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The clinical management of metastatic urothelial carcinoma (mUC) is undergoing a major paradigm shift; the integration of immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) into the mUC therapeutic strategy has succeeded in improving platinum-based chemotherapy outcomes. Given the expanding therapeutic armamentarium, it is crucial to identify efficacy-predictive biomarkers that can guide an individual patient's therapeutic strategy. We reviewed the literature data on mUC genomic alterations of clinical interest, discussing their prognostic and predictive role. In particular, we explored the role of the fibroblast growth factor receptor (FGFR) family, epidermal growth factor receptor 2 (HER2), mechanistic target of rapamycin (mTOR) axis, DNA repair genes, and microsatellite instability. Currently, based on the available clinical data, FGFR inhibitors and HER2-directed ADCs are effective therapeutic options for later lines of biomarker-driven mUC. However, emerging genomic data highlight the opportunity for earlier use and/or combination with other drugs of both FGFR inhibitors and HER2-directed ADCs and also reveal additional potential drug targets that could change mUC management.

Introduction: The primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in cats and possible associations with bodyweight, age, sex, sexual status, breed and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were evaluated., Materials and Methods: Two hundred and sixteen cats of 15 different breeds that underwent maxillofacial, oral and dental procedures from April 2015 to December 2021 were included. Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified on the occlusal radiographic view of the rostral mandibles as fused or open, and with parallel or divergent margins., Results: Bodyweight ranged from 2.2 to 12.5 kg (median 4.0 kg), age from 4 months to 17 years and 4 months (median 6 years and 4 months). At the first evaluation DV symphyseal mobility was 0 in 177 cases (82%), 1 in 32 cases (14.8%) and 2 in 7 cases (3.2%), LM mobility was 0 in 61 cases (28.3%), 1 in 110 cases (50.9%) and 2 in 45 cases (20.8%). 81.1% of the radiographs were included in the statistical analysis. Three symphyses (1.6%) were classified as fused and 190 (98.4%) as open, 129 (68.8%) having divergent margins and 61 (31.6%) parallel. One hundred and forty-eight cases (76.7%) did not show the presence of odontoclastic replacement resorption on the canine teeth (TR subgroup 1), 23 (11.9%) showed stage ≤3 lesions (TR subgroup 2) and 22 (11.4%) stage 4 lesions (TR subgroup 3). Logistic regression models exploring factors that affected DV and LM mobility were statistically significant ( p  < 0.0001; p  < 0.0001) with an increase in LM mobility predicting an increase in DV mobility, and vice versa. An increase in DV mobility was associated with an increase in age and in having resorptive lesions. A decrease in LM symphyseal mobility was associated with being brachycephalic., Conclusion: The great majority of cases showed some degree of LM symphyseal mobility, and 18% showed DV mobility. Symphyseal bony fusion is rare but possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Minei, Auriemma, Bonacini, Kent and Gracis.)

Introduction: The primary objective of this retrospective study was to document the normal variation of clinical mobility of the mandibular symphysis in dogs, and evaluate possible associations with breed, bodyweight, age, sex, and skull morphology. Secondarily, the radiographic appearance of the mandibular symphysis and possible associations with the analyzed data were also evaluated., Methods: Medical records of dogs that underwent anesthetic procedures for maxillofacial, oral and dental evaluation from April 2015 to December 2021 were included., Results: 567 dogs of 95 different breeds were included, with a total of 695 evaluations. Body weight ranged from 0.8 kg to 79 kg (median 14.4 kg) and age from 3 months to 16 years and 4 months (median 6 years and 9 months). Clinical mobility was evaluated under general anesthesia using a 0 to 3 scale, in lateromedial (LM) and dorsoventral (DV) directions. The symphysis was radiographically classified as being fused or open. The open symphyses were further radiographically divided in having parallel or divergent margins. At the time of the first evaluation DV mobility was 0 in 551 cases (97.2%) and 1 in 16 cases (2.8%). LM mobility was 0 in 401 cases (70.7%), 1 in 148 cases (26.1%) and 2 in 18 cases (3.2%). There was not a significant change in mobility over time for cases examined more than once ( P = 0.76). All cases had an intraoral radiographic examination. 83.8% of the radiographs were included in the statistical analysis. Two symphyses (0.4%) were classified as fused and 473 (99.6%) as open, 355 (74.7%) having divergent margins and 118 (24.8%) parallel margins. Logistic regression models exploring factors that affected DV and LM mobility were statistically significant ( P < 0.0001; P < 0.0001), with an increase in LM mobility predicting an increase in DV mobility, and vice versa. An increase in age and in bodyweight was associated with a decrease in mobility. There was no statistical difference in clinical mobility across specific breeds or sexes. Increased probability of a divergent symphysis and increased DV mobility was found to be associated with a brachycephalic conformation. The increase in LM mobility was comparatively higher in small brachycephalic breeds compared with larger brachycephalic breed., Discussion: The majority of the cases showed little to no mobility of the mandibular symphysis and radiographically bony fusion can be rarely seen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor FV declared a shared affiliation with the author MK at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Minei, Auriemma, Bonacini, Kent and Gracis.)

