Comparison of postoperative pain after needle grasperassisted single-incision laparoscopic appendectomy versus single-incision laparoscopic appendectomy: a prospective randomized controlled trial (PANASILA trial)

Purpose@#This study was performed to compare the efficacies of newly developed needle grasper-assisted (Endo Relief) single-incision laparoscopic appendectomy (NASILA) and single-incision laparoscopic appendectomy (SILA). @*Methods@#This study enrolled 110 patients with acute appendicitis without periappendiceal abscess, diagnosed using computed tomography, who were randomized to the SILA (n = 54) and NASILA groups (n = 56) between December 2017 and August 2018 (6 patients withdrawn). The NASILA technique entailed a small umbilical incision for the glove port (equivalent to that for a 12-mm trocar), and a 2.5-mm suprapubic incision for the needle grasper. @*Results@#The SILA and NASILA groups included 49 (male, 61.2%) and 55 (male, 54.5%) patients, respectively. Age, body mass index, abdominal surgical history, symptom duration, and use of patient-controlled analgesia did not differ significantly between the 2 groups. The main wound size was significantly smaller in the NASILA group than in the SILA group (1.8 ± 0.4 cm vs. 2.2 ± 0.4 cm, P < 0.001). The operative time and estimated blood loss did not differ significantly between both groups. The immediate postoperative pain score, i.e., the primary endpoint, was significantly lower in the NASILA group than in the SILA group (2.33 ± 0.98 vs. 2.82 ± 1.29, P = 0.031). The complaints for scar status 1 month postoperatively did not differ significantly between the groups. @*Conclusion@#NASILA could attenuate postoperative pain by minimizing the size of the surgical wound; further, NASILA may not be inferior to SILA in terms of cosmetic results.

Abdominal Digital Radiography with a Novel Post-Processing Technique: Phantom and Patient Studies

Purpose@#The aim of this study was to evaluate the diagnostic image quality of low dose abdominal digital radiography processed with a new post-processing technique. @*Materials and Methods@#Abdominal radiographs from phantom pilot studies were post-processed by the novel and conventional post-processing methods of our institution; the proper dose for the subsequent patient study of 49 subjects was determined by comparing image quality of the two preceding studies. Two radiographs of each patient were taken using the conventional and derived dose protocols with the proposed post-processing method. The image details and quality were evaluated by two radiologists. @*Results@#The radiation dose for the patient study was derived to be half of the conventional method. Overall half-dose image quality with the proposed method was significantly higher than that of the conventional method (p < 0.05) with moderate inter-rater agreement (κ = 0.60, 0.47). @*Conclusion@#By applying the new post-processing technique, half-dose abdominal digital radiography can demonstrate feasible image quality compared to the full-dose images.

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma

PURPOSE: Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma (HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). MATERIALS AND METHODS: First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosed resectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determine their influence on survival. RESULTS: Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031–25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031–25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027–0.497; p=0.004). CONCLUSION: AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.

Peri-Transplant Change in AFP Level: a Useful Predictor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.

Risk Factors for the Adverse Events after Conversion from Twice-Daily to Once-Daily Tacrolimus in Stable Liver Transplantation Patients

Despite the therapeutic equivalence between twice-daily and once-daily tacrolimus, patient safety after conversion is still a concern. We reviewed 218 liver transplantation (LT) patients who converted twice-daily to once-daily tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse events after conversion, with a liver function test (LFT) abnormality being the most common adverse event (n = 17). Despite the decrease in serum tacrolimus of > 30% after conversion, none of the patients who were converted to a dosage ratio (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT abnormality. Most patients with an LFT abnormality improved after increasing the once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or added another immunosuppressant (n = 15). One patient had acute cellular rejection, which improved after steroid pulse treatment, and another patient had graft failure. In patients with a dosage ratio ≤ 1, the conversion time within 5 years after LT was the only significant risk factor for an LFT abnormality after conversion (odds ratio: 11.850, 95% confidence interval: 1.321–106.325, P = 0.027). In conclusion, the dosage ratio and time after LT should be carefully considered during conversion from twice-daily to once-daily tacrolimus.

