Dual near-infrared II laser modulates the cellular redox state of T cells and augments the efficacy of cancer immunotherapy.

Immunotherapy, including immune checkpoint inhibitors, has revolutionized cancer treatment, but only a minor fraction of patients shows durable responses. A new approach to overcome this limitation is yet to be identified. Recently, we have shown that photobiomodulation (PBM) with near-infrared (NIR) light in the NIR-II window reduces oxidative stress and supports the proliferation of CD8+ T cells, suggesting that PBM with NIR-II light could augment anti-cancer immunity. Here, we report a novel approach to support tumor-infiltrating CD8+ T cells upon PBM with NIR-II laser with high tissue penetration depth. Brief treatments of a murine model of breast cancer with dual 1064 and 1270 nm lasers reduced the expression of the programmed cell death protein 1 (PD-1) in CD8+ T cells in a syngeneic mouse model of breast cancer. The direct effect of the NIR-II laser treatment on T cells was confirmed by the enhanced tumor growth delay by the adoptive transfer of laser-treated CD8+ T cells ex vivo against a model tumor antigen. We further demonstrated that specific NIR-II laser parameters augmented the effect of the immune checkpoint inhibitor on tumor growth. PBM with NIR-II light augments the efficacy of cancer immunotherapy by supporting CD8+ T cells. Unlike the current immunotherapy with risks of undesirable drug-drug interactions and severe adverse events, the laser is safe and low-cost. It can be broadly combined with other therapy without modification to achieve clinical significance. In addition, our study established a path to develop a novel laser-based therapy to treat cancer effectively.

Evaluating gastric remnant ischemia by indocyanine green fluorescence-guided surgery after distal gastrectomy in a patient with prior Nissen fundoplication: A case report.

INTRODUCTION: Recent studies showed that intraoperative indocyanine green (ICG) fluorescence imaging-guided surgery helped evaluate organ perfusion. Whereas whether the gastric remnant can be preserved after distal gastrectomy for the cases of post-Nissen fundoplication remains unclarified. This case report demonstrated the applicability of intraoperative ICG fluorescence-guided surgery to assess the gastric remnant's blood supply after distal gastrectomy. CASE PRESENTATION: A 68-year-old man who previously underwent Nissen fundoplication for esophageal hiatal hernia was diagnosed with early gastric cancer in the lower body of the stomach. We performed laparoscopic distal gastrectomy to preserve the left gastroepiploic vessels considering the dissection of a part of the short gastric vessel from the previous Nissen fundoplication. After completing Billroth I reconstruction, the color of the serosal surface did not show any signs of ischemia. However, intraoperative esophagogastroduodenoscopy showed an ischemic change of the remnant stomach. In addition, ICG fluorography revealed insufficient blood supply to the gastric remnant compared with that to the pancreas and liver. Consequently, we converted to total gastrectomy to avoid necrosis in the gastric remnant. CONCLUSION: We performed intraoperative ICG fluorescence-guided surgery in patients with early gastric cancer after Nissen fundoplication. ICG fluorescence may be useful in preventing postoperative gastric remnant ischemia, especially in high-risk patients.

Gastric Emptying Improved Significantly After PRG Compared to Billroth-I Reconstruction: Assessment of Gastric Emptying With a 13C-Breath Test.

BACKGROUND: We advocated the usefulness of pylorus-reconstruction gastrectomy (PRG) to improve quality of life following surgery for gastric cancer. The current study assessed gastric emptying following PRG in comparison with those who underwent conventional Billroth-I (B-I) reconstruction and in healthy controls using a 13C breath test. PATIENTS AND METHODS: The study group consisted of 24 patients who underwent PRG from September 20, 2007 to July 26, 2012 at the Department of Surgery at Daisan Hospital (affiliated with The Jikei University School of Medicine). These patients underwent the 'standard' version of a gastric-emptying study using a 13C breath test at 20.5±11.8 months after surgery. During the study, the half gastric-emptying time (T1/2) and gastric retention at 5 min after ingestion (RR5) were measured. The data of the PRG group were compared to those for 26 patients who underwent conventional B-I reconstruction and with a group consisting of 20 healthy controls. RESULTS: RR5 was 69.6±21.8% in the patients who underwent PRG, 45.3±28.6% in those who underwent B-I reconstruction, and 93.7±5.7% in healthy controls. T1/2 was 17.0±13.0 min in patients who underwent PRG, 5.9±4.0 min in those who underwent B-I reconstruction, and 23.3±4.9 min in healthy controls. Gastric emptying was delayed in patients who underwent PRG compared to those who underwent B-I reconstruction (RR5: p<0.0014, T1/2: p<0.0002), and was comparable to that of healthy controls. CONCLUSION: Gastric emptying improved significantly after PRG compared to B-I reconstruction, and approached that of healthy controls.

