The Albumin-bilirubin Grade as Prognostic Indicator for Recurrent Hepatocellular Carcinoma Needing Repeat Liver Resection.

BACKGROUND/AIM: This study aimed to evaluate the utility of the albumin-bilirubin grade for predicting the prognosis after repeat liver resection for patients with recurrent hepatocellular carcinoma. PATIENTS AND METHODS: Ninety patients with intrahepatic recurrent hepatocellular carcinoma who underwent repeat liver resection at our institution between 2005 and 2019 were retrospectively analyzed. Cox proportional-hazards regression models evaluated independent preoperative prognostic factors, including the albumin-bilirubin grade. Prognosis differences between patients with albumin-bilirubin grades 1 and 2 were analyzed using the Kaplan-Meier method. RESULTS: Cox proportional-hazards regression analysis revealed that albumin-bilirubin grade 2 (p=0.003) and early recurrence within one year from the initial surgery (p=0.001) were independently associated with poor recurrence-free survival, and albumin-bilirubin grade 2 (p=0.020) was independently associated with poor overall survival. The five-year recurrence-free (31% and 17%, respectively) and overall (86% and 60%, respectively) survival rates after repeat liver resection for patients with albumin-bilirubin grades 1 and 2 were significantly different between groups (both p=0.003). CONCLUSION: The albumin-bilirubin grade is useful for preoperatively predicting favorable survival rates after repeat liver resection for patients with recurrent hepatocellular carcinoma. Patients with an albumin-bilirubin grade 1 are better candidates for surgical treatment of recurrent hepatocellular carcinoma.

Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

BACKGROUND: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. METHODS: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. RESULTS: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. CONCLUSIONS: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Spontaneous rupture of splenic hilar lymph node metastasis from hepatocellular carcinoma.

Spontaneous rupture of a primary hepatocellular carcinoma (HCC) is a frequently observed and fatal complication. However, the rupture of lymph node (LN) metastases from HCC is rare. A 79 year-old male with hepatitis B underwent three liver resections for HCC. Two years and 6 months after the last liver resection, enhanced computed tomography (CT) revealed a nodule with a diameter of 3 cm in the lower pole of the spleen. Splenic metastasis of HCC was suspected, and splenectomy was scheduled. During our hospital stay for a urinary tract infection before the scheduled operation, he complained of acute left-sided abdominal pain, and CT showed intra-abdominal hemorrhage due to rupture of the splenic tumor. Emergency splenectomy was performed, and the postoperative course was uneventful. Histopathological examination revealed a poorly differentiated HCC in the lower splenic pole lesion, which contained LN structures. The ruptured lesion was diagnosed as splenic hilar LN metastasis of HCC. Although laparoscopic partial liver resection was performed for intrahepatic recurrence, and atezolizumab plus bevacizumab therapy was administered for peritoneal metastases, the patient was alive 25 months after the splenectomy. Our case suggests that emergency surgery for LN metastatic rupture can achieve hemostasis and lead to improved survival outcomes.

Utility of plasma D-dimer for diagnosis of venous thromboembolism after hepatectomy.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of hepatectomy. The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding. Therefore, we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy. AIM: To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy. METHODS: The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed. Patients were divided into two groups according to whether or not they developed VTE after hepatectomy, as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities. Clinicopathological factors, including demographic data and perioperative D-dimer values, were compared between the two groups. Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value. Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors. RESULTS: In total, 234 patients who underwent hepatectomy were, of whom (5.6%) were diagnosed with VTE following hepatectomy. A comparison between the two groups showed significant differences in operative time (529 vs 403 min, P = 0.0274) and blood loss (530 vs 138 mL, P = 0.0067). The D-dimer levels on postoperative days (POD) 1, 3, 5, 7 were significantly higher in the VTE group than in the non-VTE group. In the multivariate analysis, intraoperative blood loss of > 275 mL [odds ratio (OR) = 5.32, 95% confidence interval (CI): 1.05-27.0, P = 0.044] and plasma D-dimer levels on POD 5 ≥ 21 µg/mL (OR = 10.1, 95%CI: 2.04-50.1, P = 0.0046) were independent risk factors for VTE after hepatectomy. CONCLUSION: Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.

