Absence of microsatellite instability in extramammary Paget's disease.

Background: Deficiency of DNA mismatch repair (MMR) induces microsatellite instability (MSI). Pembrolizumab, an antibody targeting PD-1 (an immune checkpoint inhibitor), is more effective against MMR-deficient tumours than against MMR-proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD). Objectives: To evaluate the status of MMR in patients with EMPD. Materials & Methods: One hundred one patients with EMPD were included. MMR status of the genomic DNA of each subject was analysed using Promega panel (approved as a companion diagnostic agent for the administration of pembrolizumab). Results: MSI testing showed the occurrence rates of MSI-high (more than two markers are unstable), MSI-low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively. Conclusion: The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.

[Clinicopathological study on the proliferation and differentiation of laryngeal carcinoma and dysplasia].

It is important to examine the proliferative activity of cells in the laryngeal carcinoma and dysplasia for the decision of the clinical treatment and the presumption of the prognosis. I studied here the proliferative activity with three indications, such as the measurement of nuclear DNA contents by flow cytometry, immunohistochemistry of Proliferating Cell Nuclear Antigen (PCNA) and intake of bromodeoxyuridine (BrdU). Furthermore, I compared the proliferative activity with cellular differentiation, which was investigated by immunohistochemistry of involucrin, a marker of human mature suprabasal squamous epithelia. Flow cytometric DNA analysis was performed in 69 patients of laryngeal carcinoma and in 15 patients of dysplasia. In laryngeal carcinoma, 41 cases (59%) had DNA aneuploid pattern, and in dysplasia, 6 cases (40%) represented aneuploid group, and 27% and 11% per 1 hour in diploid group, respectively. The mean of DNA Index (DI) was 1.21 in the carcinoma and 1.13 in the dysplasia. In the cases of recurrent carcinoma and transformed carcinoma, aneuploid pattern was predominant and DI was high. I performed double staining of BrdU and involucrin in these cases. The former is an index of cellular proliferation and the latter is a marker of the differentiation, as described above. These two markers showed reciprocal relationship in normal squamous cell layers, dysplasia and many areas of squamous cell carcinoma. But, some cells of the carcinoma in advanced stage represented concomitantly positive result in these two markers. This finding suggests the biological disorder in these carcinoma cells and requires the follow-up examination of these cases.

Reconstruction of the skin in three-dimensional collagen gel matrix culture.

The skin comprises three layers: epidermis, dermis, and hypodermis. We report here on a skin, reconstructed in vitro, that is composed of all three layers. The top-most layer, epidermis, was exposed to air by a new method. The exposure induced an extensive proliferation, and differentiation, i.e. keratinization was eventually observed in the cultured epidermal cells. Skin thus cultured will be a useful graft of transplantation and provide an ideal model system in which to study diseases of the skin.

[Clinico-pathological study on prostatic cancer, stage A using step section technic].

Of 52 male bladder cancer cases treated with radical cystectomy, 12 cases (23.9%) were incidentally diagnosed as stage A prostatic cancer. Histological analysis was done according to the "general rules for clinical and pathological studies on prostatic cancer." The average age of the prostatic cancer cases was 62.0 years with a range of 50 to 78 years. Three cases were of well differentiated adenocarcinoma, and 9 cases were of moderately differentiated adenocarcinoma. Six cases were at pT1, 3 at pT2, and 3 at pT3. One case was stage A1, and 11 were stage A2 cases. Perineural and capsular invasions were found in 3 cases each. Neither lymphatic nor vascular invasion was found in any case, and no evidence of seminal vesicular, urethral, bladder and rectal invasion was found in any case. Lymph node metastasis was not found in any of the 3 pelvic lymph node dissected cases.

Acute hemorrhagic cystitis caused by adenovirus type 11 after renal transplantation.

A case of acute hemorrhagic cystitis caused by adenovirus type 11, which occurred in an allograft recipient 6 months after a living-related renal transplantation, is described. The patient lacked a neutralizing antibody to adenovirus type 11 before transplantation. Adenovirus type 11 was isolated from his urine and he developed a neutralizing and complement-fixing antibody to this virus. Although adenovirus type 11 isolates had been obtained from 2 of 18 renal allograft recipients, only 1 patient suffered acute hemorrhagic cystitis. Adenovirus type 11 may play a role in acute hemorrhagic cystitis in renal allograft recipients during immunosuppressive therapy.