Background: The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as 'cytokines', as potential biomarkers in patients with head and neck cancer treated with nivolumab., Materials and Methods: A total of 18 circulating cytokines were analyzed. Samples were gathered at baseline (T0) and after 3 courses of nivolumab (T1) in patients with relapsed/metastatic disease. The data extracted at T0 were linked to survival; the comparison of T0-T1 explored the effect of immunotherapy., Results: A total of 22 patients were accrued: 64% current heavy smokers, 36% female and 14% had PS = 2. At T0, ROC analysis showed that IL-6, IL-8, IL-10 and TGF-β were higher in patients with poor survival. Cox analysis demonstrated that only patients with the IL-6 and TGF-β discriminate had good or poor survival, respectively. Longitudinal increments of CCL-4, IL-15, IL-2 and CXCL-10 were observed in all patients during nivolumab treatment., Conclusion: In this small population with poor clinical characteristics, this study highlights the prognostic role of IL-6 and TGF-β. Nivolumab treatment is associated with a positive modulation of some Th1 cytokines, but it does not correlate with the outcome.

An 8-month-old, male, crossbreed dog was presented for macroglossia, reduced mandibular extension, ptyalism, dysphagia, and regurgitation. Serum creatine kinase and aspartate aminotransferase activity were markedly increased. Thoracic radiographs showed an axial gastro-esophageal hiatal hernia, diaphragmatic thickening, and asymmetry. Magnetic resonance imaging of the head showed a severely enlarged tongue, symmetric increase in size of the geniohyoid and mylohyoid muscles, and diffuse masticatory hypomyotrophy. Whole-body CT ruled out other musculoskeletal abnormalities and further characterized the radiographic and MRI findings. Muscular histopathology was consistent with Becker muscular dystrophy., (© 2022 American College of Veterinary Radiology.)

Introduction: Among the risk factors for squamous cell carcinoma of the head and neck, smoking is still the most important today. Several studies agree on the effect of smoking on tumor microenvironment, while the definition of former smokers and the time of smoking cessation on biologic effect differs among papers., Methods: We conducted a narrative review on smoking effects in HNSCC., Results: There is evidence that smoker patients have a poorer prognosis than never smokers and former smokers. Translational studies show a relationship between smoking status and gene expression and support the importance of smoking cessation, for instance, demonstrating an inverse relationship between tumor-infiltrating lymphocytes and smoking., Conclusion: Convincing data suggest that quitting smoking at any time may improve patient outcomes. We advocate smoking cessation also after cancer diagnosis., (© 2022 S. Karger AG, Basel.)

Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle, such as cigarette smoking, or by viruses, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV). HNSCC remains a clinical challenge, notwithstanding the improvements observed in the past years, involving surgery, radiotherapy, and chemotherapy. Recurrent/metastatic (R/M) disease represents an unmet clinical need. Immunotherapy has improved the prognosis of a small proportion of these patients, but most still do not benefit. In the last decade, several preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME), identifying important differences between smoking-associated and virus-associated HNSCCs. This review aims to present how different etiologies affect the HNSCC TIME, affecting immune escape mechanisms and sensitivity to immunotherapy.

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments. This article describes the correlation between chemotherapy and the immune changes induced in the tumor microenvironment. Our ultimate aim is to pave the way for the identification of the best drugs or combinations, the doses, the schedules and the right sequences to use when chemotherapy is combined with immunotherapy., Competing Interests: The authors declare no conflict of interest.