Association between tumor morphology and efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

AIM: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. METHODS: Ninety-five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non-simple nodular (non-SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. RESULTS: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non-SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non-SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non-SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non-SN lesions underwent sequential local therapy. CONCLUSIONS: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non-SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non-SN lesions.

A Novel Method Using Gadolinium-Ethoxybenzyl Diethylenetriamine Pentaacetate Acid-Enhanced Magnetic Resonance Imaging for Predicting Post-Hepatectomy Liver Failure in Hepatocellular Carcinoma Patients with a Major Portal Vein Tumor Thrombus.

INTRODUCTION: The usefulness of gadolinium-ethoxybenzyl diethylenetriamine pentaacetate acid-enhanced magnetic resonance imaging (EOB-MRI) in assessing the functional future remnant liver volume (fFRLV) to predict post-hepatectomy liver failure (PHLF) has been previously reported. Herein, we evaluated the efficacy of this technique in patients with hepatocellular carcinoma (HCC) with a major portal vein tumor thrombus (PVTT). METHODS: This study included 21 patients with PVTT in the ipsilateral first-order branch (Vp3) and 30 patients with PVTT in the main trunk/contralateral branch (Vp4). To evaluate fFRLV, the signal intensity (SI) of the remnant liver was determined on T1-weighted images, using both conventional and newly developed methods. The fFRLV was calculated using the SI of the remnant liver and muscle, remnant liver volume, and body surface area. Preoperative factors predicting PHLF (≥grade B) in HCC patients with Vp3/4 PVTT were evaluated. RESULTS: In the Vp3 group, we found fFRLV area under the receiver-operating characteristic curves (AUCs) above 0.70 (AUC = 0.875, 0.750) using EOB-MRI results calculated using either the plot or whole method. None of the parameters in the Vp4 group had an AUC greater than 0.70. CONCLUSION: The fFRLV calculated by EOB-MRI using the whole method can be as useful as the conventional method in predicting PHLF (≥grade B) for HCC patients with Vp3 PVTT.

Efficacy of S-1 Adjuvant Chemotherapy for Resected Biliary Tract Cancer: A Retrospective Propensity-Matched Analysis.

INTRODUCTION: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. METHODS: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. RESULTS: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. DISCUSSION: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.

Liver ischemia-reperfusion injury: From trigger loading to shot firing.

An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.

Impact of GLIM criteria-based malnutrition diagnosis on outcomes following liver resection for hepatocellular carcinoma.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM), comprising several of the major global clinical nutrition societies, suggested the world's first criteria for diagnosis of the severity of malnutrition. However, the impact of the resulting diagnosis on patient outcomes for those with hepatocellular carcinoma (HCC) following liver resection (LR) has not been investigated. METHODS: A retrospective analysis of 293 patients with HCC who underwent LR between January 2011 and December 2018 was performed. We compared overall survival (OS) and recurrence-free survival (RFS) and evaluated prognostic factors after LR using Cox proportional hazards regression models. RESULTS: Preoperative patient nutritional status, n (%), was classified as follows: normal, 130 (44%), moderate malnutrition, 116 (40%), and severe malnutrition, 47 (16%). The median OS (129 vs. 43 months, p < 0.001) and median RFS (54 vs. 20 months, p = 0.001) were significantly greater in the normal group than in the severe malnutrition group. Multivariate analysis showed that severe malnutrition was a significant risk factor for OS (p = 0.006) and RFS (p = 0.010) after initial LR. CONCLUSION: Severe malnutrition, as diagnosed by the GLIM criteria, is a significant prognostic factor for survival and recurrence in patients with HCC after LR.

Risk Factors for Recurrence of Cholangitis After Pancreaticoduodenectomy and Comparison of Stents in Hepaticojejunostomy.

