New predictors of microvascular invasion for small hepatocellular carcinoma ≤ 3 cm.

BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative recurrence of hepatocellular carcinoma (HCC), even in early-stage HCC. In small HCC ≤ 3 cm, treatment options include anatomical resection or non-anatomical resection, and MVI has a major effect on treatment decisions. We aimed to identify the predictors of MVI in small HCC ≤ 3 cm. METHODS: We retrospectively studied 129 patients with very early or early-stage HCC ≤ 3 cm who had undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography and subsequent hepatic resection from January 2016 to August 2023. These patients were divided into the derivation cohort (n = 86) and validation cohort (n = 43). We examined the risk factors for MVI using logistic regression analysis, and established a predictive scoring system in the derivation cohort. We evaluated the accuracy of our scoring system in the validation cohort. RESULTS: In the derivation cohort, a Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), prothrombin induced by vitamin K deficiency or antagonist-II (PIVKA-II), and metabolic tumor volume (MTV) were independent predictors of MVI. We established the scoring system using these three factors. In the validation test, there were no MVI-positive cases with a score of 0 and 1, and all cases were MVI-positive with a score of 4. Moreover, with a score ≥ 2, the sensitivity, specificity, and accuracy of our scoring system were 100%, 71.4%, and 81.4%, respectively. CONCLUSIONS: Our scoring system can accurately predict MVI in small HCC ≤ 3 cm, and could contribute to establishing an appropriate treatment strategy.

Impact of the serum creatinine and cystatin C ratio for prediction of sarcopenia and prognosis in biliary tract cancer.

BACKGROUND: Sarcopenia is a poor prognostic factor in cancer patients. In recent years, there have been reports that serum creatinine and cystatin C (Cr/CysC) ratio is associated with sarcopenia. However, the prognostic value of the Cr/CysC ratio in biliary tract cancer is unclear. We evaluated the impact of the Cr/CysC ratio on sarcopenia and prognosis in biliary tract cancer. METHODS: We retrospectively reviewed the records of 190 patients with biliary tract cancer who had undergone surgical resection from January 2017 to March 2023. Frozen serum samples collected at the time of surgery were used to measure CysC. We calculated the Cr/CysC ratio and investigated the relationship with sarcopenia and the prognostic significance. RESULTS: We calculated the cutoff value of the Cr/CysC ratio for low skeletal muscle index (SMI) (< 42 cm2/m2 for males and < 38 cm2/m2 for females). The optimal cutoff value of the Cr/CysC ratio was 0.848. The low Cr/CysC ratio group was significantly associated with higher preoperative CRP and lower albumin, lower SMI, lower handgrip strength, and higher intramuscular adipose tissue content. In multivariate analysis, patients with a low Cr/CysC ratio showed poorer overall survival (hazard ratio 2.60, 95% confidence interval 1.07-6.29, p = 0.033), which was significantly worse than in those with a high Cr/CysC ratio. CONCLUSIONS: In patients with biliary tract cancer, the Cr/CysC ratio showed weak correlation with sarcopenic indicators. However, the Cr/CysC ratio could be strong prognostic factor in biliary tract cancer.

Lower Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict Postoperative Prognosis in Patients with Hepatocellular Carcinoma.

Increasing evidence suggests that nutritional indices, including the geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI), are predictors of poor prognosis in patients with hepatocellular carcinoma (HCC). Hence, this study aimed to explore the value of the GNRI and PNI in evaluating postoperative prognosis in patients with HCC, particularly regarding its recurrence patterns. We performed a retrospective analysis of 203 patients with HCC who underwent initial hepatic resection. Patients were divided into two groups according to the GNRI (cutoff: 98) and PNI (cutoff: 45). The GNRI and PNI were significantly associated with body composition (body mass index and skeletal muscle mass index), hepatic function (Child-Pugh Score), tumor factors (tumor size and microvascular invasion), and perioperative factors (blood loss and postoperative hospitalization). Patients with a low PNI or low GNRI had significantly worse overall survival (OS) and recurrence-free survival. Patients with early recurrence had lower PNI and GNRI scores than those without early recurrence. Patients with extrahepatic recurrence had lower PNI and GNRI scores than those without extrahepatic recurrence. The PNI and GNRI might be useful in predicting the prognosis and recurrence patterns of patients with HCC after hepatic resection.

