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Introduction: This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy. Methods: Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial. Results: Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05). Conclusion: Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy.

Given the increased incidence of esophageal cancer (EC) in individuals over 80 years old, the optimum therapeutic strategy for elderly patients is needed to be established with scientific evidence. Here, we studied the short-term and long-term outcomes after treatment of patients aged 80 years old or older with EC.Eighty patients with EC aged 80 years old or older, who underwent esophagectomy (n=23), definitive chemoradiotherapy (dCRT) (n=46) or best supportive care (n=11) between January 2010 and March 2019 were included in this study, and clinical data were compared among these groups.Surgery had a great benefit on the 3-year overall survival (OS) compared to dCRT (68.4% vs. 29.3%, p0.01). The cure rates of treatment were 86.9% in surgery and 34.8% in dCRT. dCRT led to a better 3-year OS compared to BSC (29.3% vs. 0%, p0.01); however, dCRT did not improved OS in patients with T4. Patients with T4 had high frequency of adverse events and treatment-related death in dCRT; CTCAE Grade 3-5 was observed in 100% of all T4 patients and Grade 5 in 57.1%. Multivariate analysis revealed that T4 was an independent risk factor of treatment-related death after dCRT (p0.01).Surgery is the first treatment option for resectable EC even in elderly patients, and dCRT can be considered as an alternative. However, dCRT may induce severe toxicity especially in T4 EC patients.

Although the occurrence of gastric cancer has gradually decreased in East Asia, it is still the fifth most common malignancy and the second leading cause of cancer-related death worldwide. The International Agency for Research on Cancer has proposed that Helicobacter pylori, rubber production, tobacco smoking, as well as X-ray and gamma radiation are risk factors for gastric cancer. Further analysis of carcinogenesis will support the early detection of gastric cancer. Since the majority of patients with gastric cancer have no signs or symptoms of the disease, it is clinically difficult to detect these patients without screening. Moreover, representative diagnostic tools that have been used to detect early gastric cancer include upper gastrointestinal barium X-ray radiography, oesophagogastroduodenoscopy, endoscopic ultrasonography, computed tomography, and fluorodeoxyglucose positron emission tomography. In particular, magnifying narrow-band imaging (M-NBI) has been a promising approach for an accurate assessment. The recent development of M-NBI is critical for the strategic utilization of treatments such as endoscopic submucosal dissection. In 2016, the Union for International Cancer Control published the eighth edition of the TNM Classification of Malignant Tumours which defined a new stage grouping for gastric cancer. It contributes to the clinical management of tumour diagnosis and treatment for patients with gastric cancer.

Minimally invasive esophagectomy (MIE) has been widely accepted as a treatment for esophageal cancer. This retrospective study compared the short-term outcomes and surgical invasiveness between thoracoscopic esophagectomy (TE) and mediastinoscopic esophagectomy with pneumomediastinum (pneumatic mediastinoscopic esophagectomy [PME]).A total of 72 patients who underwent TE or PME were included and assessed for their surgical findings, postoperative complications, and inflammatory responses on postoperative day (POD) 1, 3, 5, and 7.The PME group exhibited a significantly shorter operative time and fewer lymph nodes retrieved than the TE group. Furthermore, the PME group tended to have greater incidences of recurrent laryngeal nerve palsy and lower incidences of atelectasis than the TE group. The PME group had significantly lower white blood cell counts on POD 5, serum C-reactive protein (CRP) levels on POD 3 than the TE group.PME seems to be less invasive than TE and can be considered the preferred option for patients with lower-stage esophageal cancer expected to have severe pleural adhesion or who cannot tolerate TE.