Malignant mesothelioma (MMe) is a rare neoplasm with few therapeutic options available. The landscape of effective therapy for this disease remained unchanged in the last two decades. Recently, however, the introduction of Immune Checkpoint Inhibitors (ICIs) led to small, but nevertheless, promising improvements. However, many efforts are still needed to radically improve the prognosis of MMe. In this review, we analyze all those therapeutic strategies for MMe that are still in a preclinical or early clinical phase of development. In particular, we focus on novel antiangiogenic drugs and their possible combination with immunotherapy. Furthermore, we describe also more complex strategies such as microRNA-loaded vectors, oncolytic viruses, and engineered lymphocytes., Competing Interests: MR reports personal fees from MSD, personal fees from Pfizer, personal fees from Novartis, personal fees from AstraZeneca, during the conduct of the study. CP reports personal fees from Angelini Pharma, personal fees from AstraZeneca, personal fees from BMS, personal fees from Eisai, personal fees from EUSA Pharma, personal fees from General Electric, personal fees from Ipsen, personal fees from Janssen, personal fees from Merck Serono, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, and Roche, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pezzicoli, Rizzo, Perrone, Minei, Mutti and Porta.)

A 54-year-old man presented with the left inguinal swelling. The operation was performed with diagnosis of the hydrocele of spermatic cord. A tumor was 3.0 cm x 2.5 cm in size, cystic with yellowish serous fluid. After the operation, this tumor is diagnosed as mesothelial cyst through the histopathologic examination. This is a rare case, however it is worth to consider that there is a possibility to be a mesothelial cyst when the tumor has been found at the inguinal region.

We describe herein a rare case of a varicocele complicating spontaneous arteriovenous fistula. A 40-year-old man was referred to our hospital in November 2006, complaining of a non-tender mass in the left scrotum at the age of 15 and thereafter. On examination, his left scrotum revealed a large varicocele, but no manifest superficial thrill was noted. Scrotal ultrasonograpy revealed approximately 7 cm large varicocele. Computed tomography angiography revealed the existence of an arteriovenous fistula between the left testicular artery and the veins of the left pampiniform plexus. We laparoscopically carried out internal spermatic vessels ligation under the diagnosis of a varicocele complicating a spontaneous arteriovenous fistula. The postoperative course was uneventful. At 18 months postoperatively, the varicocele and fistula had not recurred.

A 66-year-old male was referred to our hospital for evaluation of tumors in his left residual ureter and the lung. He had a history of left nephrectomy due to "malignant renal tumor", performed by a general surgeon at another hospital 16 years ago. Since a definitive diagnosis of the kidney was uncertain, we speculated that the original renal disease was a renal pelvic cancer and had metastasized in the residual ureter and the lung. We performed systemic chemotherapy followed by resection of residual ureter with bladder cuff Pathological examination revealed urothelial carcinoma. However, the lung tumors did not respond to salvage chemotherapy and slowly progressed. Bronchoscopic biopsy was performed 2 years later and histological finding showed clear cell type renal cell carcinoma.

A 72-year-old woman with asymptomatic macrohematuria was referred to our hospital. Cystoscopy revealed a 7 cm sessile tumor on the left lateral wall of the bladder. Subsequently an intravenous pyelography revealed left hydronephrosis. We performed transurethral biopsy and resection of the bladder tumor under the diagnosis of ordinary malignant bladder tumor. Histopathologically, the lesion was shown to be an undiffentiated urothelial carcinoma, G3, > or = pT2, containing syncytiotrophoblastic giant cells. The level of serum human chorionic gonadotropin-beta (hCG-beta) level was slightly elevated (0.3 ng/ml; normal value: < 0.1). Because a further examination revealed an invasion into the surrounding fat tissue of the bladder and left ureter, a total cystohysterectomy with an ileal conduit were performed. The final histopathological classification was choriocarcinoma of the urinary bladder, pT3a, pN1, pMx. An adjuvant combination chemotherapy was carried out using methotrexate, vinblastine, adriamycin and cisplatin (MVAC). After two courses of chemotherapy, the serum hCG-beta levels returned to normal. Eleven months postoperatively, however, there was evidence of multiple lung metastases. The patient died 12 months after the surgery as a result of complications caused by widespread metastases.

