How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation.

PURPOSE: To evaluate the association between pelvic bone marrow (BM) dose volume parameters and probability of acute hematological toxicity (HT), a cohort of cervical cancer patients receiving definitive chemoradiation (CRT) was assessed. MATERIALS AND METHODS: Medical records of patients treated by CRT (45 Gy in 25 fractions, without dose constraints applied to the BM) were reviewed. Baseline and weekly hematological parameters were collected. BM was retrospectively delineated and divided into sub-sites: iliac crests, lower pelvis, lumbosacral region. BM volumes (V) receiving 5, 10, 20, 30, 40 Gy (V5, V10, V20, V30, V40, respectively) and mean dose (Dm) were calculated. Logistic regression was used to analyze associations between HT and dose-volume histograms parameters. RESULTS: 114 patients were included. 75.4% were treated with 3D radiation therapy and 24.6% were receiving intensity modulated radiation therapy (IMRT). Neither age, chemotherapy regimen (cisplatin vs carboplatin), number of chemotherapy cycles, performance status, body mass index, or para-aortic irradiation were associated with HT. In univariate analysis, more frequent grade 3+ leukopenia was found in the IMRT group (odds ratio [OR]: 3.5; 95% CI, 1.4-9.1; p=0.007). In multivariate analysis, grade 4 HT was associated with lower pelvis V5>95% (OR 4.1; 95% CI, 1.6-14. p=0.02), lower pelvis V20>45% (OR 3.5; 95% CI, 1.1-13.4; p=0.05), total pelvic bone V20>65%, and iliac crests Dm >31 Gy (OR 4.5; 95% CI, 1.4-14.7; p=0.02). CONCLUSION: The following dose constraints could be proposed to decrease acute HT risk: lower pelvis V5<95%, lower pelvis V20≤45%, total pelvic bone V20<65%, and iliac crests Dm <31 Gy.

Does PSA reduction after antibiotic therapy permits postpone prostate biopsy in asymptomatic men with PSA levels between 4 and 10 ng/mL?

PURPOSE: We investigated the effect of antibiotics on PSA in asymptomatic patients with mild PSA elevation. MATERIALS AND METHODS: We prospectively evaluated, in a non-randomized design, 106 asymptomatic patients with PSA of 4-10 ng/mL, with a negative digital rectal examination and with no urinary tract infection evidence for 2 years. Patients were divided into two groups: those treated with antibiotics for 3 weeks (G1) and those who were not treated (G2). PSA was taken six weeks after and prostate biopsy was performed in all patients. RESULTS: PCa was diagnosed in 25 of 106 patients (23.6%): 16 (25.0%) in G1 and 9 (21.4%) in G2 (p>0.05). PSA normalization was experienced in 24.5%. In G1, PSA returned to <4 ng/mL in 15 (23.4%) patients compared to 11 (26%) patients in G2. In the patients with a positive biopsy, no significant variation was noted in PSA, fPSA, %fPSA and DPSA after antibiotic treatment. A significantly lower cancer detection rate was noted with decreased PSA, fPSA, and DPSA after antibiotic use. A PSA reduction rate of ≥ 10% occurred in 58.5%, and this was similar in both G1 and G2 groups. The sensibility, specificity and accuracy of PSA reduction of ≥ 10% were 31%, 23% and 25%, respectively. CONCLUSION: Empirical antibiotic therapy in asymptomatic male patients is not related to PSA reduction. The greater than 10% PSA reduction after antibiotic in this population cannot postpone prostate biopsy.

Does PSA reduction after antibiotic therapy permits postpone prostate biopsy in asymptomatic men with PSA levels between 4 and 10ng/mL?

