Robert K. Kerlan

Excellent Outcome Following Down-Staging of Hepatocellular Carcinoma Prior to Liver Transplantation: An Intention-to-Treat Analysis

We previously reported encouraging results of down‐staging of hepatocellular carcinoma (HCC) to meet conventional T2 criteria (one lesion 2–5 cm or two to three lesions <3 cm) for orthotopic liver transplantation (OLT) in 30 patients as a test of concept. In this ongoing prospective study, we analyzed longer‐term outcome data on HCC down‐staging in a larger cohort of 61 patients with tumor stage exceeding T2 criteria who were enrolled between June 2002 and January 2007. Eligibility criteria for down‐staging included: (1) one lesion >5 cm and up to 8 cm; (2) two to three lesions with at least one lesion >3 cm and not exceeding 5 cm, with total tumor diameter up to 8 cm; or (3) four to five lesions with none >3 cm, with total tumor diameter up to 8 cm. A minimum observation period of 3 months after down‐staging was required before OLT. Tumor down‐staging was successful in 43 patients (70.5%). Thirty‐five patients (57.4%) had received OLT, including two who had undergone live‐donor liver transplantation. Treatment failure was observed in 18 patients (29.5%), primarily due to tumor progression. In the explant of 35 patients who underwent OLT, 13 had complete tumor necrosis, 17 met T2 criteria, and five exceeded T2 criteria. The Kaplan‐Meier intention‐to‐treat survival at 1 and 4 years after down‐staging were 87.5% and 69.3%, respectively. The 1‐year and 4‐year posttransplantation survival rates were 96.2% and 92.1%, respectively. No patient had HCC recurrence after a median posttransplantation follow‐up of 25 months. The only factor predicting treatment failure was pretreatment alpha‐fetoprotein >1,000 ng/mL. Conclusion: Successful down‐staging of HCC can be achieved in the majority of carefully selected patients and is associated with excellent posttransplantation outcome. (HEPATOLOGY 2008.)

Liver Transplantation for Hepatocellular Carcinoma: Validation of the UCSF‐Expanded Criteria Based on Preoperative Imaging

We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5‐year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1‐ and 5‐year recurrence‐free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1‐ and 5‐year recurrence‐free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under‐staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1‐ and 5‐year recurrence‐free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under‐staging when compared to the Milan criteria.

Two-year outcome following transjugular intrahepatic portosystemic shunt for variceal bleeding: Results in 90 patients

BACKGROUND/AIMS Transjugular intrahepatic portosystemic shunt (TIPS) is a new therapy for variceal bleeding. Immediate technical and short-term clinical results have been reported. This study was undertaken to evaluate mid-term outcome after TIPS in patients who successfully underwent the procedure for variceal bleeding. METHODS Ninety patients were followed up prospectively by clinical examination and radiological shunt evaluation including Doppler sonography and transjugular portal venography. RESULTS The average follow-up in surviving patients was 2.2 years. The cumulative survival rate was 60% at 1 year and 51% at 2 years. The rate of cumulative rebleeding was 26% at 1 year and 32% at 2 years. A shunt abnormality was noted in all rebleeding patients. Rebleeding was successfully controlled in all but 1 of the patients who underwent shunt revision. Cumulative detection of stenosis or occlusion was 31% at 1 year and 47% at 2 years. Thirty-eight percent of shunt abnormalities were detected by routine surveillance. Percutaneous shunt revision was attempted in 22 patients and was successful in 21 (95%). CONCLUSIONS Although mid-term primary patency is limited in many patients by the development of a shunt stenosis or occlusion, shunt function can be maintained in most patients by careful surveillance and periodic percutaneous intervention.

