Pelvic radiograph (PXR) is essential for detecting proximal femur and pelvis injuries in trauma patients, which is also the key component for trauma survey. None of the currently available algorithms ...can accurately detect all kinds of trauma-related radiographic findings on PXRs. Here, we show a universal algorithm can detect most types of trauma-related radiographic findings on PXRs. We develop a multiscale deep learning algorithm called PelviXNet trained with 5204 PXRs with weakly supervised point annotation. PelviXNet yields an area under the receiver operating characteristic curve (AUROC) of 0.973 (95% CI, 0.960-0.983) and an area under the precision-recall curve (AUPRC) of 0.963 (95% CI, 0.948-0.974) in the clinical population test set of 1888 PXRs. The accuracy, sensitivity, and specificity at the cutoff value are 0.924 (95% CI, 0.912-0.936), 0.908 (95% CI, 0.885-0.908), and 0.932 (95% CI, 0.919-0.946), respectively. PelviXNet demonstrates comparable performance with radiologists and orthopedics in detecting pelvic and hip fractures.
Polo‐like kinases (PLKs) are potent regulators of cell proliferation and cell survival. Polo‐like kinases are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly ...disease. The therapeutic effects of volasertib, a PLK inhibitor, was evaluated for the treatment of ATC either alone or in combination with sorafenib. Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose‐dependent manner. Volasertib caused ATC cells to accumulate in G2/M phase, activated caspase‐3 activity, and induced apoptosis. Combination therapy using volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single‐agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals that received either single‐agent or combination treatment. These preclinical findings suggest that volasertib could be an effective drug in treating ATC.
Anaplastic thyroid cancer is a rare but deadly disease. Polo‐like kinases (PLKs) are potent regulators of cell proliferation and cell survival. We found that PLK inhibitor volasertib, either alone and in combination with sorafenib, was effective in the treatment of anaplastic thyroid cancer in vitro and in vivo.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The oral absorption of a therapeutic peptide (such as exenatide; EXT) that can improve glycemic control in the treatment of type 2 diabetes is limited by multiple barriers of the intestinal ...epithelium. This work presents an oil‐structured nanoemulsion system that consists of a phase‐changeable fatty acid that allows EXT (EXT@PC/NEMs) to be delivered orally and absorbed efficiently in the small intestine. To construct an appropriate vehicle to encapsulate EXT, an oil‐in‐water single emulsion is generated at 37 °C, which is well above the melting point of the fatty acid but below the denaturation temperature of the peptide drug. The as‐prepared EXT@PC/NEMs are physically stable when stored at 4 °C, as they form a solid core, which prevents drug leakage. Upon their oral delivery at body temperature, the deformable liquid EXT@PC/NEMs may undergo effective cellular uptake, enhancing their permeability across the intestinal epithelium. The orally administered PC/NEMs significantly improve the bioavailability of EXT via intestinal lymphatic transport, ultimately accumulating in the pancreas, suggesting the possibility of orally delivering labile peptide drugs. The delivered EXT may act on pancreatic β‐ and α‐cells to stimulate insulin release and suppress glucagon secretion, respectively, reducing the blood glucose level, eventually having antidiabetic effects.
Phase‐changeable nanoemulsions are used to encapsulate a peptide drug during emulsification at 37 °C and are physically stable when stored at 4 °C. Upon oral ingestion at body temperature, the deformable liquid nanoemulsions undergo effective cellular uptake, enhancing their permeability across the intestinal epithelium, ultimately accumulating in the pancreas via lymphatic transport to exert their beneficial antidiabetic effects.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Laparoscopic cholecystectomy (LC) with associated procedures and endoscopic retrograde cholangiopancreatography (ERCP) have been the standard treatments for both common and rare biliary ...diseases. Mirizzi syndrome (MS) is a rare and complex biliary condition. We report our experience with MS treatment and investigate the value of laparoscopic procedures and ERCP in patient management.
Methods
From 2004 to 2017, 100 consecutive patients with MS were diagnosed by ERCP and underwent surgery in a referral center. Sixty patients were treated with intended LC, and 40 patients were treated with open cholecystectomy (OC). The clinical manifestations, ERCP and associated procedures, surgical procedures, and postoperative outcomes were investigated.
