Background
Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation ...surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection.
Methods
The SENORITA trial was an investigator‐initiated, open‐label, parallel‐assigned, non‐inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3‐year disease‐free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study.
Results
A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach‐preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien–Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647).
Conclusion
The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 (
http://www.clinicaltrials.gov).
Antecedentes
La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND).
Métodos
El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio.
Resultados
Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien‐Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647).
Conclusión
El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.
The prospective, multicentre, randomized controlled phase III SENORITA trial evaluated the surgical and oncological outcomes of laparoscopic sentinel node navigation surgery (LSNNS) compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection (LND) for early gastric cancer (EGC). LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality compared with LSG and LND. ESD, endoscopic submucosal dissection; mITT, modified intention to treat; FAS, full analysis set; OGJ, oesophagogastric junction; LDG, laparoscopic distal gastrectomy; LTG, laparoscopic total gastrectomy; LPPG, laparoscopic pylorus‐preserving gastrectomy; LPG, laparoscopic proximal gastrectomy; ODG, open distal gastrectomy; OTG, open total gastrectomy; PP, per protocol; SBD, sentinel basin dissection; EFTR, endoscopic full‐thickness resection; LWR, laparoscopic wedge resection; LSR, laparoscopic segmental resection.
Similar morbidity
Background
Whether rescue surgery confers a survival benefit in patients undergoing non‐curative endoscopic resection of early gastric cancer remains controversial.
Methods
This was a retrospective ...review of patients who underwent non‐curative endoscopic resection of at least one lesion of differentiated‐type early gastric cancer between 2000 and 2011. Patients with a positive lateral resection margin as the only non‐curative factor were excluded. Outcome was investigated by univariable (Kaplan–Meier) and multivariable (Cox proportional hazards) analysis.
Results
Some 341 patients underwent non‐curative endoscopic resection for at least one lesion of differentiated‐type early gastric cancer. Sixty‐seven patients with a positive lateral resection margin as the only non‐curative factor were excluded, leaving 274 patients for analysis; 194 had rescue surgery and 80 had no additional treatment. The median duration of follow‐up was 60·5 months. Patients who had rescue surgery were younger, had a lower Charlson co‐morbidity index score, smaller tumours and a higher lymphovascular invasion rate than patients with no treatment. Among 194 patients who had rescue surgery, intragastric local residual tumours were found in ten (5·2 per cent) and lymph node metastases in 11 (5·7 per cent). Patients with lymph node metastasis were significantly older than those without metastasis; no other significant differences were found. Univariable analysis showed that patients aged less than 65 years, those with a Charlson co‐morbidity index score below 4 and patients undergoing rescue surgery had significantly longer overall survival. Five‐year overall survival rates in the rescue surgery and no‐treatment groups were 94·3 and 85 per cent respectively. In multivariable analysis, rescue surgery was identified as the only independent predictor of overall survival after non‐curative endoscopic resection of early gastric cancer.
Conclusion
Rescue surgery confers a survival benefit after non‐curative endoscopic resection of early gastric cancer.
Improves survival in fit patients
Summary
Background
The risk of spontaneous bacterial peritonitis (SBP) associated with proton pump inhibitor (PPI) use has been raised in cirrhotic patients with ascites. However, this is based on ...case–control studies, often with a small series.
Aim
To determine whether PPI use increases the risk of SBP using a large cohort.
Methods
This retrospective cohort study included 1965 cirrhotic patients with ascites diagnosed between January 2005 and December 2009. The SBP incidence rate was compared between the PPI and non‐PPI groups before and after propensity score matching to reduce the effect of selection bias and potential confounders. Multivariate analysis was conducted to confirm the association of PPI use with SBP.