Heterogeneous living donor hepatic fat distribution on MRI chemical shift imaging

PURPOSE: We evaluated the heterogeneity of steatosis in living donor livers to determine its regional differences. METHODS: Between June 2011 and February 2012, 81 liver donors were selected. Fat fraction was estimated using magnetic resonance triple-echo chemical shifting gradient imaging in 13 different regions: segment 1 (S1), S2, S3, and each peripheral and deep region of S4, S5, S6, S7, and S8. RESULTS: There were differences (range, 3.2%-5.3%) in fat fractions between each peripheral and deep region of S4, S6, S7, and S8 (P < 0.001, P = 0.004, P < 0.001, and P = 0.006). Fat deposit amount in S1, S2, S3 and deep regions of S4-S8 were significantly different from one another (F [4.003, 58.032] = 8.684, P < 0.001), while there were no differences among the peripheral regions of S4-S8 (F [2.9, 5.3] = 1.3, P = 0.272) by repeated measure analysis of variance method. And regional differences of the amount of fat deposit in the whole liver increased as a peripheral fat fraction of S5 increased (R2 = 0.428, P < 0.001). CONCLUSION: Multifocal fat measurements for the whole liver are needed because a small regional evaluation might not represent the remaining liver completely, especially in patients with severe hepatic steatosis.

Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, > or = moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.

Fatigue and related factors after liver transplantation

BACKGROUNDS/AIMS: Fatigue is common in chronic hepatitis and end-stage liver disease. However, little is known about fatigue after liver transplantation (LT). We therefore evaluated the prevalence, severity, and related factors of fatigue after LT. METHODS: We retrospectively reviewed adult recipients who responded to our survey at outpatient clinics between April and May 2013. Fatigue and its severity were assessed using a questionnaire with the Fatigue Severity Scale (FSS). We defined fatigue as FSS of 4.0 or more and severe fatigue as FSS of 5.1 or more. The related factors including hepatocellular carcinoma and complications were analyzed. RESULTS: A total of 93 patients were included in this study. The mean age was 54.9 (19-76) years and two-thirds were men (67.7%). Living donor LT was 77.4%. Hepatitis B related liver disease was the main underlying disease (77.4%), with hepatocellular carcinoma accompanied in 33.3%. The mean follow-up period was 66.8+/-43.2 (2-171) months. The mean FFS was 2.83+/-1.48 (1.0-6.7) overall and 5.10+/-0.82 (4.0-6.7) in the fatigue group. Of the 93 adult patients, fatigue was presented in 20 patients (21.5%). Among these, 9 patients (45.0%) showed severe fatigue. Even though post-LT complications tended to be greater in the fatigue group (50.0% vs. 30.1% in the non-fatigue group, p=0.098), there were no significant related factors of fatigue after LT, including hepatocellular carcinoma and major complication. CONCLUSIONS: Fatigue is present in a considerable portion of recipients after LT, and almost half of them have severe fatigue. Further efforts are needed to decrease fatigue in LT recipients.

Preoperative Selective Desensitization of Live Donor Liver Transplant Recipients Considering the Degree of T Lymphocyte Cross-Match Titer, Model for End-Stage Liver Disease Score, and Graft Liver Volume

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

Long Term Outcomes of Pediatric Liver Transplantation According to Age

Liver transplantation (LT) has been the key therapy for end stage liver diseases. However, LT in infancy is still understudied. From 1992 to 2010, 152 children had undergone LT in Seoul National University Hospital. Operations were performed on 43 patients aged less than 12 months (Group A) and 109 patients aged over 12 months (Group B). The mean age of the recipients was 7 months in Group A and 74 months in Group B. The patients' survival rates and post-LT complications were analyzed. The mean Pediatric End-stage Liver Disease score was higher in Group A (21.8) than in Group B (13.4) (P = 0.049). Fulminant hepatitis was less common in Group A (4.8%) than in Group B (13.8%) (P = 0.021). The post-transplant lymphoproliferative disorder and portal vein complication were more common in Group A (14.0%, 18.6%) than in Group B (1.8%, 3.7%) (P = 0.005). However, the 1, 5, and 10 yr patient survival rates were 93%, 93%, and 93%, in Group A and 92%, 90%, and 88% in Group B (P = 0.212). The survival outcome of pediatric LT is excellent and similar regardless of age. LTs in infancy are not riskier than those of children.

Living Donor Liver Transplantation for an Infant with Osteogenesis Imperfecta and Intrahepatic Cholestasis: Report of a Case

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by bone fragility and connective tissue manifestations. We report a successful liver transplantation (LT) in an 8-month-old boy with OI and cholestatic biliary cirrhosis. After 4 cycles of intravenous pamidronate, LT was performed under intravenous anesthesia using a left lateral section from his mother without mechanical retractors. The operation time was 420 min and estimated blood loss was 520 mL requiring one unit of RBC transfusion. He was discharged without surgical complications. Therefore, LT should be considered for patients with end stage liver disease and OI under organic multidisciplinary cooperation.

