Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery.

Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066.

Postoperative long­term outcomes of acute normovolemic hemodilution in pancreatic cancer: A propensity score matching analysis.

Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, the impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the impact of ANH on long-term outcomes in patients with PDAC undergoing radical surgery. Data from 155 resectable PDAC cases were collected. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH. A total of 44 patients (28.4%) were included in the ANH group and 30 patients (19.4%) were included in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group had the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P=0.043) and DSS (P=0.029) compared with the STD group before applying Bonferroni correction; however, no significant difference was observed after applying Bonferroni correction. Cox regression analysis identified ANH as an independent prognostic factor for RFS [relative risk (RR), 1.696; P=0.019] and DSS (RR, 1.876; P=0.009). After PSM, the ANH group exhibited less favorable RFS [median survival time (MST), 12.1 vs. 18.1 months; P=0.097] and DSS (MST, 32.1 vs. 50.5 months; P=0.097) compared with the STD group; however, these differences were not statistically significant. In conclusion, while ANH was not as harmful as ABT, it exhibited potentially more negative effects on long-term postoperative outcomes in PDAC than STD.

Exploration of Malignant Characteristics in Neoadjuvant Chemotherapy-Resistant Rectal Cancer, Focusing on Extramural Lesions.

BACKGROUND: Extramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD. METHODS: From 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared. RESULTS: The NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047). CONCLUSIONS: We defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.

Three-dimensional analysis of perineural invasion in extrahepatic cholangiocarcinoma using tissue clearing.

Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.

Long-Term Outcomes of Hearing Preservation After Retrosigmoid Removal of Large Vestibular Schwannoma.

Background: Hearing preservation after large vestibular schwannoma (VS) removal is challenging and the long-term outcomes of postoperatively preserved hearing have not been elucidated. Objective: We aimed to clarify long-term outcomes of hearing preservation after the retrosigmoid large VS removal and to recommend a strategy for treating large VS. Materials and Methods: Hearing preservation with total/nearly total (T/NT) tumor removal was accomplished in six of 129 patients who underwent retrosigmoid large VS (≥3 cm) removal. We evaluated the long-term outcomes of these six patients. Results: Preoperative hearing of these six patients was 15-68 dB by pure tone audiometry (PTA) (Class I: 2, II: 3, and III: 1 by the Gardner-Robertson (GR) classification). Postoperatively, magnetic resonance imaging (MRI) with gadolinium administration confirmed T/NT removal, the preserved hearing was 36-88 dB (Class II: 4 and III: 2), and no facial palsy occurred. After long-term follow-up (8-16 [median: 11.5] years), five patients maintained hearing of 46-75 dB (Class II: 1 and III: 4) while one lost hearing. Three patients showed small tumor recurrence on MRI; two recurrences were controlled by gamma knife (GK) and one showed minimal change only by observation. Conclusions: Hearing preserved after T/NT removal of large VS is maintained for a long time (>10 years), though tumor recurrence on MRI is somewhat common. Detecting small recurrence early, and regular MRI follow-up contributes to the long-term maintenance of hearing. Hearing preservation with tumor removal is a challenging yet worthwhile strategy in large VS patients with preoperative hearing.

Use of time­density curves of dynamic contrast­enhanced computed tomography for determination of the histological therapeutic effects of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma.

