Background
The treatment strategy for pancreatic metastasis (PM) from renal cell carcinoma (RCC) is unclear due to its rarity. The aim of this study was to reveal the role of surgery for PM from RCC.
...Methods
A systematic literature search was conducted using PubMed and the Cochrane Library. The effectiveness of surgery for PM was evaluated based on the primary outcome of overall survival (OS), which was investigated in relation to surgical procedures and metastatic sites via subgroup analyses.
Results
There was no significant difference in the rate of 2-year OS between the surgery and control group (OR 0.43, 95% CI 0.14–1.26,
P
= 0.12). However, the rate of 5-year OS was significantly higher in the surgery group than the control group (OR = 0.41, 95% CI 0.18–0.93,
P
= 0.03). The rates of the complications and OS were not significantly different between radical and conservative pancreatectomies. The rate of 5-year OS of the patients with PM was higher than that with other metastases (OR 0.38, 95% CI 0.20–0.74,
P
= 0.004).
Conclusion
Surgical resection for PM from RCC is associated with good prognosis. Limited surgery may be a useful option depending on the location of the lesion.
Endoscopic submucosal dissection (ESD) is challenging in the right colon. Traction devices can make it technically easier. In this study, we evaluated a flexible grasper with articulating tip and ...elbow-like bending (IgE) through a double-balloon surgical platform (DESP), compared with an earlier generation grasper without elbow-like bending (Ig). The reach of Ig/IgE was investigated at eight locations using a synthetic colon within a 3D model. Using a fresh porcine colorectum, 4 cm pseudo-polyps were created at the posterior wall of the ascending colon. Fifty-four ESD procedures were performed using three techniques: standard ESD (STD), ESD using Ig (DESP + Ig), and ESD using IgE (DESP + IgE). IgE was able to reach the full circumference at all the locations, whereas the medial walls proximal to the descending colon were out of Ig's reach. Compared with the STD, both DESP + Ig and DESP + IgE showed significantly shorter procedure time (STD vs. DESP + Ig vs. DESP + IgE = median 48.9 min vs. 38.6 vs. 29.9) and fewer injuries (1.5 vs. 0 vs. 0). Moreover, the DESP + IgE had a shorter procedure time than the DESP + Ig (p = 0.0025). The IgE with DESP increased instrument reach compared to Ig, and likely represented a traction tool for excision of large pseudo-polyps in the right colon.
Background
Endoscopic submucosal dissection (ESD) is a challenging procedure for the removal of colorectal tumors, especially tumors located in the right colon. The use of traction could make this ...procedure technically easier and reduce procedure times and complication rates. In this study, we demonstrated the feasibility and utility of a traction technique utilizing an endoscopic snare through an overtube, a double-balloon endolumenal interventional platform (DEIP) in a porcine colorectal model.
Methods
A total of 120 procedures were performed using three different techniques: standard ESD technique (STD), ESD with DEIP (DEIP alone), and ESD with DEIP and a snare (DEIP + Snare). The snare was passed inside the overtube and used as a grasper on the tissue to provide traction. Lesions 3 or 4 cm in diameter were removed with a 5 mm margin from the anterior and posterior walls of the proximal Transverse Colon, the Hepatic Flexure, and the posterior wall of the Cecum. The outcomes measured included procedure times and the number of muscularis propria injuries.
Results
The DEIP + Snare group showed significantly shorter total procedure and submucosal dissection times for lesions in all locations (median 28.1 min (DEIP + Snare,
n
= 32) vs 39.8 (STD,
n
= 32) vs 39.7 (DEIP alone,
n
= 32); 7.5 min vs 25.3 vs 25.1) and had fewer muscularis propria injuries (median 0 range 0–2 vs 2 0–7 vs 1 0–6) than the two other groups. Larger lesions (4 cm) were successfully removed by regrasping the tissue in DEIP + Snare group, which showed significantly shorter total procedure time 31.4 min (DEIP + Snare,
n
= 8) vs 40.1 (STD,
n
= 8) vs 45.6 (DEIP alone,
n
= 8) and submucosal dissection time (12.3 min vs 27.6 vs 29.1) than the two other groups.
Conclusions
ESD traction technique with an endolumenal platform and snare enables faster removal of large polyps in the right colon with fewer injuries than standard methods of ESD.
