HCC and Tumor Biomarkers: Does One Size Fits All?

Hepatocellular carcinoma (HCC) is a highly malignant disease and early diagnosis rates remain to be unsatisfactory. Owing to this limitation, advances in treatment options including liver transplantation (LT) are limited to improve survival. Recent HCC guidelines no longer recommend alpha-fetoprotein (AFP) as a surveillance and diagnostic tool for HCC. Hence, utilization of novel biomarkers has become imperative to improve disease management strategies. Noninvasive, serum-based biomarkers are potential options to aid early diagnosis as well as prompting treatment. However, further studies are required to find out the accuracy and potential of these approaches and introduce into clinical practice.

Author Correction: Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria.

The original version of this article unfortunately contained a mistake in the author group section.

Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria.

Survival was examined from a Turkish liver transplant center of patients with HCC, to identify prognostic factors. Data from 215 patients who underwent predominantly live donor liver transplant for HCC at our institute over 12 years were included in the study and prospectively recorded. They were 152 patients within and 63 patients beyond Milan criteria. Patients beyond Milan criteria were divided into two groups according to presence or absence of tumor recurrence. Recurrence-associated factors were analyzed. These factors were then applied to the total cohort for survival analysis. We identified four factors, using multivariate analysis, that were significantly associated with tumor recurrence. These were maximum tumor diameter, degree of tumor differentiation, and serum AFP and GGT levels. A model that included all four of these factors was constructed, the 'Malatya criteria.' Using these Malatya criteria, we estimated DFS and cumulative survival, for patients within and beyond these criteria, and found statistically significant differences with improved survival in patients within Malatya criteria of 1, 5, and 10-year overall survival rates of 90.1%, 79.7%, and 72.8% respectively, which compared favorably with other extra-Milan extended criteria. Survival of our patients within the newly defined Malatya criteria compared favorably with other extra-Milan extended criteria and highlight the usefulness of serum AFP and GGT levels in decision-making.

Determination of risk factors affecting mortality in patients with gastrointestinal perforation after pediatric liver transplantation.

Gastrointestinal perforation (GIP) is one of the most serious complications occurring after liver transplantation (LT), especially in pediatric patients. This study aimed to determine the risk factors affecting mortality in pediatric patients with GIP after LT. GIP developed in 37 (10%) of 370 pediatric patients who underwent LT at our institute. Patients were divided into two groups: alive (n = 22) or dead (n = 15), and both groups were compared in terms of demographic and clinical parameters using univariate analysis. There was no statistically significant difference between groups in either demographic or clinical parameters, except for perforation site (P = 0.001) and median follow-up (P = 0.001). Stomas arose in 17 (45.9%) patients: 76% of patients with stomas and 45% of those without survived (P = 0.052). Kaplan-Meier analysis indicated that patients with stomas had a significantly higher overall survival (P = 0.029) and that patients with duodenal and colonic perforation had a significantly lower overall survival. Multivariate analysis showed that re-perforation was an independent risk factor for mortality (P = 0.035; OR: 17.674; 95% CI for OR: 1.233-253.32). Although there are many options for management of GIP, including primary repair, resection plus anastomosis, and resection plus end or loop ostomy, gastrointestinal diversion is still the best option.

The evaluation of the effect of vaginal delivery and aging on anal sphincter anatomy and function.

OBJECTIVE: This study was conducted to evaluate the effect of vaginal delivery and aging on anal sphincter anatomy and function. METHOD: Asymptomatic thirty women were included in this prospective study. Group 1 included 10 women (age range: 18-50) who had never been pregnant. Group 2 included 10 women (age range: 18-50) who had vaginal delivery. Group 3 included 10 women over 50 who had vaginal delivery. RESULTS: There was no statistically significant difference between the three groups in terms of resting and squeeze pressures. It was found that sphincter thickness showed statistically significant difference between the group 1 and group 3, and also group 2 and group 3. There was not statistically significant difference between the group 1 and group 2 in terms of sphincter thickness. There was a positive correlation between the age and sphincter thickness in all groups. In terms of sphincter thickness and pressure findings there was a positive correlation between the squeeze pressure and external anal sphincter thickness only in group 3. CONCLUSION: The vaginal delivery did not have a negative influence on the structure and function of the anal sphincter in asymptomatic women. However, it was found that anal sphincter thickness changed strongly in a positive manner with aging.