The present study aimed to investigate the histological changes caused by neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC), and to demonstrate the use of time­density curves (TDCs) of dynamic contrast­enhanced computed tomography (CECT) for determination of the histological therapeutic effects of NAC for PDAC. A total of 96 patients with PDAC were examined; 46 underwent NAC (NAC group) and 50 did not undergo NAC (non­NAC group). Based on histological therapeutic effect and using the area of residual tumor (ART) grading system, the NAC group was divided into low­responders and high­responders. Histological analysis was used to evaluate the densities of cancer cells, cancer­associated fibroblasts (CAFs), microvessels and stromal collagen fibers in the NAC and non­NAC groups. Radiological analysis was used to evaluate the TDCs of three slopes of the NAC group, namely slopes between the non­contrast and arterial phases (δ1 and δ1'), between the arterial and portal phases (δ2 and δ2'), and between the portal and equilibrium phases (δ3 and δ3'). δ1­Î´3 were before NAC, whereas δ1'­Î´3' were after NAC. Changes in δ1, δ2 and δ3 before and after NAC were denoted as δδ1 (=δ1'­Î´1), δδ2 (=δ2'­Î´2) and δδ3 (=δ3'­Î´3). ART grading system, histological examination and radiological examination data were also statistically analyzed. Histological examination revealed a significant decrease in cancer cells and CAFs, and a significant increase in stromal collagen fibers due to NAC (P<0.01). Radiological examination revealed that δ1' was significantly higher than δ1 in low­responders (P<0.05), whereas δ2' was significantly lower than δ2 in high­responders (P<0.01). δδ2 was significantly lower and δδ3 was significantly higher in high­responders than in low­responders (P<0.01 and P<0.05, respectively). Receiver operating characteristic curve showed that δδ2 and δδ3 were effective indicators of the histological therapeutic effect of NAC. In conclusion, the TDC of dynamic CECT may be useful for determining the histological therapeutic effect of NAC for PDAC.

Cyst-to-Mastoid Antrum Diversion as an Alternate Pathway for Management of Small Symptomatic Petrous Apex Cholesterol Granuloma Without Anteromedial Expansion Using an Extradural Middle Fossa Approach: A Technical Case Report.

BACKGROUND AND IMPORTANCE: Cholesterol granuloma (CG) is the most common petrous apex (PA) cystic lesion. Posterolateral expansion of a PA CG (PACG) compresses the internal auditory canal (IAC), leading to vestibulocochlear (VC) and facial nerve dysfunction. Even small, symptomatic PACGs are managed surgically. The preferred strategy is not complete removal, but drainage and aeration. PACG with anteromedial expansion using an endoscopic endonasal approach provides natural drainage into the nasal sinus without risking VC and facial dysfunction. Endoscopic endonasal approach is inappropriate for small PACGs without anteromedial expansion because of potential damage to the petrous internal carotid artery. Small PACGs without anteromedial expansion are managed using extradural middle fossa (EMF) approach, which lacks a natural drainage pathway, thus necessitating an artificial drainage pathway for PACG aeration to prevent recurrence. We introduced EMF approach for CG decompression and cyst-to-mastoid antrum (MA) diversion for managing small, symptomatic PACGs without anteromedial expansion. CLINICAL PRESENTATION: A 48-year-old woman presented with headache, vertigo, tinnitus, and left hemifacial spasm with preserved hearing because of IAC compression caused by a small PACG without anteromedial expansion. Using the EMF approach, the CG and IAC were safely decompressed. Effective and long-standing artificial drainage for CG aeration was established by anterior petrosectomy and silicone tubing from the CG into the MA. Surgery resolved the symptoms, which have not recurred in 3 years. CONCLUSION: Granuloma decompression and cyst-to-MA diversion using silicone tubing using the EMF approach is a safe and effective surgical management for small, symptomatic PACG without anteromedial expansion.

Validation of a novel iPhone application for evaluating near functional visual acuity.

Monitoring dynamic changes in near vision is important for early detection of presbyopia. This study assessed the accuracy and reliability of a new smartphone-based application, the Smart Vision Check (SVC), compared with those of a conventional device (AS-28; Kowa, Aichi, Japan), for measuring near functional visual acuity (NFVA). We enrolled 115 healthy volunteers aged ≥ 20 years with bilateral best-corrected visual acuity of ≥ 20/25. The SVC was designed for use on an Apple iPhone SE2 to measure NFVA by tapping on the orientation icon manually. Conventional FVA was measured using the AS-28 with - 2.50 D added to the best distance correction at baseline. There was no significant difference in NFVA-related measurements between the AS-28 and SVC (P > 0.05). The Spearman correlation coefficients of NFVA measurements between the two devices were over 0.60 (P < 0.001). The Bland-Altman plot indicated minimal bias with limits of agreements of ± 0.34 logMAR for NFVA with habitual correction when comparing the AS-28 and SVC. The intraclass correlation coefficient of the repeated SVC-measured NFVA was 0.915 (95% CI 0.800-0.969). In summary, the SVC has the potential to evaluate NFVA in a relatively easy manner. Applied clinically, the SVC can be useful for presbyopia screening.

