Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy.

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

High L-Type Amino Acid Transporter 1 Levels Are Associated with Chemotherapeutic Resistance in Gastric Cancer Patients.

INTRODUCTION: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. METHODS: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. RESULTS: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). CONCLUSION: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.

Post-esophagectomy Adjuvant Chemotherapy Benefits Esophageal Cancer Patients.

BACKGROUND/AIM: Postoperative chemotherapy is an absolutely imperative treatment for advanced esophageal cancer patients, while preoperative chemotherapy is the standard therapy for clinical stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this study was to report the effect of postoperative chemotherapy on survival after esophagectomy due to thoracic esophageal squamous cell carcinoma. PATIENTS AND METHODS: One hundred thirteen consecutive patients with esophageal carcinoma who underwent esophagectomy were included. Several regiments were performed at various times. RESULTS: Adjuvant chemotherapy brought a significantly superior overall survival (p=0.002), although there was no significant difference in cancer-specific survival (p=0.054) for clinical stage II or stage III esophageal cancer patients. Depth of invasion (p=0.003), number of lymph node metastases (p=0.048), and venous invasion (p<0.001) were risk factors for recurrence in the adjuvant-chemotherapy group with positive lymph nodes. Additionally, a not well-differentiated type, lymphatic and venous invasions were risk factors for recurrence in the surgery-alone group without positive lymph nodes. CONCLUSION: Postoperative adjuvant chemotherapy contributes to the prognosis of clinical stage II or III esophageal cancer patients.

Correlation between high FBXW7 expression in pretreatment biopsy specimens and good response to chemoradiation therapy in patients with locally advanced esophageal cancer: A retrospective study.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) exhibits good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance in cancer cells. However, the correlation between FBXW7 expression and CRT sensitivity in patients with clinical ESCC has been investigated only in few studies. Therefore, this study aimed to elucidate the significance of FBXW7 expression in pretreatment biopsy specimens from patients with ESCC receiving CRT. METHODS: We investigated the relationship between FBXW7 expression and CRT sensitivity in 30 pretreatment biopsy specimens with histological grades of post-CRT surgically resected tumors. Furthermore, we evaluated the effects of high FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and nedaplatin, and radiation in ESCC cells in vitro. RESULTS: High FBXW7 expression before CRT correlated with a good pathological CRT response in patients with advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1. CONCLUSIONS: The evaluation of FBXW7 expression before CRT treatment is a potential predictor of good responders among patients with ESCC receiving CRT.

Planned Esophagectomy after Neoadjuvant Hyperthermo-Chemoradiotherapy using Weekly Low-Dose Docetaxel and Hyperthermia for Advanced Esophageal Carcinomas.

BACKGROUND/AIMS: The optimal treatment for locally advanced esophageal carcinoma has not yet been determined. We report results of neoadjuvant hyperthermo-chemoradiotherapy (HCRT) using weekly low-dose docetaxel followed by surgery in patients with advanced esophageal squamous cell carcinoma. METHODOLOGY: Twenty-four patients were enrolled. 7 patients were considered to have inoperable tumors or rejected surgery after HCRT, and the remaining 17 patients had an esophagectomy. Clinical responses, HCRT toxicity and survival after surgery were evaluated. RESULTS: In the 24 patients, the response rate was 41.7%. The pathological complete response (pCR) rate was 17.6% in the 17 patients. HCRT toxicity grade 2 occurred in six patients (25.0%: esophagitis, 4; leukopenia, 6; neutropenia, 4) and grade 3 (pneumonia) in 3 patients (12.5%). The 3- and 5-year survival rates were 56.3% and 50.0%, respectively. When the patients were divided into a pCR group and a pathological partial response (pPR) group, the 3-year survival rates were 66.7% and 42.9% and the 5-year survival rates were 66.7% and 42.9%, respectively (log-rank P = .5842). CONCLUSIONS: Esophagectomy after docetaxel HCRT may have potential for prolonging survival in patients with locally advanced esophageal cancer. A larger randomized, controlled study will be required to confirm the benefit of esophagectomy after HCRT.

Development of a non-scanning vibrational sum-frequency generation detected infrared super-resolution microscope and its application to biological cells.

We report single-cell infrared (IR) imaging of onion (Allium cepa) root cells using an IR super-resolution microscope based on vibrational sum-frequency generation (VSFG). The resolution of recorded IR images was less than 2 microm and IR super-resolution was achieved by virtue of the VSFG detection. In addition, IR spectra measurements were successfully performed on distinct intra-cellular assemblies. The IR absorption intensity of the cell nuclear edge and the nucleolus in the 3055-3130 cm(-1) region was stronger than that from the cytoplasmic part. This is because the cell nucleus and nucleolus contain larger amounts of nucleic acid. Thus, the obtained IR spectra reflect differences in chemical composition among different cellular structures. In addition, the ability of our novel IR super-resolution microscope to obtain distinct information on both VSFG and two-photon fluorescence is demonstrated.

[Effects of reduced dialysate calcium on mineral metabolism in hemodialysis patients].

AIM: To study the effects of decreased dialysis calcium on mineral metabolism. METHODS: Dialysis calcium concentration was switched from 3.0 mEq/L to 2.5 mEq/L. Changes of serum Ca, P, and PTH were monitored for 6 months in 58 hemodialysis patients. RESULTS: Serum calcium decreased 2 weeks after the switch of dialysate, although it returned to the basal level after 6 months because of increased dosage of vitamin D. Phosphorus transiently increased after the switch. I-PTH increased in patients whose i-PTH before the switch was less than 100 pg/mL. PTH decreased in patients whose i-PTH exceeded 300 pg/mL. CONCLUSION: Decreased dialysis calcium produced lower serum calcium and better PTH control.