Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas.

OBJECTIVE: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). PATIENTS: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. RESULTS: Gender (P=0.0086), UICC stage (P=0.0140) and R-class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19-9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I-II):UICC (III-IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19-9 (<100 U/ml):CA 19-9 (> or =100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3-4, 5 and 6 points (P=0.000001) and clinical groups with 3-4 and 5-6 points (P=0.0103) achieved statistically significant difference. CONCLUSIONS: We propose a clinical and prognostic scoring system predictive of long-term survival after surgical resections for ICC.

R0 liver resections for primary malignant liver tumors in the noncirrhotic liver: a diagnosis-related analysis.

BACKGROUND: Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. RESULTS: Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. CONCLUSIONS: R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.

Survival and recurrence rates after resection for hepatocellular carcinoma in noncirrhotic livers.

BACKGROUND: Hepatocellular carcinoma occurring in noncirrhotic livers is rare. The purpose of this article was to evaluate the outcomes and prognostic factors after hepatectomy in this setting. STUDY DESIGN: Between June 1998 and May 2005, 83 patients underwent liver resection for hepatocellular carcinoma in noncirrhotic livers at our institution. Preoperative treatment data, intraoperative details, pathologic findings, and information on tumor recurrence, treatment of recurrence, and survival were available for 80 of these patients. RESULTS: Postresection, the 3- and 5-year-survival rates were 48% and 30%, respectively. After R0 resection (n=66), the calculated 3- and 5-year-survivals were 54% and 39%, compared with 23% and 0%, respectively, after R1/2-resection (p<0.005). After a median followup of 25 months, tumor recurred in 40 of 63 (63%) patients after R0 resection. In univariate analysis, Union Internationale Contre le Cancer (UICC) stage, vascular invasion, and tumor grading were identified as important findings for recurrence and poor survival after R0 resection. For tumors without vascular invasion, the 3- and 5-year-survivals were 79% and 65%, respectively, which compared favorably with 21% and 7%, respectively, for tumors with vascular invasion (p<0.0001). Similarly, 3- and 5-year-survival rates (95% each) were considerably better for G1 tumors than the corresponding 36% and 22% rates in G2 and 60% and 30% in G3 tumors, respectively. CONCLUSIONS: The 3- and 5-year survivals of 54% and 39%, respectively, after R0 resections suggest that surgery is an option in hepatocellular carcinoma arising in noncirrhotic livers. Longterm results, however, are hampered by high recurrence rates. Union Internationale Contre le Cancer stage, vascular invasion, and tumor grades are predictors of tumor recurrence and diminished survival, and may help to identify candidates for potential adjuvant therapies.

Left hepatic trisectionectomy for hepatobiliary malignancies.

BACKGROUND: Left hepatic trisectionectomy is the most extended hepatic resection. To date, few data are available on longterm outcomes after this operation. STUDY DESIGN: Between June 1998 and July 2004, a total of 52 patients underwent left trisectionectomy for primary or secondary hepatobiliary tumors at our institution. Data were analyzed with regard to patient characteristics, intraoperative details, pathologic findings, perioperative morbidity and mortality, and outcomes as determined by survival. RESULTS: Left trisectionectomy was combined with caudate lobectomy and hilar lymph node dissection in 29 and 35 patients, respectively. In addition, 43 procedures were performed in 31 patients: resection of hilar bifurcation (n = 15), bile-duct revision (n = 5), wedge resection of segment VI/VII (n = 10), gastrectomy (n = 1), and resection or reconstruction of hepatic vessels or the inferior vena cava (n = 12). Operative morbidity and mortality were 50% and 11.9%, respectively. By multivariate analysis, additional operative procedures constituted the only positive predictor of postoperative morbidity. One-, 3-, and 5-year survival rates were 65%, 52%, and 33%, respectively. After R0 resection (n = 37), 1-, 3-, and 5-year survival rates were 78%, 68%, and 44% compared with 38%, 15%, and 7% after R1 resection (p = 0.0004). Survival corresponding to the four most frequent tumor types (hepatocellular carcinoma, cholangiocellular carcinoma, hilar cholangiocarcinoma, and colorectal metastases) was comparable with survival data reported in the literature after less-extensive resections. CONCLUSIONS: Left trisectionectomy provides acceptable survival rates in both locally advanced primary hepatobiliary malignancies and large metastatic liver tumors. Despite major progress in surgical technique and perioperative management, left trisectionectomy is still associated with higher operative mortality and morbidity than less-extensive resections. Because selection criteria for this type of procedure are not clearly defined, particular attention should be focused on the oncologic benefits when considering this operation.