[Treatment Strategy for Stage â £ Rectal Cancer Considering Local Treatment Outcomes].

We investigated 36 patients with Stage Ⅳ rectal cancer who underwent primary resection in our department between November 2015 and June 2020. Tumor localization was upper in 20 cases and lower in 16 cases. Six patients had the cT4b stage at initial diagnosis, and lateral lymph node metastases were detected in 6 cases. Preoperative treatment consisted of doublet chemotherapy in 20 cases, in combination with bevacizumab in 17 cases. Surgery for distant metastases was performed in 21 patients, and the final results were curative(Cur B)in 20 patients and palliative(Cur C)in 16 patients. Perioperative mortality was observed only in Cur C patients(5.6%). The local R1 resection rates in Cur B and Cur C patients were 10.0% and 18.8%, respectively, and the corresponding local RM≤1 mm rates were 55.0% and 43.8%. Additionally, the local recurrence rates were 25.0% and 0%, and the 3-year OS rates were 80.9% and 25.5%, respectively, in Cur B and Cur C patients. In Cur B, the local RM≤1 mm rates in the preoperative and non-preoperative treatment groups were 38.5% and 85.7%, respectively, and the corresponding local R1 resection rates were 7.7% and 14.3%. Additionally, the 3-year local recurrence-free survival rates were 68.2% and 66.7% and the 3-year OS rates were 82.1% and 80.0%, respectively, in the preoperative and non-preoperative treatment groups. We determined that preoperative chemotherapy alone is not sufficient for the local treatment of Stage Ⅳ rectal cancer, and concomitant preoperative radiotherapy should be considered. The prognosis of patients with Cur C is poor, and surgery-related deaths have been observed, which can be a problem for the palliative resection strategy.

CT-based deep learning enables early postoperative recurrence prediction for intrahepatic cholangiocarcinoma.

Preoperatively accurate evaluation of risk for early postoperative recurrence contributes to maximizing the therapeutic success for intrahepatic cholangiocarcinoma (iCCA) patients. This study aimed to investigate the potential of deep learning (DL) algorithms for predicting postoperative early recurrence through the use of preoperative images. We collected the dataset, including preoperative plain computed tomography (CT) images, from 41 patients undergoing curative surgery for iCCA at multiple institutions. We built a CT patch-based predictive model using a residual convolutional neural network and used fivefold cross-validation. The prediction accuracy of the model was analyzed. We defined early recurrence as recurrence within a year after surgical resection. Of the 41 patients, early recurrence was observed in 20 (48.8%). A total of 71,081 patches were extracted from the entire segmented tumor area of each patient. The average accuracy of the ResNet model for predicting early recurrence was 98.2% for the training dataset. In the validation dataset, the average sensitivity, specificity, and accuracy were 97.8%, 94.0%, and 96.5%, respectively. Furthermore, the area under the receiver operating characteristic curve was 0.994. Our CT-based DL model exhibited high predictive performance in projecting postoperative early recurrence, proposing a novel insight into iCCA management.

Robotic surgery contributes to the preservation of bowel and urinary function after total mesorectal excision: comparisons with transanal and conventional laparoscopic surgery.

