Efficacy and safety of postoperative preemptive use of tolvaptan for patients with cirrhosis undergoing hepatectomy for hepatocellular carcinoma.

PURPOSE: Optimal choice of diuretics in perioperative management remains unclear in enhanced recovery after liver surgery. This study investigated the efficacy and safety of tolvaptan (oral vasopressin V2-receptor antagonist) in postoperative management of patients with liver injury and hepatocellular carcinoma. METHODS: The patients clinically diagnosed with liver cirrhosis were included in this study. Clinical outcomes of 51 prospective cohort managed with a modified postoperative protocol using tolvaptan (validation group) were compared with 83 patients treated with a conventional management protocol (control group). RESULTS: Postoperative urine output were significantly larger and excessive body weight increase were reduced with no impairment in renal function or serum sodium levels in the validation group. Although the total amount of discharge and trend of serum albumin level were not significantly different among the groups, global incidence of postoperative morbidity was less frequent (19.6% vs. 44.6%, P=0.005) and postoperative stay was significantly shorter (8 days vs.10 days, P=0.008) in the validation group compared with the control group. CONCLUSIONS: Tolvaptan could be safely used for the patients with injured liver in postoperative management after hepatectomy and potentially advantageous in the era of enhanced recovery after surgery with its strong diuretic effect and better fluid management.

A preoperative risk score based on multifrequency bioelectrical impedance analysis in patients undergoing liver resection.

PURPOSE: To investigate if body composition parameters measured by bioelectrical impedance analysis (BIA) and are reportedly correlated with clinical outcomes of patients undergoing digestive tract surgery could be useful for reliably evaluating the perioperative risk in patients undergoing hepatectomy. METHODS: Consecutive 200 patients who underwent BIA before hepatectomy were retrospectively reviewed. A risk prediction model for postoperative morbidity was created using the initial 100 patients, and its performance was validated using the remaining 100 patients. RESULTS: Based on the correlation with postoperative morbidity, a novel risk prediction model, the protein-edema score, was created using net protein weight and extracellular water/total body water ratio measured through BIA. The protein-edema score (score 0 vs. ≥ 1) showed a reproducible correlation with Clavien-Dindo 2 or greater postoperative morbidity in the validation set (17.7% vs. 46.4%, P = 0.002) as observed in the training set (18.8% vs. 49.0%, P = 0.002) after statistical adjustment. Similar tendency was also confirmed in Clavien-Dindo 3a or greater postoperative morbidity (5.9% vs. 18.2%, P = 0.037) and postoperative refractory ascites (5.5% vs. 17.4%, P = 0.037) in the validation set. CONCLUSIONS: The protein-edema score created based on BIA is significantly correlated with postoperative morbidity in patients undergoing liver resection.

Clinical impact of the new "twin U-stitch method" of pancreaticogastrostomy in pancreaticoduodenectomy.

PURPOSE: The optimal pancreaticogastrostomy (PG) method for reducing pancreatic fistula (PF) incidence remains unclear. This retrospective review aimed to evaluate the clinical impact of the "twin U-stitch method" and compared it with the conventional invagination method. METHODS: Data of 183 consecutive patients who underwent PG after pancreaticoduodenectomy (PD) between January 2015 and November 2020 were evaluated. PF incidence was compared between patients who experienced twin U-stitch PG (twin U-stitch group) and those who experienced conventional invagination PG (conventional PG group). RESULTS: The twin U-stitch and conventional PG methods were performed in 97 and 86 patients, respectively. The time required for twin U-stitch PG was shorter than conventional PG (9.3 min vs 20.0 min, P < 0.001). The twin U-stitch group showed a lower incidence of PF than the conventional PG group (8% vs. 19%, P = 0.038). Multivariate analysis confirmed that twin U-stitch PG was significantly correlated with a decreased risk of PF (odds ratio, 0.23; P = 0.006), independent of the texture of the pancreas. Subgroup analysis of patients with soft-textured pancreas showed that the median drain amylase levels in the twin U-stitch group on postoperative days (POD) 1 and 3 were significantly lower than those in the conventional PG group (POD 1: 1,335 vs. 5,991 U/L, P < 0.001; POD 3: 212 vs. 518, P = 0.001). CONCLUSION: The twin U-stitch method was simple and preferable to the conventional method for preventing PF in patients with PD.

