Gender and cystectomy for bladder cancer: A high-volume tertiary urologic care center experience.

BACKGROUND: Differences have often been reported in the outcomes of bladder cancer (BC) patients according to gender. OBJECTIVE: This study aims to provide data on patients undergoing radical cystectomy (RC) in a high-volume tertiary urologic center and to assess whether gender discrepancies do exist in terms of surgical options and clinical outcomes. MATERIALS AND METHODS: Consecutive BC patients treated between 2016 and 2020 at a single center (Careggi University Hospital, Florence, Italy) were included in the study. The impact of gender on disease stage at diagnosis, overall survival (OS), and type of surgery was analyzed. RESULTS: The study series comprised 447 patients (85 females and 362 males). At a median follow-up of 28.3 months (IQR: 33.5), OS was 52.6% and cancer-specific survival was 67.6%. Significant differences in OS emerged for age, acute myocardial infarction (AMI), Charlson Comorbidity Index (CCI), pT, and pN. OS rates were higher in patients undergoing robot-assisted surgery and in those receiving open orthotopic neobladder (ONB) (p = 0.0001). No statistically significant differences were found between male and female patients regarding surgical offer in any age group, surgical time, early postoperative complications, pathologic stage, and OS. CONCLUSIONS: After adjustment for pathologic tumor stage and treatment modalities, female and male patients showed similar oncologic outcomes. Further studies should be undertaken to evaluate functional results in women subjected to RC.

Results of endoscopic middle ear surgery for cholesteatoma treatment: a systematic review.

Traditional surgery for cholesteatoma of the middle ear is performed by microscopic approaches. However, in recent years endoscopic instrumentation, techniques and knowledge have greatly improved, and in our opinion endoscopic surgical techniques will gain increasing importance in otologic surgery in the future. The aim of this study was to focus on outcomes obtained using endoscopic surgery for the treatment of middle ear cholesteatoma. A systematic review of the literature was performed. A total of 7 articles comprising 515 patients treated exclusively with endoscope or with a combined technique were found. During post-surgical follow-up, 48 (9.3%) patients showed a residual or recurrent pathology. Despite the small number of patients analyzed in our review, the outcomes of this technique appear to be promising. In particular, concerning the rates of recurrences and residual disease, endoscopic middle ear surgery appears to guarantee similar results in comparison to classic microscopic approaches with the advantage of performing minimally invasive surgery.

Synchronous bilateral testicular germ cell tumour: case report and review of the literature.

We report a case of a 30 years old male affected by synchronous bilateral germ cell tumor with a history of unilateral cryptorchidism; the patient underwent surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac lymphnodes. Patients with synchronous tumors usually present with a higher stage disease in contrast to those with unilateral testicular carcinoma, yet the prognosis remains equally favorable.

Sclerosing variant of PEComa: report of a case and review of the literature.

Tumours of perivascular epithelioid cells (PEComas) are a heterogeneous group of uncommon mesenchymal neoplasms which exhibit a peculiar immunohistochemical co-expression of muscle and melanocytic markers. PEComas occur at various visceral and soft tissue sites, generally with a benign clinical course. Nevertheless, there has been evidence of cases having an unfavourable outcome, thus prompting investigation of pathological criteria for malignancy. A sclerosing variant of PEComa, more frequently encountered in the retroperitoneum of middle-aged women, has been reported. Prognosis has generally been regarded as favourable and complete surgical excision appears to be adequate treatment. To the best of our knowledge, only two cases of sclerosing PEComa displayed high-grade malignant morphology and were associated with adverse outcome. An additional case of retroperitoneal sclerosing PEComa with a two-year follow-up and indolent behaviour is herein described. Light and electron microscopy were performed, along with immunohistochemical analysis. Further studies are needed to clarify the histogenesis and to predict the biological behaviour of this uncommon entity.

Therapy of unilateral vocal fold paralysis with polydimethylsiloxane injection laryngoplasty: our experience.

