Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

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.

Risk-adjusted benchmarks in laparoscopic liver surgery in a national cohort.

BACKGROUND: This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry. METHODS: LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment. RESULTS: A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis. CONCLUSION: Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.

ANTECEDENTES: Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales. RESULTADOS: Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.

ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.

The role of minimally invasive surgery in the treatment of cholangiocarcinoma.

Cholangiocarcinoma (CC) is the second most common type of primary liver cancer after hepatocellular carcinoma. Surgical resection is considered the only curative treatment for CC. In general, laparoscopic liver surgery (LLS) is associated with improved short-term outcomes without compromising the long-term oncological outcome. However, the role of LLS in the treatment of CC is not yet well established. In addition, CC may arise in any tract of the biliary tree, thus requiring different types of treatment, including pancreatectomies and extrahepatic bile duct resections. This review presents and discusses the state of the art in the laparoscopic and robotic surgical treatment of all types of CC. An electronic search was performed to identify all studies dealing with laparoscopic or robotic surgery and cholangiocarcinoma. Laparoscopic resection in patients with intrahepatic CC (ICC) is feasible and safe. Regarding oncologic adequacy, as R0 resections, depth of margins, and long-term overall and disease-free survival, laparoscopy is comparable to open procedures for ICC. An adequate patient selection is required to obtain optimal results. Use of laparoscopy in perihilar CC (PHC) has not gained popularity. Further studies are still needed to confirm the benefit of this approach over conventional surgery for PHC. Laparoscopic pancreaticoduodenectomy for distal CC (DCC) represents one of the most advanced abdominal operations owing to the necessity of a complex dissection and reconstruction and has also had small widespread so far. Minimally invasive surgery seems feasible and safe especially for ICC. Laparoscopy for PHC is technically challenging notably for the caudate lobectomy. Not least as for the LLR, the robotic approach for DCC appears technically achievable in selected patients.

Liver Transplantation and Abuse of Drugs and Alcohol: A Correlation Between Scales of the MMPI-2.

BACKGROUND: Clinical practice requires an accurate psychological assessment of subjects with clinical history of alcohol abuse and/or substance abuse (abuse history [AH]) for therapeutic choice. This study aims to identify significant correlations between the Minnesota Multiphasic Personality Inventory (MMPI)-2 scales in patients awaiting liver transplantation. METHODS: We evaluated a personality questionnaire containing MMPI-2 scales in the sample of 308 patients (81.8% males and 18.2% females) awaiting liver transplantation. The AH group composed 44.49% of patients and in the abuse free (AF) group, 55.51%. Scales were compared using Shapiro-Wilk test and Mann-Whitney U test. Interrelationships were examined using Spearman's correlation. RESULTS: This analysis found 27 scales of the MMPI-2 that were statistically different between 2 groups (AF and AH). In the AH group, we found a significant correlation between the following pairs of scales: Schizophrenia Scale (Sc) with the Addictions Potential Scale, Social Introversion scale (Si) with the Psychopathic Deviate scale (Pd), and Social Discomfort scale with Pd; the ES scale was negatively correlated with the Sc and Si scales. This interim study showed that the understanding of these indicators is crucial both for the assessment accuracy and for a prediction of the degree of therapy compliance after the transplantation. CONCLUSIONS: The scales of the MMPI-2 indicated a marked tendency to emotional rigidity, a lack of self-esteem and susceptibility judgment. Social introversion and social discomfort trends lead to impulsive behavior and deviant actions that combine poorly with good compliance with treatment.

Hepatoblastoma in a 14 month-old female.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Complete surgical resection is the best treatment choice with a good prognosis in most cases. We present the case of a 14 month-old female patient was admitted to the pediatric surgery unit due to an abdominal mass localized in the right upper quadrant. The diagnosis retained was hepatoblastoma, so the patient underwent preoperative chemotherapy. The final size of the tumor permitted a complete surgical resection through a right subcostal incision enlarged to the left. Hepatoblastoma is the most common malignant liver tumor in children, more frequent in male than in female and typically presenting before 3 years of age as an abdominal mass found accidentally. Recent treatment strategies, consisting of chemotherapy combined with extensive surgery and in extreme cases liver transplantation, have improved the prognosis during the last years although HB's etiology and management are still subjects of debate.

