Higher hematocrit level associated with higher 5-aminolevulinic acid-induced perioperative blood pressure change.

BACKGROUND: 5-aminolevulinic acid (5-ALA) is used for photodynamic diagnosis-assisted surgeries. Hypotension is among 5-ALA-related adverse effects. 5-ALA metabolism requires iron. The red cell life span is 120 days and heme iron is daily recycled. Higher hematocrit is likely to correlate with higher recycled iron. We previously reported 5-ALA-induced hemodynamics in urological surgery. This analysis aimed to determine the association between 5-ALA-induced perioperative systolic blood pressure (SBP) changes and the hematocrit. METHODS: This retrospective study enrolled consecutive patients who underwent transurethral resection of bladder tumor from August 2018 to December 2020. The patients were classified into the 5-ALA-pretreated patients (5-ALA group; n = 26) and non-pretreated patients (control group; n = 97). We evaluated the correlation between SBP change rates and hematocrit levels. The primary analyses included the difference in correlations between the two groups. Subsequently, the correlations were analyzed in the 5-ALA group and control group, respectively. RESULTS: The correlations significantly differed between the two groups preoperatively (P<0.001), during surgery (P = 0.014), postoperatively (P = 0.001), and on the following morning (P = 0.002). The correlations between SBP changes and the hematocrit in the 5-ALA group were significant before patients entered the operation room (Spearman's rank correlation coefficient [rS]=-0.449, P = 0.024), before anesthesia induction (rS=-0.584, P = 0.002), during surgery (rS=-0.401, P = 0.047), after operation (rS=-0.658, P<0.001), and on the following morning (rS=-0.547, P = 0.004). Those in the control group were not significant. CONCLUSIONS: The hematocrit levels were significantly correlated with perioperative 5-ALA-induced SBP changes. The association was again observed the next day. Higher hematocrit may be a factor for 5-ALA-induced hemodynamic changes.

Differences in 5-Aminolevulinic Acid-Induced Hemodynamic Changes between Patients Undergoing Neurosurgery and Urological Surgery.

INTRODUCTION: Oral 5-aminolevulinic acid (5-ALA) is often used for photodynamic diagnosis-assisted glioma or bladder tumor surgery. 5-ALA affects blood pressure (BP). In fact, hypotension is a well-known adverse effect of 5-ALA in urology. However, information regarding 5-ALA-induced hemodynamic changes in neurosurgery remains limited. Furthermore, the duration of hypotension and how 5-ALA affects the heart rate (HR) are yet to be determined. Thus, in this study, we aimed to elucidate 5-ALA-induced perioperative hemodynamic changes in neurosurgery and urological surgery by examining real-world data. METHODS: Consecutive patients who underwent neurosurgery (neurosurgery patients; 5-ALA-pretreated vs. non-pretreated [17 vs. 16], from January 2014 to March 2021) and urological surgery (urological surgery patients; 5-ALA-pretreated vs. non-pretreated [26 vs. 101], from August 2018 to September 2020) were enrolled. Differences in hemodynamics were evaluated using the linear mixed model. BP and HR in 5-ALA-pretreated patients were compared with those in non-pretreated patients. Differences in 5-ALA-induced preoperative BP changes were compared between the neurosurgery patients and urological surgery patients. RESULTS: 5-ALA scarcely affected the hemodynamics in neurosurgery patients, whereas 5-ALA-induced hemodynamic changes were clearly observed in urological surgery patients. Hemodynamic parameters were found to be not significantly different between 5-ALA-pretreated and non-pretreated neurosurgery patients. The preoperative, intraoperative, and postoperative BP in 5-ALA-pretreated urological surgery patients were significantly lower than those in the non-pretreated patients. Preoperatively, two 5-ALA-pretreated urological surgery patients had severe postural hypotension (systolic BP <50 mmHg), and one of them did not continue with the surgery because of prolonged severe hypotension. The BP in 5-ALA-pretreated urological surgery patients tended to be persistently lower for 9 h after 5-ALA pretreatment. The preoperative and postoperative HR values were higher in 5-ALA-pretreated urological surgery patients. Cumulative incidences of BP reduction and HR elevation were significantly higher in 5-ALA-pretreated urological surgery patients. The preoperative BP reduction in 5-ALA-pretreated urological surgery patients was significantly larger than that in neurosurgery patients. CONCLUSIONS: 5-ALA-induced hemodynamics may differ between neurosurgery patients and urological surgery patients. 5-ALA may affect BP for at least 9 h.

