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Long-Term Survival of a Patient with Invasive Signet-Ring Cell Carcinoma of the Urinary Bladder Managed by Combined S-1 and Cisplatin Adjuvant Chemotherapy  [PDF]
Takashi Hamakawa,Yoshiyuki Kojima,Taku Naiki,Yasue Kubota,Takahiro Yasui,Keiichi Tozawa,Yutaro Hayashi,Kenjiro Kohri
Case Reports in Urology , 2013, DOI: 10.1155/2013/915874
Abstract: Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor. The disease usually presents at advanced stages because the cancer progresses rapidly. The only option for effective treatment is radical cystectomy, and no effective chemotherapy has been established for this variant. We report a case of signet-ring cell carcinoma of the urinary bladder with a long-term survival of 90 months owing to radical cystectomy and combination adjuvant chemotherapy with S-1 and cisplatin. To our knowledge, this is the first report to demonstrate the long-term therapeutic activity of combination S-1 and cisplatin adjuvant chemotherapy against invasive signet-ring cell carcinoma of the urinary bladder. 1. Introduction Adenocarcinoma of the urinary bladder accounts for 0.5%–2% of all bladder cancers with signet-ring cell carcinoma being an aggressive phenotype characterized by signet-ring cells containing intracellular mucin-filled vacuole, which displaces the hyperchromatic nucleus to one side of the cell [1]. Primary signet-ring cell carcinoma of the urinary bladder (SRCCU) is a rare neoplasm that has a very high mortality rate and can be primary (arising from the bladder wall or urachus remnants) or metastatic (tumors originating in the stomach, colon, or breast) [2]. It accounts for approximately 0.24% of all bladder malignancies. This disease usually presents at advanced stages, and patient survival is therefore usually poor with a reported mean 5-year survival rate of 27%–30% [3, 4]. One quarter of the patients were found to have distant metastases at the time of diagnosis and 60% of patients died within 1 year [5]. Patients are usually treated with several types of combination chemotherapy after radical cystectomy, but survival does not improve significantly. Here we report a case of advanced SRCCU successfully treated with combination chemotherapy of S-1 and cisplatin. 2. Case Report A 53-year-old Japanese man with a history of pain on urination and hematuria for several months was referred to our hospital. He had no past medical history and was treated with a course of antibiotics for urethritis, which did not resolve the complaint. Urinalysis revealed RBC 50–99/HPF and WBC 10–19/HPF and was negative for bacteria and for urinary cytology. Serum tumor markers including carcinoembryonic antigen were within normal limits. Cystoscopy revealed widely prevalent nonpapillary raised lesions and edematous mucosa on the posterior wall of the bladder. Pelvic computed tomography (CT) scan demonstrated marked diffuse bladder
Primary signet-ring cell carcinoma of the urinary bladder successfully managed with cisplatin and gemcitabine: a case report  [cached]
El Ammari Jalal Eddine,Ahsaini Mustapha,Riyach Omar,El Fassi Mohammed Jamal
Journal of Medical Case Reports , 2013, DOI: 10.1186/1752-1947-7-37
Abstract: Introduction Primary signet-ring cell carcinoma of the urinary bladder is a rare variant of mucus-producing adenocarcinoma constituting approximately 0.5% to 2.0% of all primary carcinomas of the bladder. This tumor initially presents as a high-grade, high-stage lesion and diffusely invades the bladder wall without forming intraluminal growth. The patients have no specific symptoms, which leads to delayed diagnosis and poor prognosis. Case presentation We report the case of a 51-year-old Moroccan Berber man consulting for gross hematuria. Ultrasonography and a computed tomography scan found a bladder tumor diffusely invading the bladder wall. A histopathological examination of the tumor chips from a transurethral resection of the bladder revealed signet-ring cell adenocarcinoma. The gastrointestinal tract exploration did not reveal any other tumor localization. A radical cystectomy and adjuvant cisplatin and gemcitabine chemotherapy were therefore performed resulting in 18 months of survival without metastasis and a good quality of life within that time. Conclusion The rarity and the successful management with carboplatin and gemcitabine as adjuvant chemotherapy of this entity, which is rarely reported in the literature, are two remarkable characteristics described in this case report.
Neoadjuvant or adjuvant chemotherapy: what is the best treatment of muscle invasive bladder cancer?