Surgery for hepatocellular carcinoma arising in hereditary hemochromatosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a well-known complication of hereditary hemochromatosis. The benefit of surgical therapy in this clinical entity is not well documented. The purpose of this study was to evaluate the outcome of such patients both in our own experience as well as in the published literature. METHODS: 320 patients with a diagnosis of HCC were evaluated at our institution to undergo either surgical resection (n = 262) or liver transplantation (n = 58) during the 4- year period from January 2001 to December 2004. We identified 5 patients with HCC arising in the setting of hemochromatosis. A literature search was performed to estimate resectability rates as well as outcomes after liver transplantation for HCC arising in hemochromatosis. RESULTS: HCC was multifocal in 4 instances and solitary in 1 case. The liver was cirrhotic in all but 1 case. Three patients underwent an exploratory laparotomy, 1 an exploratory laparoscopy, and 1 underwent transplantation. HCC was unresectable in all cases. The patient with a solitary tumor and cirrhosis underwent 5 sessions of transarterial chemoembolization and is alive 37 months after surgical exploration. The 3 patients with multifocal tumors who underwent exploratory laparotomies died within 6 months after the intervention. The fifth patient who underwent a deceased donor split liver transplantation for multifocal tumor is alive without recurrence 3 years after transplantation. These results are similar to those in the literature that concur with the low resectability rate and the favorable outcome after liver transplantation. CONCLUSION: Resectability rates of HCCs arising in hemochromatosis are extremely low, given that tumors are usually multifocal and the livers cirrhotic in the majority of the instances. Early detection of hemochromatosis as well as intensive tumor screening of cirrhotic patients with hemochromatosis could possibly optimize the role of surgery or accelerate the decision to proceed with liver transplantation.

Resectability of hepatocellular carcinoma: evaluation of 333 consecutive cases at a single hepatobiliary specialty center and systematic review of the literature.

BACKGROUND/AIMS: To determine resectability rates in patients with hepatocellular carcinoma (HCC) evaluated for surgical therapy. Liver resection constitutes a potentially curative treatment for HCC. However, because of the co-existing cirrhosis or the late diagnosis, only a percentage of the patients evaluated can undergo surgery. METHODOLOGY: We evaluated 333 patients with HCC admitted to our center with the intent to treat by means of tumor resection during a 6-year time period. RESULTS: Surgical resection with curative intent was undertaken in 116 patients (35%). In our series, resectability rates were significantly higher in patients with solitary HCCs (p<0.001), unilobar tumor distribution (p=0.03), and no cirrhosis (p <0.001). Transarterial chemoembolization (TACE) was the most frequent approach for nonresectable cases (18% of patients). A systematic literature review was performed in order to estimate resectability rates at other hepatobiliary centers offering multimodal treatment approaches to HCC. Results showed an overall resectability rate of 30%, with 1808 resections reported in 6108 cases. Resectability rates were significantly higher in Japanese and Eastern series when compared to American and Western studies respectively (p<0.001). CONCLUSIONS: Treatment strategies for HCC require a multidisciplinary comprehensive approach encompassing surgeons, hepatologists, radiologists, and oncologists. Surgical resection was possible in only 35% and 30% of patients with HCC evaluated for surgical therapy in our series and in the world literature, respectively. TACE was the primary treatment modality for non-resectable cases. A "no therapy" option was chosen in 21% of cases worldwide.

Liver transplantation and incidentally found hepatocellular carcinoma in liver explants: need for a new definition?