Combination therapy of tegafur/uracil (UFT) and leucovorin (LV) is widely used to treat colorectal cancers. Although this therapy has a significant therapeutic effect, severe adverse effects occur ...frequently. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A useful assay that can quantitate plasma levels of 5-FU, uracil, and tegafur simultaneously for TDM has been desired, but such a method is not currently available. In this study, we aimed to develop a sensitive method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). After preparing plasma samples by protein precipitation and liquid extraction, 5-FU, uracil, and tegafur were analyzed by UPLC-MS/MS in negative electrospray ionization mode. Validation was performed according to US Food and Drugs Administration guidance. The calibration curves were linear over concentration ranges of 2-500 ng/mL for 5-FU, 20-5000 ng/mL for uracil, and 200-50,000 ng/mL for tegafur. The corresponding average recovery rates were 79.9, 80.9, and 87.8%. The method provides accuracy within 11.6% and precision below 13.3% for all three analytes. Matrix effects of 5-FU, uracil, and tegafur were higher than 43.5, 84.9, and 100.2%, respectively. This assay was successfully applied to assess the time courses of plasma 5-FU, uracil, and tegafur concentrations in two patients with colorectal liver metastasis who received UFT/LV therapy after hepatectomy. In conclusion, we succeeded to develop a sensitive and robust UPLC-MS/MS method for simultaneous quantification of 5-FU, uracil, and tegafur in human plasma. This method is potentially useful for TDM in patients receiving UFT/LV combination therapy.
The prognosis of distal cholangiocarcinoma (dCCA) remains poor; thus, the identification of new therapeutic targets is warranted. Phosphorylated S6 ribosomal protein indicates a mammalian target of ...rapamycin complex 1 (mTORC1) activity, and mTORC1 plays a central role in controlling cell growth and regulating glucose metabolism. We aimed to clarify the effect of S6 phosphorylation on tumor progression and the glucose metabolic pathway in dCCA.
Thirty-nine patients with dCCA who underwent curative resection were enrolled in this study. S6 phosphorylation and the expression of GLUT1 were evaluated by immunohistochemistry, and their relationship with clinical factors was investigated. The effect of S6 phosphorylation on glucose metabolism with PF-04691502 treatment, an inhibitor of S6 phosphorylation, was examined in cancer cell lines by Western blotting and metabolomics analysis. Cell proliferation assays were performed with PF-04691502.
S6 phosphorylation and the expression of GLUT1 were significantly higher in patients with an advanced pathological stage. Significant correlations between GLUT1 expression, S6 phosphorylation, and SUV-max of FDG-PET were shown. In addition, cell lines with high S6 phosphorylation levels showed high GLUT1 levels, and the inhibition of S6 phosphorylation reduced the expression of GLUT1 on Western blotting. Metabolic analysis revealed that inhibition of S6 phosphorylation suppressed pathways of glycolysis and the TCA cycle in cell lines, and then, cell proliferation was effectively reduced by PF-04691502.
Upregulation of glucose metabolism via phosphorylation of S6 ribosomal protein appeared to play a role in tumor progression in dCCA. mTORC1 may be a therapeutic target for dCCA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
We have implemented Smart Endoscopic Surgery (SES), a surgical system that uses artificial intelligence (AI) to detect the anatomical landmarks that expert surgeons base on to perform ...certain surgical maneuvers. No report has verified the use of AI-based support systems for surgery in clinical practice, and no evaluation method has been established. To evaluate the detection performance of SES, we have developed and established a new evaluation method by conducting a clinical feasibility trial.
Methods
A single-center prospective clinical feasibility trial was conducted on 10 cases of LC performed at Oita University hospital. Subsequently, an external evaluation committee (EEC) evaluated the AI detection accuracy for each landmark using five-grade rubric evaluation and DICE coefficient. We defined LM-CBD as the expert surgeon’s “judge” of the cystic bile duct in endoscopic images.
Results
The average detection accuracy on the rubric by the EEC was 4.2 ± 0.8 for the LM-CBD. The DICE coefficient between the AI detection area of the LM-CBD and the EEC members’ evaluation was similar to the mean value of the DICE coefficient between the EEC members. The DICE coefficient was high score for the case that was highly evaluated by the EEC on a five-grade scale.
Conclusion
This is the first feasible clinical trial of an AI system designed for intraoperative use and to evaluate the AI system using an EEC. In the future, this concept of evaluation for the AI system would contribute to the development of new AI navigation systems for surgery.
Purpose
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is an aggressive malignancy associated with poor prognosis because of recurrence, metastasis, and ...treatment resistance. Aberrant glycosylation of cancer cells triggers their migration and invasion and is considered one of the most important prognostic cancer biomarkers. The current study aimed to identify glycan alterations and their relationship with the malignant potential of PDAC.
Methods
Using a lectin microarray, we evaluated glycan expression in 62 PDAC samples. Expression of fucosyltransferase 8 (FUT8), the only enzyme catalyzing core fucosylation, was investigated by immunohistochemistry. The role of FUT8 in PDAC invasion and metastasis was confirmed using an in vitro assay and a xenograft peritoneal metastasis mouse model.