The objective of this study was to document functional results and to compare objective and subjective voice measures after endoscopic laryngoplasty with injection of polydimethylsiloxane (PDMS) for the treatment of unilateral vocal fold paralysis, and to verify PDMS biocompatibility in vocal fold. The design used was a longitudinal prospective study. Fifteen patients with unilateral vocal fold paralysis underwent endoscopic injection of PDMS in general anesthesia. Accurate voice evaluation protocol (acoustic and aerodynamics analyses, GIRBAS [Grade, Instability, Roughness, Breathiness, Asthenia, and Strain] scale, videostrobolaryngoscopy, and Voice Handicap Index test) before, after surgery, and at follow-up time was performed. The median follow-up was 21.7 months (range, 6-35). Data obtained were statistically significant. All acoustic, aerodynamics, perceptive, and subjective evaluations showed a significant improvement. No complications due to PDMS were reported. Functional results were found comparable to framework surgery. Endoscopic injection laryngoplasty with PDMS is a safe and long-term option for treatment of unilateral vocal fold paralysis.

Renal cell carcinoma of native kidney after renal transplantation: clinical relevance of early detection.

BACKGROUND: Life expectancy after transplantation has improved, and cancer may soon be the leading cause of late death after transplantation. The guidelines of the American and European societies of nephrology and urology have not yet established the optimal frequency for screening for renal cell carcinoma (RCC) of native kidneys in patients who have undergone renal transplantation. OBJECTIVE: To evaluate the prevalence, prognosis, and risk factors of RCC in a series of patients followed up for 16 years in our transplantation unit. MATERIALS AND METHODS: Our study is a follow-up observational cohort study conducted in 694 consecutive renal transplant recipients admitted to our institution from July 1991 through July 2007. At our institution, ultrasound studies of the native kidneys were performed every 6 months after renal transplantation. RESULTS: In the patient cohort studied, 10 patients developed a renal tumor (1.6% incidence). Three patients died of causes other than recurrence of RCC. Seven patients are alive with no evidence of RCC recurrence or metastatic disease after a mean (range) follow-up of 41 (12-96) months. Acquired cystic kidney disease and dialysis duration were positively associated with development of RCC. CONCLUSIONS: The incidence of RCC in the literature varies between 0.3% and 4.8%. The variability depends on the timing of follow-up, with a higher incidence in prospective studies with strict follow-up. We advise ultrasound studies performed by specialized physicians every 6 months after transplantation. More detailed guidelines designed by the major international transplantation societies are necessary.

Weekly administration of docetaxel and epirubicin as first-line treatment for hormone-refractory prostate carcinoma.

Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 years, range 68-77) and normal hepatic, renal, and cardiac function. The chemotherapy protocol provided for the IV administration of DOX (30 mg/m2) and EPI (30 mg/m2) on days 1, 8, and 15 every 28 days. Treatment was continued for 6 months or until disease progression and/or unacceptable toxicity was observed. Serum levels of prostate-specific antigen (PSA) were monitored in all patients, and reductions from baseline values of >50% were considered indicative of positive responses to treatment. Thirty-four patients were included in the analysis of toxicity, and objective responses to treatment were assessed in the 28 patients with measurable lesions. Nineteen patients (56%) experienced PSA reductions of >50% that persisted for more than 4 weeks. The response to therapy was classified as complete in 1 of the 28 patients (4%) with measurable disease (at the lymph node level). Thirteen others (13/28, 46%) had partial responses, in nine (32%) the disease remained unchanged, and progression was observed in the remaining five (18%); overall response rate was 50% (CR + PR). Of the 27 patients with pain at the time of enrollment, 16 (59%) experienced pain reduction during treatment. The median time to disease progression was 11.7 months (95% CI: 7.7-15.7) while the median survival time was 18.7 months (95% CI: 12.3-25.1). During the study, four patients developed grade 3 anemia and leukopenia, which was reversible in all cases. Lower grades of asthenia, nausea, vomiting, diarrhea, and peripheral edema were also observed. There were no cases of cardiotoxic effects. Alopecia was frequent but reversible in all cases. The results of this preliminary study indicate that the combined administration of DOX and EPI for treatment of AIPC is effective and well tolerated. The weekly administration of the drug combination appears to be a promising approach to the treatment of these tumors.

Transnasal endoscopic treatment of cerebrospinal fluid leak: 17 years' experience.