Living-Donor Liver Transplant for Fibrolamellar Hepatocellular Carcinoma With Hilar Lymph Node Metastasis: A Case Report.

Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver neoplasm. Benefits from liver transplant for patients with fibrolamellar hepatocellular carcinoma have not yet been reported. Here, we report a 19-year-old female patient who presented with abdominal pain. A computed tomography scan revealed bilobar and multiple solid lesions with the largest measuring 15 cm in diameter on the right lobe of her liver. Her blood alpha-fetoprotein level and viral hepatitis markers were normal. A fine-needle biopsy of the largest lesion detected fibrolamellar heptocellular carcinoma. Because no distant metastasis was evident and the carcinoma was unresectable, a right lobe living-donor liver transplant with hilar lymph node dissection was performed. A pathology report revealed poorly differentiated fibrolamellar hepatocellular carcinoma, and further testing indicated microvascular invasion and hilar lymph node metastasis. The largest tumor measured 12 cm. She was discharged on postoperative day 14. During postoperative month 22, multiple vertebral metastases were detected, and she died with diffuse metastasis during postoperative month 26. Our patient, with poor prognostic criteria such as hilar lymph node metastasis, microvascular invasion, and poor differentiation, had 22 months of tumor-free survival and 26 months of overall survival after having undergone living-donor liver transplant.

Outcomes of surgery for gallbladder cancer: A single-center experience.

OBJECTIVE: Gallbladder cancer (GBC) is a rare clinical entity that has a poor prognosis. Radical resection with meticulous lymph node dissection is the only treatment option. The aim of the present study is to evaluate the efficacy of radical resection for GBC in the early postoperative period with the viewpoint of clinicopathological correlation. METHODS: Patients (n=24) who underwent radical resection with lymph node dissection for GBC between 2015 and 2017 were included. Demographic data, histopathologic tumor type, preoperative tumor markers, pathologic tumor size/stage (depth of invasion), lymph node metastasis and metastasis rates, and postoperative early mortality were evaluated. The patients were grouped in two groups according to lymph node metastases: Group 1 (without lymph node metastasis) and Group 2 (with lymph node metastasis). RESULTS: The median age of the patients in Group 1 and Group 2 was 65 (range, 42-89) years and 68 (range, 48-87) years, respectively (p>0.05). The female/male ratio in Group 1 and Group 2 was 4/4 and 13/3, respectively (p>0.05). There was a tendency for increased metastasis in Group 2 compared with Group 1 (31% vs. 0%) (p>0.05). Also, 88% of the tumors in Group 2 were in the advanced stage, whereas the rate was 37% in Group 1 (p<0.05). There was early postoperative mortality in seven patients who underwent resection. Four of the seven patients (43%) were from Group 2 and three (37%) from Group 1 (p>0.05). CONCLUSION: Lymph node metastasis in GBC indicates advanced tumor stage. This causes a more complex surgical resection and therefore results in higher early postoperative mortality.

A surgical technique for secondary repair of obstetric anal sphincter injuries; sphinctero-vagino-perineoplasty.

OBJECTIVE: This study was conducted to present the preliminary results of seven patients treated with sphinctero-vagino-perineoplasty for secondary repair of obstetric anal sphincter injuries. MATERIALS AND METHODS: This retrospective study was conducted on the records of seven patients who underwent secondary repair of obstetric anal sphincter injuries at the colorectal surgery unit of a tertiary care center between February 2015 and December 2017. RESULTS: All patients with solid stool incontinence were fully recovered at postoperative month 3. The Wexner incontinence score was significantly improved (decreased from 14.12 [range: 8-20] to 2.28 [range: 1-4]). The complication rate was 85.7% (wound infection, abscess, hematoma, detachment). CONCLUSION: Combined repair of anal sphinchters, perineal body, superficial transverse perineal muscles, and bulbospongious muscles, which contribute to anal continence, may improve surgical outcomes in patients with obstetric anal sphincter injuries.