Preoperative nutritional score predicts underlying liver status and surgical risk of hepatocellular carcinoma.

BACKGROUND: Given the scarce evidence regarding the impact of preoperative nutritional status on surgical outcomes of patients with hepatocellular carcinoma, predictive powers of nutritional/inflammatory scores for short-term surgical outcomes in patients with hepatocellular carcinoma were investigated. METHODS: Outcomes of 1272 patients with hepatocellular carcinoma were reviewed, and predictive powers of nine nutritional/inflammatory scores for short-term surgical outcomes were compared using the receiver-operating characteristic curve analysis. Clinical relevance of the best nutritional score was then studied in detail to clarify its utility as an alternative predictive measure for surgical risk of patients with hepatocellular carcinoma. RESULTS: Receiver-operating characteristic curve analysis showed the controlling nutritional status score has the best performance in prediction of morbidity after hepatectomy for hepatocellular carcinoma (area under the curve, 0.593; 95% confidence interval: 0.552-0.635; p < 0.001), and multivariate analysis confirmed its correlation with the risk of any morbidity (odds ratio per +1 point, 1.17; 95% confidence interval: 1.08-1.27; p < 0.001) and major morbidity (odds ratio per +1 point, 1.14; 95% confidence interval: 0.99-1.27; p = 0.052). The undernutrition grade based on the controlling nutritional status score showed strong correlation with the degree of fibrosis in the liver (p < 0.001), platelet count (p < 0.001), and indocyanine green retention rate at 15 min (p < 0.001). In addition, the controlling nutritional status undernutrition grade well stratified the risk of postoperative morbidity especially in cirrhotic subpopulation (odds ratio, 1.17 per +1 point; 95% confidence interval: 1.05-1.29 for any morbidity and odds ratio, 1.20 per +1 point; 95% confidence interval: 1.03-1.40 for major morbidity). CONCLUSIONS: The controlling nutritional status score could be an alternative measure for underlying liver injury and the surgical risk of hepatocellular carcinoma.

Significance of preoperative nutritional status as a predictor for short-term and long-term outcomes of patients undergoing surgery for stage IV colorectal cancer.

PURPOSE: The clinical impact of the preoperative nutritional status has not fully been understood in an aggressive surgical approach for stage IV colorectal cancer (CRC). METHODS: The clinical records of 399 patients with stage IV CRC who underwent surgery for the primary tumor were reviewed. The predictive powers of reported nutritional/inflammatory indices of postoperative morbidity were compared, and their correlations with both the short- and long-term outcomes were investigated. RESULTS: Among the 10 tested nutritional/inflammatory indices, the Controlling Nutritional Status (CONUT) score showed the highest performance for predicting major morbidity (area under the curve [AUC], 0.605; P = 0.067) and any morbidity (AUC, 0.605; P = 0.001). When stratifying the population into 4 undernutrition grades based on the CONUT score, the CONUT undernutrition grades were found to show good correlations with the Clavien-Dindo grades of postoperative morbidity (P < 0.001) and the length of hospital stay (P < 0.001). Multivariate analysis confirmed the CONUT undernutrition grade was significantly associated with the survival outcomes in patients with stage IV CRC (light: hazard ratio [HR], 1.12; 95% CI, 0.80-1.58; moderate: HR, 1.54; 95% CI, 1.02-2.33; severe: HR, 3.61; 95% CI, 1.52-8.62). CONCLUSIONS: Preoperative nutritional status is a useful predictive marker for both the short- and long-term outcomes of surgical interventions for stage IV CRC.