BACKGROUND: Determine whether robotic surgery is more effective than transanal and conventional laparoscopic surgery in preserving bowel and urinary function after total mesorectal excision (TME). METHODS: Of 79 lower rectal cancer patients who underwent function-preserving TME between 2016 and 2020, 64 patients consented to a prospective questionnaire-based functional observation study (52 responded). At 6 months post-resection or ileostomy closure, Wexner, low anterior resection syndrome (LARS), modified fecal incontinence quality of life, and international prostate symptom scores were used to evaluate bowel and urinary function, comparing robotic surgery (RTME) with transanal (taTME) or conventional laparoscopic surgery (LTME). RESULTS: RTME was performed in 35 patients (54.7%), taTME in 15 (23.4%), and LTME in 14 (21.9%). While preoperative bowel/urinary functions were similar in all three procedures, and the distance from the anal verge to tumor was almost the same, more hand-sewn anastomoses were performed and the anastomotic height from the anal verge was shorter in taTME than RTME. At 2 years post-resection, 8 patients (12.5%) had a permanent stoma; RTME showed a significantly lower rate of permanent stoma than taTME (2.9% vs. 40%, p < 0.01). Despite no significant difference, all bowel function assessments were better in RTME than in taTME or LTME. Major LARS was observed in all taTME and LTME cases, but only 78.8% of RTME. No clear difference arose between RTME and taTME in urinary function; urinary dysfunction was more severe in LTME than RTME (36.4% vs. 6.1%, p = 0.02). CONCLUSIONS: In function-preserving TME for lower rectal cancer, robotic surgery was suggested to be more effective than transanal and conventional laparoscopic surgery in terms of bowel and urinary functions.

Short-term outcomes of robotic-assisted surgery following neoadjuvant chemotherapy for lower rectal cancer.

INTRODUCTION: There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery. METHODS: From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC. RESULTS: The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P = .024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P < .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P < .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group. CONCLUSIONS: Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.

Intraoperative Allogeneic Red Blood Cell Transfusion Negatively Influences Prognosis After Radical Surgery for Pancreatic Cancer: A Propensity Score Matching Analysis.

OBJECTIVE: We aimed to investigate the real impact of allogeneic red blood cell transfusion (ABT) on postoperative outcomes in resectable pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Of 128 patients undergoing resectable PDAC surgery at our facility, 24 (18.8%) received ABT. Recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ABT. RESULTS: In the entire cohort, ABT was significantly associated with decreased RFS (P = 0.002) and DSS (P = 0.014) before PSM. Cox regression analysis identified ABT (risk ratio, 1.884; 95% confidence interval, 1.015-3.497; P = 0.045) as an independent prognostic factor for RFS. Univariate and multivariate analysis identified preoperative hemoglobin value, preoperative total bilirubin value, and intraoperative blood loss as significant independent risk factors for ABT. Using these 3 variables, PSM analysis created 16 pairs of patients. After PSM, the ABT group had significantly poorer RFS rates than the non-ABT group (median, 9.8 vs 15.8 months, P = 0.022). Similar tendencies were found in DSS rates (median, 19.4 vs 40.0 months, P = 0.071). CONCLUSIONS: This study revealed certain negative effects of intraoperative ABT on postoperative survival outcomes in patients with resectable PDAC.

Prediction of massive bleeding in pancreatic surgery based on preoperative patient characteristics using a decision tree.

Massive intraoperative blood loss (IBL) negatively influence outcomes after surgery for pancreatic ductal adenocarcinoma (PDAC). However, few data or predictive models are available for the identification of patients with a high risk for massive IBL. This study aimed to build a model for massive IBL prediction using a decision tree algorithm, which is one machine learning method. One hundred and seventy-five patients undergoing curative surgery for resectable PDAC at our facility between January 2007 and October 2020 were allocated to training (n = 128) and testing (n = 47) sets. Using the preoperatively available data of the patients (34 variables), we built a decision tree classification algorithm. Of the 175 patients, massive IBL occurred in 88 patients (50.3%). Binary logistic regression analysis indicated that alanine aminotransferase and distal pancreatectomy were significant predictors of massive IBL occurrence with an overall correct prediction rate of 70.3%. Decision tree analysis automatically selected 14 predictive variables. The best predictor was the surgical procedure. Though massive IBL was not common, the outcome of patients with distal pancreatectomy was secondarily split by glutamyl transpeptidase. Among patients who underwent PD (n = 83), diabetes mellitus (DM) was selected as the variable in the second split. Of the 21 patients with DM, massive IBL occurred in 85.7%. Decision tree sensitivity was 98.5% in the training data set and 100% in the testing data set. Our findings suggested that a decision tree can provide a new potential approach to predict massive IBL in surgery for resectable PDAC.