Purpose We investigated the effect of antibiotics on PSA in asymptomatic patients with mild PSA elevation. Materials and Methods We prospectively evaluated, in a non-randomized design, 106 asymptomatic patients with PSA of 4-10ng/mL, with a negative digital rectal examination and with no urinary tract infection evidence for 2 years. Patients were divided into two groups: those treated with antibiotics for 3 weeks (G1) and those who were not treated (G2). PSA was taken six weeks after and prostate biopsy was performed in all patients. Results PCa was diagnosed in 25 of 106 patients (23.6%): 16 (25.0%) in G1 and 9 (21.4%) in G2 (p>0.05). PSA normalization was experienced in 24.5%. In G1, PSA returned to <4ng/mL in 15 (23.4%) patients compared to 11 (26%) patients in G2. In the patients with a positive biopsy, no significant variation was noted in PSA, fPSA, %fPSA and DPSA after antibiotic treatment. A significantly lower cancer detection rate was noted with decreased PSA, fPSA, and DPSA after antibiotic use. A PSA reduction rate of ≥10% occurred in 58.5%, and this was similar in both G1 and G2 groups. The sensibility, specificity and accuracy of PSA reduction of ≥10% were 31%, 23% and 25%, respectively. Conclusion Empirical antibiotic therapy in asymptomatic male patients is not related to PSA reduction. The greater than 10% PSA reduction after antibiotic in this population cannot postpone prostate biopsy. .

Gene expression profiling in insulinomas of Men1 beta-cell mutant mice reveals early genetic and epigenetic events involved in pancreatic beta-cell tumorigenesis.

Mutations of the MEN1 gene lead to the occurrence of multiple endocrine neoplasia type 1 (MEN1). To gain insights into the mechanisms of the tumorigenesis related to MEN1 inactivation, we have used mice in which the Men1 gene was specifically disrupted in pancreatic beta-cells. In these mice, we observed full penetrance of insulinoma with defined histological characteristics of tumorigenesis. To identify the genetic factors taking part in the tumour development, we performed gene expression profiling analysis of these insulinomas at different stages. Here, we show that in late stage insulinomas, 56 genes are up-regulated and 194 are down-regulated more than fourfold compared with normal pancreatic islets. Clustering analysis reveals the deregulation of Hox gene family and the genes involved in cell proliferation and cell cycle control. The altered expression of Igf2, Igfbp3 and Igfbp6 as well as cyclin A2, B2 and D2 are confirmed by quantitative RT-PCR, with the overexpression of all the three cyclins found in early stage insulinomas. Moreover, an increased proportion of cyclin A2- and D2-expressing cells and the overexpression of insulin-like growth factor 2 (IGF2) protein are detected in mouse Men1 insulinomas by immunostaining. Interestingly, the analysis of DNA methylation patterns by quantitative serial pyrosequencing reveals that four specific CpGs in the intragenic differentially methylated region 2 (DMR2) region of the Igf2 gene known to augment transcription through methylation are significantly hypermethylated in insulinomas of Men1 beta-cell mutant mice at 6 and 10 months of age, even before IGF2 overexpression can be detected. Thus, our data indicate the involvement of both genetic and epigenetic mechanisms in early tumorigenesis of beta-cells related to MEN1 inactivation.

Reconstruction of conjunctiva with amniotic membrane after excision of large conjunctival melanoma: a long-term study.

PURPOSE: To evaluate, on a long- term basis, the role of amniotic membrane in the reconstruction of large conjunctival defects after excision of large conjunctival melanoma. METHODS: Four consecutive patients with diffuse conjunctival melanoma involving both bulbar and palpebral conjunctiva were studied. Conjunctival melanoma was completely excised (with wide clinically disease-free margins) and amniotic membrane immediately sutured to the surrounding conjunctiva and sclera to cover the conjunctival defect. Minimum follow-up was 48 months. RESULTS: Successful conjunctival surface reconstruction and physiologic fornical depth were achieved in all patients within 6 weeks. No recurrence of primary melanoma was observed during long-term follow-up. CONCLUSIONS: Amniotic membrane transplantation is an effective alternative in ocular surface repairing surgery after removal of large conjunctival tumors.

