Secondarily estimated cure fraction and five-year recurrence-free conditional survival probabilities among patients undergoing surgical resection for hepatocellular carcinoma presenting with minor gross vascular invasion.

BACKGROUND: Surgical resection (SR) has been selectively applied in hepatocellular carcinoma (HCC) presenting with minor gross vascular invasion (mGVI) which is defined when tumor invasion is confined to second-order portal branches or segmental branches of hepatic vein. However, little data of long-term outcomes are available for supporting the role of SR as a potentially curable therapeutic option for HCC presenting with mGVI. This study is aimed to estimate a statistical cure fraction and the improvement of recurrence-free conditional survival (RFCS) over time among patients undergoing SR for HCC presenting with mGVI. METHODS: The literature search was conducted focusing on previous studies that investigated the long-term survival rates of patients after SR for HCC presenting with mGVI. The reference cohort was extracted from a study including patients undergoing SR for HCC without vascular invasion. A non-mixture cure model was adopted to estimate the statistical cure fraction. The 5-year RFCS probabilities were also calculated. RESULTS: Three retrospective studies were secondarily analyzed. The probability of being statistically cured after SR for HCC presenting with mGVI was 7.3% (95% confidence interval, 4.4%-11.2%) in the mGVI group, lower than that of the reference cohort (hazard ratio, 1.81; 95% confidence interval, 1.59-2.05). The estimated 5-year RFCS probabilities improved with each additional year of survival. Moreover, 1 year after SR, the 5-year RFCS probabilities of patients with HCC presenting with mGVI was essentially the same as that of the reference cohort. CONCLUSIONS: This study shows that a cure can be expected in around seven percent of patients undergoing SR for HCC presenting with mGVI. Furthermore, recurrence-free survival expectancy improves dramatically over time among those patients who do not have recurrence. Overall, these findings suggest that SR should be considered as a potentially curable treatment for patients with HCC presenting with mGVI.

Prognostic significance of microvascular invasion in tumor stage for hepatocellular carcinoma.

BACKGROUND: The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection. METHODS: A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI). RESULTS: The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival. CONCLUSIONS: McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis.

Mucosa-associated lymphoid tissue (MALT) lymphoma as an unusual cause of malignant hilar biliary stricture: a case report with literature review.

BACKGROUND: Biliary strictures at the hilum of the liver arise from heterogeneous etiologies. The majority is malignant entities, but some may have benign etiologies. It is difficult to distinguish between malignant and benign biliary strictures preoperatively. It has been reported that 5~15 % of preoperative diagnoses of hilar cholangiocarcinoma turn out to be benign lesions or even other types of malignancies. Primary non-Hodgkin's lymphoma of the extrahepatic bile duct is very rare, with only a few cases reported as mucosa-associated lymphoid tissue (MALT) lymphoma arising from the hepatic duct bifurcation. We herein report a case of a female patient presenting with perihilar bile ducts obstructed by primary MALT lymphoma resembling hilar cholangiocarcinoma, along with a review of the literature. CASE PRESENTATION: An 86-year-old female was referred to our hospital manifesting obstructive jaundice and abdominal pain. The reported imaging studies revealed distended intrahepatic bile duct with the stricture of common hepatic duct including bifurcation, which was suspicious of cholangiocarcinoma of the bile duct. The initial laboratory-confirmed cholestasis with a total bilirubin of 8.6 mg/dL, aspartate amino transferase (AST) 178 U/L, alanine transferase (ALT) 105 U/L, and the tumor marker CA 19-9 was elevated with a value of 167 U/mL. Viral markers for hepatitis B and C viruses were negative. She underwent extrahepatic bile duct resection and hepaticojejunostomy. Histological examination of the resected specimen revealed MALT lymphoma. Postoperative follow-up of 1 year has been completely uneventful, without any symptoms or disease recurrence. CONCLUSIONS: In exceptional cases, in which radiologic and clinical features point to cholangiocarcinoma, the actual reason for obstructive jaundice and abdominal pain can be a non-Hodgkin's lymphoma. In the case of a MALT lymphoma, it can be cured with complete resection.

Transforaminal endoscopic lumbar foraminotomy for octogenarian patients.

