Recurrence Pattern Is an Independent Surgical Prognostic Factor for Long-Term Oncological Outcomes in Patients with Hepatocellular Carcinoma.

BACKGROUND: The perioperative outcomes of a partial hepatectomy for hepatocellular carcinoma (HCC) have improved. However, high recurrence rates after a curative hepatectomy for HCC is still an issue. This study aimed to analyze the difference between various recurrence patterns. METHODS: We retrospectively reviewed 754 patients with HCC who underwent a curative hepatectomy between January 2012 and March 2021. Patients with recurrent events were categorized into three types: regional recurrence (type I), multiple intrahepatic recurrence (type II), or presence of any distant metastasis (type III). RESULTS: The median follow-up period was 51.2 months. Regarding recurrence, 375 (49.7%) patients developed recurrence, with 244 (32.4%), 51 (6.8%), and 80 (10.6%) patients having type I, II, and III recurrence, respectively. Type III recurrence appeared to be more common in male patients and those with major liver resection, vascular invasion, a large tumor size (>5 cm), a higher tumor grade, and higher levels of AST and AFP (p < 0.05). Patients who had distant metastasis at recurrence had the shortest recurrence time and the worst overall survival (p < 0.001 and p < 0.001). CONCLUSIONS: our study demonstrated that recurrence with distant metastasis occurred earliest and had the worst outcome compared to regional or multiple intrahepatic recurrences.

The Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Poor Prognosis Factor in Patients with Hepatocellular Carcinoma: An Analysis of Microvessel Density.

The outcomes of patients with hepatocellular carcinoma (HCC) are unsatisfactory because of its high recurrence rate. The Vessels that encapsulate tumor clusters (VETC) pattern is a unique vascular structure. In this study, we investigated the clinical−pathological features of HCC patients with the VETC pattern. We retrospectively reviewed patients with HCC who underwent curative hepatectomy at Chang Gung Memorial Hospital between 2007 and 2013. The form of the VETC pattern was established using an anti-CD31 stain. The results were classified into positive (VETC+) and negative (VETC−) patterns. We investigated and compared demographic data between these two groups. Overall, 174 patients were classified into either the VETC+ or VETC− groups. The median followed-up period was 80.5 months. There were significant differences in the number of hepatitis B carriers, the occurrence of vascular invasion, tumor size, TNM staging, microvessel density, and recurrence (all p < 0.05). Regarding the prediction of disease-free survival, after COX regression multivariate analysis, VETC+ remained independently associated with recurrent episodes (p = 0.003). The intra-tumoral microvessel density, demonstrated by CD-31, was the only clinical−pathological feature independently associated with VETC+. Our study demonstrated that the VETC pattern is an independent factor of poor prognosis for DFS. Higher intra-tumoral microvessel density was significantly associated with the VETC pattern. Further studies are needed to validate our findings.

Differential Response to Sorafenib Administration for Advanced Hepatocellular Carcinoma.

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion.

Reappraisal of the Role of Alkaline Phosphatase in Hepatocellular Carcinoma.

Background: Alkaline phosphatase (ALP) is a marker of liver function and is associated with biliary tract disease. It was reported as a prognostic factor for hepatocellular carcinoma (HCC). The genetic expression in tumor-tissue microarrays and the perioperative serologic changes in ALP have never been studied for their correlation with HCC prognosis. Methods: The genetic expression of ALP isoforms (placental (ALPP), intestinal (ALPI) and bone/kidney/liver (ALPL)) was analyzed in tumor and non-cancerous areas in 38 patients with HCC after partial hepatectomy. The perioperative change in ALP was further analyzed in a cohort containing 525 patients with HCC to correlate it with oncologic outcomes. A total of 43 HCC patients were enrolled for a volumetry study after major and minor hepatectomy. Results: The genetic expression of the bone/kidney/liver isoform was specifically and significantly higher in non-cancerous areas than in tumors. Patients with HCC with a higher ALP (>81 U/dL) had significantly more major hepatectomies, vascular invasion, and recurrence. Cox regression analysis showed that gender, major hepatectomies, the presence of satellite lesions, higher grades (III or IV) and perioperative changes in liver function tests were independent prognostic factors for recurrence-free survival, and a postoperative increase in the ALP ratio at postoperative day (POD) 7 vs. POD 0 > 1.46 should be emphasized. A liver regeneration rate more than 1.8 and correlation analysis revealed that the ALP level at POD 7 and 30 was significantly higher and correlated with remnant liver growth. Conclusions: This study demonstrated that the perioperative ALP change was an independent prognostic factor for HCC after partial hepatectomies, and the elevation of ALP represented a functional biomarker for the liver but not an HCC biomarker. The higher regeneration capacity was possibly associated with the elevation of ALP after operation.

The Combination of SOFA Score and Urinary NGAL May Be an Effective Predictor for Ventilator Dependence among Critically Ill Surgical Patients: A Pilot Study.

