Background
A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study ...was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent.
Methods
This was an open‐label, multi‐institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease‐free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence‐free survival and incidence of adverse events.
Results
Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no‐EIPL groups respectively). The 3‐year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3‐year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence‐free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed.
Conclusion
EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).
Antecedentes
Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa.
Métodos
Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease‐free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos.
Resultados
Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5‐71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3‐67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57‐1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1‐81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9‐80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60‐1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62‐1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL.
Conclusión
El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.
This trial was conducted to clarify the effects of extensive intraoperative peritoneal lavage (EIPL) therapy after curative gastrectomy for resectable cT3 gastric cancer. The 3‐year DFS rate was slightly better in the EIPL group (63·9 per cent) than in the no‐EIPL group (59·7 per cent), but the difference was not statistically significant (hazard ratio 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). Superiority of EIPL therapy was not demonstrated.
No benefit
Background
Postoperative pancreatic fistula (POPF) remains a major cause of morbidity after distal pancreatectomy. The aim of this study was to investigate whether duct‐to‐mucosa ...pancreaticogastrostomy of the pancreatic stump decreased clinical POPF formation compared with handsewn closure after distal pancreatectomy.
Methods
This multicentre RCT was performed between April 2012 and June 2014. Patients undergoing distal pancreatectomy were assigned randomly to either duct‐to‐mucosa pancreaticogastrostomy or handsewn closure. The primary endpoint was the incidence of clinical POPF. Secondary endpoints were rates of other complications and length of hospital stay.
Results
Some 80 patients were randomized, and 73 patients were evaluated in an intention‐to‐treat analysis: 36 in the pancreaticogastrostomy group and 37 in the handsewn closure group. The duration of operation was significantly longer in the pancreaticogastrostomy group than in the handsewn closure group (mean 268 versus 197 min respectively; P < 0·001). The incidence of clinical POPF did not differ between groups (7 of 36 versus 7 of 37; odds ratio (OR) 1·03, 95 per cent c.i. 0·32 to 3·10; P = 1·000). The rate of intra‐abdominal fluid collection was significantly lower in the pancreaticogastrostomy group (6 of 36 versus 21 of 37; OR 0·15, 0·05 to 0·45; P < 0·001). There were no statistically significant differences in the rates of other complications or length of hospital stay.
Conclusion
Duct‐to‐mucosa pancreaticogastrostomy did not reduce the incidence of clinical POPF compared with handsewn closure of the pancreatic stump after distal pancreatectomy. Registration number UMIN000007426 (http://www.umin.ac.jp).
Pancreatic fistula rate similar
N-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, ...membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2
, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.
Background
The aim of this study was to determine the added value of portal or superior mesenteric vein (PV/SMV) resection during pancreatoduodenectomy for pancreatic head carcinoma.
Methods
A ...multicentre observational study was conducted in patients with pancreatic head carcinoma who underwent pancreatoduodenectomy in seven Japanese hospitals between 2001 and 2012. Clinicopathological factors were compared between patients who did and did not undergo PV/SMV resection. Those with an impact on survival were identified by univariable and multivariable analysis.
Results
Of the 937 patients who underwent pancreatoduodenectomy, 435 (46·4 per cent) had PV/SMV resection, whereas the remaining 502 (53·6 per cent) did not. Some 71·5 and 63·9 per cent of patients with and without PV/SMV resection respectively had lymph node‐positive disease. Patients who underwent PV/SMV resection had more advanced tumours. Perioperative mortality and morbidity rates did not differ between the two groups. Multivariable analysis revealed that PV/SMV resection was not an independent prognostic factor for overall survival (P = 0·268). Among the 435 patients in whom the PV/SMV was resected, borderline resectable tumours with arterial abutment (P = 0·021) and absence of adjuvant chemotherapy (P < 0·001) were independent predictors of poor survival in multivariable analysis. Patients with resectable or borderline resectable tumours with PV/SMV involvement had a median survival time with additional adjuvant chemotherapy of 43·7 and 29·7 months respectively. Median survival time in patients with borderline resectable tumours with arterial abutment was 18·6 months despite adjuvant chemotherapy.
Conclusion
Pancreatoduodenectomy with PV/SMV resection and adjuvant chemotherapy in patients with pancreatic head carcinoma may provide good survival without increased mortality and morbidity.