BACKGROUND: "Incidentally" identified hepatocellular carcinoma (iHCC) in liver explants after liver transplantation (LTx) is a frequently reported finding, which is characterized with a good prognosis. The purpose of this study was to evaluate the outcome of patients with these tumors in our series and in literature reports, and to compare their prognosis to that of HCC diagnosed preoperatively. METHODS: From April 1998 to December 2003, 432 patients underwent deceased-donor LTx at our center for nonmalignant indications. An additional 31 patients with a preoperative known HCC (pkHCC) received deceased-donor grafts. A literature search was performed intending to estimate the incidence of iHCC in liver explants and the outcome after LTx. RESULTS: iHCC was found in 5 of the 432 patients. All five patients are currently alive without evidence of tumor recurrence after a median follow-up of 43 months. On the other hand, in the group of the 31 patients with pkHCC, 22 of them are at the moment alive in a median follow-up of 28 months. When comparing the two groups, no difference in survival could be found (P=0.1419 in log-rank test). Literature reports of 705 instances with iHCC over the past 20 years showed a statistical "better survival" in only 24 cases. CONCLUSION: Literature reports showed a remarkable "deviation" of the expected tumor characteristics for the iHCC. Obviously, this is because of a widely characterization of iHCC, including also tumors which are rather undetected HCC during the waiting time to LTx. A more precise definition for the iHCC is needed.

Liver transplantation for hepatocellular carcinoma in cirrhosis within the Eurotransplant area: an additional option with "livers that nobody wants".

BACKGROUND: Liver transplantation is recognized as the treatment of choice for small hepatocellular carcinomas (HCC) in patients with end-stage liver failure. However, because of limited organ availability, not all those who qualify can benefit from it. METHODS: Over a 3-year period, we accepted and subsequently transplanted 10 deceased donor liver allografts allocated through Eurotransplant. These organs had been officially offered to and rejected by other transplant centers a total of 40 times due to medical or logistical reasons prior to our acceptance. They were implanted into patients in the waiting list with HCC and cirrhosis. Recipients without HCC transplanted with such "undesirable" grafts were not included in this study. RESULTS: Two patients had initial poor graft function but subsequently recovered. There was one arterial complication requiring reintervention. Median intensive care unit and hospital stays were 6 and 28 days respectively. One patient developed renal insufficiency, but recovered after 3 months. One patient developed HCC recurrence in the allograft and underwent a successful atypical liver resection 23 months after transplantation. All patients are currently alive, with follow-up periods ranging from 5 to 36 months. CONCLUSIONS: Liver transplantation with such "livers that nobody wants" constitutes an additional option for patients with HCC and cirrhosis. The risk-benefit ratio in these instances should be evaluated on a case-by-case basis.

Surgical treatment of pancreatic metastases of renal cell carcinoma.

CONTEXT: The pancreas is an unusual site for metastases of renal cell carcinoma origin, sometimes occurring many years after nephrectomy. We herein present two cases of pancreatic metastases of renal cell carcinoma which occurred 17 and 19 years after the primary diagnosis. CASE REPORT: In the first case, metastases were found in the head of the pancreas, upper right arm and the right lobe of the thyroid gland. In the second case, a tumor was found in the tail of the pancreas and a remnant of the right kidney. This was the third recurrence of the original tumor after an initial left nephrectomy and two subsequent partial right nephrectomies in the past. Treatment in the first case consisted of excision of the tumor in the upper right arm, a Whipple operation, and a thyroidectomy. In the second case, a distal pancreatectomy and remnant right nephrectomy were undertaken. Both patients recovered from the operations without complications and remain free of tumor in follow-up periods of 54 and 8 months respectively. CONCLUSIONS: Resection of renal cell carcinoma metastases involving the pancreas provides satisfactory long-term survival, and should be undertaken whenever possible.

Awareness of diagnosis, and information-seeking behavior of hospitalized cancer patients in Greece.

