Citations

Abstract The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1 st edition of the Tokyo Guidelines 2007 ( TG 07) was revised in 2013. According to that revision, the TG 13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG 13 diagnostic criteria of acute cholecystitis. On the other hand, the TG 13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG 13 severity grading for acute cholecystitis was significantly associated with parameters including 30‐day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG 13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG 18/ TG 13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.

AbstractThe initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Abstract Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high‐risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 ( TG 18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high‐risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound‐guided gallbladder drainage can be considered in high‐volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso‐gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound‐guided gallbladder drainage studies. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.

Abstract Bile duct injury ( BDI ) during laparoscopic cholecystectomy remains a serious iatrogenic surgical complication. BDI most often occurs as a result of misidentification of the anatomy; however, clinical evidence on its precise mechanism and surgeons’ perceptions is scarce. Surgeons from Japan, Korea, Taiwan, and the USA, etc. ( n = 614) participated in a questionnaire regarding their BDI experience and near‐misses; and perceptions on landmarks, intraoperative findings, and surgical techniques. Respondents voted for a Delphi process and graded each item on a five‐point scale. The consensus was built when ≥80% of overall responses were 4 or 5. Response rates for the first‐ and second‐round Delphi were 60.6% and 74.9%, respectively. Misidentification of local anatomy accounted for 76.2% of BDI . Final consensus was reached on: (1) Effective retraction of the gallbladder, (2) Always obtaining critical view of safety, and (3) Avoiding excessive use of electrocautery/clipping as vital procedures; and (4) Calot's triangle area and (5) Critical view of safety as important landmarks. For (6) Impacted gallstone and (7) Severe fibrosis/scarring in Calot's triangle, bail‐out procedures may be indicated. A consensus was reached among expert surgeons on relevant landmarks and intraoperative findings and appropriate surgical techniques to avoid BDI .

Abstract Glioma stem cells (GSC) and epithelial–mesenchymal transition (EMT) are strongly associated with therapy resistance and tumor recurrence, but the underlying mechanisms are incompletely understood. Here, we show that S100A4 is a novel biomarker of GSCs. S100A4+ cells in gliomas are enriched with cancer cells that have tumor-initiating and sphere-forming abilities, with the majority located in perivascular niches where GSCs are found. Selective ablation of S100A4-expressing cells was sufficient to block tumor growth in vitro and in vivo. We also identified S100A4 as a critical regulator of GSC self-renewal in mouse and patient-derived glioma tumorspheres. In contrast with previous reports of S100A4 as a reporter of EMT, we discovered that S100A4 is an upstream regulator of the master EMT regulators SNAIL2 and ZEB along with other mesenchymal transition regulators in glioblastoma. Overall, our results establish S100A4 as a central node in a molecular network that controls stemness and EMT in glioblastoma, suggesting S100A4 as a candidate therapeutic target. Cancer Res; 77(19); 5360–73. ©2017 AACR.

100 Background: Combining BEV with CT significantly improved progression-free survival (primary endpoint) in the E2100, AVADO, and RIBBON-1 trials in the 1st-line setting and the RIBBON-2 trial in the 2nd-line setting. Primary efficacy and safety results from RIBBON-2 have been published; here we present final OS results. Methods: Eligible patients (pts) had MBC that had progressed on 1st-line CT without BEV. 2nd-line CT (taxane, gemcitabine, capecitabine, or vinorelbine) was chosen before 2:1 randomization to CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or PL continued until progression. Stratification factors were 2nd-line CT, hormone receptor status, and time from MBC diagnosis to 1st progression. All pts could receive BEV at progression. The primary endpoint was PFS. Final analysis of OS, a secondary endpoint, in the intent-to-treat population was planned after 557 events and provided 80% power to detect a hazard ratio (HR) of 0.77 (median OS increased from 14.0 to 18.2 months) at α=0.04. Results: At the time of data cutoff (Oct. 31, 2011), 184 (82%) of 225 pts in the CT/PL arm and 376 (82%) of 459 pts in the CT/BEV arm had died. BEV was administered in subsequent treatment lines in 12% vs 6% of pts, respectively. There was no difference in OS between treatment arms: HR 1.013 (95% CI 0.845–1.215), log-rank p=0.8843. Median OS was 17.8 months with CT/PL vs 18.6 months with CT/BEV. The 1-year OS rates were 69% vs 71%, respectively. Subgroup analyses by CT cohort showed HRs ranging from 0.86 (95% CI 0.58–1.29) in the capecitabine cohort (n=144) to 1.44 (95% CI 0.82–2.53) in the vinorelbine cohort (n=76). HRs were close to 1 for the two largest CT cohorts (taxane and gemcitabine). Exploratory analysis in the subgroup of patients with triple-negative MBC showed a HR of 0.85 (95% CI 0.58–1.26). Updated safety results were similar to those previously reported from the primary analysis. There were fewer fatal adverse events in the CT/BEV arm (1.5%) than in the CT/PL arm (3.2%). Conclusions: Final OS results from RIBBON-2 reveal no difference between treatment arms. No new safety signals were observed.

