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.

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.

[A Case of Delayed Anastomotic Leakage after Ileocecal Resection in a Hemodialysis Patient].

A 66-year-old man was referred to our department with the diagnosis of ascending colon cancer. He was undergoing dialysis for chronic renal failure due to diabetic nephropathy. Laparoscopic ileocecal resection was planned for the ascending colon cancer, but the procedure was converted to laparotomy owing to intraoperative bleeding. The patient was discharged from the hospital after 7 days. On the 14th postoperative day, the patient presented with purulent drainage from the wound and fever and was diagnosed to have a minor anastomotic leak. The suture of the anterior sheath was exposed in part of the wound. The patient's general condition was stable, and conservative treatment was planned. However, when he coughed, the wound separated and the intestine prolapsed, and emergency surgery was performed. Intraoperative findings showed leakage of intestinal fluid from the anastomotic border, and we diagnosed delayed suture failure. We present a rare case of delayed anastomotic leakage in a hemodialysis patient.

Utility of Robot-assisted Laparoscopic Transabdominal Preperitoneal Repair of Inguinal Hernia Following Robot-assisted Laparoscopic Radical Prostatectomy.

BACKGROUND: To evaluate the utility of robot-assisted laparoscopic transabdominal preperitoneal repair (R-TAPP) of postprostatectomy inguinal hernia (PIH) in patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP). PATIENTS AND METHODS: This was a prospective, single-centre retrospective cohort study. R-TAPP was conducted in 74 consecutive patients from September 2016 to March 2020. With the exception of women and patients who underwent previous abdominal surgery, 70 patients were classified into two groups based on the absence or presence of PIH. Their data were retrospectively compared to those who had not undergone RALP. RESULTS: The median operative time for the PIH group was longer compared to the non-PIH group. However, postoperative complications, including seroma formation, haematoma and surgical site infections, were not significantly different between the groups. The estimated blood loss was small, and hospitalisation duration was 1 day in all cases. Moreover, there were no hernia recurrences within the 90-day follow-up period in either group. CONCLUSION: R-TAPP is a feasible and safe approach for inguinal hernia repair, even in patients who undergo RALP for prostate cancer.

Laparoscopic low anterior resection for rectal cancer associated with Leriche syndrome: a case report.

A 78-year-old male presented with a positive fecal occult blood test. Rectal cancer was detected during lower gastrointestinal endoscopy, and further investigations led to a diagnosis of cT1N0M0 cStage I (UICC classification, 8th edition). Preoperative contrast-enhanced computed tomography (CT) showed that the patient also had Leriche syndrome, which is associated with reduced blood flow to the rectum that may result in ischemic anastomosis during rectal cancer surgery with anastomotic reconstruction. The inferior epigastric arteries often function as collateral pathways to the lower limbs in patients with Leriche syndrome; therefore, care is needed to avoid vascular damage during trocar insertion when performing laparoscopic surgeries. We herein described a case of safe laparoscopic low anterior resection in a rectal cancer patient with Leriche syndrome using vascular architecture images obtained by preoperative CT angiography.

A goal-directed therapy protocol for preventing acute kidney injury after laparoscopic liver resection: a retrospective observational cohort study.

PURPOSE: Postoperative acute kidney injury (AKI) remains a serious complication of liver resection with restrictive fluid therapy. However, unlike open hepatectomy, laparoscopic liver resection (LLR) does not have established anesthesia management strategies. We compared our goal-directed therapy (GDT) protocol for LLR with/without carperitide and the conventional restrictive method regarding AKI prevention. METHODS: The GDT thresholds in this retrospective observational cohort study were as follows: stroke volume variation, ≤ 15%; pulse pressure variation, ≤ 13%; oxygen delivery index, ≥ 600 mL/min/m2; and mean arterial pressure (MAP), ≥ 55 mmHg. If the thresholds were not achieved, a 250 mL infusion fluid bolus was administered. The MAP target was changed to > 65 mmHg if the urine output was < 0.3 mL/kg/h. Postoperative AKI within 48 h and perioperative outcomes within 90 days were analyzed. RESULTS: Forty-seven propensity score-matched pairs from 127 patients were investigated. We adjusted for AKI risk factors and surgical difficulty; 46.8% of the GDT group received carperitide. The GDT group had a lower postoperative AKI rate (10.6% vs. 27.7%, P = 0.04) and shorter overall (P = 0.04) and postoperative (P < 0.01) hospital stays than the conventional group. Furthermore, the GDT group received more intraoperative fluid (P = 0.001) and phenylephrine (P = 0.02), without significant increases in blood loss and transfusion volume, than the conventional group. CONCLUSIONS: GDT reduced the AKI rates post-LLR.

