Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

Preoperative chronic kidney disease is predictive of oncological outcome of radical cystectomy for bladder cancer.

PURPOSE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes after radical cystectomy (RC) for bladder cancer. METHODS: We reviewed the medical records of patients with urothelial bladder carcinoma who underwent RC with curative intent at seven hospitals between 1990 and 2013. After excluding patients with a history of upper urinary tract urothelial cancer or neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative estimated glomerular filtration rate (eGFR) was calculated using the three-variable Japanese equation for GFR estimation from serum creatinine level and age. Patients were divided into four groups of different CKD stages based on eGFR values (mL/min/1.73 m2), i.e., ≥ 60 (CKD stages G1-2), 45-60 (G3a), 30-45 (G3b), and < 30 (G4-5). Survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses addressed survivals after RC. RESULTS: Median age of patients was 67 years. Patients were classified into CKD stages: G1-2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%), and G4-5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164 patients showed cancer progression and died of bladder cancer, with the 5-year progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and 70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater, advanced pT stage, lymph node metastasis, and positive lymphovascular invasion were independent poor prognostic factors for PFS and CSS. CONCLUSIONS: We demonstrated that the advanced preoperative CKD stage was significantly associated with poor oncological outcomes of the bladder cancer after RC.

Oncologic Outcome of Metastasectomy for Urothelial Carcinoma: Who Is the Best Candidate?

BACKGROUND: Resection of metastatic lesions (metastasectomy) is performed for highly selected patients with metastatic urothelial carcinoma (mUC). This study aimed to identify the clinicopathologic factors associated with oncologic outcome for patients who underwent metastasectomy for mUC. METHODS: This analysis included 37 UC patients who underwent metastasectomy with curative intent at nine Japanese hospitals. The primary end point was cancer-specific survival. The Kaplan-Meier method with the log-rank test and the multivariable Cox proportional hazards model addressed the relationship between clinical characteristics and survival. RESULTS: Metastasectomy was performed for pulmonary (n = 23), nodal (n = 7), and other (n = 7) metastases. The median survival time was 35.4 months (interquartile range [IQR] 15.5, not reached) from the detection of metastasis and 34.3 months (IQR 13.1, not reached) from metastasectomy. The 5-year cancer-specific survival rate after detection of metastasis was 39.7%. In the multivariate analysis, the time from primary surgery to detection of metastasis (time-to-recurrence [TTR]) of 15 months or longer (hazard ratio [HR] 0.23; p = 0.0063), no symptoms of recurrence (HR 0.23; p = 0.0126), and serum C-reactive protein (CRP) levels lower than than 0.5 mg/dl (HR 0.24; p = 0.0052) were significantly associated with better survival. CONCLUSIONS: Long-term survival could be achieved for some patients with mUC who underwent metastasectomy. Lung and lymph nodes were predominant sites for metastasectomy. Symptoms, TTR, and CRP value were identified as associated with survival and should be taken into account when metastasectomy is considered.

Nomogram for predicting survival of postcystectomy recurrent urothelial carcinoma of the bladder.

PURPOSE: We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). MATERIALS AND METHODS: Among 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. RESULTS: Of the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8-8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72-0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. CONCLUSIONS: We identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.

Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder.

PURPOSE: Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. METHODS: We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). CONCLUSIONS: Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

The safety and effect of chemotherapy with short hydration for urothelial cancer on patients' quality of life.

OBJECTIVE: Our aim was 2-fold: first, to assess the safety of short hydration treatment for urothelial cancer; and second, to assess the resultant quality of life of patients who received the treatment. METHODS: We assessed 61 patients including 31 outpatients and 30 inpatients, who received a combination of gemcitabine and cisplatin chemotherapy with short hydration. The serum creatinine (Cr) level and the estimated glomerular filtration rate were measured to assess renal function using linear mixed model analysis. To assess quality of life, the patients were asked to respond to the Functional Assessment of Cancer Therapy-General questionnaire. The responses were then analyzed using the paired t-test. RESULTS: Patients who received short hydration chemotherapy showed no significant change in serum Cr level (P = 0.423) or estimated glomerular filtration rate  (P = 0.582). There was also no significant change in serum Cr level or estimated glomerular filtration rate between patients who received short hydration chemotherapy and those who received consecutive hydration chemotherapy (P = 0.154 and 0.311, respectively). In every patient, the Functional Assessment of Cancer Therapy-General total score and subscale scores both improved as a result of outpatient chemotherapy with short hydration (P < 0.01). CONCLUSIONS: The short hydration gemcitabine and cisplatin regimen for patients with urothelial cancer was safe. Further, the outpatient chemotherapy was found not only to be safe, but also to have improved the patients' quality of life.