Total lesion glycolysis by 18F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma. METHODS: We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance. RESULTS: The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG. CONCLUSIONS: Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

Primary duodenal carcinoma suspected to arise from ectopic gastric mucosa: a case report.

BACKGROUND: Ectopic gastric mucosa mainly occurs in the duodenal bulb, and its etiology is thought to be congenital straying of gastric tissues. Primary duodenal carcinoma is a rare disease; however, reports of carcinoma arising from ectopic gastric mucosa are extremely rare. We report a case of primary duodenal carcinoma suspected to arise from ectopic gastric mucosa, which discovered as a result of duodenal stenosis. CASE PRESENTATION: The patient was a 71-year-old man with persistent weight loss and white stools. Enhanced computed tomography showed stenosis of the third portion of the duodenum and main pancreatic duct dilatation. Upper gastrointestinal endoscopy revealed irregularity of the duodenal mucosa from the anorectal side of the papilla of Vater to the stenosis of the third portion. No malignant cells were found by biopsies from the duodenal mucosa. Endoscopic ultrasonography did not detect the tumor in the pancreatic head. The possibility of a pancreatic tumor could not be ruled out based on findings of main pancreatic duct dilatation in the pancreatic head, and the patient had long-term poor oral intake because of duodenal stenosis; thus, surgical treatment was planned. Intraoperative findings showed palpable induration of the third portion of the duodenum and white nodules on the serosal surface. This was diagnosed as primary duodenal carcinoma, and pylorus-preserving pancreatoduodenectomy was performed. Histopathological diagnosis revealed ectopic gastric mucosa in the papilla of Vater and well-differentiated tubular adenocarcinoma invaded the normal duodenal submucosa and extended to the duodenal serosa. No mass lesion was detected in the pancreas, and an intraductal papillary mucinous neoplasm was observed in the branch pancreatic duct. The main pancreatic duct stricture was caused by the duodenal carcinoma invasion. CONCLUSIONS: This case of primary duodenal carcinoma was suspected to arise from ectopic gastric mucosa and review the relevant literature.

A case of Mirizzi syndrome accompanied by a pseudoaneurysm that ruptured into the gallbladder: successfully treated by embolization of aneurysm and sequential surgery.

BACKGROUND: Although visceral aneurysms are relatively rare, it can be life-threatening in case it ruptures. We report a case of Mirizzi syndrome accompanied by a pseudoaneurysm that ruptured into the gallbladder. CASE PRESENTATION: The patient was a 73-year-old woman with persistent gastrointestinal bleeding and progressive jaundice. Examination revealed a pseudoaneurysm in the gallbladder artery or hepatic artery branch, and biliary hemorrhage due to gallbladder perforation was suspected. Urgent abdominal angiography revealed a pseudoaneurysm measuring 50 × 32 mm that had ruptured directly from the right hepatic artery or the cystic artery into the gallbladder. The pseudoaneurysm was successfully coiled and the bleeding was stopped. The presence of ongoing obstruction due to Mirizzi syndrome resulted in an emergency cholecystectomy being performed on the same day. On removing the impacted gallstone from the neck of the gallbladder, we found an obstruction between the lateral wall of the common bile duct and the gallbladder, this condition was diagnosed as Mirizzi syndrome with a biliobiliary fistula. After removing the impacted gallstone, a T-tube was inserted into the common bile duct. Bile leakage was observed postoperatively, but it improved with drainage. The patient fully recovered. CONCLUSIONS: We present our experience with a case of Mirizzi syndrome accompanied by a ruptured pseudoaneurysm successfully treated with coil embolization followed by cholecystectomy. In this case, the pseudoaneurysm may have been caused by inflammation due to cholecystitis or compression of the arterial wall by a gallstone. To the best of our knowledge, Mirizzi syndrome associated with pseudoaneurysm rupture is rare. Our study suggested that cholecystectomy preceded by transcatheter arterial embolization is an effective strategy to control bleeding in patients with hemobilia due to aneurysm.

Number and Brightness Analysis: Visualization of Protein Oligomeric State in Living Cells.

Number and brightness (N&B) analysis helps to visualize protein oligomer and its localization in a living cell. N&B analysis provides apparent brightness, which reflects the oligomeric state of a fluorescently labeled protein, by analyzing the temporal intensity fluctuation at each pixel. N&B analysis is useful in understanding the dynamic oligomerization in signal transduction and neurodegenerative diseases. Furthermore, it also helps in gaining useful insights regarding the controlling mechanisms in protein function. In this chapter, we describe the basic theory and notations of N&B analysis implemented with confocal laser scanning microscopy for quantitative analyses.