Determination of the Standard Visual Criterion for Diagnosing and Treating Presbyopia According to Subjective Patient Symptoms.

Presbyopia treatments using various modalities have been developed recently; however, no standard criteria exist for the diagnosis and treatment endpoint. This study assessed the relationship between the near visual acuity (NVA) and the subjective symptoms of phakic presbyopia and determined the numerical NVA threshold to diagnose phakic presbyopia and evaluate the effectiveness of presbyopia treatment. The binocular distance, NVA with habitual correction, and monocular conventional VA were measured. Patients were asked about their awareness of presbyopia and difficulty performing near tasks. This prospective observational study included 70 patients (mean age, 56 years; range, 32-77). Most patients became aware of presbyopia in their late forties, although some had difficulty with vision-related near tasks before becoming aware of presbyopia. Eighty three percent of patients (20/24) experienced difficulty with near vision-related tasks even with excellent NVA at 40 cm with habitual correction of 0.0 logMAR (20/20 in Snellen VA). In conclusion, the current study showed that patients became aware of presbyopia in their late forties, although some had difficulty with near vision-related tasks before becoming aware of presbyopia. Further investigation should include the proposal of appropriate diagnostic criteria for presbyopia and better management for patients with presbyopia.

[A Case of Descending Colon and Rectal Cancer with Acute Myeloid Leukemia Performed Robot‒Assisted Hartmann's Procedure].

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. A second course of CAG therapy was started 15 days postoperatively. However, he was then diagnosed with exacerbation of the AML; remission induction therapy (daunorubicin, cytarabine)was started in November. In December, he developed a fever and abdominal pain, and on CT scan, it was discovered that an abscess had formed around the rectal resection site. Myelosuppression from AML led to prolonged sepsis; and by January 2020, the sepsis was systemic. His actual cause of death was given as circulatory failure. We report this, because only a few cases on the treatment of overlapping AML and colorectal cancers can be found in the literature.

[Surgical Resection of the Rib Fragment to Prevent Lung Injury in a Patient with Chest Trauma:Report of a Case].

An 82-year old man was admitted for a left fifth rib fracture with traumatic pneumothorax. Computed tomography showed a sharp rib fragment protruding into the thoracic cavity. Thoracic drainage was not performed before surgery to avoid lung injury by the rib fragment. At surgery, fifth rib fragment protruding into the thoracic cavity was found, but lung injury was not present. The bone fragment was removed, and the patient's postoperative course was uneventful.

Randomized, crossover clinical efficacy trial in humans and mice on tear secretion promotion and lacrimal gland protection by molecular hydrogen.

The incidence of dry eye disease is increasing worldwide because of the aging population and increasing use of information technology. Dry eye disease manifests as tear-layer instability and inflammation caused by osmotic hypersensitization in tear fluids; however, to our knowledge, no agent that treats both pathologies simultaneously is available. Molecular hydrogen (H2) is known to be effective against various diseases; therefore, we aimed to elucidate the effects of H2 on tear dynamics and the treatment of dry eye disease. We revealed that administering a persistent H2-generating supplement increased the human exhaled H2 concentration (p < 0.01) and improved tear stability (p < 0.01) and dry eye symptoms (p < 0.05) significantly. Furthermore, H2 significantly increased tear secretion in healthy mice (p < 0.05) and significantly suppressed tear reduction in a murine dry eye model (p = 0.007). H2 significantly and safely improved tear stability and dry eye symptoms in a small exploratory group of 10 human subjects, a subset of whom reported dry eye symptoms prior to treatment. Furthermore, it increased tear secretion rapidly in normal mice. Therefore, H2 may be a safe and effective new treatment for dry eye disease and thus larger trials are warranted.