Reconstruction of Anomalous Portal Venous Branching in Right Lobe Living Donor Liver Transplantation: Malatya Approach.

Reconstruction of anomalous portal vein branching (APVB) during right lobe living donor liver transplantation (LDLT) can be challenging. The goal of this article is to describe our surgical technique, named the Malatya Approach, in case of APVB during right lobe LDLT. The technique unifies the APVB and obtains a funnel-shaped common extension with a circumferential fence by a saphenous vein conduit. In total, 126 (10.6%) of 1192 right lobe grafts had APVB that were divided into 2 groups according to the adopted surgical techniques: the Malatya Approach group (n = 91) and the previously defined other techniques group (n = 35). Both groups were compared regarding portal vein thrombosis (PVT), postoperative 90-day mortality and survival. PVT developed in 3 patients (3.3%) in the Malatya Approach group and developed in 10 (28.6%) patients for the other group (P < 0.001). There were 8 (8.8%) 90-day mortalities in the Malatya Approach group (1 PVT related) and 15 patients (9 PVT related) died in the other techniques group (P < 0.001). Mean follow-up time for both groups was similar (999.1 days for the Malatya Approach group versus 1024.7 days for the other group; P = 0.47), but longterm survival in the Malatya Approach group was better than in the other group (84.6% versus 40%; P < 0.001). Multivariate analysis revealed that the Malatya Approach group showed less PVT development and longer survival (P < 0.001). This technique is promising to avoid PVT and mortalities in cases of APVB during right lobe LDLT. Liver Transplantation 23 751-761 2017 AASLD.

Low Pressure is Necessary to View and to Protect Corona Mortis During Totally Extraperitoneal Hernia Repair.

BACKGROUND: The identification of retropubic vasculature is not easy under the pressure of insufflated gas during totally extraperitoneal (TEP) inguinal hernioplasty. We aimed to present the usefulness of a maneuver that allows the clear identification of retropubic vasculature. METHODS: Vascular anatomy on the retropubic surface in 364 patients who underwent the TEP procedure from January 2005 to September 2015 was evaluated. In patients after July 2014, the pressure in the workspace was decreased from 14 to 8 mmHg before fixation of the mesh to clearly identify the veins. The results before and after July 2014 were compared. RESULTS: Demographic features were not significantly different between two periods. The number of hemipelvises in the first and second periods was 398 and 77, respectively. The rate of identification of venous corona mortis was 31% in the second period, whereas it was 1.0% in the first period (P = .000). The identification of thick (5.5% versus 10.3%; P = .123) and thin (22.8% versus 36.3%; P = .014) arterial structures and their sum were increased in the second period (28.4% versus 46.7%; P = .002). The rate of retropubic bleeding was zero in the second period, while it was 1.5% in the first period. CONCLUSIONS: During TEP hernioplasty, the pressure of insufflated gas more than 10 mmHg in the preperitoneal space hinders the correct identification of vessels on the retropubic surface. The proposed maneuver, to decrease the pressure in the workspace to 8 mmHg, can provide clear identification of all vessels, which decreases the potential risk of vascular injury.

Incisional hernia in recipients of adult to adult living donor liver transplantation.

