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Biomedical subjects

Nabil K Bissada

Publications and source records attributed to Nabil K Bissada.

At least 19 recordsLinked to original sources
PubMed2007

Multiple/bilateral renal tumors in patients with Birt-Hogg-Dubé syndrome.

OBJECTIVE: To describe our findings in four patients with multiple/bilateral renal cell carcinoma (RCC) and Birt-Hogg-Dubé (BHD) syndrome. PATIENTS AND METHODS: A series of four patients with BHD syndrome and RCC is analyzed. Patient charts were reviewed for age, sex, presentation, various clinical manifestations, imaging, management and outcome. RESULTS: Patients included 2 males and 2 females. Age ranged from 40 to 65 years (mean 56 years). The interval between the diagnosis of skin lesions characteristic of the disease and the development of renal tumors ranged between 1 and 35 years. Three of the patients had bilateral renal tumors (2 synchronous and one metachronous), one patient had multiple renal tumors in one kidney. In one patient the renal mass was diagnosed with a screening CT scan of the abdomen after the diagnosis of BHD syndrome. One patient had associated spontaneous pneumothorax and thyroid tumor. Only one of the 4 patients had prior family history of BHD syndrome. Renal tumors were clear cell type in 3 patients, and chromophobe tumor in one. Tumor size ranged from 2 to 9 cm. CONCLUSION: BHD syndrome is associated with multiple diseases and tumors. We describe four patients with BHD syndrome with multiple or bilateral RCC. Two of the patients were asymptomatic. A high index of suspicion should be present in patients who present with the characteristic skin lesions of BHD syndrome and screening for the presence of renal tumors should be done in those patients. Long term follow up is necessary after treating renal tumors in these patients.

Adult↗
PubMed2006

Outcome of penile cancer in circumcised men.

PURPOSE: We previously reported on a group of patients with post-circumcision carcinoma of the penis. We now study the long-term outcome of these patients. MATERIALS AND METHODS: We retrospectively reviewed the available charts of 22 patients presenting between October 1979 and May 2000. RESULTS: Of 22 patients 18 underwent ritual circumcision with extensive scar development. Median age at diagnosis was 62.4 years. The penile lesion was dorsal and proximally located in 15 patients. Median delay before diagnosis was 12 months. Clinically 14 patients had stage T1-T2 disease, with 13 having no lymph node involvement and none with distant metastasis, 8 patients had stage T3-T4 disease. A total of 15 patients were treated surgically with total penectomy (10) or conservative local excision (5), inguinal lymph node dissection (9) and subsequent penile reconstruction (3). Pathological staging in 15 patients revealed 10 patients with stage T1 and in 8 patients with lymph node dissection none had nodal metastasis. Histopathological classification was 20 squamous cell carcinoma, 1 sarcoma and 1 verrucous carcinoma. Six patients refused surgery and 1 was referred for palliation. Median followup was 14.5 months and median survival was 14.5 months. The 3-year survival was 42% for stage T1-T2 and 13% for T3-T4 (p = 0.0052). Median survival for the surgical group was 34 months whereas for nonsurgical group was 3 months (p = 0.0016). Recurrence-free survival in the surgical group was 50%. CONCLUSIONS: Penile carcinoma in circumcised men is a distinct disease commonly following nonclassic vigorous circumcision. Delayed diagnosis and deferring surgical treatment are associated with increased mortality.

Adult↗
PubMed2006

Evaluation of survivin reverse transcriptase-polymerase chain reaction for noninvasive detection of bladder cancer.