Empirical Bayes method using surrounding pixel information for number and brightness analysis.

Number and brightness (N&B) analysis is useful for monitoring the spatial distribution of the concentration and oligomeric state of fluorescently labeled proteins in cells. N&B analysis is based on the statistical analysis of fluorescence images by using the method of moments (MoM). Furthermore, N&B analysis can determine the particle number and particle brightness, which indicate the concentration and oligomeric state, respectively. However, the statistical accuracy and precision are limited in actual experiments with fluorescent proteins, owing to low excitation and the limited number of images. In this study, we applied maximum likelihood (ML) estimation and maximum a posteriori (MAP) estimation coupled with the empirical Bayes (EB) method (referred to as EB-MAP). In EB-MAP, we constructed a simple prior distribution for a pixel to utilize the information of the surrounding pixels. To evaluate the accuracy and precision of our method, we conducted simulations and experiments and compared the results of MoM, ML, and EB-MAP. The results showed that MoM estimated the particle number with many outliers. The outliers hampered the visibility of the spatial distribution and cellular structure. In contrast, EB-MAP suppressed the number of outliers and improved the visibility notably. The precision of EB-MAP was better by an order of magnitude in terms of particle number and 1.5 times better in terms of particle brightness compared with those of MoM. The proposed method (EB-MAP-N&B) is applicable to studies on fluorescence imaging and would aid in accurately recognizing changes in the concentration and oligomeric state in cells. Our results hold significant importance because quantifying the concentration and oligomeric state would contribute to the understanding of dynamic processes in molecular mechanism in cells.

Two-detector number and brightness analysis reveals spatio-temporal oligomerization of proteins in living cells.

Number and brightness analysis (N&B) is a useful tool for the simultaneous visualization of protein oligomers and their localization, with single-molecule sensitivity. N&B determines particle brightness (fluorescence intensity per particle) and maps the spatial distribution of fluorescently labeled proteins by performing statistical analyses of the image series obtained using laser scanning microscopy. The brightness map reveals presence of the oligomers of the targeted protein and their distribution in living cells. However, even when corrections are applied, conventional N&B is affected by afterpulsing, shot noise, thermal noise, dead time, and overestimation of particle brightness when the concentration of the fluorescent particles changes during measurement. The drawbacks of conventional N&B can be circumvented by using two detectors, a novel approach that we henceforth call two-detector number and brightness analysis (TD-N&B), and introducing a linear regression of fluorescence intensity. This statistically eliminates the effect of noise from the detectors, and ensures that the correct particle brightness is obtained. Our method was theoretically assessed by numerical simulations and experimentally validated using a dilution series of purified enhanced green fluorescent protein (EGFP), EGFP tandem oligomers in cell lysate, and EGFP tandem oligomers in living cells. Furthermore, this method was used to characterize the complex process of ligand-induced glucocorticoid receptor dimerization and their translocation to the cell nucleus in live cells. Our method can be applied to other oligomer-forming proteins in cell signaling, or to aggregations of proteins such as those that cause neurodegenerative diseases.

Hemodynamic changes in child acute respiratory distress syndrome with airway pressure release ventilation: a case series.

BACKGROUND: Airway pressure release ventilation (APRV) is widely used in adult critical care settings. However, information on the use of APRV in the pediatric population is limited. METHODS: All patients admitted to the medical-surgical pediatric intensive care unit with a diagnosis of acute respiratory distress syndrome (ARDS) who received APRV for at least 12 h between 2007 and 2009 were reviewed. RESULTS: Thirteen patients with a variety of etiologies of ARDS were included, with a mean weight of 18.2 ± 15.0 kg, a mean age of 68 ± 57 months and a predicted mortality (based on Pediatric Index of Mortality version 2) of 23.9 ± 13.8%. Patients were placed on APRV for a median of 4 days (range 1-10 days). There was no change in blood gas parameters after 1 h or 12 h of APRV when compared with pre-APRV. There was no statistical difference in hemodynamic parameters, including mean arterial blood pressure, central venous blood pressure and heart rate, while the patients were on APRV. CONCLUSION: APRV could be safely used in pediatric ARDS patients, without significant hemodynamic compromise or side effects.