We present an extraordinarily rare finding of a testicular seminoma apparently in the process of spontaneous regression without accompanying metastatic lesion. A 35-year-old man visited our institute for persistent scrotal induration after the administration of antibiotics for several weeks. Ultrasonography and magnetic resonance imaging showed a capsulized tumor in his left atrophic testicle, without other visceral tumor or lymphadenopathy. We performed left radical orchiectomy. Histological examination revealed a fibrotic tumor with a small area of pure seminoma apparently undergoing spontaneous regression, and an intratubular germ cell neoplasia, unclassified, occurring diffusely. The patient is free of disease at 1 year after surgery.

Paraganglioma, extra-adrenal pheochromocytomas, are relatively rare in adults, with most arising from para-aortic sympathetic and visceral organs, such as the bladder. Paraganglioma localized at the extravesical retroperitoneal pelvic cavity is extremely rare. We report a case of symptomatic perivesical pheochromocytoma in a 34-year-old man treated by surgical excision. Symptoms related to cathecolamine secretion ceased after surgery, and the patient has remained disease-free for 24 months.

Proximal-type epithelioid sarcomas are rare soft tissue neoplasms occuring in the soma or thigh and often repeat recurrence and metastasis. We present a case of locally recurrenced proximal-type epithelioid sarcoma that could be treated by regional excision alone. A 62-year-old man visited our institute for a growing mass in the perineal region. Computed tomography (CT) showed a periurethral tumor 22 x 13 mm in diameter in the perineal region. The tumor was excised regionally, and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. Local recurrence of the tumor occurred 2 years 7 months later without any metastatic lesion, and regional excision was performed again. Pathological diagnosis was proximal type epithelioid sarcoma and it was identical to the primary tumor. The patient is free of the disease 1 year after the second surgery of the tumor.

A 48-year-old man was referred to our institute for the evaluation of a concomitant gastric submucosal tumor and right adrenal tumor, incidentally found by ultrasound examination. Computed tomography showed a mass with a diameter of 6 cm adjacent to the stomach and the right adrenal tumor with a diameter of 3 cm. These tumors had similar characteristics in both plain and enhanced imagings. By magnetic resonance imaging, the intensity of the right adrenal tumor was equivalent to the liver in both T1 and T2 weighted images. On the other hand, the gastric submucosal tumor showed low intensity in T1 weighted images and high intensity in T2 weighted images. An adosterol scintigram showed slight accumulation at the region of adrenal tumor. The results of all conducted serum and urinary hormonal examinations were found to be within the normal range. Adrenalectomy and partial gastrectomy were performed laparoscopically. Pathological diagnosis of the adrenal tumor was a cortical adenoma, and that of the gastric submucosal tumor was gastrointestinal stromal tumor (GIST). The gastric tumor was immunohistochemically stained positive with the C-kit and CD34 and negative for s-100 protein and desmin. Histopathological diagnosis was coincident with gastric GIST and right adrenocortical adenoma, and the GIST was diagnosed as a high risk tumor because its diameter was over 5 cm.

We describe herein a rare case of a retroperitoneal bronchogenic cyst successfully treated by laparoscopic surgery. A 39-year-old man with low-grade fever was referred to our hospital because of suspicion of an adrenal tumor. Abdominal computerized tomography (CT) and ultrasonography revealed a homogenous solid mass, 35 x 30 mm in diameter, in the left suprarenal region. Laboratory studies showed that the levels of adrenal hormones were normal except for the white blood cell count of 9,700/microL and C-reactive protein of 1.7 mg/dl. We diagnosed it as a non-functioning adrenocortical adenoma or an adrenal cyst. However, one year later he underwent laparoscopic surgery because the mass had gradually increased by 10 mm and the low-grade fever persisted. Pathological evaluation of the surgical specimens established the diagnosis of retroperitoneal bronchogenic cyst. The low-grade fever disappeared after the surgery.

Objective: To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer., Material and Methods: Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay., Results: Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416)., Conclusions: It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.