Results
After excluding 411 patients, 1554 were analysed. Among them, 512 patients (32.9%) were included in the PPI group. The annual SBP incidence rate was higher in the PPI group than in the non‐PPI group (10.6% and 5.8%, P = 0.002) before matching. Indications for PPI use and dose of PPI were similar between patients with and without SBP. In the propensity score matched cohort (402 pairs), the SBP incidence rate was also higher in the PPI group than in the non‐PPI group (10.8% vs. 6.0%, P = 0.038). Multivariate analysis revealed that PPI use (Hazard ratio 1.396; 95% confidence interval, 1.057–1.843; P = 0.019) was the independent risk factor for SBP.
Conclusions
Proton pump inhibitor use significantly increases the risk of spontaneous bacterial peritonitis in cirrhotic patients with ascites. Proton pump inhibitor use should be undertaken with greater caution and appropriately in patients with cirrhosis.
Summary Objectives Arthritis with intra-articular inflammation was accompanied by joint pain, swelling, and stiffness leading to significant functional impairment. Thus, regulation of joint ...inflammation is a good therapeutic approach for patients with arthritis. In this study, the effect of low intensity ultrasound (LIUS) applied to an adjuvant-induced arthritic rat model on the synovium was investigated. Design Synovial inflammation was induced by complete Freund's adjuvant (CFA)-injection into the rat knee joint. LIUS (200 mW/cm2 ) was applied on the ipsilateral knee everyday for 10 min beginning 1 day after inflammation induction. The expression of proinflammatory factors and immunohistochemical staining pattern of the synovium were assessed. Results CFA induced an increase of the knee circumference that was significantly diminished by LIUS. Synovial membrane hyperplasia in the ipsilateral joint was also affected by LIUS. The inflammatory mediators, COX-1/2, IL-1β, and iNOS, but not TNF-α, in the synovial membrane were induced after 3 days, and they closely correlated with the degree of edema. In the synovial membrane, the expression of inflammatory mediators was reduced by LIUS. The chemoattractant chemokine receptor CCR5 also was involved. On immunohistochemical analysis, CFA caused increased infiltration of CD11b-positive cells in the synovium. After 3 days, neutrophils, myeloperoxidase (MPO)-positive cells filled the inflammatory core; later, monocytes and macrophages, ionized calcium binding adaptor molecule 1 (Iba1)-positive cells in the periphery infiltrated the core by day 5. LIUS markedly reduced CFA-induced inflammatory cells infiltration. Conclusion LIUS showed a potent anti-inflammatory effect in this animal arthritis model with reduced infiltration of inflammatory cells into the synovium.
Background
Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the ...manufacturer of high‐resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO.
Methods
We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow‐up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia).
Key Results
Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non‐relevant group (n = 115).
Conclusions & Inferences
Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow‐up is essential.
Our results suggest that 20 mm Hg is the optimal cut‐off value of integrated relaxation pressure for diagnosing esophagogastric junction outflow obstruction in the Sandhill system. Dysphagia and compartmentalized pressurization on manometry are crucial clinicomanometric factors that can segregate clinically relevant esophagogastric junction outflow obstruction patients.
Background
With the widespread use of endoscopy, small and low‐grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological ...behaviour and appropriate treatment strategy for these NETs remain unclear.
Methods
Patients with biopsy‐proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long‐term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade.
Results
Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty‐two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow‐up of 59 (range 6–102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases.
Conclusion
Low‐grade type 3 gastric NET has non‐aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.
Limited resection suffices in selected patients
Summary Objective Many osteoarthritis (OA) models have been developed in mice to understand OA progression and evaluate new OA therapies. However, the individual variation of the joint lesions ...remains a critical problem in most of the current OA models. We established an OA model in C57BL/6 mice that is more reproducible and amenable to therapeutic intervention by controlling their movement. Design OA was induced in 9-week-old C57BL/6 mice by destabilizing the medial meniscus. The mice were then raised in the standard cage for free movement or in a confined cage customized to restrict movement. Mice in the confined cage were subjected to no exercise or exercise of 400, 800, and 1200 m/day. Results OA lesions of mice in the confined cage were more severe in the exercise group and showed much less variation. However, the patterns of OA lesions over time were quite different depending on the amount of daily exercise; the patterns increased linearly until 8 weeks in 400 m/day exercise group, but showed plateauing after 4 weeks in 800 m/day and 1200 m/day groups. The validity of our novel OA model with movement control was proven by successfully discriminating the therapeutic effect of hyaluronic acid (HA) in histological scores, while the OA model using standard caging showed a statistically insignificant difference. Conclusion The mouse OA model using the confine cage and enforced periodic exercise of mice is more reproducible and reliable than standard caging methods.