The clinical trial on the safety and effectiveness of the photodynamic diagnosis of non-muscle-invasive bladder cancer using fluorescent light-guided cystoscopy after oral administration of 5-aminolevulinic acid (5-ALA).

OBJECTIVE: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. METHODS: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. RESULTS: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body. CONCLUSIONS: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.

METASTATIC SMALL CELL CARCINOMA OF THE URINARY BLADDER TREATED WITH SYSTEMIC CHEMOTHERAPY INCLUDING AN AMRUBICIN; A CASE REPORT.

We report a 59-year-old male patient with metastatic small cell carcinoma of the bladder treated with systemic chemotherapy including an amrubicin. The patient was referred to our hospital complaining of macrohematuria. A cytoscopy revealed a non-papillary, broad-based tumor extending from the right to the posterior wall of the bladder. A computed tomography showed bilateral hydronephrosis caused by the bladder tumor and multiple metastases to the para-aortic and common iliac lymph nodes. The histopathological findings following a transurethral resection of the bladder tumor revealed a T2N3M1, LYM, stage IV small cell carcinoma. We administered two courses of systemic chemotherapy consisting of cisplatin (CDDP) plus an etoposide (VP-16), a first-line treatment usually administered to patients with small cell carcinoma of the lung. We then administered second-line chemotherapy consisting of CDDP plus an irinotecan. When the first and second-line therapies failed to halt progression of the disease, we decided to use amrubicin as the third-line therapy concomitant with radiotherapy for local control. Although the NSE (neuron-specific enolase) value decreased, the patient died 11 months after the initial examination. To our knowledge, this is the first case in which small cell carcinoma of the bladder was treated with amrubicin.

Validation of major prognostic models for metastatic urothelial carcinoma using a multi-institutional cohort of the real world.

BACKGROUND: Several prognostic models predicting survival of patients with metastatic urothelial carcinoma (UC) have been developed; however, of them, the first model by Bajorin in 1999 is still the most representative and widely used, and validations of newer models are lacking. This study aimed to validate three major prognostic models for metastatic UC constructed based on clinical trials. METHODS: We reviewed 200 patients with metastatic UC who received first-line chemotherapy at our five affiliate institutions between 2003 and 2011. Using this multi-institutional cohort, we validated the following models: the "Bajorin model," a model consisting of visceral metastasis and performance status; the "Apolo model," a nomogram including visceral metastasis, performance status, albumin and hemoglobin; and the "Galsky model," a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis. Harrell's c-index was calculated for each model. Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Among 200 patients, 171 (85.5%) died during the follow-up, with a median survival of 12.0 months. Multivariate analysis demonstrated ECOG performance status, visceral metastasis and leukocyte count to be independent predictors of overall survival. C-index results (95% confidence interval) were Bajorin: 0.86 (0.74-0.95); Apolo: 0.89 (0.78-0.98); and Galsky: 0.82 (0.69-0.93). CONCLUSIONS: All models were demonstrated to have high external validities in real-world patients, and of them, the "Apolo model" achieved the highest c-index in the present population. Further studies with larger populations are needed for establishment of the next standard model.

Pyuria predicts poor prognosis in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin.

This study was conducted to evaluate the utility of pyuria as a predictive marker of bacillus Calmette-Guérin (BCG) treatment for non-muscle-invasive bladder cancer (NMIBC). A cohort of 243 NMIBC patients treated with BCG through intravesical instillation between 1994 and 2007 at the Tokyo Metropolitan Tama Medical Center were enrolled in this retrospective study. Pyuria was defined as urine containing ≥10 white blood cells per high-power field. A total of 30 of the patients with pyuria (30/37, 81%) and 87 patients of those without pyuria (87/206, 42%) exhibited recurrence following BCG treatment. The 3-year recurrence-free survival rate of patients with and without pyuria following BCG treatment was 20 and 62%, respectively. The multivariate Cox proportional hazards regression model indicated that pyuria was an independent predictor of disease recurrence following BCG treatment. Patients with inflammatory NMIBC exhibited resistance to therapy with intravesical instillation of BCG.

Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of survival in patients with metastatic urothelial carcinoma: A multi-institutional study.

