Background
This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric ...cancer with extensive lymph node metastasis.
Methods
Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006.
Results
This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (
n
= 22) and arm B (
n
= 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3–4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (
p
= 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (
p
= 0·072) in resected patients, respectively.
Conclusions
Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
The purpose of this study is to clarify the resection rate, safety, and significance of conversion surgery for highly selected patients with unresectable pancreatic cancer (URPca).
Methods
We ...studied 434 URPca patients. Conversion surgery was permitted only for patients who met following requirements: responders to first-line therapy, showing sufficient reduction of the local tumor to enable complete resection, at least 6 months of disease control, and no metastatic lesions detected on radiological examinations (for patients with metastatic disease). The overall survival (OS) was compared between patients who underwent surgery and those who did not. Furthermore, a multivariate analysis was performed to identify possible predictive factors for both total patients with URPca and responders.
Results
Conversion surgery was performed in 18 patients (4.1%). The pathologically complete resection rate was 88.9% (16/18). The median operative time, blood loss, and hospitalization duration were 450 min, 780 ml, and 29 days, respectively. The OS was significantly better in patients who underwent surgery than in those who did not. In a multivariate analysis, conversion surgery was shown to be significantly correlated with the OS both in total patients and responders.
Conclusions
A satisfactory outcome was achieved for highly selected patients with URPca in exchange for a lower resection rate (4.1%).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
Transcriptional and post‐translational regulations are important in peripheral nerve injury–induced neuropathic pain, but little is known about the role of post‐transcriptional modification. ...Our objective was to determine the possible effect of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyze posttranscriptional RNA editing, in tactile allodynia, a hallmark of neuropathic pain. Seven days after L5 spinal nerve transection (SNT) in adult mice, we found an increase in ADAR2 expression and a decrease in ADAR3 expression in the injured, but not in the uninjured, dorsal root ganglions (DRGs). These changes were accompanied by elevated levels of editing at the D site of the serotonin (5‐hydroxytryptamine) 2C receptor (5‐HT2CR), at the I/V site of coatomer protein complex subunit α (COPA), and at the R/G site of AMPA receptor subunit GluA2 in the injured DRG. Compared to Adar2+/+/Gria2R/R littermate controls, Adar2‒/‒/Gria2R/R mice completely lacked the increased editing of 5‐HT2CR, COPA, and GluA2 transcripts in the injured DRG and showed attenuated tactile allodynia after SNT. Furthermore, the antidepressant fluoxetine inhibited neuropathic allodynia after injury and reduced the COPA I/V site editing in the injured DRG. These findings suggest that ADAR2 is a mediator of injury‐induced tactile allodynia and thus a potential therapeutic target for the treatment of neuropathic pain.—Uchida, H., Matsumura, S., Okada, S., Suzuki, T., Minami, T., Ito, S. RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury. FASEB J. 31, 1847–1855 (2017). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in ...spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. Methods We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien-Dindo (CD) grade greater than or equal to II. The secondary endpoints are the incidence of all CD grade greater than or equal to II and greater than or equal to IIIA postoperative complications, the incidence of CD grade greater than or equal to IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. Discussion This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. Trial registration The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( Keywords: Stomach neoplasms, Robotic surgery, Minimally invasive surgery, Postoperative complication, Multicenter study, Randomized controlled trial
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this study is to clarify the survival benefit and acceptable extent of surgery for very elderly patients with pancreatic cancer. Patients (n=55) ≥80 years with resectable pancreatic ...cancer were studied. 29 underwent pancreatectomy, 16 underwent chemotherapy, and 10 received best supportive care. Uni and multivariate analysis were performed to explore predictive factors for overall survival (OS) with surgery and chemotherapy (n=45). Postoperative survival of PD (pancreatoduodenectomy) and DP (distal pancreatectomy) and of PD-PVR (PD with portal vein resection) and PD were compared. OS was equivalent with surgery and chemotherapy (median survival time MST; 685 vs. 626 days, respectively; p=0.057); 6 patients surivived ≥3 years after surgery. Pancreatectomy was not a prognostic factor. Survival was significantly worse with PD-PVR than with PD, but equivalent with PD and DP. Within 2 years after PD-PVR, 8 patients have died. Surgery was not a positive prognostic factor for very elderly patients with pancreatic cancer, but was the sole chance for survival ≥3 years. Indication for PD-PVR for very elderly patients should be determined more cautiously compared with that for non-elderly patients.