PURPOSE: Survivin, a member of the inhibitor of apoptosis gene family, is expressed in most common cancers. We investigated the expression pattern of survivin in the tumors of patients with bladder cancer and assessed the diagnostic potential of RT-PCR detection of survivin mRNA in urine. MATERIALS AND METHODS: RT-PCR was used to analyze mRNA expression of survivin in 161 cases of bladder cancer, including TCC in 97, SCC in 53 and adenocarcinoma in 11, and their matched nontumor tissues. Urine specimens (50 ml) were collected from 84 patients in whom bladder cancer was documented by transurethral resection or biopsy, 41 with nonbladder cancer urological diseases and 42 healthy volunteers. Total RNA was extracted from urine sediments and RT-PCR was performed for survivin. RESULTS: Survivin expression was detected in all bladder cancer tissues. In contrast, survivin was not detectable in normal urothelium specimens. Urinary survivin was detected in urine samples from 51 of 53 patients with TCC, 22 of 25 with SCC and 6 of 6 with adenocarcinoma. Overall sensitivity was 94%. Survivin mRNA was not detected in any healthy volunteers. Positive results were obtained in 2 patients with renal cell carcinoma, 1 with hematuria and 1 with a contracted bladder but in none with other urological diseases. Overall specificity was 95%. CONCLUSIONS: Survivin mRNA detection in urine sediment using RT-PCR shows high sensitivity and specificity for bladder cancer. It may prove useful for the routine screening and monitoring of patients.

Gene Expression Regulation, Neoplastic↗
PubMed2006

Subtotal urethral duplication.

Urethral duplication is considered a rare congenital anomaly. The exact embryology is still controversial. A patient with subtotal urethral duplication is presented and the technique utilized to excise the anomalous structure is detailed.

Humans↗
PubMed2005

Prognostic and functional significance of thromboxane synthase gene overexpression in invasive bladder cancer.

Thromboxane synthase (TXAS) is one of the enzymes downstream from cyclooxygenase-2 and catalyzes the synthesis of thromboxane A(2) (TXA(2)). TXAS was among the genes we identified based on its overexpression in invasive bladder tumors. TXAS is overexpressed in common forms of bladder tumors: 69 of 97 (71.1%) transitional cell carcinoma (TCC), 38 of 53 (71.6%) squamous cell carcinoma, and 5 of 11 (45.5%) adenocarcinoma relative to nontumor tissue. Overall, 112 of 161 (69.5%) invasive tumors exhibited elevated expression. Significantly, patients with tumors having >4-fold levels of TXAS expression showed significant statistical evidence of lower overall survival expressed by the estimated hazard ratio of 2.74 with P = 0.009 in Cox's regression analysis. TXAS mRNA expression was found to be an independent prognostic marker for patients with bladder cancer. Treatment of bladder cancer cell lines (T24 and TCC-SUP) with TXAS inhibitors and TXA(2) (TP) receptor antagonists reduced cell growth, migration, and invasion, whereas TP agonists stimulated cell migration and invasion. The positive correlation between elevated TXAS expression and shorter patient survival supports a potential role for TXAS-regulated pathways in tumor invasion and metastases and suggests that modulation of the TXAS pathway may offer a novel therapeutic approach.

Adenocarcinoma↗
PubMed2005

Complete response to adriamycin and ifosfamide in a patient with sarcomatoid renal cell carcinoma.

Sarcomatoid renal cell carcinoma (SRCC) is a heterogeneous disease with generally unreliable response to various therapies in clinical studies. We illustrate a case report in which a woman with metastatic SRCC had a complete and durable response to adriamycin and ifosfamide chemotherapy. We find this to be incongruous with expectations from some recently published data. It underscores the fact that the biology of SRCC needs to be studied in more detail for further subcataloging of the disease into diverse prognostic categories.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Secondary hormonal manipulations in the management of advanced prostate cancer.

Prostate cancer is a heterogeneous disease and clinical outcomes vary considerably after failure of primary androgen ablation. With the development of new therapeutics the management of patients with androgen independent prostate cancer has changed considerably over the last few years. Multiple secondary hormonal manipulations are available and may lead to prolonged periods of clinical response. These maneuvers include the use of oral antiandrogens, antiandrogen withdrawal, ketoconazole, aminoglutethimide, corticosteroids and use of estrogenic compounds. This article reviews the clinical activity of these agents in management of patients with advanced prostate cancer.

Androgens↗
PubMed2005

Evolving management of pediatric urinary tract infection.