Background: Radiculopathy caused by lumbar foraminal stenosis in older people has become more common in the aging general population. However, patients aged ≥80 years rarely undergo conventional open surgery under general anesthesia because of the high risk of peri-operative morbidity and adverse events. Therefore, less invasive surgical alternatives are needed for older or medically handicapped patients. Transforaminal endoscopic lumbar foraminotomy (TELF) under local anesthesia may be helpful in at-risk patients, although only limited information is available regarding the clinical outcomes of this procedure in octogenarians. Therefore, this study aimed to investigate the safety and efficacy of TELF for treating radiculopathy induced by foraminal stenosis in octogenarian patients. Methods: Overall, 32 consecutive octogenarian patients with lumbar foraminal stenosis underwent TELF between January 2019 and January 2021. The inclusion criterion was unilateral radiculopathy secondary to lumbar foraminal stenosis. The pain focus was confirmed using imaging studies and selective nerve blocks. Full-scale foraminal decompression was performed using a percutaneous transforaminal endoscopic approach under local anesthesia. Surgical outcomes were assessed using the visual analog pain score, Oswestry Disability Index, and modified MacNab criteria. Results: The pain scores and functional outcomes improved significantly during the 24-month follow-up period, and the rate of clinical improvement was 93.75% in 30 of the 32 patients. None of the patients experienced systemic complications. Conclusion: TELF under local anesthesia is an effective and safe treatment for foraminal stenosis in octogenarian or medically compromised patients. The mid-term follow-up did not reveal any significant progression in spinal stability. Therefore, this endoscopic procedure can be an effective alternative to aggressive surgery for managing lumbar foraminal stenosis in octogenarian patients with intractable radiculopathy.

Efficacy of Transforaminal Endoscopic Lumbar Discectomy in Elderly Patients Over 65 Years of Age Compared to Young Adults.

OBJECTIVE: Spine surgery rates are increasing in the elderly population due to social aging, and it is known that prognoses related to surgery are worse for the elderly compared to younger individuals. However, minimally invasive surgery, such as full endoscopic surgery, is considered safe with low complication rates due to minimal damage to surrounding tissues. In this study, we compared outcomes of transforaminal endoscopic lumbar discectomy (TELD) in elderly and younger patients with disc herniation in the lumbosacral region. METHODS: We retrospectively analyzed the data of 249 patients who underwent TELD at a single center between January 2016 to December 2019, with a minimum follow-up of 3 years. Patients were allocated to 2 groups: a young group aged ≤ 65 years (n = 202) or an elderly group aged > 65 years (n = 47). We evaluated baseline characteristics, clinical outcomes, surgery-related outcomes, radiological outcomes, perioperative complications, and adverse events during the 3-year follow-up period. RESULTS: Baseline characteristics, including age, general condition based on American Society of Anesthesiologist physical status classification grade, age-Charlson Comorbidity Index, and disc degeneration, were worse in elderly group (p < 0.001). However, except for leg pain at 4 weeks after surgery, overall outcomes, including pain improvement, radiological change, operation time, blood loss, and hospital stay, were not different between the 2 groups. Furthermore, the rates of perioperative complications (9 patients [4.46%] in the young group and 3 patients [6.38%] in the elderly group, p = 0.578) and adverse events over the 3-year follow-up period (32 patients [15.84%] in the young group and 9 patients [19.15%] in the elderly group, p = 0.582) were comparable in the 2 groups. CONCLUSION: Our findings suggest that TELD produces similar outcomes in both elderly and younger patients with a herniated disc in the lumbosacral region. TELD can be considered a safe option for appropriately selected elderly patients.

Comparing efficacies of different treatment regimens in patients with hepatocellular carcinoma accompanied by portal vein tumor thrombus using network meta-analysis.

Purpose: Although various treatment regimens have been introduced for hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT), comprehensive and direct comparisons between them are limited. Thus, the purpose of this study was to perform a network meta-analysis (NMA) to compare the efficacies of different treatment regimens for HCC accompanied by PVTT. Methods: A systematic review was conducted to identify studies comparing 2 or more treatment regimens for HCC accompanied by PVTT without extrahepatic metastasis and reporting each overall survival (OS). Endpoints of this NMA were to hazard ratios with confidential intervals for OS and mean survival time difference of each treatment regimen comparison using a random-effects model. Each treatment regimen was then ranked using the P-score to assess the probability of the superiority of each one. Results: Eleven studies involving 1,623 patients that yielded 16 comparisons were identified and enrolled in this NMA. There were 12 different treatment regimens as comparators, including sorafenib therapy alone (reference treatment). The NMA suggested that the following 4 treatment regimens improved OS compared to sorafenib: surgical resection followed by portal vein chemotherapy (SR plus PVC), SR, radiofrequency ablation plus sorafenib, and transarterial chemoembolization combined with selective internal radiation therapy. SR plus PVC was ranked the best treatment regimen for OS (P-score, 93.9%). Conclusion: Comparative efficacy based on this NMA may help clinicians select treatment for HCC accompanied by PVTT. If amenable, aggressive locoregional treatment regimens such as SR plus PVC should be considered for HCC accompanied by PVTT.