The ALPPS procedure for hepatocellular carcinoma.

BACKGROUND: The main limiting factor to major hepatic resections is the amount of the future liver remnant (FLR). Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a procedure which induces a rapid hypertrophy of the FLR in patients with non-resectable liver tumours. METHODS: ALPPS is a surgical technique of in-situ splitting of the liver along the main portal scissura or the right side of the falciform ligament, in association with portal vein ligation in order to induce a rapid hypertrophy of the left FLR. RESULTS: The median FLR volume increase was 18.7% within one week after the first step and 38.6% after the second step. At the first step the median operating time was 300 min, blood transfusions were not required in any case, median blood loss was 150 cc. At the second step median operating time was 180 min, median blood loss was 50 cc, none of the patients required intra-operative blood. All patients are alive at a median follow up of 9 months. CONCLUSIONS: This novel strategy seems to be feasible even in the context of a cirrhotic liver, and demonstrates the capacity to reach a sufficient FLR within a shorter interval of time.

Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C.

BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11±3.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration >80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.

Downstaging Hepatocellular Carcinoma with Yttrium-90 radioembolization: resection or transplantation?

Trans Arterial Radio Embolization with Yttrium 90 in the treatment of Hepatocellular Carcinoma is becoming a new interesting tool in the treatment of patients that are considered non resectable and non transplantable. A successful downstaging could improve the number of patients that could benefit from a resection or a liver transplantation, but some points still need to be addressed.

Subtotal gastrectomy for gastric cancer: long term outcomes of Billroth I reconstruction at a single European institute.

BACKGROUND/AIMS: The role of Billroth I (BI) subtotal gastrectomy (SG) for gastric cancer (GC) remains controversial in Western countries. The aim of the study is to critically analyze the long term outcomes of this procedure in a large single-institution experience. METHODOLOGY: Between 1990 and 2004, 158 patients underwent BI SG for GC at the Regina Elena Cancer Institute of Rome. Evaluation focused on cancer recurrence of the gastric stump, functional outcome and endoscopic findings. RESULTS: Actuarial survival rate 10 years after resection in stage I-II was 70.7 per cent. After curative resection, primary cancer of the gastric stump occurred in one patient seven years after resection (0.7 per cent), whereas two patients had early recurrence (1.4 per cent) one and three years postoperatively. There were no oesophageal cancers. In survivors, Visick grades I and II achieved 95 per cent, and postoperative endoscopy showed no evidence of mucosal changes in 85 per cent of the patients. Twelve per cent of the patients took acid blocker regularly, however, the incidence of functional failure was 5 per cent. CONCLUSIONS: In selected patients, Billroth I subtotal gastrectomy is a safe and effective procedure that provides long-term survival and very good functional outcome.

Hanging of the hepatic veins septa: a safe control prior and during outflow anastomosis in liver transplantation.

Inferior vena cava (IVC) preservation during orthotopic liver transplantation (OLT) is known as the "piggyback" technique. The end-to-side anastomosis is constructed between the graft's IVC and recipient's hepatic veins using a Satinsky side clamp applied in a transverse position. To stabilize the large Satinsky clamp and preserve a sufficient vascular stump after hepatectomy and before graft implantation, we propose a technical innovation consisting of hanging the septa between the left and middle hepatic vein and between the middle and right hepatic vein using 2 tapes. This technique showed some advantages when performing the caval outflow anastomosis, representing a further technical refinement of the piggyback end-to-side technique for the implantation on the 3 hepatic veins. From November 2001 to September 2012, we performed 272 consecutive OLT at our institution with the piggyback technique using the hanging of the hepatic veins septa in all cases. In conclusion, the hanging of the 3 hepatic veins septa presented in this study represents a simple, safe and reproducible technique for the outflow anastomosis using the piggyback technique.

De novo malignancies following liver transplantation: results from a multicentric study in central and southern Italy, 1990-2008.

OBJECTIVE: The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. METHODS: Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990-2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/10(3) PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2-1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. CONCLUSIONS: These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

De novo malignancies after organ transplantation: focus on viral infections.