Preanesthetic severe postural hypotension following 5-aminolevulinic acid pretreatment in patients for photodynamic diagnosis-assisted urological surgery.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) is utilized for photodynamic diagnosis-assisted (PDD) surgery. However, it has been associated with vasodilation, hence, occasional hypotension. CASE PRESENTATION: We encountered two patients who had severe postural hypotension following 5-ALA pretreatment prior to an operation. They were scheduled for urological PDD surgery, but upon standing to walk to the operation room, they felt sick because of severe hypotension. One of them underwent the surgery after recovery, but the other surgery was canceled due to a prolonged hypotension that lasted for more than a day. CONCLUSIONS: Severe postural hypotension may develop as a result of the high concentration of porphyrin precursors, which may affect the nervous system. Severe postural hypotension may be due to 5-ALA-induced autonomic dysfunction as well as vasodilative action of 5-ALA. These observations suggest that in addition to the careful monitoring of patients' vital signs, standing should be avoided following 5-ALA pretreatment.

[Case report : bleeding from ileal conduit in a patient with portal hypertension due to liver cirrhosis type C].

A 68-year-old man treated for type C liver cirrhosis was referred to our hospital for evaluation of a bladder tumor. The patient underwent transurethral resection of bladder tumor. The histopathological diagnosis was urothelial cancer (G2>G3, T2) and he underwent radical cystectomy with ileal conduit urinary diversion. Starting 3 months postoperatively, he experienced bleeding from the mucosa of the ileal conduit. Computed tomography showed vascular dilatation around the ileal conduit. This was considered to be attributable to portal hypertension resulting from liver cirrhosis. Conservative therapy failed to achieve hemostasis. The patient was not considered to have indications for a transjugular intrahepatic portosystemic shunt (TIPS). He died from bleeding 22 months after radical cystectomy.

Different clinicopathological features between patients who developed early and late recurrence following surgery for renal cell carcinoma.

BACKGROUND: To evaluate the clinicopathological features and identify predictive factors in patients with early and late recurrence following initial surgery for localized renal cell carcinoma. METHODS: From April 1988 to January 2013, 486 patients without metastases at the initial diagnosis underwent either radical nephrectomy or partial nephrectomy and were followed up thereafter. Patients were divided into 3 groups; no recurrence, early recurrence (recurrence within 5 years), and late recurrence (recurrence after 5 years). Cancer-specific survival after recurrence was analyzed by using the Kaplan-Meier method. Multivariate logistic regression analysis was applied to define clinical and pathological factors correlated to early and late recurrence following surgery. RESULTS: Seventy-seven (15.8 %) and 18 (3.7 %) patients developed early and late recurrence, respectively. In multivariate logistic regression analysis, positive symptoms at diagnosis, ≥pT2, positive lymphovascular invasion, and grade 3 were independent predictive factors for early recurrence. Age at surgery and ≥pT2 were significantly correlated to late recurrence. The 5-year cancer-specific survival rate after recurrence was 72.4 and 52.9 % in the late and the early recurrence groups, respectively (P = 0.044). CONCLUSIONS: The risk factors for clinical recurrence differed according to the time that had elapsed between initial surgery and the first metastasis in patients with localized renal cell carcinoma. Our study showed age at initial surgery and the pT stage were independent predictive factors for late recurrence. Further investigation of a larger number of patients is required to predict which patients may develop recurrence in the future and to choose appropriate treatment.

[Efficacy and safety of maintenance intravesical instillation therapy with bacillus Calmette-Guerin and epirubicin for non-muscle invasive bladder cancer].