Nabil Ismaili,Sanaa Elmajjaoui,Youssef Bensouda,Rhizlane Belbaraka
Oncology Reviews , 2011, DOI: 10.4081/33
Abstract: Bladder cancer is the fourth most common cancer for men and the eighth most common cancer for women. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting the treatment is based on cisplatin chemotherapy regimens type MVAC, MVAC-HD or gemcitabine plus cisplatin. The standard treatment of muscle invasive operable bladder cancer (T2–T4) used widely was radical cystectomy with pelvic lymph nodes dissection; the anatomical extent of pelvic lymphadenectomy has not accurately been defined so far. However, in the last decade, the treatment of tumors was improved by the introduction of chemotherapy as part of the management of the disease. Neoadjuvant chemotherapy should be considered at first, as standard treatment of choice, before local treatment for patients with good performance status (0–1) and good renal function–glomerular filtration rate (GFR) >60 mL/min. For patients treated with primary surgery, adjuvant chemotherapy is a valuable option in the case of lymph nodes involvement. This brief review would provide the evidence of the role of neoadjuvant chemotherapy in the management of operable muscle invasive (T2–T4) bladder cancer.
Isolated cardiac metastasis from plasmacytoid urothelial carcinoma of the bladder
Joshua R Peck, Charles L Hitchcock, Sara Maguire, Jennifer Dickerson, Charles Bush
Experimental Hematology & Oncology , 2012, DOI: 10.1186/2162-3619-1-16
Abstract: Bladder cancer is the fourth most common cancer in men in the United States. Most patients (69%) with metastatic bladder cancer have multiple organs involved; conversely, our patient had a PET scan indicating his disease was localized to the heart. Plasmacytoid urothelial carcinoma is a rare subtype of bladder cancer, and is estimated to make up less than three percent of all invasive bladder carcinomas. At the time of this publication we are aware of only three other reported instances of isolated cardiac metastasis with urothelial bladder origin; none of which were the plasmacytoid variant.This case highlights a previously unreported presentation of plasmacytoid urothelial carcinoma. Clinicians must remember that even superficial cancers can have significant metastatic potential.Urothelial cell carcinoma (UCC) with metastasis exclusively to the heart is an extremely rare and atypical presentation of a relatively common malignancy. A review of current literature yields only three other instances of this unusual metastatic pattern [1-3]. We present a 57-year-old male with plasmacytoid urothelial carcinoma (PUC) of the bladder and isolated metastasis to the heart. To our knowledge, an isolated cardiac metastasis from this rare type of UCC has never been reported in the literature.A 57-year-old male with a past medical history of hypertension, type-2 diabetes and superficial UCC presented with shortness of breath, substernal chest pain, and fevers. He was found to have a bladder mass four months earlier, for which he underwent cystoscopy and surgical removal. Pathology demonstrated high-grade superficial PUC extending into the submucosa but not the muscularis propria. Given the superficial nature of his bladder cancer, a cystectomy was deferred. He was subsequently lost to follow-up care.Upon presentation to our emergency department, the patient was tachycardic and tachypneic with distant heart sounds. An electrocardiogram (ECG) showed an incomplete right bundle branc
Comparison of the clinical and pathologic staging in patients undergoing radical cystectomy for bladder cancer
Mclaughlin, Sean;Shephard, Jon;Wallen, Eric;Maygarden, Susan;Carson, Culley C.;Pruthi, Raj S.;
International braz j urol , 2007, DOI: 10.1590/S1677-55382007000100005
Abstract: purpose: radical cystectomy (rcx) is perhaps the most effective therapeutic approach for patients with muscle-invasive bladder cancer. unfortunately, clinical staging is imprecise and the degree of understaging remains high. this study retrospectively evaluated patients undergoing rcx with regard to pathologic outcomes and degree of upstaging to better identify features that may lessen clinical understaging. materials and methods: 141 consecutive patients with urothelial bladder carcinoma who were candidates for rcx with curative intent were retrospectively evaluated. preoperative clinical and pathological (i.e. turbt) features were compared to pathological outcomes in the cystectomy specimen. patients were also evaluated as to whether cystectomy was performed as their primary (n = 91) versus secondary (n = 50) treatment for recurrent/progressive disease. date of cystectomy (< 5 years vs. > 5 years prior to study) was also analyzed. results: of the 141 patients, 54% were upstaged on operative pathology. the greatest degree of upstaging occurred in those with invasive disease preoperatively (ct2-t3). twenty-six percent of all patients had node-positive disease, and 75% of ct3 patients were node-positive. seven of 101 (7%) patients with clinical t2 disease were unresectable at the time of surgery. in the primary (vs. secondary) rcx group, more patients were upstaged (63% vs. 40%), non-organ confined (62% vs. 38%), and ln positive (31% vs. 20%). in the more modern cohort, the degree of upstaging was not improved. conclusions: pathologic findings after rcx often do not correlate with preoperative staging. over half of patients undergoing cystectomy are upstaged on their operative pathology. an improved understanding of the relative frequency of upstaging in cystectomy patients may have important implications in the decision-making and selection for neoadjuvant and adjuvant therapies for these high-risk populations.