BACKGROUND: Postoperative cholangitis is a common complication of pancreaticoduodenectomy. Frequent cholangitis impairs patients' quality of life after pancreaticoduodenectomy. However, the risk factors for recurrence of cholangitis remain unclear. Hence, this retrospective study aimed to identify risk factors for recurrence of cholangitis after pancreaticoduodenectomy. METHODS: The medical records of patients who underwent pancreaticoduodenectomy between 2015 and 2019 in our institution were retrospectively reviewed. At least two episodes of cholangitis a year after pancreaticoduodenectomy were defined as 'recurrence of cholangitis' in the present study. Univariate and multivariate analyses were performed. RESULTS: The recurrence of cholangitis occurred in 40 of 207 patients (19.3%). Multivariate analysis revealed that internal stent (external, RR: 2.16, P = 0.026; none, RR: 4.76, P = 0.011), firm pancreas (RR: 2.61, P = 0.021), constipation (RR: 3.49, P = 0.008), and postoperative total bilirubin>1.7 mg/dL (RR: 2.94, P = 0.006) were risk factors of recurrence of cholangitis. Among patients with internal stents (n = 54), those with remnant stents beyond 5 months had more frequent recurrence of cholangitis (≥5 months, 75%; <5 months, 30%). CONCLUSIONS: Internal stents, firm pancreas, constipation, and postoperative high bilirubin levels are risk factors for cholangitis recurrence after pancreaticoduodenectomy. In addition, the long-term implantation of internal stents may trigger cholangitis recurrence.

Advantages of the Laparoscopic Approach for the Initial Operation in Patients who Underwent Repeat Hepatectomy.

BACKGROUND: Less intra-abdominal adhesions are expected following laparoscopic surgery. Although an initial laparoscopic approach for primary liver tumors may have advantages in patients who require repeat hepatectomies for recurrent liver tumors, this has not been sufficiently investigated. METHODS: Patients who underwent repeat hepatectomies for recurrent liver tumors at our hospital between 2010 and 2022 were retrospectively analyzed. Of 127 patients, 76 underwent laparoscopic repeat hepatectomy (LRH), of whom 34 patients initially underwent laparoscopic hepatectomy (L-LRH) and 42, open hepatectomy (O-LRH). Fifty-one patients underwent open hepatectomy as both the initial and second operation (O-ORH). We analyzed surgical outcomes between L-LRH and O-LRH groups and between L-LRH and O-ORH groups using propensity-matching analysis for each pattern. RESULTS: Twenty-one patients each were included in L-LRH and O-LRH propensity-matched cohorts. The L-LRH group had a lower rate of postoperative complications than the O-LRH group (0 vs 19%, P = 0.036). When we compared surgical outcomes between L-LRH and O-ORH groups in another matched cohort with 18 patients in each group, in addition to the lower rate of postoperative complications, the L-LRH group had additional favorable surgical outcomes including shorter operation time and lower blood loss volume than the O-ORH group (291 vs 368 min, P = 0.037 and 10 vs 485 mL, P < 0.0001). CONCLUSIONS: An initial laparoscopic approach would be favorable for patients undergoing repeat hepatectomies, as it leads to lower risk of postoperative complications. Compared with O-ORH, the advantage of the laparoscopic approach may be enhanced when it is repeatedly adopted.

The Usefulness of Total Tumor Volume as a Prognostic Factor and in Selecting the Optimal Treatment Strategy of Chemotherapeutic Intervention in Patients with Colorectal Liver Metastases.

BACKGROUND: Few reports have discussed the association between total tumor volume (TTV) and prognosis in patients with colorectal liver metastases (CRLM). The present study aimed to evaluate the usefulness of TTV for predicting recurrence-free survival and overall survival (OS) in patients receiving initial hepatic resection or chemotherapy, and to investigate the value of TTV as an indicator for optimal treatment selection for patients with CRLM. PATIENTS AND METHODS: This retrospective cohort study included patients with CRLM who underwent hepatic resection (n = 93) or chemotherapy (n = 78) at the Kobe University Hospital. TTV was measured using 3D construction software and computed tomography images. RESULTS: A TTV of 100 cm3 has been previously reported as a significant cut-off value for predicting OS of CRLM patients receiving initial hepatic resection. For patients receiving hepatic resection, the OS for those with a TTV ≥ 100 cm3 was significantly reduced compared with those with a TTV < 100 cm3. For patients receiving initial chemotherapy, there were no significant differences between the groups divided according to TTV cut-offs. Regarding OS of patients with TTV ≥ 100 cm3, there was no significant difference between hepatic resection and chemotherapy (p = 0.160). CONCLUSIONS: TTV can be a predictive factor of OS for hepatic resection, unlike for initial chemotherapy treatment. The lack of significant difference in OS for CRLM patients with TTV ≥ 100 cm3, regardless of initial treatment, suggests that chemotherapeutic intervention preceding hepatic resection may be indicated for such patients.

