Laparoscopically Limited Anatomic Liver Resections: A Single-Center Analysis for Oncologic Outcomes of the Conceptual Procedure.

BACKGROUND: Limited anatomic resections (LARs), such as segmentectomies, performed using a fully laparoscopic approach, have gained popularity for liver malignancies. However, the oncologic efficacy of laparoscopic LARs (Lap-LARs) needs further investigation. This cohort study evaluated the oncologic outcomes of Lap-LAR for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). METHODS: At a Japanese referral center, 112 patients underwent Lap-LAR using the Glissonean approach and indocyanine green (ICG) fluorescence navigation. Recurrence-free survival (RFS), overall survival (OS), time to interventional failure (TIF), and time to surgical failure (TSF) were assessed. RESULTS: Among the 112 patients (median age, 74 years [range, 66-80 years]; 80 men [71.4 %]), Lap-LAR showed promising results. The median operative time was 348 min (range, 280-460 min), and the median blood loss was 190 mL (range, 95.5-452.0 mL). The median error between the estimated and actual liver volumes was 2 % (1.2-4.8 %). Complications greater than Clavien-Dindo 3a were observed in 11.6 % of the patients. The 5-year RFS, OS, and TIF rates for HCC were 45.1 % ± 7.9 %, 73.1 % ± 6.7 %, and 74.2 % ± 6 .6 %, respectively. The 5-year RFS, OS, and TSF rates for CRLM were 36.8 % ± 8.7 %, 60.1 % ± 13.3 %, and 63.6 % ± 10.4 %, respectively. CONCLUSIONS: Lap-LAR showed favorable oncologic outcomes for HCC and CRLM. Its precise technique makes it a promising therapeutic option for liver malignancies. Further comparisons with conventional approaches are warranted.

Combining preoperative C-reactive protein values with the Tokyo Guidelines 2018 grading criteria can enhance the prediction of surgical difficulty in early laparoscopic cholecystectomy for acute cholecystitis.

BACKGROUND: Early laparoscopic cholecystectomy (ELC) is the standard treatment for acute cholecystitis (AC). However, predicting the difficulty of this procedure remains challenging. The present study aimed to develop an improved prediction model for surgical difficulty during ELC, surpassing the current Tokyo Guidelines 2018 (TG18) grading system. METHODS: We analyzed data from 201 consecutive patients who underwent ELC for AC between 2019 and 2021. Surgical difficulty was defined as the failure to achieve the critical view of safety (non-CVS). We developed a scoring system by conducting multivariate analysis on demographics, symptoms, laboratory data, and radiographic findings. The predictive accuracy of our scoring system was compared to that of the TG18 grading system (Grade I vs. Grade II/III). RESULTS: Through multivariate logistic regression analysis, a novel scoring system was formulated. This system incorporated preoperative C-reactive protein (CRP) values (≥5: 1 pt, ≥10: 2 pts, ≥15: 3 pts) and TG18 grading score (duration >72 h: 1 pt, image criteria for Grade II AC: 1 pt). Our model, a cutoff score of ≥3, exhibited a significantly elevated area under the curve (AUC) of 0.721 compared to the TG18 grading system alone (AUC 0.609) (p = 0.001). CONCLUSION: Combining preoperative CRP values with TG18 grading criteria can enhance the accuracy of predicting intraoperative difficulty in ELC for AC.

Benefits of laparoscopic liver resection in elderly patients.