Objective: Genetic aberration such as the amplification of c-myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c-myc gene), related to the progression and survival in advanced (Stage C) prostate cancer., Materials and Methods: We used dual-probe fluorescence in situ hybridization with a centromere-specific probe for chromosome 8 (8cen), and with a region-specific probe for c-myc (8q24) to evaluate genetic changes in tumor samples from 50 patients who had undergone radical retropubic prostatectomy from 1986 to 2001., Results: We classified the 8cen and c-myc copy numbers as normal, gain and amplification. The carcinoma foci with extra copies of c-myc, which was defined in 35 cases (70%), were divided into two groups: (a) a simple gain of the whole chromosome 8 (no increase in the c-myc copy number relative to the chromosome 8 centromere), which was identified in 15 cases (30%); and (b) a substantial amplification of c-myc (additional increases [AI] in the c-myc copy number relative to the chromosome 8 centromere), which was detected in 20 cases (40%). AI-c-myc was strongly associated with higher histopathological grades and Gleason's scores (P = 0.0330, 0.0190, respectively). Patients with the AI-c-myc had earlier disease progression (P = 0.0029) and earlier cancer death (P = 0.0087) than did patients with normal patterns., Conclusion: Identification of an AI-c-myc may serve as a potential marker of prostate cancer progression.

The purpose of this study was to further define the immunohistochemical and ultrastructural characteristics of neuroendocrine (NE) differentiated prostatic carcinomas. Seventy-seven specimens were obtained from prostatic carcinoma tumors during prostatectomy, transurethral resection of prostate or biopsy in 77 prostate cancer patients, and analyzed by immunohistochemical staining for chromogranin A (CgA). Nine of these tumors were also studied by elctron microscopy and 4 were examined by pre-embedding immunoelectron microscopy. CgA-stained cells were detected in 36 tumors (47%). Clinically advanced tumors or tumors with higher histological grades were associated with increased NE differentiation. Three of the tumors studied by electron microscopy contained cells showing unequivocal NE differentiation revealed by the presence of neurosecretory granules, while the poorly NE-differentiated malignant cells contained pleomorphic granules, which were lysosomal-like rather than NE-type granules. Immunoelectron microscopy demonstrated the presence of CgA immunoreactivity on the pleomorphic granules in the poorly differentiated malignant glands. This study suggests that NE-differentiated malignant cells in prostate cancer tissues may induce aggressive behavior in adjacent proliferating neoplastic cells via a paracrine mechanism.

Background and Purpose: Laparoscopic adrenalectomy is generally performed with carbon dioxide insufflation of the cavity and requires multiple trocars. This study reports the outcomes of retroperitoneoscopic adrenalectomy (RA) for adrenal tumors via a single port using a large cylinder without carbon dioxide insufflation., Patients and Methods: Fifty-four patients with adrenal tumors were treated using RA via a single large port. The average tumor size was 2.6 cm. For surgery, patients were placed in the lateral decubitus position with slight flexion, and a 4.5-cm skin incision was performed below the 12th rib in the midaxillary line. The retroperitoneal space was dissected using index fingers and a balloon dilator. A rectoscope tube with a 4-cm diameter was inserted, and the adrenal glands were removed endoscopically via the single large port without carbon dioxide insufflation., Results: This procedure was completed in 53 patients (98.1%). The average duration of surgery was 203 minutes, and the mean estimated blood loss was 252 mL. Four patients (7.4%) required blood transfusion. Postoperative major complications, including fulminant hepatitis and pulmonary thrombosis, were observed in two patients (3.7%), and the patient with hepatic disease died on the 14th postoperative day. The mortality rate after surgery thus was 1.9%. However, no local tumor recurrence or hormonal relapse has occurred at a median follow-up of 34 months., Conclusions: This procedure appears to be effective and relatively minimally invasive. However, it is limited by the narrow working space and restriction of the manipulation of instruments.