Aim of this report is to describe the long-term results of endoscopic endonasal repair of cerebrospinal fluid leak using a septal mucoperichondrial graft. A case series of 52 patients operated for cerebrospinal fluid rhinorrhea between 1990 and 2006 is presented. All patients underwent surgical treatment for endoscopic endonasal closure of a cerebrospinal fluid leak using a septal mucoperichondrial graft. No lumbar drain and fluorescein tests were used. The intra-operative localization of the fistula was aided by Valsalva's manoeuvre by the anaesthetist. The success rate, after the first attempt, was 88.5% (46/52 patients); for the remaining 11.5% (6/52 patients), a second attempt was necessary which proved successful in 5 cases, raising the overall success rate to 98.1% (51/52 patients). Relapse occurred in only one case (1.9%), after the second attempt. In conclusion, a free mucoperichondrial graft offered good results for cerebrospinal fluid leak repair. In the Authors' experience, a high success rate can be achieved without the use of intrathecal fluorescein and lumbar drain.

Syndecan-1 and Wingless-type protein-1 in human ameloblastomas.

BACKGROUND: Aberrant Wingless type 1 glycoprotein (Wnt) pathway in ameloblastomas and a role of syndecan-1 (SDC1) in activating Wnt signalling were perspected. SDC1 shifting from epithelium to stroma was reported in invasive non-odontogenic neoplasms. The aim of this study was to reveal the role of SDC1 and Wnt1 in intraosseous ameloblastomas (IA(s)). METHODS: SDC1 and Wnt1 expressions were investigated in 29 ameloblastoma subtypes and seven tooth buds. RESULTS: SDC1 immunostaining strongly depicted stromal cells, extracellular matrix (ECM) and basement membranes of ameloblastomas. It also showed epithelial tumour cells in the acanthomatous and plexiform subtypes, and it often occurred in stellate reticulum cells and basal ameloblasts of tooth buds. Parallel Wnt1 expression occurred in ameloblastomatous epithelial cells, but it was common in basal cells of tooth buds too. Statistically, a significant correlation was found between the percentage of IA(s)-bearing SDC1-positive stromal cells and ECM and the percentage of IA(s)-bearing Wnt1-positive epithelial cells. CONCLUSIONS: A role of SDC1 in stromal cells and ECM can be hypothesized as a critical factor for carcinogenesis and local invasiveness of IA(s).

The treatment of fistulae and ureteral stenosis after kidney transplantation.

INTRODUCTION: The incidence of urological complications after kidney transplantation varies from 3% to 14%, with a probable loss of the graft in 10% to 15% of cases and a mortality rate of up to 15%, despite improvements in prevention, diagnosis, and treatment as well as the use of new immunosuppressive therapies. Urinous fistulae, which are considered early complications of transplantation, are due to ischemic damage or necrosis generally occurring in the distal third of the ureter. Preservation of accessory arteries to the lower portion of the kidney is important, as they may constitute the blood supply of this segment of the collecting system or ureter. Their ligation may lead to necrosis and urinary fistulae. Ureteral stenosis, as late complication, is related to a pathology of the ureter itself, to infections, to abscesses, to fibrosis, and to ischemia. An early endoscopic approach permits resolution in 70% of cases. The aim of this retrospective study was to determine incidence and treatment of these complications. MATERIALS AND METHODS: From 1991 to 2004 we performed 453 kidney transplantations both from cadaveric and living donors. In 199 patients we performed a transvesical ureteroneocystostomy (UNCS), and in 260, an extravesical UNCS. RESULTS: The nine patients who showed fistulae (1.9%) underwent surgical treatment. In eight we used a direct ureteral reimplantation, and in one, a Boari flap technique. Nephrectomy was necessary in four patients, including two who died of septic complications. In all 26 cases of ureteral stenosis (5.6%), we used an endourological approach (anterograde or retrograde), with surgical treatment afterward in 11 patients (42%) nine direct reimplants, one anastomosis to the native ureter (transplantation from a living donor), and in one case a Boari flap technique four patients who underwent surgical treatment showed progressive damage to graft function. CONCLUSIONS: In all patients who showed fistulae we suggest surgical review: for patients with ureteral stenosis, we suggest first an endourological approach and only when it is not successful do we consider surgical treatment.

Weekly paclitaxel and epirubicin in the treatment of symptomatic hormone-refractory advanced prostate carcinoma: report of a phase II trial.