BACKGROUND: The indications of laparoscopic liver resection (LLR) have expanded to high-risk patients, such as elderly people. However, to date, little evidence has been established of the safety and feasibility of LLR in elderly patients. The short-term outcomes of LLR in elderly patients as compared to non-elderly patients were investigated. METHODS: Data of a total of 297 patients who underwent LLR were reviewed. Among these 297 patients, 181 patients were < 75 years age (non-elderly) and 116 patients were ≥ 75 years age (elderly), and the surgical outcomes were compared between the groups. In addition, we evaluated the risk factors for postoperative morbidity (Clavien-Dindo grade ≥ IIIa) utilizing the preoperative, operative, and postoperative variables RESULTS: The preoperative liver/renal function, frequency of anti-thrombotic drug use, number of comorbidities, and American Society of Anesthesiologists-physical status classification were more unfavorable in elderly patients than in non-elderly patients. No significant inter-group differences were observed in the operation time, blood loss, conversion rate, postoperative morbidity, or 30-day mortality. The 3-year overall survival rate was comparable between the two groups. Multivariate analysis identified anti-thrombotic drug use, operation time > 7 h, and peak serum total bilirubin > 2 mg/dl within postoperative day 3 as independent risk factors for Clavien-Dindo ≥ IIIa postoperative morbidity (P = 0.016, P < 0.001, and P = 0.001, respectively). CONCLUSIONS: LLR in elderly patients may provide comparable short-term outcomes to those in non-elderly patients.

Time required for indocyanine green fluorescence emission for evaluating bowel perfusion in left-sided colon and rectal cancer surgery.

BACKGROUND: Indocyanine green fluorescence imaging (ICG-FI) has been reported to be useful in reducing the incidence of anastomotic leakage (AL) in colectomy. This study aimed to investigate the correlation between the required time for ICG fluorescence emission and AL in left-sided colon and rectal cancer surgery using the double-stapling technique (DST) anastomosis. METHODS: This retrospective study included 217 patients with colorectal cancer who underwent left-sided colon and rectal surgery using ICG-FI-based perfusion assessment at our department between November 2018 and July 2022. We recorded the time required to achieve maximum fluorescence emission after ICG systemic injection and assessed its correlation with the occurrence of AL. RESULTS: Among 217 patients, AL occurred in 21 patients (9.7%). The median time from ICG administration to maximum fluorescence emission was 32 s (range 25-58 s) in the AL group and 28 s (range 10-45 s) in the non-AL group (p < 0.001). The cut-off value for the presence of AL obtained from the ROC curve was 31 s. In 58 patients with a required time for ICG fluorescence of 31 s or longer, the following risk factors for AL were identified: low preoperative albumin [3.4 mg/dl (range 2.6-4.4) vs. 3.9 mg/dl (range 2.6-4.9), p = 0.016], absence of preoperative mechanical bowel preparation (53.8% vs. 91.1%, p = 0.005), obstructive tumor (61.5% vs. 17.8%, p = 0.004), and larger tumor diameter [65 mm (range 40-90) vs. 35 mm (range 4.0-100), p < 0.001]. CONCLUSION: The time required for ICG fluorescence emission was associated with AL.

Early laparoscopic cholecystectomy for acute cholecystitis following the Tokyo Guidelines 2018: a prospective single-center study of 201 consecutive cases.

BACKGROUND: Early laparoscopic cholecystectomy (ELC) for acute cholecystitis (AC) poses multiple challenges. The Tokyo Guidelines 2018 (TG18) eliminated the time limit (< 72 h) and expanded the surgical indication to severe AC. This study aimed to evaluate the clinical outcomes of ELC for AC following the TG18 in a single high-volume center. METHODS: From 2019 to 2021, we managed all AC patients with a TG18 flowchart and prospectively enrolled those who underwent ELC within 7 days of symptom onset. The primary outcome was overall morbidity, with a comparison between mild (Grade I) and moderate/severe (Grade II/III) AC. RESULTS: During the study period, 201 patients underwent ELC was for Grade I (56.2%), II (40.3%), and III (3.5%) ACs. Mean age was 69 ± 15.2 years and time to surgery from symptom onset was 0 (12.9%), 1-3 (66.7%), and 4-7 days (20.4%). Mean operative time and blood loss were 118.9 ± 42.7 min and 57.8 ± 99.4 mL, respectively. The critical view of safety (CVS) was achieved in 76.1% of patients, and bailout procedures were performed in 21.4%. There were no open conversions or bile duct injuries. Major morbidities (Clavien-Dindo classification ≥ IIIa) were observed in 5.5% of cases and mortality in 0.5%. Comparing Grades II/III to Grade I, operative time was longer (112.3 vs. 127.3 min, p = 0.014), blood loss was higher (40.3 vs. 80.1 mL, p = 0.005), the CVS rate was lower (83.2 vs. 67.0%, p = 0.012), and the major morbidity rate was higher (1.8 vs. 10.2%, p = 0.012). In the subgroup analysis of Grade II/III, there were no significant differences in major morbidities (p = 0.288) between the two groups (0-3 vs. 4-7 days). CONCLUSION: ELC for AC following TG18 is feasible with low morbidity rates. However, ELC for Grade II/III ACs remains challenging, and surgeons must carefully assess intraoperative difficulties and surgical risks before proceeding.

Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN).

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) involves adenoma (IPMA), a precancerous lesion, cancer (IPMC) including high-grade dysplasia (HGD), and invasive carcinoma (IC). DNA markers of IPMN are required for detection of invasive disease, and cysteine dioxygenase 1 (CDO1) gene promoter hypermethylation is a potential candidate. However, it has never been investigated in the context of IPMN. PATIENTS AND METHODS: A total of 107 IPMN tumor tissues, including 41 IPMC and 66 IPMA, were studied. CDO1 promoter methylation was quantified using TaqMan quantitative methylation-specific polymerase chain reaction (qMSP) in patients with IPMN and other pancreatic cystic disorders after pancreatectomy. RESULTS: The methylation values (TaqMeth Vs) of CDO1 increased when noncancerous pancreas tissues were compared with IPMA and HGD (p < 0.0001). Among IPMC, the TaqMeth Vs in IC were not significantly higher than in HGD. The TaqMeth Vs of the solid tumors were higher than those of the cystic tumors (p = 0.0016), which were in turn higher than the corresponding noncancerous tissues (p < 0.0001). Prognostic analysis revealed that high TaqMeth Vs (≥ 14.1) resulted in a poorer prognosis than low TaqMeth Vs (< 14.1) (p < 0.0001). In other pancreatic cystic diseases, only malignant mucinous cystic neoplasm showed DNA hypermethylation of its promoter. A pilot study in pancreatic juice confirmed methylation in all IPMN samples but not in benign pancreatic diseases (p = 0.0277). CONCLUSIONS: CDO1 promoter hypermethylation is extremely specific to IPMN and may accumulate with IPMN tumor progression during the adenoma-carcinoma sequence. It might be a promising candidate as a diagnostic marker of pancreatic cystic diseases.

Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer.

DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation-specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound-fine needle aspiration (EUS-FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS-FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS-FNA cytology.

WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability.

BACKGROUND: WiNTRLINC1 is a long non-coding RNA (lncRNA) that positively regulates the Wnt pathway via achaete-scute complex homolog 2 (ASCL2) in colorectal cancer. ASCL2 was recently reported to play a critical role in chemoresistance, however clinical relevance of the WiNTRLINC1/ASCL2 axis remains obscure in colon cancer. PATIENTS AND METHODS: WiNTRLINC1/ASCL2 expression was investigated at messenger RNA (mRNA) level in 40 primary colon cancer tissues and the corresponding normal mucosa tissues, together with Wnt-related genes (c-Myc/PRL-3) and other lncRNAs (H19, HOTAIR, and MALAT1). Knock-down experiments of WiNTRLINC1 clarified its role in their expression and chemoresistance. RESULTS: Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed definite overexpression of WiNTRLINC1 mRNA in primary colon cancer compared with the corresponding normal colon mucosa tissues (p = 0.0005), such as ASCL2, c-Myc, and PRL-3 (p < 0.0001). The four gene expression signatures were tightly associated in the center of the ASCL2 gene (r = 0.72, p < 0.0001) in clinical samples. WiNTRLINC1 was not significantly associated with prognostic factors in colon cancer and other lncRNAs, while the WiNTRLINC1/ASCL2/c-Myc signatures were unique to young-onset colon cancer with differentiated histology. On the other hand, undifferentiated histology was significantly associated with H19 expression. Knockdown of the WiNTRLINC1 gene reduced the expression of ASCL2/c-Myc, but rather augmented PRL-3 at mRNA level, and robustly affected cell viability in colon cancer cell lines. CONCLUSION: The enhanced WiNTRLINC1/ASCL2/c-Myc axis involved in Wnt pathway activation is a common pathway essential for differentiated colon tumorigenesis, especially with young onset, and may be essential for a viable phenotype of colon cancer.