Introduction: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint., Methods: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5-540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared., Results: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2-18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2-45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029)., Conclusions: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate., (2005 S. Karger AG, Basel)

Abstract A 72-year-old man complaining of upper abdominal discomfort was diagnosed as having retroperitoneal liposarcoma by means of diagnostic imaging. He then underwent an operation. One mass existed on the curvatura ventriculi major, extending to the hilum splenicum and pressing back the pancreal head and body. There was another mass to the left of the first, situated on the ventral side of the left kidney. Also, another mass was intramurally found adjacent to the curvatura ventriculi major. Histologically, the mass on the curvatura ventriculi major ranged from the peritoneal cavity to the retroperitoneum Its intraperitoneal portion was classified as a differentiated lipoma-like type and the retroperitoneal mass was of mucous type. The mass on the left kidney was of a differentiated fibrosing type. The intramural mass in the gastric curvature was found to be a differentiated lipoma-like type. The patient has been under observation for 12 months and has shown no recurrence.

Objective: To evaluate the relationship between neuroendocrine differentiation (NED) status and hormone refractory prostate cancer (HRPC) following hormone therapy based on immunohistochemical study., Methods: Seventy-two prostate cancer specimens obtained at radical prostatectomy and 21 prostate cancer autopsy specimens from patients who died from HRPC after androgen deprivation therapy were examined for NED status using an antibody against chromogranin A. These specimens were classified into 3 arms: 38 radical prostatectomy specimens from patients with no neoadjuvant hormone therapy (Group 1); 34 from patients with neoadjuvant hormone therapy for 3 to 6 months (Group 2); and 21 autopsy specimens from patients with HRPC following androgen deprivation therapy for more than 1 year (Group 3). Staining of prostatic carcinoma was scored as: 0 = no staining; 1 = staining cells <10%; 2 = staining cells 10-20%; and 3 = staining cells >20%. Differences in scores among the groups were compared using the Kruskal-Wallis rank test. Multivariate analysis using a logistic regression model was performed to examine whether NED status was associated with pathological stage (pT), grade and group., Results: Forty-nine (53%) tumors had CgA stained cells. NED status increased with longer duration of hormone therapy (p<0.0001). The mean staining score (and standard deviation) was 0.4+/-0.7 in Group 1, 0.7+/-0.7 in Group 2, and 1.4+/-1.1 in Group 3, respectively. By multivariate analysis Group 3 had a relative risk of 5.46 (95%CI 1.28-23.29) for NED compared to the other groups. But other variables were not related to NED. HRPC following Long-term hormonal therapy was the only independent predictor of NED., Conclusions: The results of this study demonstrated that NED status was significantly increased in patients with HRPC following long-term androgen deprivation therapy, but it could not be discriminate whether the increase of NED is attributable to condition of hormone refractoriness or long-term hormonal therapy.

Background: Intravesical instillation of bacillus Calmette-Guerin (BCG) is efficient for prophylaxis of superficial bladder cancer and treatment for carcinoma in situ (CIS) of the upper urethelial cancer. However, the incidence of adverse effects is relatively high, and those include reactive arthritis. We retrospectively evaluated the incidence and the outcome of reactive arthritis following intravesical BCG therapy for urothelial cancers., Patients and Methods: Intravesical instillations of BCC were performed in 192 cases (218 courses) between January 1998 and January 2002. BCG was instilled for prophylaxis of superficial bladder cancer recurrence in 170 (195 courses), treatment for CIS in 7 (8 course), and treatment for CIS in 7 (8 courses), and treatment for CIS in upper urinary tract in 15 (15 courses)., Results: Arthritis was recognized in 8 cases (3.7%, 8/218 courses), and 7 of them were identical to reactive arthritis following BCG therapy. Remaining 1 patient was diagnosed as rheumatoid arthritis (RA), and the relation between arthritis and intravesical BCG instillation was unclear. Mean number of BCG instillation was 5.6 (3-8 times). All reactive arthritis were occurred within 4 weeks after the last BCG instillation, i.e., BCG induced urinary tract infection, and 6 of them were polyarthritis. Concurrence of conjunctivitis was seen in one patient. HLA-B27 was negative in 4 examined patients. A nonsteroidal anti-inflammatory drug (NSAID) was used in all 8 patients, anti-tuberculous agents were used in 3, and prednisolone was added in 3, Arthritis was improved within 2 months in patients received prednisolone, however, it persisted longer than 3 months in patients without prednisolone., Conclusion: Arthritis was recognized in higher incidence than previous reports following intravesical instillation of BCG. All cases except one, diagnosed as RA, were diagnosed as reactive arthritis (Reiter's syndrome). However, correlation between HLA-B27 and arthritis was not clear in this study. Administration of steroidal drug was thought to improve arthritis in shorter duration.