Summary Objective To investigate whether granulocyte macrophage-colony stimulating factor (GM-CSF) can be used to increase the number of mesenchymal stem cells (MSCs) in blood clots formed by ...microfracture arthroplasty (MFX) and whether it can improve the therapeutic outcome for cartilage repair. Methods Thirty-six New Zealand white rabbits were divided into four groups: (1) control, (2) GM-CSF, (3) MFX, and (4) GM-CSF+MFX. GM-CSF was administrated intravenously (IV) at 10μg/kg body weight 20min before the MFX surgery. The repaired tissues were retrieved and examined by histological observation, quantitative assessment, and biochemical assays at 4, 8, and 12 weeks after treatment. The number of MSCs was measured in the blood clots by the colony forming unit-fibroblast (CFU-F) assay. The kinetic profile and distribution of GM-CSF in vivo was also evaluated by NIR fluorescence imaging and enzyme-linked immune sorbent assay (ELISA). Results In the histological observations and chemical assays examined at 4, 8, and 12 weeks, the MFX after GM-CSF administration showed better cartilage repair than the one without GM-CSF. The CFU-F assay showed a significantly larger amount of MSCs present in the blood clots of the GM-CSF+MFX group than in the blood clots of the other groups. The blood concentration of GM-CSF peaked at 10min and decreased back to almost the initial level after a couple of hours. GM-CSF was distributed in many organs including the bone marrow but was not observed clearly in the joint cavity. Conclusion Intravenous administration of GM-CSF together with MFX could be a promising therapeutic protocol to enhance the repair of cartilage defects.
Abstract
Spin-valley locking in monolayer transition metal dichalcogenides has attracted enormous interest, since it offers potential for valleytronic and optoelectronic applications. Such an exotic ...electronic state has sparsely been seen in bulk materials. Here, we report spin-valley locking in a Dirac semimetal BaMnSb
2
. This is revealed by comprehensive studies using first principles calculations, tight-binding and effective model analyses, angle-resolved photoemission spectroscopy measurements. Moreover, this material also exhibits a stacked quantum Hall effect (QHE). The spin-valley degeneracy extracted from the QHE is close to 2. This result, together with the Landau level spin splitting, further confirms the spin-valley locking picture. In the extreme quantum limit, we also observed a plateau in the
z
-axis resistance, suggestive of a two-dimensional chiral surface state present in the quantum Hall state. These findings establish BaMnSb
2
as a rare platform for exploring coupled spin and valley physics in bulk single crystals and accessing 3D interacting topological states.
Skin-like field-effect transistors are key elements of bio-integrated devices for future user-interactive electronic-skin applications. Despite recent rapid developments in skin-like stretchable ...transistors, imparting self-healing ability while maintaining necessary electrical performance to these transistors remains a challenge. Herein, we describe a stretchable polymer transistor capable of autonomous self-healing. The active material consists of a blend of an electrically insulating supramolecular polymer with either semiconducting polymers or vapor-deposited metal nanoclusters. A key feature is to employ the same supramolecular self-healing polymer matrix for all active layers, i.e., conductor/semiconductor/dielectric layers, in the skin-like transistor. This provides adhesion and intimate contact between layers, which facilitates effective charge injection and transport under strain after self-healing. Finally, we fabricate skin-like self-healing circuits, including NAND and NOR gates and inverters, both of which are critical components of arithmetic logic units. This work greatly advances practical self-healing skin electronics.
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