Histopathologic factors affecting tumor recurrence after hepatic resection in colorectal liver metastases

PURPOSE: Hepatic resection is a standard method of treatment for colorectal liver metastases (CRLM). However, the pathologic factors of metastatic lesions that affect tumor recurrence are less well defined in CRLM. The aim of this study was to evaluate the risk factors for recurrence of CRLM, focusing on histopathologic factors of metastatic lesions of the liver. METHODS: From January 2003 to December 2008, 117 patients underwent curative hepatic resection for CRLM were reviewed. Tumor size and number, differentiation, tumor budding, angio-invasion, dedifferentiation and tumor infiltrating inflammation of metastatic lesions were investigated. RESULTS: The mean number of hepatic tumors was 2 (range, 1-8). The mean size of the largest tumor was 2.9 cm (range, 0.3-18.5 cm) in diameter. The moderate differentiation of the hepatic tumor was the most common in 86.3% of the patients. Tumor budding, angio-invasion, and dedifferentiation were observed in 81%, 34%, and 12.8% of patients. Inflammation infiltrating tumor was detected in 6.8% of patients. Recurrence after hepatic resection appeared in 69 out of 117 cases (58.9%). Recurrence-free survival at 1, 2 and 5 years were 62.4%, 43.6%, and 34.3%. The multivariate analysis showed the number of metastases > or =3 (P = 0.007), the tumor infiltrating inflammation (P = 0.047), and presence of dedifferentiation (P = 0.020) to be independent risk factors for tumor recurrence. CONCLUSION: Histopathological factors, i.e., dedifferentiation and tumor infiltrating inflammation of the metastatic lesion, could be one of the risk factors of aggressive behavior as well as the number of metastases even after curative resection for CRLM.

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

Interstitial lung disease caused by TS-1: a case of long-term drug retention as a fatal adverse reaction / 대한외과학회지

TS-1 is an oral anti-cancer agent for gastric cancer with a high response rate and low toxicity. We report a case of long-term drug retention of TS-1 causing interstitial lung disease (ILD) as a fatal adverse reaction. A 65-year-old woman underwent a total gastrectomy with pathologic confirmation of gastric adenocarcinoma. She received 6 cycles of TS-1 and low-dose cisplatin for post-operative adjuvant chemotherapy followed by single-agent maintenance therapy with TS-1. After 8 months, the patient complained of a productive cough with sputum and mild dyspnea. A pulmonary evaluation revealed diffuse ILD in the lung fields, bilaterally. In spite of discontinuing chemotherapy and the administration of corticosteroids, the pulmonary symptoms did not improve, and the patient died of pulmonary failure. TS-1-induced ILD can be caused by long-term drug retention that alters the lung parenchyma irreversibly, the outcome of which can be life-threatening. Pulmonary evaluation for early detection of disease is recommended.

Laparoscopic Approach to a Case of Appendicular Schwannoma

Appendicular schwannoma is a rare tumor originating from Schwann's cells in the Auerbach plexus. The preoperative diagnosis is difficult because the clinical features are nonspecific, and it is mostly found accidentally via a radiologic image as a tumor, mimicking malignancy. We report a case of an appendicular schwannoma coexisting with an adenocarcinoma in the lung. A laparoscopic appendectomy was done with a clear resection margin, and the immunohistochemical staining showed positive S-100 protein, which confirmed the schwannoma. The patient also underwent a left upper lobectomy of the lung. The patient has been free of recurrence for the 6 months since the operation. The laparoscopic approach could be available for treatment of an appendicular schwannoma, thus avoiding an unnecessary laparotomy.

Omental Actinomycosis Coexisting with Colon Cancer

Actinomycosis is a rare infection caused by Actinomyces species, normal commensal inhabitants of the human bronchial and gastrointestinal tract. Infection occurs after preceding mucosal break-down by variable causes. A preoperative diagnosis is difficult because of its nonspecific clinical features, mimicking malignancy, tuberculosis or other inflammatory diseases. We report a case of abdominal actinomycosis presenting as an omental mass, which coexists with ascending colon cancer. Actinomycosis was diagnosed by histopathologic demonstration of sulfur granules in a specimen resected by laparoscopic exploration. Following surgery, the patient was treated with IV penicillin (20 million IU/day) for 3 weeks, and follow-up colonoscopy showed adenocarcinoma in the ascending colon. The patient underwent right hemicolectomy, then treated with intravenous penicillin for 4 weeks postoperatively and oral penicillin for 6 months. The patient has been free of recurrence for 6 months.