BACKGROUND: After receiving a living donor liver transplant (LDLT), an incisional hernia is a potentially serious complication that can affect the patient's quality of life. In the present study we evaluated surgical hernia repair after LDLT. MATERIALS AND METHODS: Medical records of patients who underwent surgery to repair an incisional hernia after LDLT in Turgut Ozal Medical Center between October 2006 and January 2010 were evaluated in this retrospective study. A reverse-T incision was made for liver transplantation. The hernias were repaired with onlay polypropylene mesh. Age, gender, post-transplant relaparatomy, the type, the result of surgery for the incisional hernia, and risk factors for developing incisional hernia were evaluated. RESULTS: An incisional hernia developed in 44 of 173 (25.4%) patients after LDLT. Incisional hernia repair was performed in 14 of 173 patients (8.1%) who underwent LDLT from October 2006 to January 2010. Relaparatomy was associated with incisional hernia (p = 0.0002). The mean age at the time of the incisional hernia repair was 51 years, and 79% of the patients were men. The median follow-up period was 19.2 (13-36) months after the hernia repair. Three patients with intestinal incarceration underwent emergency surgery to repair the hernia. Partial small bowel resection was required in one patient. Postoperative complications included seroma formation in one patient and wound infection in another. There was no recurrence of hernia during the follow-up period. CONCLUSIONS: The incidence of incisional hernia after LDLT was 25.4% in this study. Relaparatomy increases the probability of developing incisional hernia in recipients of LDLT. According to the results of the study, repair of an incisional hernia with onlay mesh is a suitable option.

Preventive effects of resveratrol against azoxymethane induced damage in rat liver.

BACKGROUND: In recent years, due to modern lifestyles and exposure to chemical carcinogens, cancer cases are steadily increasing. From this standpoint, azoxymethane (AOM), a chemical carcinogen which causes de novo liver damage, and resveratrol, which is an antioxidant found in foods and protects against oxidative stress damage, are of interest. We here aimed to evaluate whether resveratrol could protect the liver tissues from the effects of AOM. MATERIALS AND METHODS: The study was conducted in 4 groups, each consisting of seven rats, the first receiving only AOM (2 times per week, 5 mg/kg), group 2 AOM and resveratrol (2 times a week, 20 mg/kg), group 3 assessed only as a control and group 4 administered only resveratrol. At the end of the seventh week, the rats were sacrificed. Rat liver MDA, NO, GSH levels were analyzed biochemically, as well as the tissues being evaluated histopathologically. RESULTS: MDA and NO increased in AOM group as signs of increased oxidative stress. The group concomitantly administered resveratrol was been found to be significantly decreased in MDA and NO levels and increased in GSH activity. However, there were no significant findings on histopathological evaluation. CONCLUSIONS: In the light of these results, resveratrol appears to exert protective effect on oxidative stress in the liver tissue due to deleterious effects of chemical carcinogens.

Polycystic liver transplant: a case report.

A liver from a donor with brain death due to a ruptured cerebral aneurysm was transplanted. The liver had multiple bilobar simple cysts; the largest was less than 3 cm in diameter. The noncystic liver volume was greater than 50%, and the liver had neither fibrosis nor venous congestion. The donor surgery was performed in accordance with the standard protocol without rupture of the cysts. The recipient was a 40-year-old man with cirrhosis associated with hepatitis B. The recipient operation was done by using the piggyback method with no complications. Excessive drainage of chylous ascites (10 000 mL/d) started in the first days after surgery and continued, gradually decreasing until the end of the second month. The patient was discharged with no complications at the end of the third month. No growth in the cysts was observed on follow-up computed tomography scans. Excluding this particular case, a total of 7 other patients have received a polycystic liver transplant. In all 7 cases, the fact that the donor had polycystic liver disease was not known but was encountered by coincidence during procurement. The case reported here is the first case where the polycystic liver disease was diagnosed before procurement and the transplant was still carried out. It appears that, if the donor liver has enough healthy noncystic volume, polycystic livers can be transplanted.

Single-center analysis of the first 304 living-donor liver transplantations in 3 years.