BACKGROUND: Ventilator dependence (VD) has been considered as a serious complication in critically ill patients in the intensive care unit (ICU). Acute kidney injury (AKI) is associated with VD as a result of lung-kidney interaction. The aim of our study was to investigate novel biomarkers in predicting ventilator dependence in critically ill surgical patients. METHODS: Patients who were admitted to surgical ICU were enrolled and their serum and urine samples were collected. Novel biomarkers including gelatinase-associated lipocalin (NGAL), calprotectin, kidney injury molecule-1 (KIM-1), cystatin C, and growth differentiation factor 15 (GDF-15) were analyzed and correlated with clinical outcome. RESULTS: A total of 33 patients were enrolled and analyzed. The majority of them received abdominal surgery prior to ICU admission. Thirteen patients were classified into the VD group, while the remaining 20 were in a non-ventilator dependence group (nVD). Statistical analysis demonstrated that the following were significantly higher in the VD group than in the nVD group: serum NGAL (420.25 ± 45.18 ng/mL vs. 314.68 ± 38.12 ng/mL, p-value 0.036), urinary NGAL (420.87 ± 41.08 ng/mL vs. 250.84 ± 39.45 ng/mL, p-value 0.002), SOFA score (11.3 ± 1.5 vs. 5.6 ± 0.7, p-value 0.001), and APACHE II score (23.2 ± 2.6 vs. 13.6 ± 0.8, p-value 0.001). The area under the ROC curve (AUROC) of urinary NGAL for VD was 0.808. The combination of urinary NGAL and SOFA score could further increase AUROC for VD to 0.835. CONCLUSIONS: The current study demonstrated the predictive capability of urinary NGAL for ventilator dependence among critically ill surgical patients. When combined with SOFA score, the predictive ability was further augmented. Further large-scale studies are warranted to validate our findings.

Successful Localization and Resection of Small Pancreatic Cystic Insulinoma Using Intraoperative Near-Infrared Fluorescence Imaging: A Case Report and Literature Review.

Pancreatic cystic insulinoma is an uncommon tumor. Perioperative localization remained challenging if the tumor is atypical with cystic feature or in small size. Near-infrared (NIR) imaging is a technique by injecting fluorescent dye intravenously, which accumulates to the target lesion and creating signal by laser sources. The signal helps surgeons to identify the lesion during operation, but little experience has been reported regarding the use of imaging NIR technique for localizing cystic insulinoma. We present a 29-year-old female patient with a symptomatic pancreatic cystic insulinoma (1.2 cm) as assessed by clinical symptom, laboratory evidence, and magnetic resonance cholangiopancreatography. With an aid of NIR imaging technique, this cystic tumor was localized easily at operation. Also, the fluorescence imaging visualized the tumor part, guided us to identify the safe margin, and preserved the normal pancreatic structure. Pathologic report confirmed that the tumor was a well-differentiated cystic insulinoma. This case demonstrates that pancreatic cystic insulinoma in small size can be intraoperatively localized by NIR imaging, a relatively safe and easy technique.

Hepatic resection for hepatocellular carcinoma in the octogenarian: is it justified?

Liver resection is a standard treatment for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of octogenarians with HCC treated with liver resection. Records of patients who underwent liver resection for HCC were reviewed, and patients older and younger than 80 years were compared. There were 77 patients 80 years of age or older and 3,309 younger than 80 years. Hepatitis C virus infection was the most common etiology among the octogenarians (43.1%), followed by non-viral causes (37.5%). The older group had more co-morbidity but less hepatitis B virus infection and cirrhosis. More than 70% of the non-viral older group had diabetes mellitus, as compared to only 21.6% in the viral older group. The older group had rates of perioperative morbidity, mortality, disease-free survival, and overall survival comparable to the younger group (all p>0.1). Multivariate analysis revealed that α-fetoprotein ≥400 ng/mL, tumor size ≥10 cm, and vascular invasion were independent prognostic factors for overall survival in the older patients. These findings demonstrate that liver resection is a justified treatment for HCC in octogenarians, and it can achieve surgical outcomes comparable to those in younger populations.

Stapleless laparoscopic left lateral sectionectomy for hepatocellular carcinoma: reappraisal of the Louisville statement by a young liver surgeon.