Purpose To investigate the clinical indications and prognostic significance of surgical interventions after chemotherapy using trastuzumab-containing regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Methods A total of 146 patients with AGC who underwent chemotherapy were enrolled in this retrospective study. Tumors with an immunohistochemistry (IHC) score of 3 + or an IHC score of 2 + plus fluorescence in situ hybridization positivity were defined as HER2-positive AGC. We devised a scoring system for predicting prognosis associated with conversion surgery. Results Thirty-three patients received trastuzumab-based chemotherapy for HER2-positive tumors. Multivariate analyses identified advanced age, peritoneal dissemination, histologically undifferentiated tumors, and tumor response of progressive disease as independent prognostic factors for a worse prognosis. Twelve patients with HER2-positive AGC underwent conversion surgery. The conversion surgery group of patients with HER2-positive AGC had a better prognosis than the chemotherapy-alone group. A prognostic scoring system based on age, peritoneal dissemination, and histological type was significantly correlated with the presence or absence of conversion surgery and the prognosis of patients with HER2-positive AGC. Conclusions Our scoring system has the clinical potential to predict prognosis associated with conversion surgery after trastuzumab-containing chemotherapy for patients with HER2-positive AGC.

Lymphatic metastasis is a major route of metastasis in distal cholangiocarcinoma (DCC). The present study aimed to elucidate the pattern of lymph node (LN) metastasis and the effectiveness of LN dissection and postoperative adjuvant chemotherapy in patients with DCC.Patients who underwent surgical resection with curative intent for DCC were enrolled. The nomenclature of the LN stations was defined according to the Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines. Effectiveness of LN dissection of each station was calculated using frequency of LN metastasis to the station and 5-year survival rate of patients with LN metastasis to that station.Of the 105 patients included in the study, 46 (43.8%) had LN metastasis, and 43 (41.0%) underwent postoperative adjuvant therapy. LN metastasis, serum carbohydrate antigen (CA) 19-9 level 37 U/mL, and positive bile duct margin were independent risk factors for shorter overall survival (OS). The most common metastatic LN station at surgery was No. 13 (32.7%), followed by No. 12 (19.2%), No. 17 (9.6%), and No. 8 (6.6%). There was no effectiveness of LN dissection of the station No. 8, 14, and 16. Adjuvant chemotherapy was significantly associated with longer OS in patients with LN metastasis but not in those with positive ductal margins or serum CA 19-9 level 37 U/mL.Postoperative adjuvant chemotherapy was associated with a better prognosis in patients with DCC and LN metastasis. However, a more effective therapeutic strategy is required to improve the prognosis of patients with other negative prognostic factors.

Supplementary Table S1 from Activation of toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors

Toll-like receptors (TLR) have been shown to be expressed on various types of cancers; however, their functional activity is not known. We examined TLR profiles of human melanoma cells and showed that TLR2, TLR3, and TLR4 were found to be highly expressed. By PCR array analysis, specific stimulation of TLR2, TLR3, and TLR4 on melanoma cells showed significant activation of the adaptor protein MyD88, as well as downstream signal transduction factors nuclear factor-κB and inflammatory response–related factors. Specific ligand activation of TLR2, TLR3, and TLR4 was shown to induce cell migration. Peripheral blood lymphocytes and melanoma purified RNA was shown to activate TLR3 on melanoma cells. These studies show expression and functional activity of specific TLRs on melanoma cells and as potential therapeutic targets to control tumor progression. [Mol Cancer Ther 2008;7(11):3642–53]

Purpose Transanal total mesorectal excision (TaTME) remains a challenging technique for rectal dissection. This study aims to evaluate the clinical and oncological outcomes of TaTME, compared to those of the laparoscopic total mesorectal excision (LaTME) in rectal cancer. Methods Using propensity score-matched analyses, we analyzed retrospective data from 134 consecutive patients with rectal cancer who underwent TaTME or LaTME from January 2011 to June 2020 in our hospital. Clinical and oncological outcomes were evaluated. The primary endpoint was the 2-year local recurrence rate. Results Before data analysis, significant group-dependent differences were observed only in the tumor height (p

