Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

THE ROLE OF SURGERY IN A PATIENT WITH CARCINOID SYNDROME, COMPLICATED BY CARCINOID HEART DISEASE.

A 55-year-old female patient was admitted for flushing and abdominal pain in the right upper quadrant. Her past medical history revealed high blood pressure and a recent echocardiography showed thickened appearance of tricuspid valve with coaptation defect and grade II tricuspid regurgitation. Contrast enhanced abdominal CT scan and MRI were subsequently performed and revealed a large macronodular liver mass, as well as other micronodular lesions disseminated in the liver parenchyma. CT guided biopsy from the main liver mass revealed neuroendocrine tumor of unknown origin (probably GI) with Ki-67 of 8%. Surgical exploration was decided. During laparotomy, the primary tumor was found in the proximal ileum and the patient underwent segmental enterectomy. Non-anatomical hepatectomy was also performed to remove the bulk of the tumor burden (more than 90%). Postoperative course was uneventful and the carcinoid syndrome relieved. At present, 15 months postoperatively, the patient is under treatment with somatostatin analogue for its antiproliferative effect, with good clinical, biochemical and tumoral control and stable heart disease. In patients with neuroendocrine liver metastases from unknown primary, surgical exploration could allow detection (and resection) of the primary tumor and surgical debulking of liver metastases to control carcinoid syndrome and carcinoid heart disease.

Liver transplantation in a patient with unresectable colorectal liver metastases -- a case report.

BACKGROUND: Due to the lower survival rates achieved, in the early period of liver transplantation era, in patients with colorectal liver metastases, and because of the organ shortage,in the last two decades colorectal liver metastases are considered a contraindication for liver transplantation. However, the increasing number of marginal donors, and the improvements in posttransplant immunossuppresion, chemotherapy and methods to assess the extrahepatic disseminationof colorectal cancer, opened the perspective of liver transplantation to certain patients with malignancies (such as HCC beyond Milan criteria, and selected patients with cholangiocarcinomaor liver metastases from neuroendocrine tumors).Since some of these patients experienced favorable outcomes,in the last years, there were authors that considered a rationalerevisitation of the benefits of liver transplantation in patients with unresectable colorectal liver metastases. Thus, in 2006, a Norwegian group started a study which aims to assess the results of liver transplantation in patients with unresectable colorect alliver metastases. Their results were unexpectedly favorable, revealing that 5-year overall survival rate was 60%, and the quality of life was excellent in the first year following transplantation.However, all the patients presented relapse of the disease in the first two years following transplantation. In the present paper we present the clinico-pathologic characteristics,the pre- and postoperative management and the outcome of a patient with unresectable colorectal liver metastases who underwent liver transplantation in a very advanced state of the disease (when he developed subacute liver failure due to insufficient functional liver parenchyma and toxicity of chemotherapy).We consider useful to present such observations,because collecting the data presented by different centers maybe contributive to identification of a selected group of patients who could benefit from liver transplantation. CASE REPORT: A 42-year old male patient, it was diagnosed with upper rectum cancer and multiple bilobar liver metastases in April 2009. Chemotherapy was started (in another hospital),and because the disease was stable after 7 cycles of FOLFOX and Bevacizumab, the patient was reffered to surgery (for a "two stage" liver resection). In October 2009 it was performed primary tumor resection associated with left lateral section ectomy and segment 4 metastasectomy. Because in November 2009 CT scan re-evaluation revealed progression of liver metastases, the second stage hepatectomy was precluded. Subsequent therapy consisted in radio embolization, multiple lines of chemotherapy,and targeted therapies. After more than 2 years, the liver metastases progressed and the patient developed progressive cholestatic subacute liver failure due to insufficient functional liver parenchyma and chemotherapy toxicity. In this state of the disease, he was admitted in our hospital, being dependant by liver dialysis and plasma exchange procedures. Due to the patients' age, and because the MDCT scan revealed the absence of extrahepatic disease (after almost three years of disease progression), and he could not benefited from any type of antineoplastic treatment due to progressive cholestatic subacute liver failure, liver transplantation with an organ from amarginal donor was considered and performed in January 2012.The postoperative course was uneventful, and the quality of his life improved (being fully reinserted social and professional).The immunosuppressive regimen consisted in Sirolimus and Mycophenolate mofetil, and the adjuvant chemotherapy started two months following liver transplantation. However,the patient developed extrahepatic relapse of the disease (lung metastases and retroperitoneal recurrence), but now, at morethan 20 months following transplantation, he is still alive in agood clinical condition. CONCLUSIONS: In patients with multiple unresectable liver onlycolorectal metastases, liver transplantation may improve overallsurvival and quality of life, by using marginal grafts whichcannot be allocated to the patients with standard indicationsfor liver transplantation. The advent of MDCT and PET CT scan and the use of m-TOR inhibitors may improve the resultsachieved by liver transplantation in patients with CLMs.Further studies could be useful in an attempt to disclosewhether a selected group of patients with unresectable liveronly colorectal metastases could become acceptable candidatesfor liver transplantation.