Two cases of cystic artery pseudoaneurysm rupture due to acute cholecystitis with gallstone impaction in the neck.

A cystic artery aneurysm is a rare cause of hemobilia. Herein, we report two cases of acute cholecystitis with a ruptured cystic artery pseudoaneurysm. Two patients (a 69-year-old man and an 83-year-old man) were admitted to our hospital because of acute cholecystitis with gallstone impaction in the neck. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed for both patients. After a few days of PTGBD, gallbladder hemorrhage was observed. Abdominal angiography showed cystic artery aneurysm. A transcatheter arterial embolization was therefore performed, followed by an open cholecystectomy.

Prevention of Post-Hepatectomy Liver Failure in Cirrhotic Patients Undergoing Minimally Invasive Liver Surgery for HCC: Has the Round Ligament to Be Preserved?

Post-hepatectomy liver failure (PHLF) represents a major cause of morbidity and mortality after liver resection. The factors related to PHLF are represented not only by the volume and function of the future liver remnant but also by the severity of portal hypertension. The aim of this study was to assess whether the preservation of the round ligament (RL) may mitigate portal hypertension, thus decreasing the risk of PHLF and ascites in cirrhotic patients while undergoing minimally invasive liver surgery (MILS). All the cirrhotic patients who underwent MILS for HCC from 2016 to 2021 in two international tertiary referral centers were retrospectively analyzed, comparing cases with the RL preserved vs. those with the RL divided. Only patients with cirrhosis ≥ Child A6, portal hypertension, and ICG-R15 > 10% were included. Main postoperative outcomes were compared, and the risk factors for postoperative ascites (severe PHLF, grade B/C) were investigated through a logistic regression. After the application of the selection criteria, a total of 130 MILS patients were identified, with 86 patients with the RL preserved and 44 with the RL divided. The RL-preserved group showed lower incidences of severe PHLF (7.0% vs. 20.5%, p = 0.023) and ascites (5.8% vs. 18.2%, p = 0.026) in comparison with the RL-divided group. After uni/multivariate analysis, the risk factors related to postoperative ascites were RL division and platelets < 92 × 103/µL, calculated with ROC analysis. The preservation of the round ligament during MILS may mitigate portal hypertension, preventing PHLF and ascites in cirrhotic patients with borderline liver function.

Latest Findings on Minimally Invasive Anatomical Liver Resection.

Minimally invasive liver resection (MILR) is being widely utilized owing to recent advancements in laparoscopic and robot-assisted surgery. There are two main types of liver resection: anatomical (minimally invasive anatomical liver resection (MIALR)) and nonanatomical. MIALR is defined as a minimally invasive liver resection along the respective portal territory. Optimization of the safety and precision of MIALR is the next challenge for hepatobiliary surgeons, and intraoperative indocyanine green (ICG) staining is considered to be of considerable importance in this field. In this article, we present the latest findings on MIALR and laparoscopic anatomical liver resection using ICG at our hospital.

Comparing the accuracy of positive and negative indocyanine green staining in guiding laparoscopic anatomical liver resection: protocol for a randomised controlled trial.