[A Case of Anastomotic Recurrence 10 Years after Excision of Sigmoid Colon Cancer with Submucosal Invasion].

A 72-year-old woman underwent sigmoid colon resection plus D2 lymph node dissection in 2008, with additional resection after endoscopic mucosal resection(EMR). Histopathological examination revealed only atypical ducts in the EMR scar, with no invasion below the submucosa. No lymphatic, venous, or nerve invasions were confirmed, and oral and anal stumps and lymph node metastases were negative. She was followed up for 5 years after the surgery, and no recurrence was detected. In 2018, she visited our hospital with the chief complaint of diarrhea and constipation. Colonoscopy revealed a circumferential lesion around the anastomosis. She underwent laparoscopic low anterior resection for suspected anastomotic recurrence, which was confirmed by histopathological diagnosis. The anastomotic recurrence 10 years after surgery for SM cancer of the colon with negative lymph node metastasis and vascular factor was extremely rare. We recognized the importance of surveillance 5 years after surgery.

Evaluation of accuracy of laparoscopic liver mono-segmentectomy using the Glissonian approach with indocyanine green fluorescence negative staining by comparing estimated and actual resection volumes: A single-center retrospective cohort study.

BACKGROUND/PURPOSE: Laparoscopic liver mono-segmentectomy (LLMS) may improve patient outcomes, but it is difficult and its accuracy and safety are unknown. We evaluated the accuracy of LLMS using Glissonian approach with indocyanine green fluorescence (ICG) negative staining. METHODS: Seventy-four patients eligible for LLMS except for segment 1 were enrolled. Preoperative three-dimensional CT-based surgical simulation was used to determine estimated liver resection volume (ELRV), which was compared with modified actual liver resection volume (ALRV) obtained from actual liver resection mass. The LLMS accuracy was also evaluated based on operator's experience (attending surgeon [AS] or trainee surgeon [TS]). RESULTS: Estimated liver resection volumes significantly correlated with ALRVs (r = .82) in all cases. Moreover, TS-conducted LLMS also showed acceptable difference between ELRV and ALRV compared with AS-conducted LLMS. There were no intergroup differences in estimated blood loss, operation time, time of Pringle maneuver, postoperative complications, and length of postoperative hospitalization (P < .05). Moreover, R0 resection was comparable between the AS and TS groups. CONCLUSIONS: Laparoscopic liver mono-segmentectomy with Glissonian approach using ICG negative imaging ensured safe and accurate procedure owing to facilitated visualization of the resection line. Our approach was effective in avoiding postoperative liver dysfunction and securing radical resection. In addition, it might be helpful in TS education of LLMS.

An inguinal hernia that arose after robot-assisted radical prostatectomy and the repair of an intraoperative external iliac vein injury: A case report.

This case involved a 63-year-old man. He underwent robot-assisted radical prostatectomy (RARP) for prostate cancer. One year after the operation, he consulted our hospital about left inguinal swelling. Under a diagnosis of a left external inguinal hernia, transabdominal preperitoneal repair (TAPP) was performed under general anesthesia. The inside of the hernia orifice had been damaged by the RARP, and the resultant fibrosis was so marked that it was difficult to dissect the preperitoneal space. Furthermore, an external iliac vein injury occurred during the operation. The bleeding was controlled, and we used laparoscopic continuous non-absorbable sutures to repair the external iliac vein injury. The number of TAPP procedures performed after radical prostatectomy has been increasing in recent years, but dissecting the preperitoneal space inside a hernia orifice is difficult. Although external iliac vein injuries are rare complications of TAPP procedures, they can be laparoscopically repaired.

Parenchymal Sparing Anatomical Liver Resections With Full Laparoscopic Approach: Description of Technique and Short-term Results.

OBJECTIVE: The aim of this study was to describe laparoscopic anatomical parenchymal sparing liver resections for hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) and report the short-term outcomes. BACKGROUND: Anatomical resections (ARs) have better oncological outcomes compared to partial resections in patients with HCC, and some suggest should be performed also for CRLM as micrometastasis occurs through the intrahepatic structures. Furthermore, remnant liver ischemia after partial resections has been associated with worse oncological outcomes. Few experiences on laparoscopic anatomical resections have been reported and no data on limited AR exist. METHODS: We performed a retrospective analysis of 86 patients undergoing full laparoscopic anatomical parenchymal sparing resections with preoperative surgical simulation and standardized procedures. RESULTS: A total of 55 patients had HCC, whereas 31 had CRLM with a median of 1 lesion and a size of 30 mm. During preoperative three-dimensional (3D) simulation, a median resection volume of 120 mL was planned. Sixteen anatomical subsegmentectomies, 56 segmentectomies, and 14 sectionectomies were performed. Concordance between preoperative 3D simulation and intraoperative resection was 98.7%. Two patients were converted, and 7 patients experienced complications. Subsegmentectomies had comparable blood loss (166 mL, P = 0.59), but longer operative time (426 min, P = 0.01) than segmentectomies (blood loss 222 mL; operative time 355 min) and sectionectomies (blood loss 120 mL; operative time 295 min). R0 resection and margin width remained comparable among groups. CONCLUSIONS: A precise preoperative planning and a standardized surgical technique allow to pursue the oncological quality of AR enhancing the safety of the parenchyma sparing principle, reducing surgical stress through a laparoscopic approach.