OBJECTIVES: To evaluate the prognostic significance of the pretreatment neutrophil-to-lymphocyte ratio in patients with metastatic urothelial carcinoma who underwent salvage chemotherapy. METHODS: We reviewed 200 metastatic urothelial carcinoma patients who received salvage chemotherapy at our five affiliate institutions between 2003 and 2011. The associations of pretreatment clinicopathological factors, including neutrophil-to-lymphocyte ratio, with cancer-specific survival and overall survival from the start of chemotherapy were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: A total of 15 cases with missing data were excluded. Among the remaining 185 patients, 157 died during follow up, with a median survival of 13.0 months. Multivariate analysis showed that the pretreatment neutrophil-to-lymphocyte ratio ≥3, Eastern Cooperative Oncology Group performance status ≥2 and liver metastasis were independent poor prognostic factors, both for cancer-specific survival and overall survival. A prognostic model predicting overall survival was constructed based on the number of these three variables (0, 1 and ≥ 2). The classified patients showed significantly different overall survival (each P < 0.0001, log-rank test), with Harrell's concordance index as high as 0.81. CONCLUSIONS: Pretreatment neutrophil-to-lymphocyte ratio elevation was an independent poor prognostic factor for metastatic urothelial carcinoma undergoing salvage chemotherapy. Our newly constructed prognostic model including the pretreatment neutrophil-to-lymphocyte ratio proved to be an excellent discriminator of overall survival.

Prognostic marker for patients with malignant ureter obstruction.

PURPOSE: To investigate the relationship between overall survival (OS) and prognostic risk factors for patients with malignant ureteral obstruction. PATIENTS AND METHODS: We retrospectively evaluated 214 patients who had received a nephrostomy for ureteral obstruction because of malignancy. Univariate and multivariate Cox regression models addressed OS. RESULTS: The median OS was 6.4 months. The OS at 1, 3, 6, and 12 months were 89.5%, 72.4%, 53.0%, and 26.5%, respectively. Using univariate Cox regression analysis, serum levels of creatinine (P = .0131), albumin (P < .0001), sodium (P < .0001), potassium (P = .0141), corrected calcium (P = .0167), C-reactive protein (P < .0001), white blood cell count (P = .0246), and the number of events related to malignant dissemination (P < .0001) were associated with OS. Using multivariate Cox regression analysis, serum levels of albumin (P = .0147), sodium (P = .0046), C-reactive protein (P < .0001), and the number of events related to malignant dissemination (P = .0002) were independent predictors of OS. CONCLUSION: Low serum levels of albumin and sodium and the number of events related to malignant dissemination before PCN were independent factors associated with a poor prognosis. High serum C-reactive protein level was also associated with a poor prognosis using multivariate analysis.

Preoperative neutrophil-lymphocyte ratio as an independent prognostic marker for patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To predict the prognosis, we evaluated the significance of the preoperative neutrophil-lymphocyte ratio (NLR) in patients with upper urinary tract urothelial carcinoma (UUTUC). PATIENTS AND METHODS: A cohort of 137 patients diagnosed with UUTUC from 1994 to 2008 at Tokyo Metropolitan Tama Medical Center was enrolled in this retrospective study. Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses. RESULTS: On univariate analysis, pathologic T stage, grade, lymphovascular invasion, C-reactive protein (CRP) level, and NLR were significantly associated with recurrence-free survival (RFS) and cancer-specific survival (CSS). The RFS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 74.3% and 30.4%, respectively. The CSS rates for an NLR < 2.5 and for one ≥ 2.5 at 5 years were 81.3% and 29.4%, respectively. The multivariate Cox proportional hazards regression models showed that the NLR could be an independent predictor for RFS and CSS. Based on the results of multivariate analysis, the scoring model was developed. RFS and CSS rates at 5 years were as follows: 0 risk factor, 97.1% and 97.0%, respectively; 1 risk factor, 91.1% and 90.9%, respectively; 2 risk factors, 39.5% and 58.6%, respectively; 3 risk factors, 26.6% and 28.6%, respectively; and 4 risk factors, 6.0% and 5.6%, respectively. CONCLUSIONS: The preoperative NLR is an independent prognostic predictor. The model based on the NLR and pathologic factors can be useful in clinical practice.

Pyuria predicts poor prognosis in patients with non-muscle-invasive bladder cancer.