BACKGROUND: Laparoscopic liver resection has been regarded as the standard treatment for liver tumors located at the left lateral liver sector. However, few studies have reported the results of laparoscopic left lateral sectionectomy (LLS) for HCC, not to mention the feasibility of this emerging technique for the less experienced liver surgeons. The current study would reappraise the Louisville statement by examining the outcome of LLS performed by a young liver surgeon. METHODS: We retrospectively reviewed two separate groups of patients who underwent open or laparoscopic left lateral sectionectomies at Chung Gung Memorial Hospital, Linkou. All laparoscopic hepatectomies were performed by the index young surgeon following a stepwise stapleless LLS. The surgical results and oncological outcomes of laparoscopic vs. open hepatectomies (LH and OH, respectively) with the surgical indication of HCC at left lateral liver sector were further compared and analyzed. RESULTS: 18 of 29 patients in the laparoscopic group and 75 patients in the conventional open group had primary HCC. The demographic data was essentially the same for the two groups. Statistical analysis revealed that the LH group had smaller tumor size, higher blood transfusion requirement, longer duration of inflow control and parenchymal transection, and longer operation time. However, no significant difference was observed in terms of complication rate, mortality rate, and hospital stay between the two groups. After adjusting for tumor size, LH and OH showed no statistical difference in the amount of blood transfusion, operation time and patient survival. CONCLUSIONS: This study demonstrated that stapleless LLS is a safe and feasible procedure for less experienced liver surgeons to resect HCC located at the left lateral liver sector. This stepwise stapleless LSS can not only achieve surgical results comparable to OH but also can provide a platform for liver surgeons to apply laparoscopic technique before conducting more complicated liver resections.

RAM score is an effective predictor for early mortality and recurrence after hepatectomy for hepatocellular carcinoma.

BACKGROUND: Liver resection had been regarded as a standard treatment for primary hepatocellular carcinoma (HCC). However, early mortality and recurrence after surgery were still of major concern. RAM (Risk Assessment for early Mortality) scoring system is a newly developed tool for assessing early mortality after hepatectomy for HCC. In this study, we compared RAM scoring system with ALBI and MELD scores for their capability of predicting short-term outcome. METHODS: We retrospectively reviewed patients with hepatocellular carcinoma who were treated with hepatectomy at Chang Gung Memorial Hospital between 1986 and 2015. Their clinical characteristics and perioperative variables were collected. We applied RAM, albumin-bilirubin (ALBI), and model for end-stage liver disease (MELD) scoring systems to predict early mortality and early recurrence in HCC patients after surgery. We investigated the discriminative power of each scoring system by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). RESULTS: A total of 1935 patients (78% male) who underwent liver resection for HCC were included in this study. The median follow-up period was 41.9 months. One hundred and forty-nine patients (7.7%) died within 6 months after hepatectomy (early mortality). All the three scoring systems were effective predictor for early mortality, with higher score indicating higher risk of early mortality (AUC of RAM = 0.723, p < 0.001; AUC of ALBI = 0.682, p < 0.001; AUC of MELD = 0.590, p = 0.002). Cox regression multivariate analysis demonstrated that the RAM class was the most significant independent predictor of early mortality after surgery, while MELD grade failed to discriminatively predict early mortality. In addition to early mortality, the RAM score was also predictive of early recurrence in HCC after surgery. CONCLUSIONS: This study demonstrated that RAM score is an effective and user-friendly bedside scoring system to predict early mortality and early recurrence after hepatectomy for HCC. In addition, the predictive capability of RAM score is superior to ALBI and MELD scores. Further study is warranted to validate our findings.

Postoperative Adjuvant Therapy Improves Survival in Pathologic Nonresponders After Neoadjuvant Chemoradiation for Esophageal Squamous Cell Carcinoma: A Propensity-Matched Analysis.

BACKGROUND: The prognosis of patients with esophageal cancer who have poor response to chemoradiotherapy (ie, pathologic nonresponders [pNRs]) remains poor. We investigated whether the use of postoperative adjuvant therapy (AT) could improve survival in this patient group. METHODS: Among patients with esophageal squamous cell carcinoma who were treated with neoadjuvant chemoradiotherapy (nCRT) and operation between 2000 and 2012, pNRs (defined as those having a postoperative T stage of equal or greater pretreatment T stage or persistent nodal disease) were identified and divided into two groups according to their subsequent management (AT versus surveillance). Survival and recurrence were compared after propensity score matching for the following five factors: age, performance status, pathological lymph node status after treatment (ypN) status, severity of postoperative complications, and length of hospital stay (LOS). RESULTS: Of the 115 pNRs, 74 and 41 received AT and surveillance alone, respectively. Patients who received AT were younger, had less major postoperative complications, and a shorter LOS. A total of 32 pairs of well-balanced patients (n = 64) were selected by propensity matching. A significant benefit in terms of disease-free survival (DFS) was observed for pNRs treated with AT compared with those undergoing surveillance (3-year DFS rate: 45% versus 22.3%, p = 0.022). However, more patients in the AT group died of causes unrelated to cancer, resulting only in a borderline increase of overall survival (OS) [3-year OS rate: 34.4% versus 21.6%, p = 0.13]. CONCLUSIONS: Postoperative AT can improve DFS in pNRs after nCRT. However, its use should be carefully weighed against a potential increase in the risk of treatment-related death.