Maspin is a member of serine protease inhibitor family with tumor suppressing activity for breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of maspin in human bladder cancer. We evaluated maspin expression in 65 series of bladder cancer samples (22 transurethral resection (TUR) and 43 radical cystectomy) and studied the regulatory mechanism of maspin gene activation in bladder cancer cells. Maspin expression was immunohistochemically detected in four (18.2%) patients with TUR and 22 (51.2%) patients with radical cystectomy whereas no expression was observed in normal transitional cells located at tumor-free area in bladder. The maspin expression was significantly correlated with the development of muscle invasive bladder cancer (P=0.00008). Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive bladder cancer cell lines as well as maspin-negative RT4 cells. Furthermore, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin in RT4 cells. Our results indicate that maspin may contribute to bladder cancer development and that DNA methylation and histone deacetylation may be important for regulating maspin gene activation in bladder cancer cells.

Purpose: We report on our experience with the Memotherm stent implanted in high-risk patients who had an indwelling catheter., Patients and Methods: Seventeen patients (mean age 80.6 years, range 55 to 93) who had an indwelling catheter were treated by placement of the Memotherm stent. The mean duration time of indwelling catheter were 12.7 months (range 1 to 60). The methods of implantation was used the special delivery system and treatment can be done with the patient under local anesthesia with non-steroidal anti-inflammatory drug. To assess the efficacy of the treatment we measured urinary peak flow rate (ml/sec), residual urine volume (ml) and residual urine rate (residual urine volume/total urine volume: %). Subjective symptoms were evaluated using the International Prostate Symptom Score (I-PSS). The mean follow-up time was 3.3 months (range 1 week to 8 months)., Results: There were no severe medical problems associated with stent placement. Sixteen patients were able to void immediately after insertion of the stent. The remaining 1 required an indwelling catheter to 2 months, however, eventually able to void. Only 7 of the 17 patients can be evaluation for urinary flow and residual urine, nevertheless the mean urinary peak flow rate showed 9.7 ml/sec, the mean residual urine volume was 77.4 ml, and the mean residual urine rate was 27.5%. Also, average I-PSS showed 13.4 in these patients., Conclusions: As a results of this study, the Memotherm stent is good conservative therapy for high-risk urinary retention patients.

Objectives: The influence and the interdependence of pathological and clinical factors on prognostic differences between renal cell carcinoma (RCC) with end-stage renal disease (ESRD) and RCC without ESRD after nephrectomy has remained unclear. We compare the clinicopathological features between RCC with and without ESRD., Materials and Methods: From June 1993 to May 2000, 150 RCC patients who underwent nephrectomy were pathologically defined to have pT1 to pT3NXM0. The patients were followed for 1 to 84 months (median 30 months) after the surgery. Total of 16 patients with ESRD and 134 patients without ESRD were studied, and the differences of clinicopathological features between two groups were statistically compared., Results: We compare the clinicopathological features between RCC with and without ESRD. Patients' age, tumor size, rate of incidental cancer, pathological T stage, and grade were not significantly different between two groups. The 5-year recurrence-free probability rate was significantly higher in patients without ESRD than in patients with ESRD (log-rank test: p = 0.04). The status of ESRD, patients age and pathological T stage were significant predictors of recurrence when analyzed by Cox proportional hazards analysis (p = 0.01, p = 0.03 and p = 0.02, respectively)., Conclusions: This study demonstrated that the ESRD is an independent prognostic factor in RCC patients after surgery. These results reflect that the patients with ESRD have higher risk of tumor progression. Therefore, early detection of tumors is particularly important in these patients by regular abdominal ultrasound or CT screening.