INTRODUCTION: Knowledge of the clinical liver anatomy has evolved with advanced imaging modalities and laparoscopic surgery. Therefore, precise anatomical resection knowledge has become the standard treatment for primary and secondary liver cancer. Segmentectomy, a parenchymal-preserving approach, is regarded as an option for anatomical resections in patients with impaired liver. Indocyanine green (ICG) staining is a promising method for understanding the anatomical borders of the liver segments. There are two methods of ICG staining (positive and negative), and the superiority of either approach has not been determined to date. METHODS AND ANALYSIS: This is a prospective randomised controlled superiority clinical trial performed in a single centre tertiary hospital in Japan. A comparison between the accuracy of positive and negative ICG staining in guiding laparoscopic anatomical liver resection is planned in this study. Possible candidates are patients with liver malignant tumours in whom laparoscopic monosegmentectomy or subsegmentectomy is planned. Fifty patients will be prospectively allocated into the following two groups: group A, ICG-negative staining group, and group B, ICG-positive staining group. The optimal dose of ICG for positive staining will be determined during the preparation phase. To assess the ability of the ICG fluorescence guidance in anatomical resection, the primary endpoint is the success rate of ICG staining, which consists of a SOS based on three components: superficial demarcation in the liver surface, visualisation of the parenchymal borders and consistency with the preoperative three-dimensional simulation. The secondary endpoints are the evaluation of short-term surgical outcomes and recurrence-free survival. ETHICS AND DISSEMINATION: The study was approved by Ageo Central General Hospital Clinical Research Ethical Committee (No: 1044) and it carried out following the Declaration of Helsinki (2013 revision). Informed consent will be taken from the patients before participating. The findings will be disseminated through peer-reviewed publications, scientific meetings and conferences. TRIAL REGISTRATION NUMBER: UMIN000049815.

Less demand on stem cell marker-positive cancer cells may characterize metastasis of colon cancer.

BACKGROUND: CD44 and CD133 are stem cell markers in colorectal cancer (CRC). CD44 has distinctive isoforms with different oncological properties like total CD44 (CD44T) and variant CD44 (CD44V). Clinical significance of such markers remains elusive. METHODS: Sixty colon cancer were examined for CD44T/CD44V and CD133 at mRNA level in a quantitative PCR, and clarified for their association with clinicopathological factors. RESULTS: (1) Both CD44T and CD44V showed higher expression in primary colon tumors than in non-cancerous mucosas (p<0.0001), while CD133 was expressed even in non-cancerous mucosa and rather decreased in the tumors (p = 0.048). (2) CD44V expression was significantly associated with CD44T expression (R = 0.62, p<0.0001), while they were not correlated to CD133 at all in the primary tumors. (3) CD44V/CD44T expressions were significantly higher in right colon cancer than in left colon cancer (p = 0.035/p = 0.012, respectively), while CD133 expression were not (p = 0.20). (4) In primary tumors, unexpectedly, CD44V/CD44T/CD133 mRNA expressions were not correlated with aggressive phenotypes, but CD44V/CD44T rather significantly with less aggressive lymph node metastasis/distant metastasis (p = 0.040/p = 0.039, respectively). Moreover, both CD44V and CD133 expressions were significantly decreased in liver metastasis as compared to primary tumors (p = 0.0005 and p = 0.0006, respectively). CONCLUSION: Our transcript expression analysis of cancer stem cell markers did not conclude that their expression could represent aggressive phenotypes of primary and metastatic tumors, and rather represented less demand on stem cell marker-positive cancer cells.

Short-term Outcomes and Difficulty of Repeat Laparoscopic Liver Resection.

Objectives: To investigate the feasibility of repeat laparoscopic liver resection (Rep-LLR), including repeat anatomical resection (Rep-AR), as compared to initial-LLR (Ini-LLR). Background: The indications of LLR have expanded to treatment of recurrent liver tumors. However, the feasibility of Rep-LLR, including Rep-AR, has not yet been adequately assessed. Methods: Data of 297 patients who had undergone LLR were reviewed. Among the 297 patients, 235 (AR: 168) had undergone Ini-LLR and 62 (AR: 27) had undergone Rep-LLR, and the surgical outcomes were compared between the groups. In addition, multivariate analysis was performed to identify predictors of the difficulty of Rep-LLR based on the operation time and volume of blood loss. Results: Of the 62 patients who had undergone Rep-LLR, 44, 14, and 4 had undergone second, third, and fourth repeat LRs, respectively. No significant intergroup differences were observed in regard to the operation time, blood loss, conversion rate to open surgery, postoperative morbidity, or postoperative hospital stay. However, the proportion of patients in whom the Pringle maneuver was used was significantly lower in the Rep-LLR group than in the Ini-LLR group. Multivariate analysis identified surgical procedure ≥sectionectomy at the initial/previous LR and an IWATE difficulty score of ≥6 as being independent predictors of the difficulty of Rep-LLR. Use of adhesion barriers at the initial/previous LR was associated with a decreased risk of failure to perform the Pringle maneuver during Rep-LLR. Conclusions: Rep-LLR can offer outcomes comparable to those of Ini-LLR over the short term.