Intrahepatic cholangiocarcinoma--a rare indication for liver transplantation. Case report and review of the literature.

BACKGROUND: While hepatocellular carcinoma is a common indication for liver transplantation, intrahepatic cholangiocarcinoma represents a controversial indication for this procedure, due to lower disease-free and overall survival rates achieved by liver transplantation in such patients. Hence, in the last years, few centers reported satisfactory survival rates after liver transplantation for cholangiocarcinoma, in highly selected groups of patients. Herein we present the clinicopathological characteristics, the pre- and postoperative management and the favorable outcome of a patient undergoing liver transplantation for an unresectable intrahepatic cholangiocarcinoma. We consider that reporting the patients with such favorable outcomes is useful, since collecting the data presented by different centers may contribute to identification of a selected group of patients with cholangiocarcinoma who may benefit from liver transplantation. CASE REPORT: A 62-year old female patient with a primary liver tumor developed on HBV liver cirrhosis, was admitted in our center for therapeutical management. Since preoperative work-up suggested that the tumor is an unresectable hepatocellular carcinoma (due to its location and underlying liver disease), we decided to perform liver transplantation. The pathological examination of the explanted liver revealed that the tumor was a stage I intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and in present, 15 months after transplantation, the patient is alive, without recurrence. CONCLUSIONS: Liver transplantation may represent a valid therapeutical option in selected patients with intrahepatic cholangiocarcinoma. Patients with early stage intrahepatic cholangiocarcinomas unresectable due to the underlying liver cirrhosis seem to benefit mostly by liver transplantation. Further studies are needed to identify the favorable prognostic factors in order to select the most appropriate candidates for liver transplantation. The most suitable immunosuppressive and (radio)chemotherapic regimens should be identified in the future, in order to improve the disease-free and overall survival rates of the patients undergoing liver transplantation for intrahepatic cholangiocarcinoma.

Simultaneous resection of the primary colorectal tumor and liver metastases--a safe and effective operation.

BACKGROUND: The aim of this retrospective study was to compare the results achieved by simultaneous resection (SR) vs. delayed resection (DR) in patients with synchronous colorectal liver metastases (SCRLM). METHODS: In "Dan Setlacec" Center of General Surgery and Liver Transplantation from Fundeni Clinical Institute, between 1995 and 2010, 117 patients underwent SR and 25 patients underwent DR. It was compared the outcome of the patients in the two groups. It was also assessed if certain subgroups of patients present a better outcome after DR than after SR. RESULTS: The location of the primary tumor, the number and diameter of liver metastases, and the proportion of major hepatectomies were similar in the two groups (p value > 0.05). For all patients, the morbidity, mortality, disease-free and overall surrvival rates were not statistically significant different between the two groups (p value > 0.05). In subgroups of patients with rectal tumors, with multiple liver metastases, and undergoing major hepatectomies, the morbidity, mortality and survival rates achieved by SR were similar to those achieved by DR. CONCLUSION: Simultaneous resection of SCRLM is similarly safe and efficient as the delayed resection, even in patients with rectal tumors, with multiple liver metastases, or undergoing major hepatectomies.