Background: To determine whether the immunosuppressive acidic protein (IAP) could be a useful marker for renal cell carcinoma (RCC), serum IAP levels were compared with clinicopathological features in RCC patients. Furthermore, IAP cutoff level to predict the recurrence was determined using receiver operating characteristics (ROC) curve analysis., Patients and Methods: Between January 1994 and December 1998, pretreatment serum IAP was measured in 123 consecutive patients with PCC at Kitasato University Hospital. Ninety-eight patients were received radical surgery and 86 patients were performed as clinically curable renal cell carcinoma (pT1-pT3N0M0). ROC curve analysis was utilized to set the cutoff value of IAP for prediction of cancer recurrence. Significance of prognostic factors in RCC recurrence was analyzed by Cox proportional hazard model., Results: The mean age of the 123 patients was 58.6 years (range 33 to 90, median 59). The mean follow-up period was 24.8 months (range 1 to 78, median 26). The median IAP levels were 447 ug/ml in stage I, 629 ug/ml in stage II, 588 ug/ml in stage III and 1,150 ug/ml in stage IV (p < 0.05). Tumor size and venous involvement were significantly associated with IAP concentrations (p < 0.05). However, tumor grade did not correlate with IAP level. Of 86 patients with clinically curable tumor, 79 patients were disease-free after median follow-up of 27 months. Using ROC curve analysis, IAP cutoff level for prediction of cancer recurrence was set at 620 ug/ml. Disease-free survival rate in patients with preoperative IAP levels of 620 ug/ml or lower was 98.5% (67/68) at 27 months postoperatively, whereas that in patients with IAP greater than 620 ug/ml was 75.0% (12/18). This difference was statistically significant (p < 0.05). Results of multivariate analysis revealed that preoperative IAP and pT stage were statistically significant factors for tumor recurrence after radical surgery (p < 0.05)., Conclusions: The present study indicates that preoperative IAP level is a useful prognostic marker in patients with RCC. In particular, patients with clinically curable tumors (pT1-3N0M0), whose preoperative IAP levels greater then 620 ug/ml may have high risk for recurrence after radical nephrectomy.

Objectives: To improve our understanding of the clinical relevance of p53, mdm2, and bcl-2 protein overexpression in renal cell carcinoma, we retrospectively investigated the immunohistochemical expression of p53, murine double minute 2 (mdm2), and bcl-2 and the relationship of this expression to clinicopathologic characteristics. p53 regulates the transcription of downstream effectors such as the oncoprotein mdm2, and bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53., Methods: The expression of p53, mdm2, and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 112 patients whose clinicopathologic data confirmed renal cell carcinoma., Results: The expression of the p53 and bcl-2 protein was recognized in 15 (13.4%) and 52 (42.0%) cases, respectively; the expression of the mdm2 protein, however, was seen in only 2 cases (1.8%). No correlation was noted between these three proteins and any clinicopathologic parameters, except p53 expression and Stage T1-2/T3-4 (P = 0.0208). However, in multivariate analysis, stage (hazard ratio 3.586; P = 0.0002), expression of p53 (hazard ratio 6.090; P = 0.0126) and of mdm2 (hazard ratio 22.016; P = 0.0156), and coexpression of p53/mdm2 (hazard ratio 6.146; P = 0.0005) demonstrated a statistically significant effect on prognosis by proportional hazards regression tests., Conclusions: Our results indicate that stage, p53 expression, mdm2 expression, and coexpression of p53/mdm2 are useful to predict the clinical outcome in patients with renal cell carcinoma.

Objectives: To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue., Methods: We performed 28 HIFU treatments in 20 patients with biopsy-proven localized prostate cancer using a modified Sonablate-200 HIFU device. All patient characteristics and the clinical outcome of 20 patients followed up more than 6 months (mean 13.5) were analyzed., Results: A complete response was obtained in 100% (20 of 20) of patients, as evidenced by a negative postoperative prostate biopsy and no elevation on three successive prostate-specific antigen (PSA) determinations. Of the 20 patients, 13 (65%), 5 (25%), and 2 (10%) had PSA nadirs of less than 0.50 ng/mL, 0.50 to 1.00 ng/mL, and 1.01 to 2.00 ng/mL, respectively. Rectourethral fistula and urethral stricture were noted in 1 and 2 patients, respectively, and 1 patient underwent transurethral resection of the prostate because of prolonged urinary retention., Conclusions: Our results show that HIFU can be performed without an incision, with a less severe side effect profile, and, unlike most other prostate treatments, is repeatable. Transrectal HIFU may be a useful option for patients with localized prostate cancer. Its long-term efficacy will be determined by additional follow-up and a Phase II trial.