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Progression of the physical weakness during neoadjuvant therapy (NAT) in patients with esophageal or gastroesophageal junction cancer is a serious problem; however, prehabilitation during NAT has the potential to overcome the unmet need. Nevertheless, systematic reviews on this topic have not been summarized. Therefore, this systematic review aimed to determine prehabilitation's effectiveness, acceptability, and safety during NAT for patients with esophageal or gastroesophageal junction cancer. An electronic search was performed in the MEDLINE, Web of Science, CENTRAL, CINAHL, and PEDro databases. A meta-analysis was conducted to assess the effectiveness of prehabilitation during NAT, along with a descriptive analysis of acceptance and safety. This study analyzed data from three randomized controlled trials (RCTs) and nine non-RCTs involving 664 patients. The meta-analysis of two RCTs demonstrated that prehabilitation during NAT may be more effective than usual care in enhancing tolerance to NAT and grip strength; moreover, one RCT and three non-RCTs revealed that prehabilitation may reduce the risk of postoperative complications. The adherence rates for exercise programs in two RCTs and seven non-RCTs were 55–76%. Additionally, two studies reported a 76% adherence rate for multimodal prehabilitation programs, including exercise, dietary, and psychological care. Six studies reported no serious prehabilitation-related adverse events during NAT. Prehabilitation during NAT may be a safe and beneficial intervention strategy for patients with esophageal or gastroesophageal junction cancer. However, the investigation of strategies to enhance adherence is essential. Furthermore, additional high-quality RCTs are needed to examine the effect of prehabilitation during NAT. [ABSTRACT FROM AUTHOR]

Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (−7.98% vs. −12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL. [ABSTRACT FROM AUTHOR]

Background: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). Methods: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. Results: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. Conclusion: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy. In this retrospective cohort study involving 3154 patients, a strong correlation between recurrence-free and overall survival was established, and this correlation was more pronounced in patients who had a more effective response to neoadjuvant chemotherapy. These findings are beneficial for expediting the development of novel neoadjuvant treatments by shortening the duration of clinical trials. [ABSTRACT FROM AUTHOR]

Background Epidural analgesia (EDA) is a main modality for postoperative pain relief in major open abdominal surgery within the Enhanced Recovery After Surgery protocol. However, it remains unclear whether EDA is an imperative modality in laparoscopic gastrectomy (LG). This study examined non-inferiority of patient-controlled intravenous analgesia (PCIA) to EDA in terms of postoperative pain and recovery in patients who underwent LG. Methods In this open-label, non-inferiority, parallel, individually randomized clinical trial, patients who underwent elective LG for gastric cancer were randomized 1:1 to receive either EDA or PCIA after surgery. The primary endpoint was pain score using the Numerical Rating Scale at rest 24 h after surgery, analysed both according to the intention-to-treat (ITT) principle and per protocol. The non-inferiority margin for pain score was set at 1. Secondary outcomes were postoperative parameters related to recovery and adverse events related to analgesia. Results Between 3 July 2017 and 29 September 2020, 132 patients were randomized to receive either EDA (n = 66) or PCIA (n = 66). After exclusions, 64 patients were included in the EDA group and 65 patients in the PCIA group for the ITT analysis. Pain score at rest 24 h after surgery was 1.94 (s.d. 2.07) in the EDA group and 2.63 (s.d. 1.76) in the PCIA group (P = 0.043). PCIA was not non-inferior to EDA for the primary endpoint (difference 0.69, one side 95% c.i. 1.25, P = 0.184) in ITT analysis. Postoperative parameters related to recovery were similar between groups. More EDA patients (21 (32.8%) versus 1 (1.5%), P < 0.001) developed postoperative hypotension as an adverse event. Conclusions PCIA was not non-inferior to EDA in terms of early-phase pain relief after LG. Registration number: UMIN000027643 (https://www.umin.ac.jp/ctr/index-j.htm). [ABSTRACT FROM AUTHOR]

Salvage surgery for esophageal cancer after definitive chemoradiotherapy (dCRT) is effective, but it is associated with a high rate of perioperative complications. The indications for robot‐assisted minimally invasive esophagectomy (RAMIE) are expanding. However, there are few reports of salvage RAMIE. A 73‐year‐old man was referred to our hospital for residual esophageal cancer with a mediastinal fistula after dCRT. The perioperative diagnosis was T3N1M0‐Stage III, and the salvage RAMIE was performed. Although the dissection was difficult due to fibrosis caused by dCRT and the esophageal mediastinal fistula, RAMIE was performed safely with no complications. Multiple features of RAMIE contributed to stable surgery. The monopolar dissection is effective for hard scar tissue caused by CRT and inflammation. [ABSTRACT FROM AUTHOR]

Simple Summary: In esophageal cancer, the 5-year survival rate for patients who underwent esophagectomy with chemoradiotherapy is poor, with an estimated rate of 32.4%. One reason for this outcome is the low response rate to preoperative chemotherapy or radiotherapy. In this study, we revealed that low-dose chemotherapy or radiotherapy causes malignant phenotypic changes, such as cancer-associated fibroblasts, in normal fibroblasts. Furthermore, radiotherapy-resistant fibroblasts significantly increased the total number of tumors in the peritoneal cavity compared to the control group in peritoneal-disseminated tumor models. Thus, conventional cancer therapy has anti-therapeutic effects via activation of fibroblasts, and it is important to determine which modality of esophageal cancer treatment is selected or combined, recognizing that inappropriate radiotherapy and chemotherapy can lead to tumor resistance. Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors. [ABSTRACT FROM AUTHOR]

Background and Aims Ulcerative colitis [UC] can lead to colitis-associated colorectal neoplasm [CAN]. Adenosine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA [ADAR], induces the post-transcriptional modification of critical oncogenes, including antizyme inhibitor 1 [AZIN1], leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. Methods We systematically analysed a cohort of 139 UC cases [40 acute phase, 73 remission phase, 26 CAN]. The degree of inflammation was evaluated using the Mayo endoscopic score [MES]. Results The type 1 interferon [IFN]-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN and tumour site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was downregulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as seen in Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium , may induce carcinogenesis in UC. Conclusions The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC. [ABSTRACT FROM AUTHOR]