UTI is a common problem in the pediatric population with significant long-term morbidity. Fecal-urinary migration is the most common route of infection, and E. coli is the most common organism. Methods of urine collection and interpretation of urinalysis must be considered when guiding therapy, and treatment is age and severity specific. VUR is an extremely common finding in febrile urinary tract infections. The algorithm of treatment is evolving with the advent of highly successful, minimally invasive therapy.

Anti-Bacterial Agents↗
PubMed2004

Urinary conduit formation using retubularized bowel from continent urinary diversion or intestinal augmentations: I. A multi-institutional experience.

OBJECTIVES: To present our multi-institutional experience with retubularized bowel conduits. Some patients with augmentation cystoplasty, augmented rectal bladder, or continent urinary reservoirs require conversion to an ileal conduit for various reasons. This is generally accomplished by construction of a de novo ileal conduit. We retubularized the bowel segment used in the augmented bladder or the urinary reservoir to form the intestinal urinary conduit. METHODS: A total of 29 patients (mean age 42 years) underwent conduit formation using the augmentation patch of enterocystoplasty, the segment of cutaneous urinary diversion reservoir or orthotopic neobladder, or the augmentation patch of an augmented rectal bladder. Patients were followed up with history, physical examination, laboratory tests, and imaging studies. RESULTS: The follow-up ranged from 12 to 130 months (mean 42). One patient developed small bowel obstruction requiring laparotomy with lysis of adhesions. None of the other patients had bowel complications. Two patients developed ureteral obstruction with hydronephrosis. One had pyocystitis requiring simple cystectomy. One patient was lost to follow-up. CONCLUSIONS: Retubularization of previously used bowel segments to construct a urinary conduit is feasible and has several advantages. It is possible to perform this procedure after several types of reconstructive procedures in which bowel was incorporated into the urinary tract.

Adult↗
PubMed2004

Experience with coapted gastric tube outlet and composite gastrointestinal reservoir for continent cutaneous urinary diversion.

PURPOSE: Established techniques for urinary diversion are not ideal for certain patients such as those with extensive pelvic irradiation, metabolic acidosis, short bowel syndrome or renal insufficiency. In a multi-institutional study a gastrointestinal reservoir was previously found to provide metabolic balance in such patients. We used a coapted gastric tube as the continent outlet in patients undergoing gastrointestinal urinary diversion. We evaluate the long-term functional results of the gastric tube to provide continence and report our long-term followup results. MATERIALS AND METHODS: A composite reservoir was constructed from gastric and transverse colon or ileal segments. In addition, a gastric strip, in continuity with the gastric segment of the composite reservoir, was tubularized and coapted to provide the continence mechanism. RESULTS: A total of 19 patients with a gastrointestinal reservoir and coapted gastric tube outlet were followed for 24 to 101 months, of whom 18 are continent day and night on intermittent catheterization every 3 to 8 hours. Four of 34 ureters (12.5%) became obstructed. One patient had significant preoperative renal insufficiency, which progressed to end stage renal disease. Another patient had slow progression of renal insufficiency. In the remaining 17 patients mean serum creatinine did not change significantly while serum chloride and bicarbonate improved or remained normal. CONCLUSIONS: A coapted gastric tube functions well as the continence mechanism in patients with a gastrointestinal urinary reservoir. We also confirm the metabolic advantages of a composite gastrointestinal urinary reservoir. Gastrointestinal cutaneous urinary diversion can be an alternative to incontinent diversion in select patients who are not suitable for other forms of diversion.

Adult↗
PubMed2004

Urinary conduit formation using a retubularized bowel from continent urinary diversion or intestinal augmentations: ii. Does it have a role in patients with interstitial cystitis?