Captopril-associated granulocytopenia in hypertension after renal transplantation.

A living related kidney transplant recipient with normal renal functioning and hypertension secondary to renal artery stenosis was treated with captopril and developed reversible granulocytopenia. Complications caused by captopril, an angiotensin converting enzyme inhibitor, have been reported previously in hypertensive patients with systemic lupus erythematosus or with renal artery stenosis after renal transplantation. It is recommended that this drug be used with caution in this setting.

[Carcinoma of the urachus--report of 4 cases].

Four cases of urachal carcinoma are presented. The first case was a 36-year-old man who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed a single tumor at the dome of the bladder. Partial cystectomy and postoperative radiation therapy were performed. Histological findings showed a well differentiated adenocarcinoma. He has been well for twelve years postoperatively. The second case was a 52-year-old man who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed a single tumor at the dome of the bladder. Partial cystectomy and postoperative radiochemotherapy were performed. Histological findings showed a moderately differentiated adenocarcinoma. He died of a recurrent tumor 30 months after operation. The third case was 70-year-old man who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed multiple tumors at the dome of the bladder, internal urethral orifice and right lateral wall. Total cystectomy, ureterocutaneostomy and postoperative chemotherapy were performed. Histological findings showed a poorly differentiated adenocarcinoma. He died of a recurrent tumor 30 months after operation. The fourth case was a 68-year-old woman who was admitted with the chief complaint of macrohematuria with mucinous debris. Cystoscopic examination revealed a single tumor at the dome of the bladder. CT scan demonstrated a mass with calcification extending from the bladder dome superiorly. Partial cystectomy and postoperative chemotherapy were performed. Histological findings showed a well differentiated adenocarcinoma. She has been well for three months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Studies on prophylaxis and therapy of pivmecillinam against post-prostatectomy urinary tract infection].

Patients received pivmecillinam (PMPC) after prophylactic use of various antimicrobial chemotherapeutic agents following prostatectomy, and their clinical responses were assessed for effectiveness in the treatment and prevention of postoperative infection. The data were also analyzed to explore the relationship between bacterial isolates obtained during the postoperative course and the antimicrobial agents administered prophylactically against postoperative infection. Therapeutic effect of PMPC: Treatment of postoperative infections with PMPC was effective in 36 (53.7%) out of 67 patients who had undergone prostatectomy. Prophylactic effect of PMPC: The use of PMPC provided effective prevention of infection in 22 (64.7%) out of 34 patients from whom no bacterial pathogen had been isolated before postoperative antimicrobial chemotherapy. Therapeutic responses to PMPC, compared between different types of operative procedure: There was little or no difference in therapeutic effectiveness of PMPC against postoperative infection when compared between two types of operative procedure, transurethral prostatectomy and subcapsular removal of the prostate. Incidence and types of bacterial isolates following prophylactic chemotherapy with various agents after prostatectomy: Possibly because cephapirin (CEPR) and ticarcillin (TIPC) were mainly administered, alone or in combination, for prophylaxis against postoperative infection, Serratia and Pseudomonas were most frequently isolated. The findings offer suggestions as to the appropriate combination of antimicrobial agents to be used for prophylactic purposes. Effectiveness of PMPC in the presence or absence of a preoperative indwelling urethral catheter: The use of PMPC was more effective both in the treatment and prevention of postoperative infection in cases without preoperative indwelling urethral catheterization than in those with it.

Carcinosarcoma of the bladder.

We report a case of carcinosarcoma of the bladder. Total cystectomy with ileal loop urinary diversion was performed. Histologically, the bulk of the tumor tissue was rhabdomyosarcoma and adenocarcinoma. At distant areas from the bulk tumor transitional cell carcinoma was noted. The literature is reviewed and the clinicopathologic condition of carcinosarcoma of the bladder is discussed.