The objectives of this study were to evaluate the efficacy and toxicity of maintenance intravesical instillation therapy with bacillus Calmette-Guerin (BCG) and epirubicin for non-muscle invasive bladder cancer. From April 1999 to March 2010, 27 eligible patients were enrolled in this study. After receiving one cycle of epirubicin (100 mg/100 ml) by intravesical instillation, all patients received 6 weekly alternate intravesical instillation of BCG (80 mg/50 ml) and epirubicin (50 mg/50 ml), followed by 10 monthly instillations. Among the 27 patients, 19 were men and 8 were women, with a median age of 62.4 years (range, 37-78 years). Tumor pathologic stage was pTa in 25 patients, pT1 in 2 and there were no concomitant carcinoma in situ cases. Median follow-up was 37.1 months (range, 11-82 months). The 3- year recurrence-free and progression-free survival rates were 75.3% and 96.1%, respectively. Furthermore, a high completion rate of 81.5% was achieved in this study. Adverse events of grade 3 or higher occurred in 3 patients (11.1%), 1 patient had anaphylaxis. There were no treatment-related deaths. Maintenance intravesical instillation therapy with BCG and epirubicin is a favorable therapeutic option for non-muscle invasive bladder cancer. Given the safety and benefit profile found in this study, appropriate patient selection is warranted in the future.

[Clinical evaluation of lower urinary tract symptoms following seed implant for prostate cancer].

A total of 320 localized prostate cancer patients including 272 at low-risk and 48 at intermediate-risk were treated with permanent iodine-125 seed implants. Changes of lower urinary tract symptoms after the treatment were analyzed for one consecutive year using international prostate symptom score, quality of life (QOL) score and uroflowmetry. These patients did not have prostate hypertrophy or were not treated with any α1 blocker before the seed implant. Tamsulosin (0.2 mg/day) was prophylactically administered to all the patients for six months beginning the day after the seed implant. Both voiding and storage symptoms developed even in patients without any urinary symptoms before seed implant and worsened during the consecutive three months; and, QOL also worsened after seed implant. Lower urinary tract symptoms continued to be significantly severe for six months compared with that before the seed implant, then improved gradually to almost the initial level after one year. It seems to take longer for storage symptoms to diminish to the initial level compared with voiding symptoms. Neoadjuvant hormone therapy improved neither voiding nor storage symptoms in patients without prostate hypertrophy less than 40 ml in volume. In conclusion, a more effective α1 blocker or other potent prophylactic drug therapy should be used on the patients after seed implant because the disadvantage of seed implant is probably only urinary disturbance.

Reduced glycosylation of α-dystroglycans on carcinoma cells contributes to formation of highly infiltrative histological patterns in prostate cancer.

BACKGROUND: α-Dystroglycan (DG) carries glycan chains that bind to laminin and thus function in homeostasis of not only skeletal muscle but also of various epithelial cells. Loss of glycosylation has been suggested to play important roles in tumor development, particularly in detachment and migration of carcinoma cells. We previously reported that glycosylation of α-DG, but not levels of α-DG core protein itself, is reduced in prostate carcinoma. In this study, we investigate the association between reduction of laminin-binding glycans on α-DG and the degree of tumor cell differentiation and/or infiltrative properties, as assessed by the Gleason grading system. METHODS: Immunohistochemical analysis of 146 biopsy specimens of prostate adenocarcinoma with various Gleason scores was carried out employing IIH6 and 6C1 antibodies, which recognize laminin-binding glycans on α-DG and α-DG core proteins, respectively. Double immunofluorescence staining was performed to evaluate colocalization of α-DG and laminin, and to determine which types of epithelial cells express laminin-binding glycans on α-DG. RESULTS: Reduction of α-DG glycosylation, rather than loss of α-DG core protein, was correlated with higher Gleason patterns. Reduction was most conspicuous at the interface between carcinoma cells and the basement membrane. In addition, in non-neoplastic prostate glands, laminin-binding glycans were expressed predominantly on the basolateral surface of basal cells. CONCLUSIONS: Reduced expression of laminin-binding glycans on α-DG may contribute to formation of highly infiltrative behavior of prostate carcinoma cells. Substantial reduction of laminin-binding glycans in carcinoma tissue could be partly ascribed to disappearance of pre-existing basal cells.

Diffusion weighted imaging in the detection of upper urinary tract urothelial tumors.