PURPOSE: Interstitial cystitis (IC) may require surgical treatment in a minority of patients in whom conservative treatment failed. This treatment includes enterocystoplasty (ECP), or continent or incontinent urinary diversion with or without cystourethrectomy. Patients with IC who underwent ECP or continent urinary diversion (CUD) occasionally have recurrent pain in the augmented bladder or continent pouch. In these patients a new ileal conduit is frequently constructed. Using part of the continent urinary diversion or bladder augmentation patch to make the ileal conduit has been reported. However, there may be some concern with performing the procedure in patients with IC because of the theoretical risk of continued pain in the converted ileal segment. We evaluated the role of conduit formation using retubularized bowel from ECP or CUD in patients with IC. MATERIALS AND METHODS: A total of 11 patients with a mean age of 45 years underwent conduit formation using the augmentation patch of ECP or part of the continent urinary reservoir. Patients were followed by history, physical examination, laboratory tests and urography. RESULTS: Followup was 20 to 80 months. One patient continued to have pelvic pain. None of the patients had residual pain in the conduit. One patient had intermittent pain in the conduit 32 months after conversion. Two patients had ureteral obstruction requiring ureteral reimplantation revision. No patient complained of new gastrointestinal problems. CONCLUSIONS: Retubularization of a previously used bowel segment from ECP or CUD to form a urinary conduit seems to be an acceptable alternative in patients with IC.

Cystitis, Interstitial↗
PubMed2004

Transitional cell carcinoma of the bladder producing parathyroid hormone-related protein (PTHrP).

Hypercalcemia associated with transitional cell carcinoma (TCC) is rarely encountered. We report a case of TCC of bladder with documented production of parathyroid hormone related protein (PTHrP). Our patient had a rapidly progressive course and died 2 months after radical cystectomy. Literature suggests that these patients present with advanced stage and carry a poor prognosis. The histopathologic features, treatment and prognosis associated with this rare paraneoplastic syndrome are reviewed.

Carcinoma, Transitional Cell↗
PubMed2004

Isolated late recurrence of renal cell carcinoma in the inferior vena cava.

The occurrence of an isolated late recurrence of renal cell carcinoma within the inferior vena cava (IVC) is a rare event. We present a case of a 55-year-old patient with recurrence in the IVC more than 3 years following her initial nephrectomy. The asymptomatic presentation of this patient with recurrent disease emphasizes the importance of close, long-term surveillance.

Carcinoma, Renal Cell↗
PubMed2003

Long-term experience with management of renal cell carcinoma involving the inferior vena cava.

OBJECTIVES: To evaluate the long-term outcome and prognosis and influence of patient and tumor characteristics and therapeutic interventions on patients with renal cell carcinoma (RCC) extending to the inferior vena cava (IVC). METHODS: The data of 75 patients (51 men and 24 women; age range 27 to 92 years) with RCC and involvement of the IVC, including 49 without and 26 with metastatic disease, treated between July 1973 and December 1998 were reviewed. The clinical presentation, laboratory and imaging investigations, extent and level of caval involvement, operative details, and estimated blood loss, as well as the postoperative course, morbidity, and actuarial and disease-free survival were analyzed. RESULTS: Seventy-five patients between 27 and 92 years old with RCC involving the IVC were studied. Of the 54 operative patients, 48 had no metastasis and 6 had metastatic disease; 32 had IVC tumor extension to the infrahepatic or low retrohepatic IVC, 7 had high intrahepatic IVC extension, and 15 had right atrial extension. In 7 patients, tumor had invaded the IVC wall. Partial IVC wall excision was done in 4 patients and resection of a complete segment of the IVC in 3 patients. Tube graft to replace a segment of the IVC was used in 2 patients. Patients with intracardiac extension were initially treated with cardiopulmonary bypass. Subsequently, profound hypothermia and circulatory arrest were also used. Three patients died in the postoperative period: two with and one without metastatic disease. The follow-up period ranged between 25 and 144 months. Of the 48 patients without evidence of metastasis at surgery, the perioperative mortality rate was 2%. Twenty-two patients (47%) were alive without evidence of metastases, 4% developed solitary metastasis, and 36% eventually developed multiple metastases. CONCLUSIONS: Our long-term experience confirms that of other investigators that nonmetastatic RCC with extension into the IVC is a potentially curable condition provided complete removal can be achieved. The level of extension of the tumor thrombus dictates the surgical techniques used for successful removal of the tumor thrombus. The treatment of patients with caval involvement and metastatic disease at presentation needs to be carefully individualized. Those with extensive multiorgan metastases continued to do poorly irrespective of the therapeutic approach chosen.