The efficacy of weekly paclitaxel in androgen-independent prostate cancer and its addictive cytotoxicity with anthracycline derivatives led us to determine the safety and efficacy of a weekly schedule of paclitaxel and epirubicin. Between October 2000 and November 2002, 32 patients were enrolled in this study. Patients characteristics included a median age of 72 years (range 68-77), adequate hepatic, cardiac, renal and bone marrow functions, ECOG performance status of 1-2, and no prior chemotherapy. All patients had received hormonal manipulation and seven patients (22%) had received prior palliative radiation therapy. The regimen consisted of paclitaxel 70 mg/m2 i.v. infusion for 2 h and epirubicin 30 mg/m2 in bolus every week. Treatment was continued for 3 months or until disease progression or unacceptable toxicity were observed. During the study, prostate-specific antigen (PSA) was monitored and response was defined as a 50% reduction in PSA levels, to be confirmed 4 weeks later. Thirty-one patients were evaluable for toxicity and 21 for objective response. Seventeen patients (57%) had a decline above 50% in PSA level that lasted more than 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 5.5 months. Ten of the 21 patients with measurable disease (47%) had a confirmed objective response (one complete response and 20 partial responses). Thirteen of 25 symptomatic patients (56 %) had improvement in pain. The median time to disease progression was 7.6 months and the median survival was 12.9. The most prominent grade 3 toxicities were reversible myelosuppression and fatigue. Nausea, vomiting, diarrhea and peripheral edema were minimal. No evidence of cardiac toxicity was recorded. Alopecia was frequent, but reversible, in all patients. We conclude that despite the small sample size, this study demonstrates that the combination of weekly paclitaxel and epirubicin is a well-tolerated regimen for androgen-independent prostate cancer. The results imply that a combination of these agents in a weekly schedule may have clinical potential in prostate cancer treatment.

Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia.

OBJECTIVE: Calcitriol analogues might represent an interesting new therapy for benign prostate hyperplasia (BPH). We here report the preclinical characterization of BXL-628, an analogue selected for an ongoing double-blind, randomized, placebo-controlled phase II trial in BPH. DESIGN: Experiments with BXL-628 were carried out in human BPH cells and in the ventral prostate of intact and castrated rats. METHODS: BPH cell and rat prostate growth were evaluated along with morphological and biochemical hallmarks of apoptosis. RESULTS: BXL-628 inhibited human BPH cell proliferation and induced apoptosis even in the presence of androgens or growth factors. It also decreased prostate growth to an extent similar to finasteride, inducing DNA fragmentation and apoptosis, both in intact and in testosterone-supplemented castrated rats. Accordingly, BXL-628, like finasteride, increased the expression of clusterin, a prostatic atrophy marker. However, BXL-628 did not inhibit 5 alpha-reductase 1 and 2, did not bind to the androgen receptor (AR) in BPH homogenates and did not affect AR-coupled luciferase activity. In addition, BXL-628 did not affect rat pituitary and testis activity or calcemia. CONCLUSIONS: BXL-628 inhibited in vitro and in vivo prostate cell proliferation, and therefore might represent a novel, interesting option for the treatment of BPH.

Anaplastic (pleomorphic) subtype embryonal rhabdomyosarcoma of the cervix.

INTRODUCTION: Embryonal rhabdomyosarcoma (RMS) of the female genital tract usually occurs in the vagina during childhood. In rare cases, RMS can originate in the uterine cervix, with an incidence peak in the second decade. Recent studies have suggested that it is possible to limit surgery to local excision in stage I cases. CASE REPORT: We present the case of a 13-year-old girl diagnosed with an anaplastic (pleomorphic) subtype embryonal RMS of the endocervix, who was treated successfully with polypectomy followed by ifosfamide-vincristine-actinomycin combination chemotherapy and brachytherapy. The patient exhibits no evidence of recurrence and has normal menstrual function 36 months following initial diagnosis.

Treatment of benign paroxysmal positional vertigo of posterior semicircular canal by "Quick Liberatory Rotation Manoeuvre".