PURPOSE: The goal of our study was to evaluate the extent of disease-related knowledge and the need for further information of cancer patients in Greece. MATERIALS AND METHODS: We evaluated 203 mentally competent adult cancer patients hospitalized in general and oncological hospitals in the city of Athens and its suburbs. Data were collected by means of semistructured interviews. Patients were evaluated as to whether they had awareness of their diagnosis. Those who did so (n = 83) were further questioned about additional disease-related information. RESULTS: The majority of patients (59%) claimed to have no knowledge of their diagnosis. Women (p = 0.004) as well as high school and university graduates (p = 0.024) showed significantly superior levels of information when compared to men and graduates of elementary schools, respectively. Age was also a factor that influenced the level of the awareness of the diagnosis and the request for additional information: patients who were informed about the diagnosis and patients who asked for more information were significantly younger than their counterparts who ignored the diagnosis (p < 0.001) and those who didn't ask for further information, respectively (p = 0.03). Hospital specialization (oncological versus general, p < 0.001) and department specialization (medical versus surgical, p = 0.004) were associated with significantly increased levels of information. The patient's educational level was associated with increased request for additional information (p = 0.006). Most patients with knowledge of their diagnosis requested detailed information about severity of their disease and prognosis. Only 13% of those in the informed group claimed they would have benefited psychologically by having been unaware of their diagnosis. CONCLUSIONS: Although Greek patients with diagnoses of malignancies want and need to be adequately informed, the amount of information they receive is inadequate. Over half of those patients evaluated were not aware of their diagnosis. Attitudes of health care professionals, preestablished family beliefs, "mind-set" difficulties, and organizational issues should not become barriers to the patients' right to be fully informed of their diagnoses and choices of potential therapies.

Efficacy of transarterial chemoembolization prior to liver transplantation for hepatocellular carcinoma as found in pathology.

BACKGROUND/AIMS: To analyze the efficacy of chemoembolization prior to liver transplantation in liver explants. METHODOLOGY: We reviewed pathological findings in the explanted livers of 21 patients with histologically proven hepatocellular carcinoma and liver cirrhosis who underwent transarterial chemoembolization (TACE) prior to liver transplantation. Nine patients had solitary nodules with a median diameter of 4 cm (range 1.5-7 cm), 7 patients had 2 or 3 tumors with a median total diameter of 5.9 cm (range 3-9 cm) and 5 patients had a multifocal tumor prior to TACE. Pathological up-staging of the clinical tumor classification was documented as "tumor-progression." Concurrence of clinical and pathological findings was documented as "steady disease". "Tumor regression" described those cases in which the pathological classification downgraded the clinical findings. RESULTS: There was no treatment-related morbidity in these patients' group. Tumor regression was proved in 11/21 patients (52.4%) whereas steady disease was observed in 7/21 patients (33.4%). In 5 patients (23.8%) no vital tumor was found by pathological examination. Tumor regression was observed only in one of the five patients having a multifocal tumor prior to TACE. Tumor progression was observed in 3/21 patients (14.3%). CONCLUSIONS: Our data show that TACE provides acceptable local tumor control as bridging treatment before liver transplantation. Although the majority of our patients (15/21, 71.4%) had 2 or more tumor lesions at the beginning of treatment, tumor progression was observed in only a minority (14.3%) of patients. However, multifocal tumors could not be successfully under-staged through this treatment and, furthermore, vital tumor was always observed in pathology; the usefulness of TACE in multifocal disease has to be re-estimated.

Living organ donation: is there still place for altruism?

Living organ donation for transplantation, the ultimate action of altruism, is nowadays the object of extended discussion in many levels. The international trend is to find the best and finest way to support and reward this action. A lot of proposals have been suggested, some of them, however, could turn the whole action into a procedure of trade. In this paper, the present status and the international trend in living organ donation are discussed; furthermore, the role of information, education and religion in the individual acceptance of "being a living donor" is evaluated. The experience of the transplantation center and the hospital volume as important factors for the medical management of the donor are also taken into consideration. Our purpose is to emphasize the mean and origins of living organ donation, which must be a well-balanced decision after detailed information, an educational procedure or a religious-based encouragement. Monetary incentives can have only short-term results in increasing the number of donors; they can also increase the exploitation of poor people and, in the long run, destroy the concept of donation, dissuading the altruistic donors.