Downregulation of HIPK2 Increases Resistance of Bladder Cancer Cell to Cisplatin by Regulating Wip1  [PDF]
Jun Lin, Qiang Zhang, Yi Lu, Wenrui Xue, Yue Xu, Yichen Zhu, Xiaopeng Hu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098418
Abstract: Cisplatin-based combination chemotherapy regimen is a reasonable alternative to cystectomy in advanced/metastatic bladder cancer, but acquisition of cisplatin resistance is common in patients with bladder cancer. Previous studies showed that loss of homeodomain-interacting protein kinase-2 (HIPK2) contributes to cell proliferation and tumorigenesis. However, the role of HIPK2 in regulating chemoresistance of cancer cell is not fully understood. In the present study, we found that HIPK2 mRNA and protein levels are significantly decreased in cisplatin-resistant bladder cancer cell in vivo and in vitro. Downregulation of HIPK2 increases the cell viability in a dose- and time-dependent manner during cisplatin treatment, whereas overexpression of HIPK2 reduces the cell viability. HIPK2 overexpression partially overcomes cisplatin resistance in RT4-CisR cell. Furthermore, we showed that Wip1 (wild-type p53-induced phosphatase 1) expression is upregulated in RT4-CisR cell compared with RT4 cell, and HIPK2 negatively regulates Wip1 expression in bladder cancer cell. HIPK2 and Wip1 expression is also negatively correlated after cisplatin-based combination chemotherapy in vivo. Finally, we demonstrated that overexpression of HIPK2 sensitizes chemoresistant bladder cancer cell to cisplatin by regulating Wip1 expression. Conclusions These data suggest that HIPK2/Wip1 signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of bladder cancer.
Surgical Treatment of Adrenal Gland Metastasis Originating from Small Cell Carcinoma of the Urinary Bladder  [PDF]
Minekatsu Taga,Hideaki Ito,Naoya Kusukawa,Yoshiji Miwa,Hironobu Akino,Yoshiaki Imamura,Osamu Yokoyama
Case Reports in Urology , 2013, DOI: 10.1155/2013/982787
Abstract: We report a rare case of a solitary adrenal metastasis from small cell carcinoma of the urinary bladder that was successfully treated with surgical resection. A 71-year-old man was suffering from bladder tamponade for hematuria. Computed tomography (CT) revealed a bladder tumor at the left wall. The patients underwent radical cystectomy. Histopathological results were obtained in small cell carcinoma of the bladder with muscle invasion. Thus, he received two courses of adjuvant etoposide and cisplatin chemotherapy, followed by the regimen for small cell lung cancer. Seven months after surgery, follow-up CT showed a gradually enlarged mass enhanced heterogeneously in the right adrenal gland. There was a solitary adrenal metastasis without any other metastasis; therefore, we performed right laparoscopic adrenalectomy. The patient has remained uneventful for four years after the adrenal gland surgery. For patients who have a solitary adrenal metastasis, adrenalectomy may provide a survival benefit. 1. Introduction Small cell carcinoma of the bladder (SCCB) is exceedingly rare and accounts for less than 1% of all bladder carcinomas. The majority of patients are elderly, with a male?:?female ratio of 3?:?1, and they often have a history of smoking. The most common symptom was gross hematuria for 68.2% of patients [1]. Because SCCB is mostly diagnosed at an advanced stage and behaves aggressively, the prognosis of patients with SCCB is poor; overall survival at five years ranges from 8% to 25% [1–3]. SCCB is frequently managed by radical cystectomy with adjuvant chemotherapy, but there is no established treatment for the disease. It is also rare that bladder carcinoma can cause a solitary adrenal metastasis, but it has been reported that surgical resection could improve survival [4]. We present a case of laparoscopic adrenalectomy as a treatment for solitary adrenal metastasis from SCCB, which was identified even after cystectomy and two courses of adjuvant etoposide and cisplatin (EP) chemotherapy. 2. Case Presentation A 71-year-old man was hospitalized for bladder bloody tamponade. Cystoscopy revealed a broad-based tumor at the left wall of the urinary bladder. Urinary cytologic findings indicated poorly differentiated urothelial carcinoma. A computed tomography (CT) scan showed a 7.0?cm bladder tumor at the left wall with a complicated left hydronephrosis (Figure 1). A magnetic resonance imaging (MRI) scan disclosed deep invasion into the muscle layers of the bladder and invasion of the left ureter. Preoperative tumor markers indicated elevation in NSE
Trial on Refinement of Early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: The TREAT protocol
Michael Kreuter, Johan Vansteenkiste, Frank Griesinger, Hans Hoffmann, Hendrik Dienemann, Paul De Leyn, Michael Thomas
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-77