Is partial hepatectomy a curable treatment option for hepatocellular carcinoma accompanied by cirrhosis? A meta-analysis and cure model analysis.

BACKGROUNDS/AIMS: It is challenging to assess the efficacy of partial hepatectomy (PH) as a treatment option for patients with hepatocellular carcinoma (HCC) accompanied by cirrhosis. This study aimed to determine the cure fraction of PH for HCC accompanied by cirrhosis compared to that for HCC without cirrhosis. METHODS: A systematic review was performed on outcomes of previous studies that compared recurrence-free survival (RFS) after PH in patients with HCC with or without cirrhosis. A meta-analysis was conducted to obtain the cumulative hazard ratio for two patient groups: cirrhosis and non-cirrhosis. Cure fractions after PH in both groups were determined using a cure model analysis. RESULTS: A total of 18 studies were eligible for meta-analysis and 13 studies were selected for the cure model analysis. The cumulative hazard ratio for RFS of the cirrhosis group compared to that of the non-cirrhosis group was 1.66 (95% confidence interval [CI], 1.43-1.93). Survival data of 3,512 patients in both groups were reconstructed from survival curves of original articles for cure model analysis. The probability of being statistically cured after PH for HCC was 14.1% (95% CI, 10.6%-18.1%) in the cirrhosis group lower than that (32.5%) in the non-cirrhosis group (95% CI, 28.6%-36.4%). CONCLUSIONS: The prognosis after PH for HCC accompanied by cirrhosis is inferior to that for HCC without cirrhosis. However, a cure can be expected for one-seventh of patients with HCC accompanied by cirrhosis after PH.

Comparison of the Outcomes of Percutaneous Endoscopic Interlaminar Lumbar Discectomy and Open Lumbar Microdiscectomy at the L5-S1 Level.

BACKGROUND: Although many studies have compared full endoscopic spine surgery and open spine surgery, few have compared the outcomes of percutaneous endoscopic interlaminar lumbar discectomy (PEILD) and open lumbar microdiscectomy (OLM) at the L5-S1 level. OBJECTIVES: We compared the clinical, surgical, and radiological outcomes of patients with disc herniation at the L5-S1 level who underwent either PEILD, or OLM, performed by a single surgeon with novice-level proficiency. STUDY DESIGN: Observational, retrospective matched cohort design. SETTING: An analysis of clinical data was performed at a single center, collected from September 2012 to August 2016. METHODS: The study enrolled 56 patients who underwent discectomy at the L5-S1 level, with a minimum one-year follow-up. Patients were allocated to 2 groups: a PEILD group (n = 27; September 2014 to August 2016), or an OLM group (n = 29; September 2012 to August 2014). Clinical, surgical, and radiological outcomes were retrospectively evaluated. RESULTS: Baseline characteristics including age, gender, past medical history, body mass index, preoperative symptom, and preoperative radiological findings did not differ significantly between the groups. Further, overall clinical outcomes including back and leg pain; surgical outcomes including blood loss, complication rate, and recurrence rate; and radiological outcomes including degree of decompression, disc height, and sagittal alignment were not different significantly between the 2 groups.However, the PEILD group showed significant advantages including lower immediate postoperative back pain (mean 1.44 [95% confidence interval (CI), 1.16-1.72] versus 2.41 [95% CI, 2.14-2.69], P < 0.001), favorable immediate postoperative Odom's criteria (excellent 57.14% versus 24.14%, P = 0.025), shorter operation time (mean 63.89 ±17.99 minutes versus 109.66 ±31.42 minutes, P < 0.001), shorter hospital stay (3.15 [95% CI, 2.21-4.09] days versus 5.72 [95% CI, 3.29-8.16] days, P < 0.001), and rapid return to work (15.67 [95% CI, 12.64-18.69] days versus 24.31 [95% CI ,19.97-28.65] days, P = 0.001). LIMITATION: Due to its retrospective nature, it was not possible to control for all variations. Moreover, the number of patients in the final cohort was relatively small. CONCLUSIONS: Our findings indicate that the PEILD group achieved better perioperative outcomes despite no significant intergroup difference in mid-term clinical and radiological outcomes.

