welcome back to behind the knife rast surgery journalcast i'm kim linden a general surgery resident from cooper university hospital today we're going to review two articles critical in developing the guidelines for patients with cirrhosis and hepatocellular carcinoma treated with transplantation patients with centrally located and unresectable hcc and have cirrhosis or patients with hcc and advanced serratic disease preventing surgical resection are considered potential candidates for transplantation per the eunos criteria a patient with hcc with a single tumor less than five centimeters in diameter or three tumors each up to three centimeters with no macro vascular involvement or extra hepatic disease can be placed on the transplant list but how did we conclude that these cancers would benefit from transplant two main articles have been cited for the basis of liver transplantation in hcp one was published in the new england journal of medicine in 1996 from a group out of milan and one was published in 2001 from the ucsf group in the journal of hepatology the milan study was a three-year prospective cohort study of 48 patients with cirrhosis and resectable hepatocellular carcinoma who received a liver transplant those that were considered transplant candidates had a t1 or t2 tumor on preoperative imaging for a reminder these include solitary tumors up to five centimeters or two to three tumors up to three centimeters they set out to look at both the efficacy of transplantation and to evaluate what tumors and patient characteristics led to a higher survival rate or a higher recurrence of cancer eight of the 48 patients died post-transplant but only two of them were cancer-related a total of four had recurrence three of the four had a higher tumor stage on pathologic evaluation than preoperatively identified two died within the four years of follow-up one of those had lung mats and was alive at 26 months and one had recurrence around a biopsy site at the skin the overall four year survival was 75 percent and the recurrence for survival was 83 percent overall the recurrence-free survival was not affected by age sex type of hepatitis virus or a child pew score at the time of transplant tumors size stage number of tumors serum afb and absence of a capsule trended to a higher recurrence rate but was not statistically significant however there was only four recurrences so the significance may have the stay may have been too low of power so from this the milan criteria was developed for patients who have hcc with cirrhosis or unresectable tumors to qualify for transplant patients can have a solitary tumor up to five centimeters or two to three tumors up to three centimeters each the ucsf group noted that there was no clear consensus on the greatest tumor diameter for solitary or multifocal lesions that might benefit from orthotopic liver transplant so then they decided to evaluate the outcomes and the impact of pathologic tumor stage on recurrence-free survival of consecutive patients with hcc and cirrhosis who underwent orthotopic liver transplant over a 12-year period over those 12 years they found 970 patients had a liver transplant and 70 of them had cirrhosis with hcc 23 of the 70 patients were found to have hcdc incidentally they found that 11 of the 70 patients had a pathologic t1 tumor 35 had a pathologic t2 tumor 18 had a pathologic t3 tumor and 6 had a pathologic t4 tumor most were well differentiated or moderately differentiated and only 8 being poorly differentiated 18 did have vascular invasion of the 23 that were incidentally found they found that two patients had a pathologic t4 tumor three patients had a pathologic t3 tumor nine patients had a pathologic t2 tumor and nine patients had a pathologic t1 tumor of the 70 patients eight did have recurrence two were pathologic t4 three were pathologic t3 and three were pathologic t2 overall survival for this cohort was broken into two groups either less than or equal to a pathologic t2 tumor or pathologic t3 tumors one year survival for less than or equal to a pathologic t2 tumor was 91 percent and five-year survival was 72.4 pathologic t3 tumors had a one-year survival of 82.4 percent and a five-year survival of 74 the differences in survival was not statistically significant a pathologic t4 tumor was the strongest predictor of mortality with a hazard ratio of eight total tumor diameter of greater than eight poorly differentiated histologic grade age greater than or equal to 55 and afp greater than a thousand nanograms per milliliter were also predictors of poor survival in univariate analysis overall they concluded that pathologic t3 tumors had an overall survival rate and recurrence-free survival rate compared to a pathologic t2 tumor or less and so they should also be considered for liver transplant so the ucsf guidelines for qualification for liver transplantation are for patients with hepatocellular carcinoma and cirrhosis with a tumor that is less than 6.5 centimeters or two to three tumors of which the largest tumor is up to 4.5 centimeters and the total tumor diameter cannot be more than eight centimeters a secondary endpoint that they looked at within the study was the accuracy of preoperative tumor staging of various imaging modalities they primarily looked at ultrasound ct and mri the sensitivity for detecting the main lesion was 79.4 with ultrasound 81.6 with ct and 88.9 with mri the lesion was correctly estimated in within one centimeter of diameter in 62 to 80 percent of the time multiple nodules however had a lower detection rate with about a 34 sensitivity in ultrasound 27.6 in ct and 42.9 for mri the overall accuracy of preoperative imaging was about 75.6 so when you compare the two major criteria the ucsf criteria has a higher cutoff for tumor sizes but the maximum number of tumors is the same so that's my review i'm kim linden a general surgery resident at cooper university hospital if you have any questions or comments you can reach me at my email or by twitter ik underscore linden underscore md thanks for listening you