Resection margin status in laparoscopic liver resection for colorectal liver metastases: literature review and future perspectives.

INTRODUCTION: Laparoscopic liver resection (LLR) has made remarkable progress over the past two decades, providing superior perioperative outcomes to open liver resection (OLR). The pros and cons of LLR for colorectal liver metastases (CRLMs) have been discussed along with the debate regarding optimal resection margins for CRLMs. EVIDENCE ACQUISITION: A literature review has been carried out (Pubmed and Embase) focusing on the resection margin status (R status) after LLR for CRLMs. EVIDENCE SYNTHESIS: LLR for CRLMs results in R1 in 7.6 to 21.3% of cases, the risk being the size and number of tumors and the amount of intraoperative blood loss. R1 is associated with shorter recurrence-free survival but has no impact on overall survival. There is insufficient evidence regarding the prognostic value of laparoscopic two-stage hepatectomy (TSH) or repeat hepatectomy (RH) for CRLMs. CONCLUSIONS: Although R0 remains the golden standard for CRLMs, the acceptability of R1 should be determined based on an overall assessment of the biological malignancy, remnant liver volume, and the proximity to major vasculature. The strategy of performing multiple LLRs for CRLMs while allowing for R1 at the initial operation is a topic for future research.

Preoperative blood circulation modification prior to pancreaticoduodenectomy in patients with celiac trunk occlusion: Two case reports.

BACKGROUND: Celiac trunk stenosis or occlusion is a common condition observed in patients undergoing pancreaticoduodenectomy (PD). The risk of upper abdominal organ ischemia or failure increases if the blood circulation in the celiac arterial system is not maintained after the surgery. CASE SUMMARY: We present two cases of elderly patients with distal cholangiocarcinoma and celiac trunk occlusion who underwent PD. We performed blood circulation modification preoperatively with transcatheter coil embolization of the arterial arcades of the pancreatic head via the superior mesenteric artery to develop collateral communication between the superior mesenteric artery and the common hepatic or splenic arteries to ensure arterial blood flow to the upper abdominal organs. The postoperative course was marked by delayed gastric emptying, but no major surgical complications, such as biliary or pancreatic fistula, or clinical, biochemical, or radiological evidence of ischemic disease, was observed. CONCLUSION: Preoperative blood circulation modification may be a valid alternative procedure for elderly patients with celiac trunk occlusion who are ineligible for interventional or surgical revascularization.

Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer.

PURPOSE: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). RESULTS: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). CONCLUSIONS: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma.

BACKGROUND: Promoter DNA methylation of Cysteine dioxygenase type1 (CDO1) gene has been clarified as a molecular diagnostic and prognostic indicator in various human cancers. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC). METHODS: CDO1 DNA methylation was assessed by quantitative methylation-specific PCR in 108 BTC tumor tissues and 101 corresponding normal tissues. BTC was composed of extrahepatic cholangiocarcinoma (EHCC) (n = 81) and ampullary carcinoma (AC) (n = 27). RESULTS: The CDO1 methylation value in the tumor tissues was significantly higher than that in the corresponding normal tissues (p<0.0001). The overall survival (OS) in EHCC patients with hypermethylation was poorer than those with hypomethylation (p = 0.0018), whereas there was no significant difference in AC patients. Multivariate analysis identified that CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in EHCC. The EHCC patients with CDO1 hypermethylation exhibited more dismal prognosis than those with hypomethylation even in low group of CA19-9 level (p = 0.0006). CONCLUSIONS: Our study provided evidence that promoter DNA methylation of CDO1 gene could be an excellent molecular diagnostic and prognostic biomarker in primary EHCC. The combination of CDO1 methylation and preoperative serum CA19-9 effectively enriched EHCC patients who showed the most dismal prognosis. These markers would be beneficial for clinical clarification of the optimal strategies in EHCC.