Transarterial chemoembolization for liver metastases of a pancreatic neuroendocrine neoplasm: a single-center experience.

Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1-6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4-6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14-41) and 27 (2-60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up.

Factors Predicting Over-Time Weight Increase After Liver Transplantation: A Retrospective Study.

BACKGROUND: Post-transplantation weight control is important for long-term outcomes; however, few reports have examined postoperative weight change. This study aimed to identify perioperative factors contributing to post-transplantation weight change. METHODS: Twenty-nine patients who underwent liver transplantation between 2015 and 2019 with an overall survival of >3 years were analyzed. RESULTS: The median age, model for end-stage liver disease score, and preoperative body mass index (BMI) of the recipients were 57, 25, and 23.7, respectively. Although all but one recipient lost weight, the percentage of recipients who gained weight increased to 55% (1 month), 72% (6 months), and 83% (12 months). Among perioperative factors, recipient age ≤50 years and BMI ≤25 were identified as risk factors for weight gain within 12 months (P < .05), and patients with age ≤50 years or BMI ≤25 recipients gained weight more rapidly (P < .05). The recovery time of serum albumin level ≥4.0 mg/dL was not statistically different between the 2 groups. The weight change during the first 3 years after discharge was represented by an approximately straight line, with 18 and 11 recipients showing a positive and negative slope, respectively. Body mass index ≤23 was identified as a risk factor for a positive slope of weight gain (P <.05). CONCLUSIONS: Although postoperative weight gain implies recovery after transplantation, recipients with a lower preoperative BMI should strictly manage body weight as they may be at higher risk of rapid weight increase.

Prognostic Impact of Malnutrition Diagnosed by the GLIM Criteria for Resected Extrahepatic Cholangiocarcinoma.

BACKGROUND/AIM: Recently, the Global Leadership Initiative on Malnutrition (GLIM), which includes the world's leading clinical nutrition societies, proposed the first global diagnostic criteria for malnutrition. However, the association between malnutrition diagnosed by the GLIM criteria and prognosis in patients with resected extrahepatic cholangiocarcinoma (ECC) remains unknown. This study aimed to investigate the predictive validity of the GLIM criteria for the prognosis of patients with resected ECC. PATIENTS AND METHODS: Between 2000 and 2020, 166 patients who underwent curative-intent resection for ECC were retrospectively analyzed. Prognostic significance of preoperative malnutrition diagnosed by the GLIM criteria was investigated using a multivariate Cox proportional hazards model. RESULTS: Eighty-five (51.2%) and 46 (27.7%) patients were diagnosed with moderate and severe malnutrition, respectively. Increased malnutrition severity tended to be correlated with increased lymph node metastasis rate (p-for-trend=0.0381). The severe malnutrition group had worse 1-, 3-, and 5-year overall survival rates than the normal (without malnutrition) group (82.2% vs. 91.2%, 45.6% vs. 65.1%, 29.3% vs. 61.5%, respectively, p=0.0159). In multivariate analysis, preoperative severe malnutrition was an independent predictor for poor prognosis (hazard ratio=1.68, 95% confidence interval=1.06-2.66, p=0.0282), along with intraoperative blood loss >1,000 ml, lymph node metastasis, perineural invasion, and curability. CONCLUSION: Severe preoperative malnutrition diagnosed by the GLIM criteria was associated with poor prognosis in patients who underwent curative-intent resection for ECC.

Successful Management of Refractory Autoimmune Hemolytic Anemia with Cold Agglutinin Disease with Splenectomy: A Case Report with Review of Literature.

BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia characterized by agglutination of red blood cells at temperatures below the normal core body temperature. In patients with CAD, splenectomy is not indicated because of its low therapeutic effect on hemolytic anemia induced by extravascular hemolysis. Herein, we report a case of refractory hemolytic anemia with CAD successfully managed with splenectomy. CLINICAL CASE: A 60-year-old man visited a municipal hospital with the chief complaint of fatigue. He was found to have hemolytic anemia and icterus with increased cold agglutination and was diagnosed with CAD. Malignant lymphoma was suspected as the underlying disease; however, no clear underlying disease was identified. Hemolytic anemia progressed during the subsequent winter seasons, and he was treated with temperature control, warming, and weekly blood transfusions. However, despite the blood transfusions, his hemoglobin level did not improve during the summer 2 years after diagnosis, and his previously observed splenomegaly had progressed. He was referred to our department, and a splenectomy was performed to diagnose any occult malignant lymphoma and improve the refractory hemolytic anemia. Because histopathological examination revealed no evidence of malignant lymphoma, a diagnosis of primary CAD was made. The hemolytic anemia improved, and no blood transfusion was required after splenectomy. CONCLUSIONS: Splenectomy significantly improved the patient's refractory hemolytic anemia due to primary CAD. Thus, it may be an effective treatment option in such cases, although further cases and studies are required to evaluate the effects of splenectomy.