Abstract: In this prospective, multi-center, open label randomized phase II study, patients with pathologically confirmed non-small cell lung cancer, stage IB, IIA, IIB, T3N1 will be randomized after complete tumor resection either to 4 cycles of the standard adjuvant vinorelbine and cisplatin regimen from the published phase III data, or to 4 cycles of pemetrexed 500 mg/m2 d1 and cisplatin 75 mg/m2 d1, q 3 weeks. Primary objective is to compare the clinical feasibility of these cisplatin doublets defined as non-occurrence of grade 4 neutropenia and/or thrombocytopenia > 7 days or bleeding, grade 3/4 febrile neutropenia and/or infection, grade 3/4 non-hematological toxicity, non-acceptance leading to premature withdrawal and no cancer or therapy related death. Secondary parameters are efficacy (time to relapse, overall survival) and drug delivery. Parameters of safety are hematologic and non-hematologic toxicity of both arms.The TREAT trial was designed to evaluate the clinical feasibility, i.e. rate of patients without dose limiting toxicities or premature treatment withdrawal or death of the combination of cisplatin and pemetrexed as well as the published phase III regimen of cisplatin and vinorelbine. Hypothesis of the study is that reduced toxicities might improve the feasibility of drug delivery, compliance and the convenience of treatment for the patient and perhaps survival.Clinicaltrials.gov NCT00349089Non-small cell lung cancer (NSCLC) accounts for the largest number of cancer deaths annually, worldwide [1]. Of these, about 30 % are early stage patients (stage I and II). For this group of patients, radical surgery with mediastinal lymph node dissection has been the mainstay of therapy with a reasonable curative option. However, 5-year survival rates for patients with pathologically staged IA-IIB disease are ranging from 67% to 39% [2]. Following surgery, distant recurrence is the most common form of relapse and eventual cause of death. Assuming that these recurrences
Neo-adjuvant chemotherapy with cisplatin and short infusional 5-FU in advanced head and neck malignancies  [cached]
Aich Ranen Kanti,Deb Asit Ranjan,Ray Amitabh
Journal of Cancer Research and Therapeutics , 2005,
Abstract: Background: Combination of radical surgery and radiotherapy is the standard management of head and neck malignancies. But due to considerable morbidity of surgery and associated cosmetic and functional deficiencies, often aggravated by adjuvant radiotherapy, many patients prefer only radiotherapy with its′ decreased chance of survival. Proper surgical facilities are also not accessible to most of our patients. Neo-adjuvant chemotherapy and loco-regional management by surgery and / or radiotherapy have emerged as a viable alternative. Aims: The purpose of this study is to find out the survival outcome as well as toxicity profile of Neo-adjuvant chemotherapy with cisplatin and short infusional (3 hours) 5-FU followed by radiotherapy in advanced head and neck malignancies. Materials and Methods: From June 2002 to December 2003, seventy four patients with advanced head and neck malignancies were planned to be treated with Cisplatin (50 mg / sq. meter) on Days 1 and 2 and 5 - FU (600 mg / sq. meter) on Days 1, 2 and 3 by 3 hour infusion on Day care basis. On completion of four cycles of chemotherapy at 21 days interval, all patients were destined to receive 6000 cGy of radiotherapy to the loco - regional site. Results: At one year follow up on completion of therapy, 57% patients were alive and 31% patients were disease free. These 31% patients enjoyed a good quality of life in terms of cosmetic and functional deficits. Toxicities were moderate and easily manageable. Conclusion: The study indicated that neo-adjuvant chemotherapy with Cisplatin and short infusional 5 - FU may be delivered on day care basis and results are comparable with Cisplatin and 96 hours continuous infusional 5 - FU. Thus avoiding the continuous infusional 5 - FU, 7 to 10 days in-patient hospitalization during each cycle may be avoided which is a constrain in developing countries like us.
Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?
Manoharan, Murugesan;Reyes, Martha A.;Rakesh, Singal;Kava, Bruce R.;Nieder, Alan M.;Soloway, Mark S.;
International braz j urol , 2006, DOI: 10.1590/S1677-55382006000500005
Abstract: objective: we examined our database of patients undergoing radical cystectomy (rc) with orthotopic neobladder (nb) to determine whether adjuvant chemotherapy in this group is safe. materials and methods: we performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. relevant clinical and therapeutic data were entered into a database. high-risk bladder cancer patients who underwent nb were identified. they were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. the incidence of complications between the 2 groups was analyzed and compared. results: over the 12-year period, 136 patients underwent rc and nb construction for bladder cancer. of these, 83 patients were at high risk for recurrence. nineteen patients received adjuvant chemotherapy and 64 did not. the complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. there were no perioperative or treatment related death. there were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. there was a statistical difference between these two groups with regard to the incidence of complications. however, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. conclusions: adjuvant chemotherapy is a safe treatment for patients undergoing rc and nb substitution. hence, the option of orthotopic nb should not be denied in selected bladder cancer patients with high risk for recurrent disease.
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