Results
The surgical mortality rate was 1%, while the surgical morbidity rate was 15%. The patients treated with intended LC suffered from less morbidity (5%). The percentage of postoperative residual biliary stones was 32% (n = 32), and only three patients underwent re‐operation (laparotomy) for stone removal. The laparotomy conversion rate in the intended LC group was 16.7% (10/60). The length of hospitalization for the patients with successful LC was significantly shorter than that for the patients with conversion and intended OC. Csendes classification was a risk factor for conversion from LC to OC (type I vs types II to V, P < .0001).
Conclusions
A combination of a laparoscopic procedure and ERCP may provide therapeutic benefits for patients with MS.
Highlight
Yeh and colleagues report that a combination of perioperative endoscopic retrograde cholangiopancreatography and laparoscopic surgery can provide clinical benefits for patients with Mirizzi syndrome with significantly less surgical morbidity and shorter hospital stay. Both preoperative diagnosis and postoperative residual biliary stones can be managed by endoscopic retrograde cholangiopancreatography with satisfactory outcomes.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Gastrointestinal stromal tumors (GISTs) originating from the interstitial cells of Cajal are mesenchymal tumors of the gastrointestinal tract and have been found to harbor
mutations and KIT (CD117) ...expression since 1998. Later,
mutations,
alterations, and other drive mutations were identified in GISTs. In addition, more and more protein markers such as DOG1, PKCθ were found to be expressed in GISTs which might help clinicians diagnose CD117-negative GISTs. Therefore, we plan to comprehensively review the molecular markers and genetics of GISTs and provide clinicians useful information in diagnostic and therapeutic strategies of GISTs. Twenty years after the discovery of KIT in GISTs, the diagnosis of GISTs became much more accurate by using immunohistochemical (IHC) panel (CD117/DOG1) and molecular analysis (
), both of which constitute the gold standard of diagnosis in GISTs. The accurately molecular diagnosis of GISTs guides clinicians to precision medicine and provides optimal treatment for the patients with GISTs. Successful treatment in GISTs prolongs the survival of GIST patients and causes GISTs to become a chronic disease. In the future, the development of effective treatment for GISTs resistant to imatinib/sunitinib/regorafenib and
-WT GISTs will be the challenge for GISTs.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
The incidence of biliary events (BE) following percutaneous cholecystostomy (PC) in acute cholecystitis (AC) patients is high. Therefore, definitive laparoscopic cholecystectomy (LC) is ...recommended. We aimed to investigate the optimal timing of LC following PC with regard to the clinical course and pathological findings.
Methods
All 744 AC patients with PC were included. The incidence and median number of BE were investigated with the concept of competing risks. The 344 patients with interval LC were divided into two groups based on the pathological findings of resected gallbladders: the acute/acute‐and‐chronic group (AANC group) (n = 221) and the chronic group (n = 123). A comparative analysis of the demographic data and perioperative outcomes was performed.
Results
Among the 744 AC patients with PC, 142 patients experienced recurrent BE. The cumulative incidence of BE was 26.6%, and the median time to recurrence was 67.5 days. The PC‐to‐LC days of the chronic group were longer than those of the AANC group (73.51 vs 63.00, P < .001). The multivariate analysis indicated that the operation time was longer in the AANC group than in the chronic group (P = .040).
Conclusion
In terms of the clinical course and sequential pathological changes in the gallbladder, a 9‐ to 10‐week interval after PC is the optimal timing for LC.
Highlight
Hung and colleagues performed a retrospective study to determine the optimal timing of laparoscopic cholecystectomy following percutaneous cholecystostomy placement for acute cholecystitis. Based on the sequential pathological changes to the gallbladder and the risk of recurrent biliary events, 9‐10 weeks after percutaneous cholecystostomy was considered the optimal timing.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Minimally invasive pancreaticoduodenectomy (MIPD), which includes laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), is a complex procedure that needs to ...be performed by experienced surgeons. However, the safety and oncologic performance have not yet been conclusively determined.