Assessment of serum and drain fluid bilirubin concentrations in liver transplantation patients.

BACKGROUND: Bile leakage is a major complication after liver transplantation and remains as a significant source of morbidity and mortality. In 2011, the International Study Group of Liver Surgery (ISGLS) defined bile leakage as a drain/serum bilirubin ratio ≥3. However, to our knowledge there is no literature assessing serum and drain bilirubin concentrations after liver transplantation. The aim of this study was to describe the natural postoperative changes in serum and drain fluid bilirubin concentrations in patients after liver transplantation. METHODS: We included 32 patients who underwent liver transplantation at Kobe University Hospital from January 2007 to December 2020. We enrolled 34 living donors who had no complications as the control group. RESULTS: The recipient serum total/direct bilirubin concentration were higher compared with the donors from postoperative day (POD) 1 to 5 with a statistical difference (P < .05). The recipient drain/serum total bilirubin ratio was lower than donors on POD 3 (0.89 ± 0.07 vs 1.53 ± 0.07: P < .0001), which was also confirmed by the recipient drain/serum direct bilirubin ratio (0.64 ± 0.10 vs 1.18 ± 0.09: P < .0001). On POD 3, the drain fluid volume (647.38 ± 89.47 vs 113.43 ± 86.8 mL: P < .001) and serum total bilirubin concentration (6.73 ± 0.61 vs 1.23 ± 0.60 mg/dL: P < .001) was higher in the recipients than in donors. Categorized in 2 groups, the higher drain fluid volume and bilirubin concentration recipients showed lower drain/serum total bilirubin ratio compared with the other group (P = .03) CONCLUSION: The drain/serum bilirubin ratio in the transplanted patients could be calculated lower compared with the hepatectomy patients because of high drain fluid volume and hyperbilirubinemia. Great care should be taken when assessing the bile leakage in liver transplant recipients using the ISGLS definition.

Laparoscopic Medial-to-Lateral Approach for the Resection of Hepatocellular Carcinoma Located at the Spiegel Lobe of the Liver.

BACKGROUND: Laparoscopic caudate lobe resection is a challenging procedure. Several researchers have reported the safety of laparoscopic liver resections;1.Transl Gastroenterol Hepatol. 1:56;2.Asian J Endosc Surg. 12:232-236;3.Ann Surg Oncol. 26:2980; however, a standardized procedure has not yet been established. Herein, we present a video showing laparoscopic Spiegel lobectomy in a patient with 6-cm hepatocellular carcinoma (HCC) using a novel approach. PATIENT AND METHODS: A 63-year-old man with a caudate lobe HCC was referred to our hospital. Computed tomography showed a 5 × 6 cm2 HCC located in the Spiegel lobe, which profoundly displaced the inferior vena cava (IVC) to the lower right side, and mobilization of the Spiegel lobe was considered difficult. To perform the dissection between the Siegel lobe and IVC safely, we performed parenchymal transection along the ventral side of the IVC initially. The Spiegel lobe was then dislocated to the left side of the IVC. We dissected the left lateral side of the IVC, including the proper hepatic vein draining the caudate lobe and the left IVC ligament with a safe operative field, and successfully removed the Spiegel lobe with large HCC. RESULTS: The operation time was 383 min. The blood loss was 10 mL. The patient was discharged on the seventh postoperative day without any complications. Histopathological examination revealed well-differentiated HCC with a negative surgical margin. CONCLUSIONS: Laparoscopic medial-to-lateral approach with initial parenchymal transection at the medial side of the Spiegel lobe followed by dissection of the left lateral side of the IVC is considered as a safe and effective procedure for large tumors in the Spiegel lobe.