Organ transplantation is an increasingly used medical procedure for treating otherwise fatal end stage organ diseases with 107,000 transplants performed worldwide in 2010. Newly developed anti-rejection drugs greatly helped to prolong long-term survival of both the individual and the transplanted organ, and they facilitate the diffusion of organ transplantation. Presently, 5-year patient survival rates are around 90% after kidney transplant and 70% after liver transplant. However, the prolonged chronic use of immunosuppressive drugs is well known to increase the risks of opportunistic diseases, particularly infections and virus-related malignancies. Although transplant recipients experience a nearly 2-fold elevated risk for all types of de-novo cancers, persistent infections with oncogenic viruses - such as Kaposi sarcoma herpes virus, high-risk human papillomaviruses, and Epstein-Barr virus - are associated with up to 100-fold increased cancer risks. This review, focusing on kidney and liver transplants, highlights updated evidences linking iatrogenic immunosuppression, persistent infections with oncogenic viruses and cancer risk. The implicit capacity of oncogenic viruses to immortalise infected cells by disrupting the cell-cycle control can lead, in a setting of induced lowered immune surveillance, to tumorigenesis and this ability is thought to closely correlate with cumulative exposure to immunosuppressive drugs. Mechanisms underlying the relationship between viral infections, immunosuppressive drugs and the risk of skin cancers, post-transplant lymphoproliferative disorders, Kaposi sarcoma, cervical and other ano-genital cancers are reviewed in details.

Quality of life and physical activity in liver transplantation patients: results of a case-control study in Italy.

The aim of the study was to assess the quality of life (QOL) and the physical activity of liver transplant recipients compared with the general population. The case-controlled pilot study was accomplished through the administration of 2 questionnaires: 36-item Medical Outcomes Study, Short-Form General Health Survey (SF-36) for quality of life (10 scores) and International Physical Activity Questionnaire (IPAQ) to estimate the physical activity (metabolic equivalent score). Fifty-four patients who underwent liver transplantation using the piggyback technique and 108 controls from the general population at the orthopedic ambulatories were enrolled between 2002 and 2009. Participants had a mean age of 55 years (range, 41-73). The multivariate analysis showed significant differences for some scales of the SF-36: liver transplant recipients displayed lower values for "Mental Composite Score" (P = .043), "physical activity" (P = .001), "role limitations due to physical health" (P = .006), "role limitations due to the emotional state" (P = .006), and "mental health" (P = .010). The metabolic equivalent positively associated with all examined SF-36 scales. The present study focused on the QOL and physical activity of liver transplant recipients, demonstrating that transplant recipients scored lower than the general population. Liver transplantation may allow full recovery of health status, but the physical and social problems persist in some patients. Interventions aimed at improving rehabilitation programs, regular psychosocial support, and follow-up in all phases of treatment may give patients a more satisfying lifestyle after transplantation.

Fatal sclerosing peritonitis associated with primary effusion lymphoma after liver transplantation: a case report.

Sclerosing peritonitis (SP) after liver transplantation has been described in 10 cases in the literature. The etiology is still unknown; however, SP is considered a consequence of chronic irritation and inflammation. It can be classified as primary (idiopathic) or secondary form. Although pathologically benign, it has a negative course, resulting in unrelenting abdominal pain, small bowel obstruction, malnutrition, and death. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. Primary effusion lymphoma (PEL) as an onset presentation of PTLD is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement and associated with Human herpes virus 8 (HHV-8) recurrence. Here in, we report a case of a 55-year-old man who rapidly developed refractory ascites and bacterial peritonitis at 1-year after orthotopic liver transplantation (OLT) with a fatal clinical course at the beginning of the second follow-up year after an uncomplicated liver transplantation due to cryptogenic cirrhosis. The diagnosis of HHV-8-positive lymphoma was established by postmortem examination with multiple solid localizations and massive dense fibrotic adhesions encompassing the small intestine, colon, liver, and porta hepatis without any involvement of body cavities.

Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial.

BACKGROUND: We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases. METHODS: This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day. RESULTS: Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction. CONCLUSION: Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.