Potential role for adjuvant chemotherapy
The prevalence and risk factors of cholelithiasis in individuals with severe or profound intellectual and motor disabilities (SPIMD) are poorly characterised. Thus, we aimed to investigate the ...prevalence and risk determinants of cholelithiasis in a cohort with SPIMD under medical care in a residential facility.
We categorised 84 patients in a residential hospital for persons with SPIMD into groups: those with (Group CL) and without (Group N) cholelithiasis. Gallstones were detected via computed tomography, ultrasonography or both. We evaluated gastrostomy status, nutritional and respiratory support, constipation, and bladder and kidney stones. Data were significantly analysed using univariate and multivariate logistic regression analyses.
The prevalence rate of cholelithiasis in our SPIMD cohort was 27%. There were no significant differences in sex, age, weight, height, or Gross Motor Function Classification System between the two groups. However, more patients received enteral nutrition (39.13% vs. 6.56%; P = 0.000751) and were on ventilator support (56.52% vs. 19.67%; P = 0.00249) in Group CL than in Group N. Enteral nutrition odds ratio (OR) 10.4, 95% confidence interval (CI) 1.98-54.7 and ventilator support (OR 20.0, 95% CI 1.99-201.0) were identified as independent risk factors for the prevalence of cholelithiasis in patients with SPIMD.
Patients with SPIMD demonstrated an increased prevalence of cholelithiasis, with a notable association between nutritional tonic use and respiratory support. Therefore, to emphasise the need for proactive screening, it is crucial to devise diagnostic and therapeutic strategies specific to patients with SPIMD. Further investigation is essential to validate our findings and explore causative factors.
Obstacles are a common cause of falls among older adults. Anticipatory motor planning for obstacle negotiation must be completed during the precrossing phase in order to step over the obstacle ...safely. This cognitive load may affect anticipatory postural adjustments (APAs) in older adults at high risk of falling. This study explored the effect of obstacle negotiation on APA during gait initiation in older adults at high risk of falling.
Seventy-six elderly volunteers (mean age: 80.5 7.6 years) from the community participated in this study. Participants performed gait initiation tasks from a starting position on a force platform under the following two conditions: (1) unobstructed (smooth walkway) and (2) obstructed (walkway with an obstacle placed at 1 m from the initial position). The reaction and APA phases were measured from the data of center of pressure. Each participant was categorized as a high-risk or a low-risk individual according to the presence or absence of a fall experience within the past year.
High-risk participants had significantly longer APA phases than low-risk participants under the obstructed condition even though there was no significant difference between groups under the unobstructed condition. Reaction phase was not significantly different between groups in either the unobstructed or the obstructed condition.
Motor performance deterioration occurred in high-risk participants in the beginning of the precrossing phase of obstacle negotiation. A slow and inefficient APA at the precrossing phase of obstacle negotiation might be one of the causes of accidental falls.
Recently, several studies have reported age-associated increases in muscle coactivation during postural control. A rigid posture induced by strong muscle coactivation reduces the degree of freedom to ...be organized by the postural control system. The purpose of this study was to clarify the effect of balance training on muscle coactivation during postural control in older adults.
Forty-eight subjects were randomized into an intervention (mean age: 81.0 ± 6.9 years) and a control group (mean age: 81.6 ± 6.4 years). The control group did not receive any intervention. Postural control ability (postural sway during quiet standing, functional reach, and functional stability boundary) was assessed before and after the intervention. A cocontraction index was measured during the postural control tasks to assess muscle coactivation.
Cocontraction index values in the intervention group significantly decreased following the intervention phase for functional reach (p < .0125). Cocontraction index values had a tendency to decrease during functional stability boundary for forward and quiet standing tasks. Functional improvements were observed in some of the tasks after the intervention, that is, functional reach, functional stability boundary for forward, one-leg stance, and timed up and go (p < .05).
Our study raised the possibility that balance training for older adults was associated with decreases in muscle coactivation during postural control. Postural control exercise could potentially lead older adults to develop more efficient postural control strategies without increasing muscle coactivation. Further research is needed to clarify in greater detail the effects of changes in muscle coactivation.
The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) ...expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC).
Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated.
High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced.
Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.
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