Purpose To investigate the alteration of passive stiffness in the supraspinatus muscle after double‐row (DR) and knotless transosseous‐equivalent (KL‐TOE) repair techniques, using shear wave elastography (SWE) in cadavers with rotator cuff tears. We also aimed to compare altered muscular stiffness after these repairs to that obtained from shoulders with intact rotator cuff tendon. Methods Twelve fresh‐frozen cadaveric shoulders with rotator cuff tear (tear size: small [6], medium‐large [6]) were used. Passive stiffness of 4 anatomic regions in the supraspinatus muscle was measured based on an established SWE method. Each specimen underwent DR and KL‐TOE footprint repairs at 30° glenohumeral abduction. SWE values, obtained at 0°, 10°, 20°, 30°, 60°, and 90° abduction, were assessed in 3 different conditions: preoperative (torn) and postoperative conditions with the 2 techniques. The increased ratio of SWE values after repair was compared among the 4 regions to assess stiffness distribution. In addition, SWE values were obtained on 12 shoulders with intact rotator cuff tendons as control. Results In shoulders with medium‐large‐sized tears, supraspinatus muscles showed an increased passive stiffness after rotator cuff repairs, and this was significantly observed at adducted positions. KL‐TOE repair showed uniform stiffness changes among the 4 regions of the supraspinatus muscle (mean, 189% to 218% increase after repair), whereas DR repair caused a significantly heterogeneous stiffness distribution within the muscle (mean, 187% to 319% after repair, P = .002). Although a repair‐induced increase in muscle stiffness was observed also in small‐sized tears, there were no significant differences in repaired stiffness changes between DR and KL‐TOE (mean, 127% to 138% and 127% to 130% after repairs, respectively). Shoulders with intact rotator cuff tendon showed uniform SWE values among the 4 regions of the supraspinatus muscle (mean, 38.2 to 43.0 kPa). Conclusions Passive stiffness of the supraspinatus muscle increases after rotator cuff repairs for medium‐large‐sized tears. KL‐TOE technique for the medium‐large‐sized tear provided a more uniform stiffness distribution across the repaired supraspinatus muscles compared with the DR technique. Clinical Relevance Based on this insight, investigating rotator cuff muscle stiffness changes, further studies using SWE may determine the optimal repair technique for various sizes of rotator cuff tears.

OBJECT The authors sought to determine whether flow diversion with the Pipeline Embolization Device (PED) can approximate microsurgical decompression in restoring function after cranial neuropathy following carotid artery aneurysms. METHODS This multiinstitutional retrospective study involved 45 patients treated with PED across the United States. All patients included presented between November 2009 and October 2013 with cranial neuropathy (cranial nerves [CNs] II, III, IV, and VI) due to intracranial aneurysm. Outcome analysis included clinical and procedural variables at the time of treatment as well as at the latest clinical and radiographic follow-up. RESULTS Twenty-six aneurysms (57.8%) were located in the cavernous segment, while 6 (13.3%) were in the clinoid segment, and 13 (28.9%) were in the ophthalmic segment of the internal carotid artery. The average aneurysm size was 18.6 mm (range 4–35 mm), and the average number of flow diverters placed per patient was 1.2. Thirty-eight patients had available information regarding duration of cranial neuropathy prior to treatment. Eleven patients (28.9%) were treated within 1 month of symptom onset, while 27 (71.1%) were treated after 1 month of symptoms. The overall rate of cranial neuropathy improvement for all patients was 66.7%. The CN deficits resolved in 19 patients (42.2%), improved in 11 (24.4%), were unchanged in 14 (31.1%), and worsened in 1 (2.2%). Overtime, the rate of cranial neuropathy improvement was 33.3% (15/45), 68.8% (22/32), and 81.0% (17/21) at less than 6, 6, and 12 months, respectively. At last follow-up, 60% of patients in the isolated CN II group had improvement, while in the CN III, IV, or VI group, 85.7% had improved. Moreover, 100% (11/11) of patients experienced improvement if they were treated within 1 month of symptom onset, whereas 44.4% (12/27) experienced improvement if they treated after 1 month of symptom onset; 70.4% (19/27) of those with partial deficits improved compared with 30% (3/10) of those with complete deficits. CONCLUSIONS Cranial neuropathy caused by cerebral aneurysm responds similarly when the aneurysm is treated with the PED compared with open surgery and coil embolization. Lower morbidity and higher occlusion rates obtained with the PED may suggest it as treatment of choice for some of these lesions. Time to treatment is an important consideration regardless of treatment modality.