The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis

IntroductionPenile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias.Materials and methodsA cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed.ResultsOur study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival.ConclusionPD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis.

INTRODUCTION: Penile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias. MATERIALS AND METHODS: A cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed. RESULTS: Our study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival. CONCLUSION: PD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

[Collagenofibrotic glomerulopathy--rare glomerulonephritis]. / Kolagenofibrotická glomerulopatia--raritná glomerulonefritída.

Glomerulopathies with fibrillary deposits form a heterogeneous group of renal diseases that can be identified only by means of electron microscopy. A case of a rare type of such a nephropathy, the collagenofibrotic glomerulopathy with focus on differential diagnostics is presented and current knowledge relating to this renal disease is reviewed.

[Atherosclerotic nephropathy in renal artery stenosis--from randomized studies to individualized therapy]. / Aterosklerotická nefropatia pri stenóze renálnej artérie--od randomizovaných stúdií k individualizácii terapie.

Randomized trials in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) mostly did not reveal any significant difference between antihypertensive treatment and revascularization (by angioplasty or bypass surgery) in their effects on blood pressure or glomerular filtration rate. This unexpected conclusion reflects a fact that in addition to potentially reversible ischemia, some other factors which are not eliminated by technically successful revascularization take part in the decrease of renal function in ARAS, including cholesterol microemboli from atherosclerotic plaques, secondary focal segmental glomerulosclerosis and hypertensive nephroangiosclerosis. Moreover, these changes have been also found in the contralateral kidney without any stenosis. Scintigraphic studies confirmed that the individual kidney function was not related to the presence of ARAS, i.e., the glomerular filtration rate in the stenotic kidney was often equal to, or paradoxically even better than that in the kidney with normal renal artery. This has obviously important consequences for the indication of revascularization which should be based on measurement of the individual kidney function rather than overall renal function. A conservative treatment of ARAS should comprise ACE inhibitors or angiotensin II receptor antagonists, statins and acetylsalicylic acid. The long-term effect of such treatment on the progression of atherosclerotic nephropathy is now being evaluated in randomized trials.

[Treatment of ascites with reinfusion of ascitic fluid concentrate]. / Liecba ascitu reinfúziou ascitického koncentrátu.

Ascites which is refractory to common therapeutical measures is a great problem. It deteriorates patient's life and is a sign of poor prognosis. Different methods of peritoneal fluid reinfusion belong to effective non-pharmaceutical therapeutic approaches. Main target of this study was to analyse the effectiveness and safety of peritoneal fluid reinfusion and to compare two methods of its administration (i.v. reinfusion and intraperitoneal reinfusion). During three years we have performed 97 reinfusions in 4 patients (2 women and 2 men; mean age 56 years). I.v. reinfusion was administered 68 times and intraperitoneal ewinfusion was performed 28 times. Usually we evacuated 8000 ml of ultrafiltrate. The most common complications were haemoperitoneum (6x) and short-term chills (2x). We didn't have any complications such as coagulopathy, peritonitis or circulation collapse. Intraperitoneal administration seems to be more advantageous when compared with i.v. application, because of less frequent detection of fibrin degradation products and D-dimers after the procedure and higher diuresis during the following days. (Tab. 2, Fig. 5, Ref. 13.).

[Fibrillary glomerulopathy]. / Fibrilárne glomerulopatie.

The authors present an account on contemporary knowledge of the diagnosis and differential diagnosis of fibrillar glomerulopathies. The latter are characterized by extracellular localized microfibrils and microtubules resp. in the glomeruli of the kidneys, their diameter being 8-60 nm. They are divided into amyloid and non-amyloid types. The others are classified according to the immunofluorescent finding into immunoglobulin positive and negative ones. The differential diagnosis is important in particular in immunoglobulin positive ones as they are present in serious diseases such as cryoglobulinaemia, monoclonal gammapathy, systemic lupus erythematosus and immunotactoid glomerulopathy.

[Chronic renal insufficiency]. / Chronická renálna insuficiencia.