[Granulomatous pneumocystis pneumonia]. / Pneumocystose à forme granulomateuse.

INTRODUCTION: Granulomatous pneumocystis pneumonia (PCP) is a rarity whose presentation may be misleading. CASE REPORT: We report the case of a patient suffering from chronic lymphatic leukaemia presenting with acute respiratory insufficiency, with a fatal outcome, due to granulomatous PCP. Broncho-alveolar lavage (BAL) remained negative and the diagnosis could only be made later by open lung biopsy. CONCLUSION: Although infrequent, granulomatous PCP should be recognised because in this situation the standard investigation (BAL) may be negative. New, more sensitive, methods of investigation such as the polymerase chain reaction (PCR) may permit earlier diagnosis.

[Bone cysts and continuous ambulatory peritoneal dialysis]. / Cisti ossee e dialisi peritoneale ambulatoriale continua.

The clinical and radiologic patterns of amyloid osteoarthropathy in long-term hemodialysis patients are well known. However, few studies about the incidence of dialysis-associated amyloidosis in continuous ambulatory peritoneal dialysis (CAPD) patients have been published to date. In a series of 27 CAPD patients, the authors found bone cysts in 63.6% of cases, at the beginning of their dialysis treatment. After a mean follow-up period of 20.9 +/- 13.8 months, carpal bone cysts were seen in 70.4% of cases and clinical patterns worsened in 26.3% of patients. Therefore, CAPD does not prevent the development of dialysis-associated amyloidosis; prolonged uremic state and decreased diuresis seem to be the main pathogenetic factors of osteoarthropathy. The incidence and the evolution of bone lesions were related to the clinical data of this series and then compared with those of a group of hemodialysis patients. This study confirms that plain wrist films are a simple and useful method in the early detection and in the follow-up of amyloidosis-related disease.

[Sarcomatoid nephrocarcinoma. Correlation of radiological, histopathological and prognostic features]. / Il nefrocarcinoma sarcomatoide. Correlazione tra il quadro radiologico, istopatologico e prognostico.

Fifteen patients with sarcomatoid renal cell carcinoma were studied from 1975 through 1987. For each case the radiological, sonographic (US), and histopathological features were reviewed. Neither ivp nor US detected any specific patterns, though demonstrating frequently-necrotic and infiltrating masses. Angiography and/or CT were more useful because they allowed the staging of the tumors and the evaluation of their vascularity. In particular, a frequent correlation was observed between the degree of vascularity and the percentage of sarcomatoid component at histopathology. Sarcomatoid renal cell carcinoma were hypo-avascular in 7 cases and hypervascular in 8. Six of the 7 hypo-avascular cases had a high percentage of sarcomatoid tissue (greater than 50%) and were highly malignant. Seven of the 8 hypervascular neoplasms had a low percentage of sarcomatoid component and presented radiological features similar to clear/granular cell tumors. The survival of the patients with sarcomatoid tumors was much shorter than that of the patients with other kidney carcinomas. Among sarcomatoid tumors, prognosis was worst for the patients with hypo-avascular neoplasms.

[Echography vs urography in the study of small-size renal carcinoma]. / Ecografia ed urografia a confronto nello studio dei nefrocarcinomi di piccole dimensioni.

Since 1981 we have studied 34 patients with renal cell carcinomas smaller than 3 cm, diagnosed by US and IVP, to evaluate the diagnostic viability of these 2 procedures. Their respective results were compared to pathologic findings and tumor grading. No correlation was found between the type of sonographic patterns and the pathologic findings. On the contrary the correlation between the acoustic pattern and the grading, performed on small tumors and on a control group of large tumors, showed that most tumors in the former group (70%) had lower grading than those in the latter. We conclude that the introduction of US has changed the approach to the diagnosis of renal tumors, allowing their early recognition and characterisation. It is thus hoped that the clinical course of such tumors will be improved.