Hepatocellular Carcinoma: Consensus Recommendations of the National Cancer Institute Clinical Trials Planning Meeting

Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver in adults and the third most common cause of cancer death worldwide. The incidence of HCC in the United States is rising steadily because of the prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis. The majority of patients have underlying hepatic dysfunction, which complicates patient management and the search for safe and effective therapies. The Clinical Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer Institutes Gastrointestinal Cancer Steering Committee to identify the key knowledge gaps in HCC and define clinical research priorities. The CTPM structured its review according to current evidence-based treatment modalities in HCC and prioritized the recommendations on the basis of the patient populations representing the greatest unmet medical need.

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco‐regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and ≤8 cm, 2 or 3 lesions at least 1 >3 cm but ≤5 cm with total tumor diameter of ≤8 cm, or 4 or 5 nodules all ≤3 cm with total tumor diameter ≤8 cm. Patients were eligible for living‐donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria. 13 A minimum follow‐up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow‐up of 16 months after OLT. The Kaplan‐Meier intention‐to‐treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow‐up is needed to further access the risk of HCC recurrence after OLT. (Liver Transpl 2005;11:1505–1514.)

Patellar and quadriceps tendon ru p tures— jumper's knee:

We reviewed 13 patients with end stage jumpers knee, 10 with patellar tendon ruptures, and 3 with ruptures of the quadriceps tendon to evaluate our long-term results in treating these tendon ruptures in an athletic population. The focus was on the natural history, the time until return, and the level of return, to athletic activity. Jumpers knee affected all patients to a varying degree prior to rupture. Basketball was the most com mon sport involved. At followup, averaging 4½ years, patients underwent functional and clinical, as well as Cybex and roentgen ographic, evaluations. Results indicated patellar tendon ruptures, where the ruptures are complete, have a more favorable prognosis than those of the quadriceps ten don which are incomplete. All of the latter patients continued to have quadriceps tendinitis following repair. In both groups, the poor results were obtained in patients with chondromalacia and/or patella alta. Cybex testing yielded results of greater than 100% strength in three patients with patellar tendon ruptures, but no patient with quadriceps rupture had comparable test results. There was no apparent relationship between ruptures and cortisone injections. Patellar and quadriceps tendon ruptures from indirect injury in athletes represent the end stage of jumpers knee and result from repetitive microtrauma. Excellent function usually follows repair of patellar tendon rup tures when surgery is performed early and care is taken to restore normal patellar tendon length. Results of quadriceps ruptures are less satisfactory since these ruptures are usually incomplete and all degenerative tissue may not be involved in the healing response.

Shoulder impingement syndrome in athletes treated by an anterior acromioplasty.

Shoulder pain caused by a impingement syndrome commonly affects an athletes performance. Thirty-five shoulders in 33 athletes had an impingement syndrome treated by an anterior acromioplasty after failure of conservative treatment. Thirty-one of 35 shoulders (89%) were subjectively judged improved by the patients from their preoperative status. The moderate and severe pain was reduced from 97% of the shoulders preoperation to 20% postoperation. The pain at rest and with activities of daily living was reduced from 71% of the shoulders preoperation to 9% postoperation. However, only 15 of 35 operated shoulders (43%) allowed return to the same preinjury level of competitive athletics, and only four of 18 athletes involved in pitching and throwing returned to their former preinjury status. This operation is satisfactory for pain relief but does not allow an athlete to return to his former competitive status. A prolonged rehabilitation program may improve the results.

The impact of pre-operative loco-regional therapy on outcome after liver transplantation for hepatocellular carcinoma