The authors submit a review on the etiopathogenesis, clinical picture and treatment of chronic renal insufficiency. They emphasize the fact that based on pathogenetic ideas it proved possible to influence the majority of pathological processes: retention and deficiency of substances as well as impaired regulation. After introduction of treatment, using erythropoietin, calcitriol as well as due to advances in the technique and quality of dialysis treatment, the patients' quality of life improved substantially. The authors draw attention also to the danger of accumulation of some drugs in renal insufficiency and its development.

[Chronic renal insufficiency. Present views on pathogenesis, clinical aspects and treatment]. / Chronická renálna insuficiencia. Súcasný pohl'ad na patogenézu, klinický obraz a liecbu.

The authors present contemporary views on the pathogenesis, clinical picture and treatment of chronic renal failure. A comprehensive approach to the pathogenesis of renal failure revealed new therapeutic methods such as treatment with erythropoietin, vitamin D etc. The authors emphasize substantial changes in the quality and range of the clinical picture which developed due to the prolonged survival of patients with dialyzation treatment. New problems developed such as e.g. dialyzation amyloidosis, aluminium intoxication, endocrine changes, increased occurrence of malignities etc. These must be foreseen, diagnosed and treated. While during the first half of this century uraemia was a fatal disease, at the end of the nineties patients survive due to the dialyzation and transplantation programme.

[Antibiotic therapy of infections in patients on dialysis]. / Antibiotická liecba infekcií u dialyzovaných pacientov.

The results obtained in treating infections in 53 patients involved in a chronic dialysis-transplantation program are reported. Higher susceptibility to infections and reduced immune functions were observed in dialyzed patients. The problem of the occurrence rate of individual infections was analyzed and infections of the respiratory system, particularly bronchopneumonia, were found to be predominant. No patient died of infection; in two patients the prescribed antibiotic of first choice had to be changed; positive clinical and laboratory effect was recorded in 51 of the 53 patients treated, and after change of the antibiotic in all the patients. Particular regimens of individual antibiotics in dialyzed patients are given along with the dialyzability of the drugs. The best results were obtained with ofloxacin and doxycycline of Czecho-Slovak make in monotherapy, in combined treatment gentamycin an amikacin with cefamezin or with cefotaxim proved to be most effective. Of the 45 pathogenic agents isolated, Staphylococcus aureus, Klebsiella spp, and Acinetobacter lwoffi, which have a good sensitivity to antibiotics, had the highest occurrence rates. (Tab. 4, Ref. 6.).

[Acute renal insufficiency after the administration of tetracycline and gentamycin]. / Akútna renálna insuficiencia po podávaní tetracyklínu a gentamicínu.

The clinical course of eight case reports of patients with acute renal failure after administration of nephrotoxic antibiotics--specially of tetracycline and gentamycin--is demonstrated. All patients were suffering on preexisting nephropathy, many of them in stage of chronic renal failure according to various etiopathogenesis. As concomitant factor inducing acute renal failure together with antibiotics are: elderly, hepatopathy, surgical interventions, administration of other nephrotoxic drugs. In 6 patients, where acute renal failure induced by nonreducted doses of antibiotics appeared, the treatment was successful, in five cases due to short term haemodialysis, once conservatively with diuretics and volume diuresis. Two patients died before the therapeutic measures and dialysis could be performed. Algorithms in diagnosis and treatment of chronic renal failure--patients where antibiotic treatment is necessary are discussed.

[Duplex ultrasonic examination of arteries of the lower extremities--comparison with angiography]. / Duplexné ultrazvukové vysetrovanie artérií dolných koncatín--porovnanie s angiografiou.

The authors compared the results of duplex ultrasonic examination of 86 sections of the ileo-femoro-popliteal portion of the arterial circulation with angiographic findings. The correlation between angiographically and ultrasonically assessed degrees of stenosis was close and highly significant (r = 0.895, p = 0.001, y = 0.782x + 17.382). The sensitivity of duplex sonography when assessing significant stenoses (60% of the arterial lumen or more) was 100%, the specificity 76.5%, the probable positive value 75%, the probable negative value 100%, the probable positive ratio 3, the reliability of the test 86%. With regard to these results the authors recommend to make a non-invasive duplex ultrasonic examination of the arteries of the lower extremities in all echocardiographic laboratories and to include it in the algorithm of angiological examinations before angiography.