Value of surgical resection compared to transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein tumor thrombus: A meta-analysis of hazard ratios from five observational studies.

BACKGROUNDS/AIMS: Although systemic therapy is recommended in advanced hepatocellular carcinoma (HCC), treatment options for advanced HCC with portal vein tumor thrombosis (PVTT) are debatable. Recent studies have recommended other treatments, such as surgical resection (SR) and transarterial chemoembolization (TACE). Therefore, we performed a meta-analysis of hazard ratio (HR) for overall survival (OS) between the two modalities using previous reports in order to compare the two treatment options. METHODS: A systematic review was performed on previously reported data that compared the survival benefits of SR and TACE in patients with advanced HCC with PVTT. Thereafter, the meta-analysis was performed to determine the cumulative HR between the two different treatment groups. We used the HR and 95% CI directly from the original data, when available; however, if these data were unavailable, reconstruction was performed with the secondary data from the original Kaplan-Meier survival curve. RESULTS: A total of seven studies were eligible; however, 2 were excluded from the meta-analysis. The remaining 5 studies that included 1422 patients (SR group=559, TACE group=863) were studied for the meta-analysis. The median OS was longer in the SR group (8.2-64 months in SR vs. 6.6-32 months in TACE), proving that SR offered survival benefits. Moreover, the HR for the OS in the TACE group was 1.64 (95% CI, 1.43-1.88) compared to SR group, depicting that TACE was a less favorable option compared to SR. CONCLUSIONS: There is evidence that SR may be a better viable option for advanced HCC with PVTT.

Clinical study on concurrent use of electro-acupuncture or Chuna manual therapy with pregabalin for chemotherapy-induced peripheral neuropathy: safety and effectiveness (open-labeled, parallel, randomized controlled trial, assessor-blinded): A study protocol.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects of chemotherapy. Its main symptoms are pain, paresthesia, and numbness. However, the mechanisms underlying the development of CIPN remain unclear and standard treatments have not been established. Recently, there has been a growing interest in various approaches to overcome the limitations of the existing treatments. This study aims to evaluate the efficacy and safety of the concurrent use of two complementary and alternative therapies: electroacupuncture (EA) and Chuna manual therapy (CMT), with pregabalin, which is the conventional pharmacotherapy for neuropathic pain. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial, which includes 90 patients with colorectal and breast cancer, who developed CIPN. After a 2-week preparation period, the patients are divided into three groups (pregabalin administration group, pregabalin + EA treatment group, and pregabalin + CMT treatment group), treated for approximately 5 weeks and followed-up 4 weeks after treatment. The primary outcome is assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale score (version 4.0) and the secondary outcome is measured using the Quality of Life Questionnaire-CIPN 20-Item Scale (version 3.0) and the quality of life questionnaire (version 3.0) developed by the European Organisation for Research and Treatment of Cancer. Moreover, exploratory efficacy and safety evaluations will be conducted based on the chemotherapy-completion rate and nerve conduction studies.

MicroRNAs associated with microvascular invasion in hepatocellular carcinoma and their prognostic impacts in patients undergoing hepatic resection.

Although microvascular invasion (McVI) has prognostic value for patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between McVI and the aberrant expression of microRNAs (miRNAs). The present study identified the miRNAs that were selectively expressed in HCC with McVI and investigated their prognostic value. Clinical data and the miRNA expression profiles of 372 patients with HCC were extracted from The Cancer Genome Atlas database. miRNAs that were differentially expressed between patients with McVI and those without vascular invasion (VI) were identified and investigated as potential prognostic factors for HCC. The results demonstrated that McVI was a significant predictor of shortened recurrence-free survival (RFS). The 3 year RFS rate in patients with HCC accompanied by McVI was 28.2 and 49.3% in HCC without VI (P<0.001). miRNA-141/-582/-9 were upregulated, while miRNA-675 was downregulated in patients with McVI when compared with HCC patients without VI. Log2 fold-changes of miRNA-141/-582/-675/-9 were 0.80 [false discovery rate (FDR), 0.005], 0.55 (FDR, 0.045), -0.99 (FDR, 0.005) and 1.22 (FDR, <0.001), respectively. Kaplan-Meier analysis indicated that the overexpression of miR-141/-582/-9 was significantly associated with poor RFS and a poor overall survival. A text mining analysis revealed that these miRNAs were significantly associated with multifaceted hallmarks of cancer, including 'invasion and metastasis'. In conclusion, the overexpression of miRNA-141/-582/-9 was associated with McVI and a poor survival in patients undergoing hepatic resection for HCC.

Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection.

BACKGROUND: Although gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance. MATERIALS AND METHODS: Eligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated. RESULTS: Thirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, three miRNAs were validated using TCGA database. miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no gross VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and low expression of miR-100-5p were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, low expression of miR-100-5p and miR-148a-3p were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including "invasion and metastasis." CONCLUSIONS: Low expressions of miR-100-5p and miR-148a-3p were associated with gross VI and poor survival of patients after hepatic resection for HCC.

Theragnosis by a miR-141-3p molecular beacon: simultaneous detection and sensitization of 5-fluorouracil resistant colorectal cancer cells through the activation of the TRIM13-associated apoptotic pathway.

We developed a molecular beacon targeting miR-141-3p, aberrantly increased in 5-fluorouracil-resistant colorectal cancer cells (R-CRCCs). It consists of a fluorophore-labeled oligonucleotide, antisense to miR-141-3p, and a quencher. It detected R-CRCCs and recovered the chemosensitivity of them to 5-fluorouracil by hybridization with miR-141-3p, which is applicable to cancer treatment.

Conditional Survival Analysis Demonstrates that Recurrence Risk of Surgically Treated Hepatocellular Carcinoma Evolves with Time.

OBJECTIVE: The study aim was to investigate long-term change in tumor recurrence risk in patients with hepatocellular carcinoma (HCC) after hepatic resection. Recurrence probability over time was estimated by conditional survival (CS) analysis. PATIENTS AND METHODS: Early-stage HCC patients with hepatic resection were selected for inclusion from our surgery database. Variables predictive of tumor recurrence were identified by univariate and multivariate analyses. Five-year recurrence-free CS probability was calculated for all patients and for risk groups stratified by independent predictors. RESULTS: In this series of 436 patients, tumor size >5 cm, microvascular invasion, positive resection margin, liver cirrhosis, and a indocyanine green retention ratio at 15 min (ICG-R15) >20% were independently predictive of tumor recurrence. The estimated 5-year recurrence-free CS probability improved with each additional year of recurrence-free survival, and the improvement was significantly greater in the high-risk than in the low- or intermediate-risk groups. CONCLUSION: CS provides added value during follow-up of early-stage HCC patients treated by surgical resection.

Bioimaging of multiple piRNAs in a single breast cancer cell using molecular beacons.

Simultaneous bioimaging of piR-36026 and piR-36743 using molecular beacons successfully visualized 4 different subtypes of breast cancer.

Multiplex bioimaging of piRNA molecular pathway-regulated theragnostic effects in a single breast cancer cell using a piRNA molecular beacon.

Recently, PIWI-interacting small non-coding RNAs (piRNAs) have emerged as novel cancer biomarkers candidate because of their high expression level in various cancer types and role in the control of tumor suppressor genes. In this study, a novel breast cancer theragnostics probe based on a single system targeting the piRNA-36026 (piR-36026) molecular pathway was developed using a piR-36026 molecular beacon (MB). The piR-36026 MB successfully visualized endogenous piR-36026 biogenesis, which is highly expressed in MCF7 cells (a human breast cancer cell line), and simultaneously inhibited piR-36026-mediated cancer progression in vitro and in vivo. We discovered two tumor suppressor proteins, SERPINA1 and LRAT, that were directly regulated as endogenous piR-36026 target genes in MCF7 cells. Furthermore, multiplex bioimaging of a single MCF7 cell following treatment with piR-36026 MB clearly visualized the direct molecular interaction of piRNA-36026 with SERPINA1 or LRAT and subsequent molecular therapeutic responses including caspase-3 and PI in the nucleus.