatectomy for a single nodule of HCC of 5 cm or smaller in patients with cirrhosis, providing a further basis for adjuvant antiviral treatment. Patients who are seropositive for HBV with poorly differentiated HCC should also be considered to be at a high risk of recurrence and possibly included in a policy of salvage liver transplantation.

BACKGROUND: We sought to determine the best strategy to overcome difficult abdominal wall closures in intestinal transplantation (ITx). METHODS: Among 38 adult recipients of 39 ITxs from deceased donors, the median number of previous laparotomies was 2.0 per patient, with a median donor-to-recipient body weight ratio of 1.1. Eight patients (21%) had full residual intestinal length before transplant. Abdominal wall closure after transplant was considered difficult in 15 (39.5%) patients (group A). To overcome size mismatching, we performed two graft reductions, five skin-only closures, one two-step abdominal wall closure, four prosthetic mesh closures, and three abdominal wall transplants. In the remaining 23 (60.5%) patients, a regular abdominal closure was performed (group B). RESULTS: Twelve patients (32%) experienced complications related to abdominal wall closure, 10 (67%) in group A and 2 (8.7%) in group B (P

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.

Hypothesis Several techniques have been introduced to minimize intraoperative bleeding in hepatic surgery. Ischemia-reperfusion injuries and intestinal congestion are the main drawbacks of vascular clamping. We hypothesized possible negative effects on early postoperative outcomes associated with different types of vascular clamping during liver resections and evaluated how attitudes have changed in the past 20 years. Design Retrospective review. Setting Academic research institute. Patients Patients who underwent 1260 consecutive liver resections, 338 of them (26.8%) in patients with cirrhosis. Main Outcome Measures Postoperative complications and mortality were analyzed relative to liver disease, blood transfusion, vascular clamping, and type of liver resection. Results Vascular clamping was applied in 594 patients (47.1%). Operative mortality was 4.4% in the vascular clamping group and 2.9% in the nonclamped group, a statistically nonsignificant difference. On multivariate analysis, blood transfusion, major hepatectomies, and the presence of cirrhosis were statistically significantly associated with postoperative complications. Among the overall cohort and among patients with cirrhosis, there was statistically significantly reduced use of vascular clamping and of blood transfusion during the past 20 years. The lowest incidences of severe complications occurred among cases of continuous or hemihepatic clamping. Among 338 patients with cirrhosis, 155 (45.9%) received some type of vascular control; morbidity and mortality rates were similar in the groups with vs those without vascular control. On multivariate analysis, only blood transfusion was statistically significantly associated with postoperative morbidity. Postoperative complications were statistically significantly reduced among patients receiving intermittent compared with continuous clamping. Conclusions Vascular clamping can be applied without additional risk during partial hepatectomy. Intermittent or hemihepatic clamping is preferable in patients with cirrhosis.