Pure Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus (with Video).

BACKGROUND: Laparoscopic liver resection has been increasingly utilized due to its less invasiveness approach compared with open surgery,1-3 but often creates challenges. Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) portends a poorer prognosis and often precludes patients from potential liver resection.4-6 We herein report a case of laparoscopic hepatectomy and thrombectomy in a patient with HCC and BDTT. METHODS: CT, ERCP, and POCS showed a 40-mm tumor located in the right lobe with BDTT. A five 12-mm trocar was inserted at the umbilicus for laparoscope, the epigastrium, both sides of the hypochondrium, and right lateral region. Moreover, a 5-mm trocar was inserted at left hypochondrium. After cholecystectomy, hepatoduodenal ligament was encircled using the tourniquet through 5-mm trocar site. The right portal vein was transected by stapler following transection of the right hepatic artery. After ICG staining (0.5 mg/body i.v.),7 hepatic parenchymal transection was performed using clamp-crashing technique. Moreover, CUSA also was used near Glissonian sheath. BDTT was removed from the right BD. Moreover, the cholangioscopy confirmed no BDTT remnants. The resection stump was then sutured. Finally, the right hepatic vein was divided with a stapler. A drainage tube was placed in the right subphrenic space. Operation time was 496 min, and blood loss was 91 ml. The patient was discharged without complications on postoperative day 11. Pathological diagnosis showed moderately differentiated HCC, tumor size 40 × 45 mm with negative surgical margins. CONCLUSIONS: Pure laparoscopic resection for HCC with BDTT is a radical, yet feasible procedure.

[Gallbladder Metastasis from Renal Cell Carcinoma Four Years after Nephrectomy-A Case Report].

An 80-year-old man who had undergone nephrectomy for renal cell carcinoma(RCC)4 years before presentation was admitted to our department for further investigation of the gallbladder tumor. The patient was diagnosed with early gallbladder carcinoma based on CT and MRI findings and treated with laparoscopic cholecystectomy. The intraoperative frozen section revealed that the identified tumor was clear cell carcinoma. Finally, morphological similarity with a previous specimen of RCC and immunostaining resulted in the diagnosis of gallbladder metastasis from RCC. Therefore, it is important to consider metastatic carcinoma of the gallbladder in the differential diagnosis of gallbladder tumors for patients with a history of renal cell carcinoma.

Geriatric Nutritional Risk Index Less Than 92 Is a Predictor for Late Postpancreatectomy Hemorrhage Following Pancreatoduodenectomy: A Retrospective Cohort Study.

Postpancreatectomy hemorrhage (PPH) is the most lethal complication of pancreatoduodenectomy (PD). The main risk factor for PPH is the development of a postoperative pancreatic fistula (POPF). Recent evidence shows that the geriatric nutritional risk index (GNRI) may be predictive indicator for POPF. In this study, we aimed to evaluate whether GNRI is a reliable predictive marker for PPH following PD. The present study retrospectively evaluated 121 patients treated with PD at Ageo Central General Hospital in Japan between January 2015 and March 2020. We investigated the potential of age, gender, body mass index, serum albumin, American Society of Anesthesiologists classification (ASA), diabetes mellitus and smoking status, time taken for the operation, estimated blood loss, and postoperative complications (POPF, bile leak, and surgical site infections) to predict the risk of PPH following PD using univariate and multivariate analyses. Ten patients had developed PPH with an incidence of 8.3%. Among them, the patients were divided into bleeding group (n = 10) and non-bleeding group (n = 111). The bleeding group had significantly lower GNRI values than those in the non-bleeding group (p = 0.001). We determined that the cut-off value of GNRI was 92 accounting for a sensitivity 80.0%, specificity 82.9%, and likelihood ratio of 4.6 using receiver operating characteristic curve analysis. A GNRI of <92 was statistically associated with PPH in both univariate (p < 0.001) and multivariate analysis (p = 0.01). Therefore, we could identify that a GNRI < 92 was an independently potential predictor of PPH risk following PD. We should alert surgeons if patients have low level GNRI before PD.