No prior studies have shown that pre‐operative loco‐regional therapy for hepatocellular carcinoma (HCC) improves survival following orthotopic liver transplantation (OLT). We performed subgroup analyses according to pathologic HCC stage among 168 patients who underwent OLT to test the hypothesis that pre‐operative loco‐regional therapy confers a survival advantage in a subgroup at intermediate risk for HCC recurrence. Patients with pathologic T3 HCC meeting the proposed UCSF expanded criteria (single lesion not exceeding 6.5 cm or two to three lesions none > 4.5 cm with total tumor diameter within 8 cm) had a similar 5‐year recurrence‐free survival as patients with pathologic T2 HCC (88.5% vs. 93.8%; p = 0.56). In the subgroup with pathologic T2 or T3 HCC, the 5‐year recurrence‐free survival was 93.8% for the 85 patients who received pre‐operative loco‐regional therapy, versus 80.6% for the other 41 patients without treatment (p = 0.049). The treatment benefit, according to 5‐year recurrence‐free survival, appeared greater for pathologic T3 (85.9% vs. 51.4%; p = 0.05) than T2 HCC (96.4% versus 87.1%; p = 0.12). In conclusion, although the lack of a randomized controlled design precludes drawing firm conclusions, our results suggest that pre‐operative loco‐regional therapy may confer a survival benefit after OLT in the subgroup with pathologic T2 and T3 HCC.

Selective arterial embolization for the control of lower gastrointestinal bleeding

BACKGROUND Transcatheter embolization is accepted as a safe method for treating acute bleeding from the upper gastrointestinal (GI) tract. Hesitancy persists using this technique below the ligament of Treitz, based on the belief that the risk of intestinal infarction is unacceptably high, despite mounting clinical evidence to the contrary. METHODS A series of 17 consecutive patients with angiographically demonstrated small intestinal or colonic bleeding was retrospectively reviewed. The success and complication rate of subselective embolization was assessed. RESULTS Bleeding was stopped in 13 of 14 patients (93%) in whom embolization was possible, and in 13 of 17 patients (76%) where there was an intention to treat. Sufficiently selective catheterization to permit embolization could not be achieved in 3 patients. No clinically apparent bowel infarctions were caused. CONCLUSION Subselective embolization is a safe treatment option for lower GI bleeding, suitable for many patients and effective in most. Careful technique and a readiness to abandon embolization when a suitable catheter position cannot be achieved are important.

Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria.

We report on the long‐term intention‐to‐treat (ITT) outcome of 118 patients with hepatocellular carcinoma (HCC) undergoing downstaging to within Milan/United Network for Organ Sharing T2 criteria before liver transplantation (LT) since 2002 and compare the results with 488 patients listed for LT with HCC meeting T2 criteria at listing in the same period. The downstaging subgroups include 1 lesion >5 and ≤8 cm (n = 43), 2 or 3 lesions at least one >3 and ≤5 cm with total tumor diameter ≤8 cm (n = 61), or 4‐5 lesions each ≤3 cm with total tumor diameter ≤8 cm (n = 14). In the downstaging group, 64 patients (54.2%) had received LT and 5 (7.5%) developed HCC recurrence. Two of the five patients with HCC recurrence had 4‐5 tumors at presentation. The 1‐ and 2‐year cumulative probabilities for dropout (competing risk) were 24.1% and 34.2% in the downstaging group versus 20.3% and 25.6% in the T2 group (P = 0.04). Kaplan‐Meiers 5‐year post‐transplant survival and recurrence‐free probabilities were 77.8% and 90.8%, respectively, in the downstaging group versus 81% and 88%, respectively, in the T2 group (P = 0.69 and P = 0.66, respectively). The 5‐year ITT survival was 56.1% in the downstaging group versus 63.3% in the T2 group (P = 0.29). Factors predicting dropout in the downstaging group included pretreatment alpha‐fetoprotein ≥1,000 ng/mL (multivariate hazard ratio [HR]: 2.42; P = 0.02) and Childs B versus Childs A cirrhosis (multivariate HR: 2.19; P = 0.04). Conclusion: Successful downstaging of HCC to within T2 criteria was associated with a low rate of HCC recurrence and excellent post‐transplant survival, comparable to those meeting T2 criteria without downstaging. Owing to the small number of patients with 4‐5 tumors, further investigations are needed to confirm the efficacy of downstaging in this subgroup. (Hepatology 2015;61:1968–1977)