BACKGROUND: To evaluate the significance of inflammation in non-muscle-invasive bladder cancer (NMIBC), we assessed the presence of pyuria at time of diagnosis. PATIENTS AND METHODS: A cohort of 805 patients with newly diagnosed NMIBC between 1994 and 2007 at the Tokyo Metropolitan Tama Medical Center were enrolled in this retrospective study. Pyuria was defined as urine containing ≥ 10 white blood cells (WBCs) per high power field (HPF). RESULTS: One hundred ninety-nine (24%) of the patients with NMIBC had pyuria. The 3-year recurrence-free survival rates of patients with and without pyuria were 10.9 vs. 45.0%, respectively. The 5-year progression-free survival rates of patients with and without pyuria were 72.3% and 95.7%, respectively. Multivariate Cox proportional hazards regression models indicated that pyuria was an independent predictor of disease recurrence and progression. After dividing the sample according to the European Organization for Research and Treatment of Cancer (EORTC) risk tables, we further classified patients into subgroups according to the presence of pyuria. The recurrence-free survival rates were higher in the pyuria-negative subgroups of the low, intermediate-low, intermediate-high, and high risk for recurrence groups. Similarly, the progression-free survival rates at 5 years were higher in the pyuria-negative subgroups of the low, intermediate-low, and intermediate-high risk for progression groups. CONCLUSION: Patients with inflammatory NMIBC exhibited poor clinical outcomes.

Metastatic renal cell carcinoma change vascularity.

Several molecular targeted agents have been approved for clinical use for metastatic renal cell carcinoma (mRCC). A case of a 32-year-old woman with mRCC is presented. These tumors could change vascularity by administration of molecular agents. We could select a drug timely based on findings of computed tomography. To our knowledge, this is the first report that tumor's character change induced by molecular targeted agents can be detected and the efficacy of molecular targeted agents can be predicted.

Neutrophil number after interferon-alfa treatment is an independent predictive marker of overall survival in metastatic renal cell carcinoma.

BACKGROUND: The purpose of this study was to assess the outcome in patients treated by immunotherapy using interferon-alpha (IFN-α) and to evaluate the significance of the neutrophil count after IFN-α immunotherapy as a predictive marker for metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: We identified 84 patients with metastatic RCC who underwent immunotherapy with IFN-α between 1998 and 2006. The predictive values of the neutrophil count before and after IFN-α treatment as well as other clinical and laboratory parameters were assessed retrospectively. RESULTS: On univariate analysis, the significant correlation with overall survival (OS) was recognized in the Eastern Cooperative Oncology Group (ECOG) performance score (PS), lactate dehydrogenase (LDH) levels, corrected calcium levels, interval from diagnosis to treatment, and the ratio of neutrophil number before and after treatment with INF-α. Multivariate analysis showed that ECOG PS, corrected calcium levels, interval from diagnosis to treatment and neutrophil number after IFN-α treatment were independent factors for OS. Using the number of neutrophils after IFN-α treatment, subgroups were identified using the Memorial Sloan-Kettering Cancer Center (MSKCC) model. The 1-year survival rate was 93% vs. 63% in the intermediate-risk group and 34% vs. 8% in the poor-risk group. In the favorable-risk group, all patients had a good decrease in neutrophil number after treatment with IFN-α. CONCLUSION: Neutrophil number after IFN-α treatment can be a good predictive marker for OS in metastatic RCC. By combining MSKCC score with neutrophil number after treatment with IFN-α, we can subdivide each group.

Primary mucinous adenocarcinoma of the testis.

Ovarian-type surface epithelial neoplasms of the testis and paratestis are uncommon, and the mucinous subtype is particularly rare. These tumors represent a counterpart to ovarian cancer. Malignant tumors have the potential for metastatic spread and are often fatal. The case of a 59-year-old man with testicular mucinous adenocarcinoma is presented. Computed tomography indicated involvement of the paraaortic and pelvic lymph nodes, so chemotherapy was initiated. To the best of our knowledge, this is the second paper regarding responsiveness to chemotherapies used in ovarian cancer.

Analysis of human tear fluid by Fourier transform infrared spectroscopy.

The purpose of this research is to find some useful spectroscopic factors in human tear fluid contents to monitor diurnal changes of the physicochemical ocular conditions noninvasively. All tear fluid samples were collected with glass microcapillary tubes from both eyes of three donors and analyzed by Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR). We measured the peak intensities at 2852, 1735, 1546, and 1242 cm(-1), and the peak intensity ratios among those peaks in the second derivative spectra. We found significant diurnal and individual variations in those peak intensities for tear fluid obtained from right and left eyes. Among these variations, we observed significant changes in tear samples between right and left eyes. In this case the peak intensity ratio between 1242 (phosphate ester) and 2852 cm(-1) (fatty acid methylene) of right eye tear fluid was increased in the afternoon (1600 to 1900 h), while that of left eye tear fluid did not change significantly. In the ratio between 1242 (phosphate ester) and 1546 cm(-1) (amide II), the difference was not observed between both eyes. We conclude that the difference in diurnal variations of biochemical constituents between right and left eye tear fluids could be monitored noninvasively and nondestructively by FTIR technique and this method could be useful in the future for tear diagnoses.