[Hepatic metastasis of colorectal cancer--current therapeutic possibilities]. / Metastazele hepatice colorectale--posibilitati terapeutice actuale.

UNLABELLED: In this article we presented the therapeutical modalities available nowadays for the treatment of patients with colorectal liver metastases (CRLM), based on a wide search in the literature. To date, due to the developments in liver surgery, anesteziology and intensive care therapy, chemotherapy, interventional radiology and radiationtherapy, the treatment of CRLM is multimodal. These advances led to a changing of the definition of the resectability, in present, resectability being defined by the quality and volume of the functional liver remnant after hepatectomy. In the last years, the timing of liver resection was recconsidered, hepatectomy being suitable (especially in patients with multiple CRLM) after neoadjuvant chemotherapy, and in patients with synchronous CRLM, resection of the primary tumor and liver metastases is reccomended to be performed simultaneously whenever this approach is safe and allows a complete resection of the tumoral tissue. Presence of the extrahepatic colorectal metastases do not represent a contraindication to liver resection, as long as complete removal of the metastases is possible. Conversion to resectability was possible for about 30% of the patients with initially unresectable CRLM, using several therapeutical strategies, giving the chance of a long-term survival to these patients. Liver re-resection is the treatment of choice for patients with recurrent liver metastases, survival rates being similar to those achieved after the first liver resection. Hyperthermic ablation is recommended in patients whose CRLM could not be resected, but the results seem to be inferior to those achieved by liver resection. CONCLUSIONS: In present, the treatment of CRLM is multimodal, involving the surgeon, oncologist, radiotherapist and radiologist. Taking into account the great variability of the patients and the multiple therapeutical possibilities, the treatment should be taylored to each patient.

[Liver transplantation--indications, surgical technique, results--the analysis of a clinical series of 200 cases]. / Transplantul hepatic--indicati, tehnica, rezultate-analiza unei serii clinice de 200 de cazuri.

INTRODUCTION: Initially considered experimental, liver transplantation (LT) has become the treatment of choice for the patients with end-stage liver diseases. MATERIAL AND METHODS: Between April 2000 and October 2009, 200 LTs (10 reLTs) were performed in 190 patients, this study being retrospective. There were transplanted 110 men and 80 women, 159 adults and 31 children with the age between 1 and 64 years old (mean age--39.9). The main indication in the adult group was represented by viral cirrhosis, while the pediatric series the etiology was mainly glycogenosis and biliary atresia. There were performed 143 whole graft LTs, 46 living donor LTs, 6 split LTs, 4 reduced LTs and one domino LT RESULTS: The postoperative survival was 90% (170 patients). The patient and graft one-year and five-year survivals were 76.9%, 73.6% and 71%, 68.2%, respectively. The early complications occurred in 127 patients (67%). The late complications were recorded in 71 patients (37.3%). The intraoperative and early postoperative mortality rate was 9.5% (18 patients). CONCLUSIONS: The Romanian liver transplantation program from Fundeni includes all types of current surgical techniques and the results are comparable with those from other international centers.

[Surgical treatment of liver metastases from colorectal cancer]. / Tratamentul chirurgical al metastazelor hepatice ale cancerului colo-rectal.