[Papillary nephrocarcinoma: radiographic and echographic aspects]. / Nefrocarcinoma papillifero. Aspetti radiografici ed ecografici.

Between 1976 and 1987, 395 patients with kidney tumors were studied with radiological techniques and sonography. In 37 cases (9.4%) histopathology diagnosed pure papillary renal cell carcinoma. Analyzing the radiographic patterns of these neoplasms, the authors observed constantly diminished vascularity (100%), frequent calcifications (35.1%) and necrotic areas (51.3%). Such X-ray features are not specific: nevertheless, their coexistence is strongly suggestive of papillary renal cell cancer. No consistent US pattern was found; however, necrotic areas were easily demonstrated in most cases. It must be stressed how patients with papillary carcinoma experienced a longer postoperative survival; it has not yet been established whether such favorable behavior is due to low biological aggressiveness or to earlier diagnosis.

[Angiographic study of the complications of vascular access in patients under hemodialysis]. / Studio angiografico delle complicanze degli accessi vascolari nei pazienti in emodialisi.

Periodic hemodialysis requires the vascular access to be capable of functioning perfectly for a long time; therefore early diagnosis of the most common complications is very important. Fifty-four patients in dialysis treatment for end-stage renal failure (ESRF) were examined over a six-year period for vascular access (VA) complications. Eighty vascular accesses were studied: 68 arteriovenous fistulas and 12 arteriovenous grafts. The most frequent radiological investigation was phlebography, followed by arteriography by direct puncture of the humeral artery, and, in few cases only, by arteriography through femoral approach; the total number of radiographic examinations performed was 101. The most frequent complications were thromboses (50%) and stenoses (21%); aneurysms, pseudoaneurysms and radial artery steals were observed in 11% of the cases. Findings prove complications to depend neither on the type of VA (fistula, prosthesis) nor on its site (proximal, distal). In 50% of the cases angiography allowed a therapy to be adopted for VA recovery. Percutaneous transluminal angioplasty (PTA), performed on 3 patients, failed. Thus, in the authors' opinion, angiography is the method of choice for the evaluation of VA pathology, and surgery is the most efficient treatment for complications. Despite failures, PTA represents a valid alternative in the treatment of stenoses in larger vessels and prostheses.

[Has echography modified the occurrence of kidney carcinoma? Considerations on 316 cases]. / L'ecografia ha modificato l'incidenza del carcinoma renale? Considerazioni su 316 casi.

An analysis of 316 renal carcinomas over an 11-year period has shown an increase in the incidence of tumors per year, together with a progressive decrease in the size of the lesions at the time of diagnosis. This effect occurred especially after the introduction of renal ultrasonography in diagnostic practice. The tumor size is an important prognostic factor, because the 5-year survival rate was 80% for tumors less than 5 cm and 30% for tumors greater than 10 cm. Ultrasonography might thus represent a screening method for renal carcinoma in patients over 50 years of age, if it were possible to define risk groups.

[Syringocele or cystic diagnosis of Cowper's gland ducts]. / Siringocele o dilatazione cistica dei dotti ghiandolari di Cowper.

Cystic dilatation of bulbo-urethral gland ducts (Cowper's syringocele) is an uncommon abnormality, frequently asymptomatic, showing various radiographic patterns. The lesion is more commonly seen in children, but it may be found in adults too, and may cause dysuria, pollakiuria, stranguria and posturinary dribbling. Fourteen patients with syringocele were observed: 6 of them were asymptomatic, while in 8 the most common symptoms were posturinary dribbling and stranguria. X-ray examination showed 7 cases of perforated syringocele, 4 cases of ruptured syringocele, 2 cases of simple syringocele and 1 case of imperforate syringocele. Various theories are reported to explain how the lesion forms and the differences are analyzed which characterize different kinds of urethral lesions.