Background
Splenectomy for proximal gastric cancer was found to have no survival benefit in a randomized trial clarifying the role of splenectomy (JCOG0110 study). However, since tumor with invasion ...to the greater curvature and Type 4 tumor were excluded in JCOG0110, the benefit of splenectomy for these tumors is not known.
Methods
A multicenter dataset of patients with gastric cancer who underwent gastrectomy between 2010 and 2014 was created. From the dataset, 114 eligible patients with proximal advanced gastric cancer with invasion to the greater curvature or Type 4 tumor were enrolled. There were 60 patients in the gastrectomy with splenectomy (Spx) group and 54 patients in the spleen-preserving (Prs) group. To balance the essential variables, propensity score analysis was performed, estimating the propensity score with a logistic regression model. Adjusted overall survival (OS) and adjusted disease-free survival (DFS) were estimated using the inverse probability of treatment weighting (IPTW) method.
Results
There were significant differences in age, performance status, comorbidity, macroscopic type, and clinical T stage between the Spx and Prs groups. The model for estimating the propensity score was well adapted (c-statistic: 0.830, 95%CI: 0.754–0.906). Adjusted OS was identical between the two groups (HR = 1.089, 95%CI: 0.759–1.563; p = 0.644). The DFS curve of Prs group was consistently tended to be lower than Spx, but the difference was not significant (HR = 0.813, 95%CI: 0.572–1.156; p = 0.249).
Conclusions
The efficacy of splenectomy was minimal for proximal advanced gastric cancer even with invasion to the greater curvature or Type 4 tumor.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Postoperative bleeding originating from pseudoaneurysms after radical gastrectomy is not common, but it can be fatal. In particular, delayed bleeding that occurs after the seventh ...postoperative day is rare.
Case presentation
A 54-year-old man underwent laparoscopic distal gastrectomy, D2 lymph node dissection, and Roux en-Y reconstruction for duodenal neuroendocrine tumors. Drainage was performed for a postoperative pancreatic fistula and abdominal abscess. On the 28th postoperative day, he passed a large amount of bloody stool; therefore, emergency esophagogastroduodenoscopy (EGD) and angiography were performed. However, neither examination demonstrated any bleeding foci or pseudoaneurysm. He was conservatively observed and discharged on the 50th postoperative day. Approximately 1 year after the surgery, he passed a bloody stool and experienced hemorrhagic shock. An EGD revealed exposed blood vessels at the duodenal blind end. His condition was diagnosed as a pseudoaneurysm arising from gastroduodenal artery, which ruptured into the duodenum, based on abdominal contrast-enhanced computed tomography findings. Emergency angiography was performed, and the pseudoaneurysm and artery were successfully embolized.
Conclusions
This case illustrates that there is a possibility of delayed bleeding even 1 year after gastrectomy. Such cases may be serious and require immediate and careful management.
Background
We aimed to clarify the utility of lymph node ratio (LNR) for assessing the prognosis of patients with node-positive gastric cancer after curative gastrectomy.
Methods
We retrospectively ...analyzed data of 973 patients with node-positive gastric cancer who had undergone curative gastrectomy at nine institutions from 2010 to 2014. Survival analysis was performed by comparing LNR low and high groups according to the optimal cutoff value of LNR, which was determined using receiver operating characteristic curve analysis.
Results
LNR high was significantly associated with shorter disease-free survival and was an independent predictor of recurrence in all patients. Moreover, we obtained the similar results from analysis of each N stage. The prevalence of lymph node and peritoneal recurrence appeared to be higher in the LNR high group. Correlation analysis showed that LNR was negatively correlated with the number of retrieved nodes within every N stage; however, disease-free survival did not differ significantly between LNR low and high groups of each N stage with 16–30, 31–40, or >40 retrieved nodes.
Conclusions
LNR is a strong prognostic factor and predictor of recurrence in patients with node-positive gastric cancer who have undergone curative gastrectomy. The combination of LNR and N staging permits more accurate prognostic stratification of patients with gastric cancer and may contribute to developing novel prognostic models.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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