Usefulness of Serum Anti-p53 Antibody Measurement in Patients Undergoing Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: While anti-p53 antibody (p53-Ab) is a potential marker for early detection of colorectal cancer, its clinical utility in patients with advanced colorectal cancer remains unknown. METHODS: The clinical significance of p53-Ab was investigated by analyzing the data of 206 patients who underwent curative resection for colorectal liver metastases. RESULTS: Of the 206 patients, 60 (29%) were seropositive and 146 were seronegative for p53-Ab before the surgery. The preoperative serum p53-Ab level showed no significant correlation with the serum CEA or serum CA19-9 levels. The perioperative changes in serum p53-Ab positivity were significantly correlated with the preoperative serum p53-Ab levels and multivariate analysis confirmed that a higher preoperative p53-Ab level was independently associated with a worse recurrence-free survival (hazard ratio [HR], 1.07; 95% CI, 1.01-1.13; P = 0.033 per + 100 U/mL), even after adjustments for other oncological factors, including the preoperative serum CEA level. CONCLUSION: Higher preoperative p53-Ab levels were associated with a higher risk of recurrence after curative resection of colorectal liver metastases.

Adipose Tissue Distribution Predicts Prognosis of Cirrhotic Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: Body composition data are reportedly correlated with patient prognosis for various cancers. However, little is known about the prognostic impact of adipose tissue distribution among patients with hepatocellular carcinoma (HCC). METHODS: Data for 181 consecutive cirrhotic patients who underwent hepatectomy for HCC were retrospectively reviewed. The clinical significance of the visceral-to-subcutaneous adipose tissue ratio (VSR) was investigated through analysis of short- and long-term surgical outcomes. RESULTS: Of the 181 patients, 60 (33%) were classified as the high-VSR group and 121 (67%) as the low-VSR group. Although VSR was not correlated with a risk of postoperative morbidity, multivariate analysis confirmed that a higher VSR was significantly correlated with a shorter time to interventional failure (hazard ratio [HR] 2.24; P = 0.008) and overall survival (HR 2.65; P = 0.001) independently of American Joint Committed on Cancer stage or preoperative nutritional status. Analysis of the recurrence patterns showed that the proportion of unresectable recurrence at the initial recurrence event was significantly higher in the high-VSR group (39% vs. 18%; P = 0.025). The yearly transition probabilities, defined by a Markov model from postoperative R0 status to advanced disease or death (7.6% vs. 1.5%, P < 0.001) and early recurrence stage to advanced disease or death (15.4% vs. 2.8%, P = 0.004), were higher in the high-VSR group, suggesting that patients with a higher VSR are vulnerable to disease progression. CONCLUSION: A high VSR was found to be an independent predictor of disease progression and poor prognosis for HCC patients with underlying liver cirrhosis having resection for HCC.

Successful Anatomic Resection of Tumor-Bearing Portal Territory Delays Long-Term Stage Progression of Hepatocellular Carcinoma.

BACKGROUND: Optimal choice of surgical procedure for hepatocellular carcinoma (HCC) remains inconclusive. This study seeks to investigate the oncological superiority of anatomic resection (AR) of the tumor-bearing portal territory and potential mechanism of survival benefit for patients undergoing AR. PATIENTS AND METHODS: In 203 patients who underwent curative resection for primary solitary HCC measuring ≤ 5 cm in diameter, which was resectable either by AR or limited resection (non-AR), long-term outcomes were compared with propensity score adjustment. Advantages of AR in local tumor control and postprogression survival were then evaluated by a multivariate analysis and a Markov model. RESULTS: The AR group showed better recurrence-free survival [hazard ratio (HR), 0.51; 95% CI, 0.28-0.91; P = 0.023), time-to-interventional failure (TIF) (HR, 0.08; 95% CI, 0.01-0.60; P = 0.014), and overall survival (HR, 0.11; 95% CI, 0.01-0.79, P = 0.029) than the non-AR group. Competing-risks regression revealed that AR significantly decreases local recurrence (HR, 0.13; 95% CI, 0.02-0.97; P = 0.047) and is correlated with smaller number and size of recurrent lesions, both of which were predictors for better TIF and postprogression survival. A Markov model demonstrated that annual transition rate from the early recurrence stage (i.e., curative-intent treatment indicated) to the intermediate stage (i.e., only palliative-intent treatment indicated) was significantly lower (9.0% versus 35.6%, P = 0.027) when AR was completed at the initial hepatectomy. CONCLUSIONS: AR is oncologically advantageous for patients with primary solitary HCC. Initial choice of surgical procedure may have significant influence on the pattern of recurrence and postprogression clinical course that may affect overall survival of patients with HCC.