We analyze our experience over a 10-year period in the surgical treatment of liver metastases from colorectal cancer. Between 01.01.1995 and 08.31.2005 189 liver resections were performed in 171 patients with liver metastases from colorectal cancer (16 re-resections - 2 in the same patient and a "two-stage" liver resection in 2 patients). In our series there were 83 patients with synchronous liver metastases (69 simultaneous resections, 12 delayed resections and 2 "two-stage" liver resection were performed) and 88 metachronous liver metastases. Almost all types of liver resections have been performed. The morbidity and mortality rates were 17.4% and 4.7%, respectively. Median survival was 28.5 months and actuarial survival at 1-, 3- and 5-year was 78.7%, 40.4% and 32.7%, respectively. Between January 2002 and August 2005 hyperthermic ablation of colorectal cancer liver metastases has been performed in 6 patients; in other 5 patients with multiple bilobar liver metastases liver resection was associated with radiofrequency ablation and one patient underwent only radiofrequency ablation for recurrent liver metastasis. In conclusion, although the treatment of colorectal cancer liver metastases is multimodal (resection, ablation, chemotherapy and radiation therapy), liver resection is the only potential curative treatment. The quality and volume of remnant liver parenchyma is the only limitation of liver resection. The morbidity, mortality and survival rates after simultaneous liver and colorectal resection are similar with those achieved by delayed resection. Postoperative outcome of patients with major hepatic resection is correlated with the surgical team experience. The long-term survival was increased using the new multimodal treatment schemes.

[Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period]. / Tratamentul multimodal al carcinomului hepatocelular. Analiza unei experiente clinice de 123 de cazuri în 5 ani.

We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.

[Orthotopic liver transplantation in adult patients with cadaveric grafts. Experience of the Fundeni Center of General Surgery and Liver Transplantation]. / Transplantul hepatic ortotopic de la donator cadavru la adult. Experienta Centrului de Chirurgie Generalai si Transplant Hepatic Fundeni.

We analyze the experience of the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest, Romania) regarding orthotopic liver transplantation (OLT) in adult recipients, with whole liver grafts from cadaveric donors, between April 2000 (when the first successful LT was performed in Romania) and December 2004. This series includes 37 OLTs in adult recipients (16 women and 21 men, aged between 29-57 years--average 46 years). Other two LT with whole liver cadaveric grafts and two reduced-size LT were performed in children; also, in the same period, due to the acute organ shortage, other methods of LT were performed in 28 patients (21 living donor LT, 6 split LT and one "do mino" LT), that were not included in the present series. The indications for OLT were HBV cirrhosis--10, HBV+HDV cirrhosis--4, HCV cirrhosis--11, HBV+HCV cirrhosis--2, biliary cirrhosis--5, Wilson disease--2, alcoholic cirrhosis--1, non-alcoholic liver disease--1, autoimmune cirrhosis--1. With three exceptions, in which the classical transplantation technique was used, the liver was grafted following the technique described by Belghiti. Local postoperative complications occurred in 15 patients (41%) and general complications in 17 (46%); late complications were registered in 18 patients (49%) and recurrence of the initial disease in 6 patients (16%). Intrao- and postoperative mortality was 8% (3/37). There were two patients (5%) who died because of immunosuppressive drug neurotoxicity at more than 30 days following LT. Four patients (11%) died lately because of PTLD, liver venoocclusive disease, recurrent autoimmune hepatitis and liver venoocclusive disease, myocardial infarction, respectively. Thirty-four patients survived the postoperative period (92%); according to Kaplan-Meier analysis, actuarial patient-survival rate at month 31 was 75%.

[Central hepatectomy]. / Hepatectomia centrala.

Central hepatectomy (CH) is a major liver resection that removes Couinaud's segments IV, V and VIII, indicated for centrally located lesions and designed to preserve functional parenchyma and prevent liver failure. During an 8-year period between January 1995-November 2002, 507 liver resections were performed in Fundeni Center of General Surgery and Liver Transplantation (Bucharest). There were three CH performed for colorectal metastases (1 case) and inflammatory pseudotumor (2 cases). The mean duration of the procedure and the mean blood loss were, respectively, 231 minutes and 915 ml. The patients had a good post-operative course, with only minor complications.