PURPOSE: Diffusion-weighted (DW) magnetic resonance imaging (MRI) provides information about the biophysical properties of tissues such as cell organization and density. DW imaging (DWI) is becoming important in the assessment of malignant tumors. The purpose of our study was to evaluate the capability and reliability of DWI in the evaluation of upper urinary tract urothelial tumors. MATERIALS AND METHODS: DWI was performed in seventeen patients with upper urinary tract urothelial tumor, previously diagnosed by either CT or retrograde pyelography. An histological evaluation was performed after surgical resection. Each MRI was carried out using a 1.5T superconductive magnet MRI system. DWI images were obtained with b value of 1000 s/mm(2) under normal breathing. The apparent diffusion coefficient (ADC) values were measured. RESULTS: In nine patients with renal pelvis tumors and seven patients with ureteral tumors, the lesions were shown as high-signal intensity in the corresponding region on DWI. In one patient with carcinoma in situ (CIS) of the ureter, the lesion was not depicted with DWI. The mean ADC value of the tumor was 1.125 + or - 0.217 x 10(-3) mm(2)/s and was significantly lower than those of the renal parenchyma (1.984 + or - 0.238 x 10(-3) mm(2)/s, p < 0.01) and the urine (2.941 + or - 0.315 x 10(-3) mm(2)/s, p < 0.01). CONCLUSIONS: In our study, the renal pelvic and ureteral tumors except CIS were shown clearly with DWI. Although further studies are required, DWI may take the place of invasive retrograde urography for detecting tumors of the upper urinary tract.

Diffusion weighted imaging in the detection of upper urinary tract urothelial tumors

Purpose: Diffusion-weighted (DW) magnetic resonance imaging (MRI) provides information about the biophysical properties of tissues such as cell organization and density. DW imaging (DWI) is becoming important in the assessment of malignant tumors. The purpose of our study was to evaluate the capability and reliability of DWI in the evaluation of upper urinary tract urothelial tumors. Materials and methods: DWI was performed in seventeen patients with upper urinary tract urothelial tumor, previously diagnosed by either CT or retrograde pyelography. An histological evaluation was performed after surgical resection. Each MRI was carried out using a 1.5T superconductive magnet MRI system. DWI images were obtained with b value of 1000 s/mm2 under normal breathing. The apparent diffusion coefficient (ADC) values were measured. Results: In nine patients with renal pelvis tumors and seven patients with ureteral tumors, the lesions were shown as high-signal intensity in the corresponding region on DWI. In one patient with carcinoma in situ (CIS) of the ureter, the lesion was not depicted with DWI. The mean ADC value of the tumor was 1.125 ± 0.217 x 10-3 mm2/s and was significantly lower than those of the renal parenchyma (1.984 ± 0.238 x 10-3 mm2/s, p < 0.01) and the urine (2.941 ± 0.315 x 10-3 mm2/s, p < 0.01). Conclusions: In our study, the renal pelvic and ureteral tumors except CIS were shown clearly with DWI. Although further studies are required, DWI may take the place of invasive retrograde urography for detecting tumors of the upper urinary tract.

[Preoperative magnetic resonance imaging in the management of the nonpalpable testis].

We evaluated the efficacy of magnetic resonance imaging (MRI) as the preoperative study in the management of the nonpalpable testis. From 1997 to 2005, a total of 41 MRI was performed for the patients with nonpalpable testis and 42 testes were evaluated. The MRI showed 19 testes from 18 patients in the inguinal region. Eighteen testes were found in the inguinal region and one was intraabdominal during groin exploration. Six testes were pointed out to be intra-abdominal by MRI. Five testes were identified in the abdomen and one was disclosed to be vanishing testis. Seventeen testes could not be detected by MRI and they underwent laparoscopic or groin exploration. Four abdominal testes were identified. Thirteen patients had a diagnosis of vanishing testis. The sensitivity and the specificity of our MRI studies in predicting the presence of nonpalpable testis were 85.7% and 92.9%, respectively. Enlarged lymph node could be misdiagnosed as abdominal testis. Inguinal undescended testes can be diagnosed accurately with MRI. MRI is informative regarding the testis location and useful for limiting the area of surgical exploration.

Permanent prostate brachytherapy for Japanese men: results from initial 100 patients with prostate cancer.