BACKGROUND/AIMS: Living donor liver transplantations (LDLT) is a definitive treatment for patients with end-stage liver disease (ESLD), especially in the countries with donation problem. Between April 2007 and April 2010, we performed LDLT in 289 patients. Fifteen of the cases required re-transplantations. This study evaluates these 304 consecutive LDLTs donor and recipient outcomes. METHODOLOGY: Complication rates and survival data of the recipients and donors of 304 LDLT cases were analyzed. RESULTS: All donors are alive and well. Overall complication rate was 27%. Early postoperative recipient complication rate was 51%. Most frequent complication was infection. In the long-term there were 57 biliary stricture and 5 chronic bile fistula cases. Chronic and acute rejection attacks developed in 7 and 103 patients, respectively. Hepatic artery thrombosis rate was 8%. One, two and three year survival rates were 82%, 79% and 75%, respectively. Recipient mortality was 25%, mostly due to vascular complications, septic complications, liver dysfunction and chronic rejection. CONCLUSIONS: More than 150 liver tranplantations per year in a single center is a challenge in Turkey, where there is a shortage of deceased donor grafts. LDLT is a safe procedure for donors and effective for ESLD. Improvement in surgical technique would provide better outcomes.

Effect of autotransfusion system on tumor recurrence and survival in hepatocellular carcinoma patients.

AIM: To investigate the therapeutic efficacy and safety of continuous autotransfusion system (CATS) during liver transplantation of hepatocellular carcinoma patients. METHODS: Eighty-three hepatocellular carcinoma (HCC) patients who underwent liver transplantation with intraoperative CATS (n = 24, CATS group) and without (n = 59, non-CATS group) between April 2006 and November 2011 at the Liver Transplant Institute of Inonu University were analyzed retrospectively. Postoperative HCC recurrence was monitored by measuring alpha-fetoprotein (AFP) levels at 3-mo intervals and performing imaging analysis by thoracoabdominal multidetector computed tomography at 6-month intervals. Inter-group differences in recurrence and correlations between demographic, clinical, and pathological data were assessed by ANOVA and χ(2) tests. Overall and disease-free survivals were calculated by the univariate Kaplan-Meier method. RESULTS: Of the 83 liver transplanted HCC patients, 89.2% were male and the overall mean age was 51.3 ± 8.9 years (range: 18-69 years). The CATS and non-CATS groups showed no statistically significant differences in age, sex ratio, body mass index, underlying disease, donor type, graft-to-recipient weight ratio, Child-Pugh and Model for End-Stage Liver Disease scores, number of tumors, tumor size, AFP level, Milan and University of California San Francisco selection criteria, tumor differentiation, macrovascular invasion, median hospital stay, recurrence rate, recurrence site, or mortality rate. The mean follow-up time of the non-CATS group was 17.9 ± 12.8 mo, during which systemic metastasis and/or locoregional recurrence developed in 25.4% of the patients. The mean follow-up time for the CATS group was 25.8 ± 15.1 mo, during which systemic metastasis and/or locoregional recurrence was detected in 29.2% of the patients. There was no significant difference between the CATS and non-CATS groups in recurrence rate or site. Additionally, no significant differences existed between the groups in overall or disease-free survival. CONCLUSION: CATS is a safe procedure and may decrease the risk of tumor recurrence in HCC patients.

Conversion to Stoppa procedure in laparoscopic totally extraperitoneal inguinal hernia repair.

BACKGROUND AND OBJECTIVES: Conversion to open surgery is an important problem, especially during the learning curve of laparoscopic totally extraperitoneal (TEP) inguinal hernia repair. METHODS: Here, we discuss conversion to the Stoppa procedure during laparoscopic TEP inguinal hernia repair. Outcomes of patients who underwent conversion to an open approach during laparoscopic TEP inguinal hernia repair between September 2004 and May 2010 were evaluated. RESULTS: In total, 259 consecutive patients with 281 inguinal hernias underwent laparoscopic TEP inguinal hernia repair. Thirty-one hernia repairs (11%) were converted to open conventional surgical procedures. Twenty-eight of 31 laparoscopic TEP hernia repairs were converted to modified Stoppa procedures, because of technical difficulties. Three of these patients underwent Lichtenstein hernia repairs, because they had undergone previous surgeries. CONCLUSION: Stoppa is an easy and successful procedure used to solve problems during TEP hernia repair. The Lichtenstein procedure may be a suitable option in patients who have undergone previous operations, such as a radical prostatectomy.

Liver transplantation from an upper midline incision.