Treatment of Benign Paroxysmal Positional Vertigo is based on Semont's Liberatory Manoeuvre and on so-called "Canalith Repositioning Manoeuvres", derived from the original Epley technique. Both manoeuvres are very effective and choice of which to use depends on the experience of the physician. Semont's manoeuvre requires a quick movement of the patient in mass in the frontal plane, from the involved, to the contralateral side, which sometimes causes symptoms such as nausea or vomiting. In this technique, a secondary liberatory nystagmus is often observed as sign of the success of the manoeuvre. Repositioning manoeuvres are less fastidious because of the slow movements, but we rarely observe an objective sign of success like the liberatory nystagmus. In the present randomised trial, 300 patients with posterior canalo/cupulolithias were divided into 3 treatment groups: 100 treated by Semont Technique; 100 by a Repositioning procedure (Parnes technique); 100 by a new manoeuvre called "Quick Liberatory Rotation". Results of treatment are also compared with the natural evolution of Benign Paroxysmal Positional Vertigo observed in 18 untreated patients. Quick Liberatory Rotation is similar in the sequence of the positions of the head in the horizontal plane, to repositioning procedures, but is more like the Semont manoeuvre in the speed of the movement (about 180 degrees in less than one second). Quick Liberatory Rotation is easy to perform, well tolerated and very effective (success rate: 98% in one-three cycles). In the present investigation, a secondary liberatory nystagmus was observed in 76.1%, with a sensitivity of 81.9% in detecting patients who had completely recovered and a specificity of 43.8% in detecting failures. Effectiveness, in short and medium period (1-15 months), is similar to Semont and Parnes techniques. Authors consider Quick Liberatory Rotation, at present, a possible first choice technique in the treatment of posterior canalolithiasis.

Inhibition of spontaneous and androgen-induced prostate growth by a nonhypercalcemic calcitriol analog.

We have recently found that analog V (BXL-353, a calcitriol analog) inhibits growth factor (GF)-stimulated human benign prostate hyperplasia (BPH) cell proliferation by disrupting signal transduction, reducing Bcl-2 expression, and inducing apoptosis. We now report that BXL-353 blocks in vitro and in vivo testosterone (T) activity. BPH cells responded to T and dihydrotestosterone (DHT) with dose-dependent growth and reduced apoptosis. Exposure of BPH cells to BXL-353 significantly antagonized both T- and DHT-induced proliferation and induced apoptosis, even in the presence of T. To verify whether BXL-353 reduced prostate growth in vivo, we administered it orally to either intact or castrated rats, supplemented with T enanthate. Nonhypercalcemic doses of BXL-353 time- and dose-dependently reduced the androgen effect on ventral prostate weight, similarly to finasteride. Comparable results were obtained after chronic administration of BXL-353 to intact rats. Clusterin (an atrophy marker) gene and protein were up-regulated by BXL-353 in rat prostate, and nuclear fragmentation was widely present. The antiandrogenic properties of BXL-353 did not interfere with pituitary and testis function, as assessed by serum determination of rat LH and T. BXL-353 did not compete for androgen binding to BPH homogenates and failed to inhibit 5alpha-reductase type 1 and type 2 activities. In conclusion, BXL-353 blocks in vitro and in vivo androgen-stimulated prostate cell growth, probably acting downstream from the androgen receptor, without affecting calcemia or sex hormone secretion. BXL-353 and other vitamin D(3) analogs might thus represent an interesting class of compounds for treating patients with BPH.

Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study.

AIMS: Hep Par 1 has been described as a specific marker of hepatocellular differentiation and its immunohistochemical use has been suggested as a helpful tool for hepatocellular carcinoma (HCC) diagnosis. Most metastatic liver tumours come from the gastrointestinal tract and usually can be distinguished from HCC only through histology. We evaluated by immunohistochemistry the specificity of Hep Par 1, studying the presence of the epitope that reacts with Hep Par 1 in primary gastric and colorectal cancers. METHODS: A series of 39 cases of primary gastric and 18 cases of colorectal carcinoma were selected. Twenty-six of the 39 gastric carcinomas were of the intestinal type, six of the diffuse type, three of the mixed type and five had hepatoid differentiation. Two of the 18 colorectal adenocarcinomas were well differentiated, 14 moderately differentiated, one poorly differentiated and one was of the mucinous type. Five-microm sections were stained by immunohistochemistry using Hep Par 1 as primary antibody. RESULTS: Immunohistochemical staining was observed in 26 gastric carcinomas (69%) and nine large bowel carcinomas (50%). Fifteen of the 26 positive-stained gastric cancers were of intestinal type, four of diffuse type and two of mixed type cases. All of the five hepatoid type cases stained positively. Two of the nine positively stained colorectal cancers were well differentiated, six were moderately differentiated and one was a mucinous type adenocarcinoma. The staining pattern was cytoplasmic and granular as described in benign and malignant hepatocytes. The percentage of immunostained cells was graded as follows: 0 (no staining); 1 (>0-5%); 2 (> 5-50%); 3 (> 50%). Of the 26 positive gastric tumours, 13 showed a staining score of 1, eight scored 2, and five scored 3. Four of the nine positive intestinal carcinomas showed a staining score of 1, and five scored 2. CONCLUSIONS: Our results show that Hep Par 1 is a highly sensitive marker of hepatocellular differentiation as demonstrated by the expression in gastric tumours with hepatoid histotype. However, the frequent reaction with neoplastic cells of gastric and bowel carcinomas shows a low grade of specificity of this antibody.