Adult↗
PubMed2003

Multi-institutional long-term experience with conservative surgery for invasive penile carcinoma.

PURPOSE: Invasive squamous cell carcinoma of the penis occurs on the glans, prepuce, glans and prepuce, coronal sulcus and shaft. Penile squamous cell carcinoma subsequently invades local structures, corpora cavernosa and the urethra, and metastasizes to the inguinal lymph nodes. Invasive squamous cell carcinoma of the penis usually requires total or partial penectomy. We studied the effect of primary tumor resections tailored to the anatomical extent of the cancer with preservation of uninvolved structures in select patients with invasive penile squamous cell carcinoma. MATERIALS AND METHODS: A total of 30 patients between 39 and 82 years old were treated with unconventional conservative surgical excision of the primary penile lesion. More than 130 patients were excluded from the study because they were treated with partial or total penectomy, Mohs' surgery or more extensive surgery. The 30 patients underwent preoperative biopsy with careful mapping of the extent of the disease. Patient age, tumor extent and grade, operative details, outcome and length of followup were analyzed. RESULTS: Tumor size ranged from 1.5 to 8 cm. in diameter. Tumors were well differentiated in 19 patients, moderately differentiated in 5 and poorly differentiated in 6. A total of 17 patients underwent ilioinguinal lymphadenectomy, 12 of whom had pathologically positive lymph nodes. Inguinal radiation was used in 2 patients. Chemotherapy was given to 7 patients with extensive inguinal lymphadenopathy and to 2 of 5 with pathologically positive lymph nodes. Followup ranged from 12 to 360 months. A total of 21 patients had no evidence of disease at last followup. Tumor resection with no sacrifice of function was performed in 2 patients in whom 3 small recurrences developed. One patient with numerous tumors had 2 small recurrences, which were completely excised with no further recurrence. Of the 7 patients with advanced lymphadenopathy 5 and of 5 patients with pathologically positive lymph nodes at presentation 1 died of the cancer but had no local recurrence in the penis. CONCLUSIONS: In a minority of patients with anatomically suitable penile cancer conservative surgical techniques are safe and provide equal tumor control compared to conventional resections. The anatomical situation and tumor characteristics should dictate the choice of treatment for the primary penile lesion. Inguinal lymph nodes should be managed by appropriately established guidelines but should not influence the extent of primary penile lesion resection.

Adult↗
PubMed2003

Alterations in PMS2, MSH2 and MLH1 expression in human prostate cancer.

DNA mismatch repair (MMR) is involved in the post-replication correction of errors due to misincorporated nucleotides or DNA slippage during DNA synthesis. We previously reported the reduction or loss of MMR protein expression in human prostate cancer cell lines and some primary tumors. In the present report, we further demonstrate the involvement of defects of MMR in the pathogenesis of prostate cancer. Immunohistochemical analysis of 39 formalin-fixed, paraffin-embedded human prostate tumors, showed reduction or absence of MMR protein expression (MLH1, MSH2, PMS2) in the epithelium of prostate tumor foci compared to normal adjacent prostate tissue. The reduction or absence of the PMS2 and MSH2 (but not MLH1) protein was correlated to the differentiation of the tumor. Poorly differentiated tumors showed greater loss of these two proteins than the well differentiated tumors (P<0.05). We previously reported that microsatellite instability was detectable by a beta-galactosidase restoration mutation assay in the prostate cancer cell lines DU145, PC3, LNCaP, p67SV40T, M2182, and M12. In this study, we detected the insertion or deletion of one nucleotide in the mononucleotide repeats located within the coding regions of BAX gene in DU145, and TGFbetaRII in M12 cells. In addition, we used an in vitro model of defective MMR to demonstrate that microsatellite instability can be induced in an otherwise stable cancer cell line by transfection with a dominant negative fragment of PMS2. These results suggest that defects in MMR may result in MSI in the secondary genes in prostate cancer. From these results, we conclude that loss of MMR function can produce MSI and target some secondary genes containing microsatellites in their coding regions. These series of events may play important roles in the development of human prostate cancer.

Adaptor Proteins, Signal Transducing↗