Impaired Gastrointestinal Function Affects Symptoms and Alimentary Status in Patients After Gastrectomy.

BACKGROUND: Postgastrectomy syndrome (PGS) remains a common complication after gastrectomy that affects patients' quality of life. Although impaired gastrointestinal (GI) function by gastrectomy procedures is thought to be the cause, the precise pathophysiology of PGS is yet to be clarified. AIM: The aim of this study was to investigate relationships between GI function and various symptoms or alimentary status in patients after gastrectomy. METHODS: Fifty-one patients who underwent total or distal gastrectomy at least 1 year previously were studied. All patients replied to a questionnaire that asked presence of symptoms (esophageal reflux, nausea, abdominal pain, early satiation, diarrhea, early dumping general, early dumping abdominal, and late dumping symptoms) and alimentary status (change in body weight, food intake per meal, frequency of meals per day). They also underwent assessment of GI function consisting of gastric emptying study by 13C-acetate breath test to examine reservoir capacity and gastric emptying, and water load drink test to evaluate tolerance to volume loading (TVL). The relationships between GI function and each symptom or alimentary status were examined. RESULTS: The patients with nausea and early dumping general symptoms had significantly smaller reservoir capacity*, the patients with diarrhea and early dumping general symptoms had significantly faster gastric emptying*, and the patients with early satiation and early dumping abdominal symptoms had significantly impaired TVL*. Significant correlations were identified between TVL and body weight changes* or food intake per meal* (* p < 0.05). CONCLUSION: Impaired postoperative GI function was closely related to symptoms or worse alimentary status.

Assessment of motor function of the remnant stomach by ¹³C breath test with special reference to gastric local resection.

BACKGROUND: Indications for gastric local resection (LR) include gastrointestinal stromal tumors, neuroendocrine tumors, and early gastric cancer. LR is expected to preserve physiological function and ameliorate postgastrectomy syndrome. METHODS: Gastric emptying was assessed by the (13)C-acetate breath test in 20 healthy volunteers (HVs) and 60 gastrectomized patients [distal gastrectomy with Billroth I reconstruction (DGBI) in 26 patients, LR in 34 patients]. For the (13)C breath test, 100 mg of (13)C-acetate sodium salt was mixed in a test meal. Breath samples were collected before intake and during the next 3 h. We compared the gastric reservoir capacity using the gastric retention rate at 5 min (RR5) and gastric emptying by the half emptying time (T½). Patients completed a questionnaire survey about their symptoms, dietary intake, body weight, and restriction of activities of daily living [reflecting quality of life (QOL)]. RESULTS: The RR5 values for the HV, LR, and DGBI groups were 93.7, 90.0, and 45.3* %, respectively (*compared to HV and LR, p < 0.0001). The T½ values were 23.3, 20.2, and 5.9* min, respectively. Dietary intake and body weight change were significantly more reduced in the DGBI group than the LR group (p < 0.05). Subgroup analysis indicated that the reservoir capacity in those with LR at the lesser curvature was more disturbed than that in patients with LR at the greater curvature. The questionnaire showed no differences in those patients' QOL. CONCLUSIONS: Because the reservoir capacity, the gastric emptying and QOL were maintained, LR is an option for selected patients with early gastric cancer.

Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent.

OBJECTIVES: The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model. BACKGROUND: Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available. METHODS: A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured. RESULTS: Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents. CONCLUSIONS: Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.

[Improving the quality of life after gastrectomy is the next issue after saving the lives of patients with gastric cancer].

Gastrectomy saves the lives of many patients with gastric cancer. However, this surgical treatment is associated with clinical problems called postgastrectomy syndrome (PGS) which affect the quality of life (QOL) of such patients. For surgeons, improving the QOL after gastrectomy is an important goal after performing curative surgery. In the clinical setting, various surgical procedures such as limited resection, function-preserving procedures, and reconstruction using gastric substitutes have been advocated to reduce the severity of PGS. However, the actual conditions and pathophysiology of PGS have not been fully investigated. Various clinical studies and basic research have partially clarified the features and pathophysiology of PGS, although the strategies developed to treat PGS have been limited. The development of standardized, reliable instruments for understanding PGS and performing large-scale collaborative studies are required to improve the diagnosis and treatment of PGS. In Japan, such a project called the PGSAS has recently been completed. The results are being analyzed and will be reported in the near future.

Laparoscopy-assisted total gastrectomy for advanced gastric cancer with carcinomatous ascites after S1 plus cisplatin chemotherapy: a case report.

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.