[Laparoscopic Hepatic Resection for a Hepatic Perivascular Epithelioid Cell Tumor-A Case Report].

A 50-year-old female who had a liver tumor was referred to our hospital for further examination. Abdominal CT and MRI revealed a 2 cm tumor in liver segment 2 that was suspected to be HCC. On the basis of the CT and MRI findings, the patient underwent needle biopsy. The pathological findings suggested the possibility of perivascular epithelioid cell tumor (PEComa). Accordingly, we performed laparoscopic liver segmentectomy. As a hepatic PEComa is relatively rare, the current case serves as an important reminder to consider PEComa in the differential diagnosis of liver tumors.

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.

Geriatric nutritional risk index serves as risk factor of surgical site infection after pancreatoduodenectomy: a validation cohort Ageo study.

BACKGROUND: Surgical site infections (SSIs), which are associated with preoperative malnutrition, are a well-known potential complication of surgery that leads to increased medical costs and longer hospitalizations. Thus, surgeons need to accurately identify patients at high-risk for SSIs. Considering that the Geriatric Nutritional Risk Index (GNRI) was designed to assess the degree of malnutrition specifically among elderly patients, previous evidence (Kawaguchi study) proved that GNRI predicted the risk of SSIs in patients following pancreatoduodenectomy (PD). In this study, we aimed to validate whether that the same index could predict the risk of SSI among patients who underwent PD in our patient cohort (Ageo study). METHODS: The current validation cohort study was retrospectively conducted on 93 patients at the Department of Surgery, Ageo Central General Hospital, Japan, from January 2015 to October 2019. All patients were subjected to nutritional screening using the GNRI and were followed up for the occurrence of postoperative complications. Additionally, risk factors for developing SSI, as well as patient's height, body mass index, and preoperative laboratory values, were recorded. RESULTS: Patients were divided into the SSI (N=30) and non-SSI (N=63) groups with a determined SSI incidence rate of 32.3% (30/93). The SSI group had significantly lower GNRI than the non-SSI group (P<0.001). Receiver operating characteristic curve analysis determined a cutoff GNRI value of 94 (sensitivity, 83.3%; specificity, 83.6%), similar to that in the previous study. Univariate and multivariate analyses confirmed that a GNRI of <94 was significantly associated with SSI (P<0.001). CONCLUSIONS: The present Ageo study confirmed the consistency of results in Kawaguchi study. Thus, lower GNRI can be a universal marker for SSI risk following PD.

Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis.

BACKGROUND & AIMS: Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival. METHODS: Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed. RESULTS: A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count <100,000/mm3, 43.5% had preoperative ascites, and 56.9% had portal hypertension. A minor hepatectomy was most commonly performed (84.6%) and 122 (48.2%) were operated on by minimally invasive surgery (MIS). Ninety-day mortality was 4.3% with 6 patients (2.3%) dying from liver failure. One hundred and eight patients (42.7%) experienced complications, of which the most common was ascites (37.5%). Patients undergoing major hepatectomies had higher 90-day mortality (10.3% vs. 3.3%; p = 0.04) and morbidity rates (69.2% vs. 37.9%; p <0.001). Patients undergoing an open hepatectomy had higher morbidity (52.7% vs. 31.9%; p = 0.001) than those undergoing MIS. A prediction model for surgical risk was constructed (https://childb.shinyapps.io/morbidity/). The 5-year overall survival rate was 47%, and 56.9% of patients experienced recurrence. Prediction models for overall survival (https://childb.shinyapps.io/survival/) and disease-free survival (https://childb.shinyapps.io/DFsurvival/) were constructed. CONCLUSIONS: Liver resection should be considered for patients with HCC and CP-B cirrhosis after careful selection according to patient characteristics, tumor pattern and liver function, while aiming to minimize surgical stress. An estimation of the surgical risk and survival advantage may be helpful in treatment allocation, eventually improving postoperative morbidity and achieving safe oncological outcomes. LAY SUMMARY: Liver resection for hepatocellular carcinoma in advanced cirrhosis (Child-Pugh B score) is associated with a high rate of postoperative complications. However, due to the limited therapeutic alternatives in this setting, recent studies have shown promising results after accurate patient selection. In our international multicenter study, we provide 3 clinical models to predict postoperative surgical risks and long-term survival following liver resection, with the aim of improving treatment allocation and eventually clinical outcomes.

Comprehensive Exploration to Identify Predictive DNA Markers of ΔNp63/SOX2 in Drug Resistance in Human Esophageal Squamous Cell Carcinoma.

BACKGROUND: OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer. METHODS: OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC). RESULTS: OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance. CONCLUSION: Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC.

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.