Results
The microarray data demonstrated that core fucose-binding lectins were significantly higher in carcinoma than in normal pancreatic duct tissues. Similarly, FUT8 protein expression was significantly higher in carcinoma than in normal pancreatic duct tissues. High FUT8 protein expression was significantly associated with lymph-node metastases and relapse-free survival. FUT8 knockdown significantly reduced the invasion in PDAC cell lines and impaired peritoneal metastasis in the xenograft model.
Conclusions
The findings of this study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.
Purpose
Postoperative weight loss is related to postoperative adherence to follow-up after bariatric/metabolic surgery, but many patients stop attending follow-up visits early. The aim of this study ...was to clarify predictors of early withdrawal from follow-up after laparoscopic sleeve gastrectomy (LSG) in a Japanese institution.
Methods
One hundred and fifty-three patients who underwent LSG were retrospectively included in this study. Multivariate analysis was performed to evaluate independent predictors of withdrawal from follow-up visits within 12 months after LSG among significant or nearly significant factors in the univariate analyses. The discrimination power of significant factors was estimated using area under the receiver operating characteristic curve (AUC).
Results
Within 12 months after LSG, 25 of the 153 patients withdrew from follow-up visits. The multivariate analysis showed that age was the only significant predictor of withdrawal. The AUC for age was 0.685, and the cut-off value was < 40 years. The younger patients (< 40 years old) had a significantly higher rate of withdrawal compared with the older patients (≥ 40 years) (27.0% vs. 8.9%).
Conclusion
Older Japanese patients (≥ 40 years old) may be better candidates for LSG. We consider it significant to continue to emphasize the importance of follow-up visits in younger patients after LSG.
Constitutive activation of the mitogen‐activated protein kinase (MAPK) signaling pathway is essential for tumorigenesis of pancreatic ductal adenocarcinoma (PDAC). To date, however, almost all ...clinical trials of inhibitor targeting this pathway have failed to improve the outcome of patients with PDAC. We found that implanted MIA Paca2, a human PDAC cell line sensitive to a MAPK inhibitor, PD0325901, became refractory within a week after treatment. By comparing the expression profiles of MIA Paca2 before and after acquisition of the refractoriness to PD0325901, we identified clusterin (CLU) as a candidate gene involved. CLU was shown to be induced immediately after treatment with PD0325901 or expressed primarily in more than half of PDAC cell lines, enhancing cell viability by escaping from apoptosis. A combination of PD0325901 and CLU downregulation was found to synergistically or additively reduce the proliferation of PDAC cells. In surgically resected PDAC tissues, overexpression of CLU in cancer cells was observed immunohistochemically in approximately half of the cases studied. Collectively, our findings highlight the mechanisms responsible for the rapid refractory response to MEK inhibitor in PDAC cells, suggesting a novel therapeutic strategy that could be applicable to patients with PDAC using inhibitor targeting the MAPK signaling pathway and CLU.
Our findings highlight the mechanisms responsible for the rapid acquisition of resistance to MEK inhibitor in PDAC cells, suggesting a novel therapeutic strategy that could be applicable to patients with PDAC using inhibitor targeting the MAPK signaling pathway and CLU.
Purposes
The choice between performing routine and selective upper gastrointestinal endoscopy (UGE) before bariatric surgery remains controversial. This study aimed to evaluate the clinical ...significance of UGE before laparoscopic bariatric procedures.
Methods
We enrolled 155 obese Japanese patients who underwent laparoscopic bariatric procedures at our institute and evaluated their endoscopic findings, such as reflux esophagitis (RE), hiatal hernia (HH), Barrett’s esophagus, gastritis, duodenitis, gastroduodenal ulcer, gastric cancer, and polyps.
Results
Preoperative endoscopy revealed abnormal findings in 102 patients (66%), including gastritis in 57 (37%), HH in 51 (32%), RE in 27 (17%), benign gastric polyps in 16 (10%), duodenitis in 6 (4%), and Barrett’s esophagus in 1 (0.6%). Two patients with definite HH were treated with simultaneous crural repair at the time of bariatric surgery. Duodenitis was graded as severe in three of these six patients and treated with a proton pump inhibitor before surgery. Eleven patients received therapy to eradicate
Helicobacter pylori
(H. pylori), either before or after the surgery. In summary, preoperative endoscopy changed the perioperative management for 16 of the 155 patients (10%).
Conclusions
Routine UGE may be necessary before bariatric procedures in obese Japanese patients.
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