Hyaluronic acid/ carboxymethyl cellulose-based adhesion barrier reduces surgical difficulty and complication in repeat hepatectomy.

BACKGROUND: There has been no solid evidence regarding the actual efficacy of adhesion barriers in liver surgery. METHODS: Difficulty grade of lysis of adhesion was evaluated in 122 patients who underwent repeat hepatectomy (ReHx) using the TORAD score. Technical difficulty of lysis of adhesion and incidence of complication were then compared between the group of patients who received a sheet-type adhesion barrier (Seprafilm®) in the previous hepatectomy (n = 70) and those who did not (n = 52) using the inverse probability weighting method. RESULTS: Use of Seprafilm was significantly associated with lower grade of difficulty of lysis of adhesion according to the TORAD score (P < 0.001). Postoperative morbidity rate was lower and postoperative stay was shorter in the Seprafilm group in the propensity-score adjusted population (37% vs. 74%, P < 0.001 and 12 days vs. 14 days in median, P = 0.048). Multivariate analysis confirmed that use of Seprafilm was independent predictor for severity of adhesion (odds ratio [OR] 0.24, 95% CI, 0.09-0.65, P = 0.005) and decreased incidence of postoperative morbidity at ReHx (OR, 0.34; 95% CI, 0.14-0.84, P = 0.020). CONCLUSIONS: Use of Seprafilm may be associated with decreased technical difficulty of lysis of adhesion and may correlate with lower risk of postoperative morbidity in patients undergoing ReHx.

Scanning electron microscopy of polycystic liver disease.

Resected specimens of PCLD by laparoscopic fenestration surgery were evaluated by scanning electron microscopy. Epithelium lining the largest cyst (26 cm in size) showed prominent villous proliferation with positivity of Ki-67, while the epithelium of the small cyst (3 cm in size) showed slight proliferation (smooth) with small positivity of Ki-67.

Cloning, sequence analysis, and expression in Escherichia coli of gene encoding N-Benzyl-3-pyrrolidinol dehydrogenase from Geotrichum capitatum.

The gene encoding N-benzyl-3-pyrrolidinol dehydrogenase (DDBJ/EMBL/GenBank accession no. AB294179), a useful biocatalyst for producing (S)-N-benzyl-3-pyrrolidinol, was cloned from the genomic DNA of Geotrichum capitatum JCM 3908. The gene contained an open reading frame consisting of 1023 nucleotides corresponding to 340 amino acid residues. The subunit molecular weight was calculated to be 39,000. The predicted amino acid sequence did not have significant similarity to those of N-benzyl-3-pyrrolidinone reductases reported previously. From 30 mM N-benzyl-3-pyrrolidinone, (S)-N-benzyl-3-pyrrolidinol was obtained with a yield >99.9% and an enantiomeric excess >99.9% in 1-h and 2-h reactions without NADH addition by the resting cells of Escherichia coli HB 101 strains harboring the expression plasmids pSG-POBS and pSF-POBS that possess the glucose dehydrogenase gene and formate dehydrogenase gene as an NADH-reproducing system, respectively, besides the N-benzyl-3-pyrrolidinol dehydrogenase gene. N-Benzyl-3-pyrrolidinol dehydrogenase activity (0.56 U/mg) was observed in E. coli (pSG-POBS), which was 17-fold the specific activity observed in G. capitatum JCM 3908.