OBJECTIVE: To evaluate the initial results of brachytherapy for prostate cancer with permanent iodine-125 implant in Japan. METHODS: The results obtained with brachytherapy in the initial 100 Japanese patients treated at Nagano Municipal Hospital were reviewed. Patients with a prostate-specific antigen (PSA) level of less than 10 ng/mL and a Gleason's scores of 5, 6, 3 + 4 were classified as having a low risk of recurrence. Patients with a PSA level of 10-20 ng/mL and/or a Gleason's score of 4 + 3 were classified as having an intermediate risk for recurrence. Seventy-eight of the low-risk patients and 19 of the intermediate-risk patients were treated by seed implants alone, or seed implants combined with preceding external radiation, respectively. A total of 53 patients received neoadjuvant hormone therapy. The efficacy and morbidity of brachytherapy were investigated using the serum PSA, International Prostate Symptom Score, quality of life score and uroflowmetry data. RESULTS: The average V100 and D90 obtained by post-implant dosimetry was 94.3 and 113.7%, respectively. Serum PSA decreased gradually after treatment, although it had still not reached a nadir after 1 year. There was little difference of the PSA level between the patients with and without neoadjuvant hormone therapy even at 1 year after seed implantation. There were no PSA biochemical failure or clinical recurrence during the follow-up period. Voiding symptoms worsened until 3 months after treatment, and then gradually improved. Acute urinary retention occurred transiently in one patient (1%). Rectal bleeding and severe diarrhea did not occur. CONCLUSION: Brachytherapy is a feasible and effective option for the treatment of prostate cancer in Japanese men. Brachytherapy may have a different effect in Japanese patients with respect to voiding symptoms. Urinary retention was rare, but voiding symptoms were persistent in Japanese patients. Neoadjuvant hormone therapy deserves investigation to determine whether it can achieve better results, especially in patients with an intermediate risk.

[Novel NMP22 quick qualitative analysis (BladderChek NMP22) for the diagnosis of urothelial tumor].

PURPOSE: The BladderChek NMP22 test was studied to determine whether it could be a useful diagnostic tool for urothelial tumor. MATERIALS AND METHODS: During the period from April to May 2004, a total of 50 patients who visited Nagano Municipal Hospital were subjected to analysis with the BladderChek NMP22 test. They consisted of 25 patients with microscopic or gross hematuria and 25 patients with urothelial tumor who were being followed after surgery. The clinical diagnosis was made by cystoscopy, abdominal CT scanning, ultrasonography or intravenous urography. BladderChek NMP22 was used in all of the patients and the test was judged to be positive when a line appeared on the glass at 30 minutes after a drop of urine was added to the sample well. Cytological examination of the urine was also done. It was defined as negative if the result was I, II or III, while it was positive if the result was IV or V. RESULTS: Seven patients who were not eligible were excluded and the remaining 43 patients were studied. Eleven of the 43 patients were diagnosed as having urothelial tumor. The sensitivity, specificity, and accuracy of BladderChek NMP22 for making a correct diagnosis was 63.6%, 62.5%, and 62.7%, respectively (p = 0.1703). As for urine cytology, the sensitivity, specificity, and accuracy was 36.3%, 100%, and 83.7%, respectively (p = 0.0027). BladderChek NMP22 was positive in all the patients whose urine cytology was positive and in three patients with low-grade, low-stage, and small tumors, although urine cytology was negative. On the other hand, false-positive BladderChek NMP22 results were obtained in patients undergoing follow-up after removal of urothelial carcinoma and in patients with urinary stones. The sensitivity of BladderChek NMP22 was superior to that of urine cytology, but its specificity was inferior. CONCLUSION: The combined use of BladderChek NMP22 and cystoscopy may be useful for the diagnosis and follow-up of urothelial tumor. On the other hand, the results obtained with BladderChek NMP22 need to be interpreted carefully because the test can yield a false-positive outcome in the presence of marked hematuria, pyuria or cytolysis of normal urotherium. When the result of BladderChek NMP22 in the monitoring of recurrent urotherial tumor following surgery was positive in spite of negative findings of cystoscopy, it is necessary to consider the presence of a tumor in the upper urinary tract or a high tendency toward tumor recurrence. In such a case, careful followup may be necessary.