Methods
A systematic literature search was performed using the Embase, Medline, and PubMed databases to identify all studies published up to March 2015. Articles written in English containing the keywords: “pancreaticoduodenectomy” or “Whipple operation” combined with “laparoscopy,” “laparoscopic,” “robotic,” “da vinci,” or “minimally invasive surgery” were selected. Furthermore, to increase the power of evidence, articles describing more than ten MIPDs were selected for this review.
Results
Twenty-six articles matched the review criteria. A total of 780 LPDs and 248 RPDs were included in the current review. The overall conversion rate to open surgery was 9.1 %. The weighted average operative time was 422.6 min, and the weighted average blood loss was 321.1 mL. The weighted average number of harvested lymph nodes was 17.1, and the rate of microscopically positive tumor margins was 8.4 %. The cumulative morbidity was 35.9 %, and a pancreatic fistula was reported in 17.0 % of cases. The average length of hospital stay was 12.4 days, and the mortality rate was 2.2 %.
Conclusions
In conclusion, after reviewing one-thousand cases in the current literature, we conclude that MIPD offers a good perioperative, postoperative, and oncologic outcome. MIPD is feasible and safe in well-selected patients.
Full text
Available for:
EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Percutaneous cholecystostomy (PC) followed by definitive cholecystectomy is an alternative treatment for acute cholecystitis (AC). We retrospectively investigated the impact of PC tube ...removal before definitive cholecystectomy on surgical outcomes.
Methods
From 2012 to 2017, 942 AC patients underwent PC at a single institute. Eligible patients were selected according to inclusion criteria. Demographic data, clinical and laboratory parameters, and treatment outcomes were extracted from medical records. Categorization of patients and subsequent subgroup analysis were based on cholangiography.
Results
The rate of emergent cholecystectomy in the PC tube removal group was higher than that in the PC tube preserved group (OR = 2.969, 95% CI 1.334–6.612, P = 0.008). In subgroup analysis of patients with patent bile flow under cholangiography, the rate of emergent cholecystectomy was higher in the PC tube removal group (OR = 3.173, 95% CI 1.182–8.523, P = 0.022), though the incidence of complications was higher in the PC tube preserved group (P = 0.012). In addition, routine preoperative cholangiography had no clinical impact on surgical outcome.
Conclusion
Percutaneous cholecystostomy tube can be removed before subsequent LC to avoid postoperative complications, though removal of the PC tube is associated with an increased likelihood of emergent cholecystectomy.
Highlight
Hung and colleagues investigated the impact of percutaneous cholecystostomy tube removal before scheduled laparoscopic cholecystectomy. Removal of the tube was associated with an increased likelihood of emergent cholecystectomy, but not with higher rates of perioperative complications. In addition, routine preoperative cholangiography via a percutaneous cholecystostomy tube may not be necessary.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cholangiocarcinoma (CCA) is a subtype of bile duct cancer usually diagnosed late with a low survival rate and no satisfactorily systemic treatment. Recently, regorafenib has been accepted as a ...second-line treatment for CCA patients. In this study, we investigated the potential signal transduction pathways mediated by regorafenib. We established a transcriptomic database for regorafenib-treated CCA cells using expression microarray chips. Our data indicate that regorafenib inhibits yes-associated protein 1 (YAP1) activity in various CCA cells. In addition, we demonstrated that YAP1 regulates epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin and SNAI2. We further examined YAP1 activity, phosphorylation status, and expression levels of YAP1 downstream target genes in the regorafenib model. We found that regorafenib dramatically suppressed these events in CCA cells. Moreover, in vivo results revealed that regorafenib could significantly inhibit lung foci formation and tumorigenicity. Most importantly, regorafenib and amphiregulin (AREG) neutralize antibody exhibited synergistic effects against CCA cells. In a clinical setting, patients with high YAP1 and EMT expression had a worse survival rate than patients with low YAP1, and EMT expression did. In addition, we found that YAP1 upregulated the downstream target amphiregulin in CCA. Our findings suggest that AREG neutralizing antibody antibodies combined with regorafenib can reverse the CCA metastatic phenotype and EMT in vitro and in vivo. These findings provide novel therapeutic strategies to combat the metastasis of CCA.
PDF