OBJECTIVES: To evaluate the minimally invasive incision to the recipient of a liver transplant. MATERIALS AND METHODS: A 55-year-old man with cirrhosis due to hepatitis B accompanied by hepatocellular carcinoma underwent a right lobe, living-donor liver transplant using an 18-cm long, upper midline incision. The recipient hepatectomy was performed from the left to the right side (from medial to lateral). Deep retractors and long surgical instruments were preferred. RESULTS: The surgical procedure was completed without problem. Both the recipient hepatectomy and implantation of the right liver took 8 hours. Postoperative recovery of the patient was rapid, and he was discharged 8 days after surgery, uneventfully. CONCLUSIONS: An upper midline incision can be preferred for liver transplant for selected cases. Minimally invasive surgery is an option for liver transplant recipients as well.

Living donor liver transplantation for acute liver failure in pediatric patients caused by the ingestion of fireworks containing yellow phosphorus.

Yellow phosphorus is a protoplasmic toxicant that targets the liver. The ingestion of fireworks containing yellow phosphorus, either by children who accidentally consume them or by adults who are attempting suicide, often results in death due to acute liver failure (ALF). We present the outcomes of 10 children who ingested fireworks containing yellow phosphorus. There were 6 boys and 4 girls, and their ages ranged from 21 to 60 months. One patient remained stable without liver complications and was discharged. Three patients died of hepatorenal failure and cardiovascular collapse, and living donor liver transplantation (LDLT) was performed for 6 patients. The patients had grade II or III encephalopathy, a mean alanine aminotransferase level of 1148.2 IU/L, a mean aspartate aminotransferase level of 1437.5 IU/L, a mean total bilirubin level of 6.9 mg/dL, a mean international normalized ratio of 6.6, a mean Pediatric End-Stage Liver Disease score of 33.7, and a mean Child-Pugh score of 11.3. Postoperatively, 2 patients had persistent encephalopathy and died on the second or third postoperative day, and 1 patient died of cardiac arrest on the first postoperative day despite a well-functioning graft. The other 3 patients were still alive at a mean of 204 days. In conclusion, the ingestion of fireworks containing yellow phosphorus causes ALF with a high mortality rate. When signs of irreversible ALF are detected, emergency LDLT should be considered as a lifesaving procedure; however, if yellow phosphorus toxicity affects both the brain and the heart in addition to the liver, the mortality rate remains very high despite liver transplantation.

The effect of caffeic acid phenethyl ester (CAPE) against cholestatic liver injury in rats.

OBJECTIVES: Caffeic acid phenethyl ester (CAPE) has been subjected to considerable investigations that have revealed its antioxidant and anti-inflammatory activities in different conditions. But there is not a previous investigation about its effect on cholestatic liver injury. The aim of this study was to investigate the effect of CAPE in rat liver against cholestatic liver injury induced by bile duct ligation. METHODS: Swiss-albino rats were recruited in the study as follows; Group 1 rats subjected to simple laparotomy known as the sham group; Group 2 rats subjected to bile duct ligation (BDL); Group 3 bile duct ligated rats treated with CAPE. The third group received CAPE (10 micromol/kg) intraperitoneally daily throughout 14 d. RESULTS: Data showed a decrease in gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase levels (ALT) of the CAPE treated rats, compared with BDL group (P < 0.001, P < 0.01, and P < 0.02, respectively). In the CAPE treated rats, tissue levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were significantly lower than that of the BDL group (P < 0.001). The levels of glutathione (GSH) in CAPE treated rats were significantly higher than that of BDL group (P < 0.001). In CAPE treated group, the levels of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) were significantly lower than that of BDL group (P < 0.03, P < 0.02, respectively). Administration of CAPE in the rats with biliary obstruction resulted in inhibition of necro-inflammation. CONCLUSION: These results suggest that treatment of CAPE maintains antioxidant defenses, reduces oxidative liver injury, cytokine damage, and necro-inflammation in bile duct ligated rats. Thus, CAPE seems to be a promising agent for the attenuation of cholestatic liver injury.