Immunohistochemical evidence of lactoferrin in hepatic biopsies of patients with viral or cryptogenetic chronic liver disease.

Lactoferrin (Lf) expression has been immunohistochemically investigated in 117 formalin-fixed paraffin-embedded liver bioptic samples obtained from an equal number of patients affected by chronic hepatitis (HCV = 76; HBV = 17; HBV + HDV = 14; cryptogenetic = 10); in addition, 10 autoptic specimens of normal liver were studied as control. The Lf immunoreactivity was evaluated by an intensity-distribution (ID) score. The Lf immunoexpression was observed in 88 out of 117 (75%) cases of chronic hepatitis; interestingly, all liver specimens from HBV hepatitis showed a constant Lf reactivity with the highest ID-score, whereas the evidence of Lf was encountered in 54/76 (71.1%) HCV as well as in 11/14 (78.6%) HDV chronic hepatitis, thus documenting a variable degree of Lf immunostaining in relation to different viruses. Moreover, in 6/10 (60%) cases of cryptogenetic hepatitis Lf immunoexpression was documented, whereas all normal liver controls were unreactive. In HCV specimens, the Lf nuclear immunoreactivity appeared to increase with the progression of the disease, with a greater expression in genotype 1. In contrast, no relationship among Lf ID-scores and different stages or grades of HBV, HDV or cryptogenetic hepatitis was encountered. This fact may suggest a role for Lf as an unspecific defensive agent in chronic inflammatory liver diseases, similarly to that elsewhere reported in other inflammatory tissue injuries.

Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor.

Data on the expression of interleukin 6 (IL-6)/interleukin 6 receptor (IL-6R) in thyroid nodules is scarce. Based on our recent data of CD30 ligand (CD30L)/CD30 receptor (CD30) in these nodules and on the knowledge that this signal stimulates IL-6 production in non-thyroid neoplasms, we wanted to evaluate the immunocytochemical expression of these 2 ligand/receptor systems in a large archival series of paraffin-embedded specimens. These specimens included 6 normal thyroids and 130 thyroid nodules. Co-expression of IL-6 and IL-6R in the epithelial (follicular) cells was observed solely in CD30L/CD30 positive nodules: 5/15 (33%) oncocytic adenomas; 6/30 (20%) follicular adenomas which belonged to 2 variants (4/4 microfollicular toxic and 2/2 hyalinizing trabecular); 9/30 (30%) papillary thyroid cancers (PTC), all belonging to the conventional variant. In PTC the proportion of tumor epithelial cells that were IL6 positive was inversely correlated with the pTNM staging (r=-0.549, p=0.01). All 15 follicular cancers (FTC), all 6 anaplastic cancers (ATC) were IL-6/lL-6R negative; 14/15 FTC and 5/6 ATC were CD30L/CD30 negative. In another oncocytic adenoma, another 4 conventional PTC and another 7 non-conventional PTC CD30L/CD30 expression was associated to expression of IL-6 only. IL-6 staining associated to absent expression of CD30L and CD30 was observed in 7 follicular adenomas (all belonging to variants different from toxic and hyalinizing trabecular), 2 oncocytic adenomas, 5 of the 30 colloid nodules and 2 normal thyroids. Of the 6 tumors arising from the parafollicular C cells (medullary thyroid cancer, MTC), all 3 that had metastasized were CD30L/CD30/IL-6 positive and IL-6R negative; only IL-6 expression was lost in both the local and distant metastases. This finding matched the loss of IL-6 expression in one PTC metastasis. All 3 non-metastasized MTC were IL-6/IL-6R negative, and 1/3 was CD30L positive/CD30 negative. We conclude that only in a subset of both benign and malignant thyroid nodules the IL-6/IL-6R signal could be induced by the CD30L/CD30. IL-6 expression is related with aggressiveness in both PTC and MTC. In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30.