In Japan, the standard therapeutic strategy for resectable advanced esophageal cancer (R-AEC) is neoadjuvant chemotherapy (NAC) followed by surgery. However, there is no strong evidence of the strategy for the elderly patients, thus the efficacy of NAC for the elderly patients with R-AEC remains controversial. Here we studied the efficacy of NAC for R-AEC in the patients aged 75 or older. This study included the patients aged 75 or older who diagnosed with R-AEC and underwent esophagectomy in our institution from 2005 to 2021. Among the total of 59 cases with R-AEC, the cases who received neoadjuvant chemoradiotherapy or who had poor follow-up were excluded, and the remaining 42 cases were enrolled in this cohort. Among 42 patients with R-AEC, 33 patients underwent UFS and 9 patients underwent NAC followed by surgery. The short- and long-term outcome was evaluated between upfront surgery (UFS) group and NAC group. There was a difference in historical background: patients in UFS group were more in 2012 or before, and patients in NAC group were more later than 2013. There was no significant differences in age, PS, Charlson comorbidity index and clinical characteristics such as TNM disease stage between two groups. The short-term outcome, the frequency of postoperative complications, curability, etc., was similar in two groups. In UFS group, only 5 cases (15.2%) underwent adjuvant chemotherapy. NAC improved 2-year RFS (UFS: 51.4% vs. NAC 76.2%, not significant), and 2-year OS (UFS 60.1% vs. NAC 71.1%, not significant). This study showed the likelihood of the benefits of NAC on the long-term outcomes without increasing the postoperative complications in patients with R-AEC aged 75 or older. There were some limitations in this study, single-institutional and retrospective study with small number of cases. The further study will be needed to clarify the efficacy of NAC in elderly patients with R-AEC.

To further improve the prognosis of locally advanced esophageal cancer patients, investigating new perioperative treatment strategies is necessary. The current study aimed to retrospectively investigate neoadjuvant radiotherapy with cisplatin and 5-fluorouracil (CF-RT) and radiotherapy with docetaxel and CF (DCF-RT) and compare their treatment outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC).We retrospectively reviewed 95 patients with ESCC who received CF-RT or DCF-RT followed by esophagectomy. The CF-RT group received chemotherapy consisting of two courses of CF repeated every 4 weeks. The DCF-RT group received chemotherapy consisting of two courses of DCF repeated every 2 weeks. A radiotherapy dose of 1.8-2 Gy was administered per session, up to a total of 40-41.4 Gy. Adverse events of neoadjuvant chemoradiotherapy, surgical outcomes, pathological responses, prognosis, and recurrence patterns were evaluated.Both the CF-RT and DCF-RT groups had equivalent pathological complete response rates of the primary tumor at 31.6% and 38.6%, respectively. However, the DCF-RT group had significantly better 5-year disease-free survival and 5-year overall survival than (HR=0.50, 95%CI=0.26-0.97, p=0.0392) than the CF-RT group.DCF-RT may be a candidate neoadjuvant therapy for locally advanced ESCC.

Totally laparoscopic colectomy with intracorporeal anastomosis (IA) is associated with less surgical trauma and wound related complications compared to laparoscopy-assisted colectomy with extracorporeal anastomosis. Delta shaped anastomosis is a widely popular IA technique. In this study, we discuss a construction technique for an overlapped delta-shaped anastomosis using a linear stapler with a reinforced bioabsorbable material.We excised the bowel at a point 10 cm from the tumour on either sides and laid them in an overlapped fashion. The entry hole was created at a point 3 cm proximal to the right stump and 7 cm distal to the left stump on the antimesenteric side. Then, a 60-mm linear stapler with reinforced bioabsorbable material was inserted inside each lumen and fired. Finally, the common entry hole was fixed with a suture in the middle, the bowel was elevated holding the bioabsorbable material, and closed using the linear stapler in a delta-shaped manner.The technique was applied in five patients with tumours in the ascending, transverse, and descending colon. The median surgery time, anastomosis construction time and postoperative stay was 329 min (range 285-682 min), 19 min (range 14-29 min), and 12 days (range 9-15 days), respectively. There were no perioperative complications and only one postoperative complication.The overlapped delta-shaped anastomosis technique using linear staplers with reinforced bioabsorbable material appears to be both safe and feasible.

The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment.We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis.An increased number of CD8Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.