Differential distribution of sequence variations in HPV-16 E6.

OBJECTIVE: The E6 regions of the oncogenic human papillomaviruses (HPVs) are important in carcinogenesis and immune recognition. We examined the E6 DNA sequence from HPV-16-associated cervical cancers to determine the frequency and degree of variation from the consensus sequence in selected populations. METHODS: Samples positive for HPV-16 were analyzed using polymerase chain reaction followed by automated DNA sequencing: 62 from U.S. women, 20 each from Italian and Indian women, and 21 from Thai women. RESULTS: Of 151 codons, 18 contained 24 base substitutions, reflecting the overall conserved nature of this region. The HPV-16 E6 region from U. S. women showed considerably more sequence variation than that from European and Asian women. Five patterns common to U.S. and European and Asian samples accounted for 78% of all tumor-associated viruses. The E6 regions known to be involved in p53 binding and degradation are involved with a surprising degree of sequence variation, whereas the carboxy end of the molecule is highly conserved. CONCLUSIONS: The area of greatest sequence variation includes a proposed human leukocyte antigen interaction site. A novel large deletion in one sample results in loss of all functional regions of E6. These findings were analyzed for possible significance with regard to immune selection and functional importance of the carboxy end of the E6 protein.

Mobile radiography CQI: an inter-national study.

Mobile or bedside radiography has been and is a staple diagnostic and follow-up tool used readily by the many medical disciplines, such as cardiology, surgery, orthopedics, pediatrics, neonatology, etc. Ironically, in the past a student or the least qualified technologist was sent to perform the bedside exam. Moreover, it was almost expected that poor but acceptable film quality would result or that repeat films were almost always to be taken. Inefficiency with respect to quality of exam, the time the exam takes, or film repeats can be costly. The price of inefficiency is the cost involved in doing things incorrectly or not in the most efficient manner, i.e., incurring inefficiencies instead of operating in an ideal manner. The purpose of this study was to compare the total cost of inefficiently organized, scheduled and performed mobile radiography at three large teaching hospitals in various locations and of diverse patient loads, as a means of determining how best to increase utilization and performance. The study was performed at the 489-bed New England Deaconess Hospital (NEDH), the 644-bed Sentara Norfolk General Hospital (SNGH), and the 1500-bed Rheinische Westfalische Technische Hochschule (RWTH) in Aachen, Germany. Similar standardized study methods were utilized at all three institutions where extended observation of mobile utilization, areas of inefficiency, time wasted per episode and number of episodes per time period were determined. Data were loggedin at three standardized time periods, summated, and then multiplied by technologist hourly pay rate. This sum was extrapolated over 52 weeks to give the total annual cost of inefficiently organized mobile radiography. For NEDH the cost of total inefficiency was $75,453, for SNGH $49,586, while for RWTH it was $9,519. Eighteen areas of inefficiency were identified and grouped, such as lack of spatial cohesiveness and lack of communication leading to film duplication, etc. While inefficiencies in the delivery of hospital based health care are well known, this study attempts to quantify and determine a dollar value for each process found as inefficient. Key inefficiencies were found to be common at large hospitals no matter whether in the United States or Europe. These impairments are responsible for a disproportionate share of overall inefficiency, and their elimination (achievable by simple solutions) would result in drastic cost reductions (ranging from 40-75% at the institutions studied). Thus this study is important in view of spiralling costs, as it is a key component of total quality management (TQM) in radiology and a continuous quality improvement (CQI) tool for mobile radiology specifically.

Adenocarcinoma of bladder.

Forty-eight patients with adenocarcinoma (21 urachal and 27 non-urachal) of the bladder were treated at the Tata Memorial Hospital between 1976 and 1992. The study group consisted of 32 men and 16 women. The urachal tumours were more common in younger patients (mean age: 49 years) than were non-urachal tumours (mean age: 58 years). The overall 5-year survival in this series was 37%. Stage and grade were powerful predictors of outcome. Patients with non-urachal tumours showed an overall survival rate of 29.9% compared with 45.7% in patients with urachal tumours (P= 0.14). Radical cystectomy was the most common treatment modality in patients with non-urachal tumours and yielded an overall 5-year survival of 35%. Patients with urachal tumours were treated with either partial cystectomy or radical cystectomy. The 5-year survival following partial cystectomy was 56.3% compared with 25.9% following a radical cystectomy and the difference between the two was not statistically significant (P = 0.76).

The impact of cisplat based chemotherapy on advanced ovarian cancer.

Cisplatinum based chemotherapy has become the standard treatment for ovarian cancers due to its proved superiority over non-cisplat based regimes. However, the therapeutic impact of cisplat based regimes compared to cheaper non-cisplatinum based regimes is questionable when multiple variables such as residual disease, histologic type, grade are introduced. This report is a study of 110 Stage III ovarian cancer patients from 1985-89, with cisplat (n = 69) and non cisplat (n = 41) based chemotherapy. The results of both regimes with reference to the multiple variable factors are presented. We conclude that cisplat based regimes appear to be superior to non-cisplat based regimes except probably in poorly differentiated ovarian tumors where the results were similar with either regimen.

Partial cystectomy for invasive bladder cancer.

Thirty two patients--23 males and 9 females with a mean age of 52.5 years--underwent planned partial cystectomy for histologically proved muscle invasive bladder cancer. Twenty patients had transitional cell carcinoma and 12 had adenocarcinoma of the bladder. One patient had well-differentiated, 18 had moderately differentiated, and 13 had poorly differentiated tumours. The tumour size was < 2 cm in 7 patients, 2-4 cm in 19 patients, and > 4 cm in 6 patients. Patients with single primary muscle invasive tumours situated in the upper half of the bladder were considered eligible for partial cystectomy. The presence of multicentric urothelial disease, of dysplasia, or carcinoma-in-situ in bladder mucosa away from the tumour on multiple random punch biopsies was considered contraindications to partial cystectomy. All patients underwent partial cystectomy with bilateral pelvic lymphadenectomy. The tumour-free margins of resection were confirmed by intraoperative frozen section examination. The bladder was closed primarily in all patients, although three patients required re-implantation of the ureter. No patient received adjuvant radiation or chemotherapy. Five patients had pathological stage B1 (T2), 18 had B2 (T3A), and 9 had C (T3B) disease. No patient had metastatic pelvic lymph nodes. There was one postoperative death due to unrelated medical cause. Five patients had minor complications that resolved with conservative measures. All patients had adequate bladder capacity of > 250 cc at 6 months after surgery, and none had symptoms attributable to reduced bladder capacity. The overall actuarial survival was 80.1% at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Superficial bladder cancer. A 10 year experience.

A total of 236 patients - 198 males and 38 females with superficial bladder cancer (stage A(TaT1)) were treated with transurethral resection of the tumours. Intravesical chemotherapy (84 patients) or immunotherapy (27 patients) was added in those patients considered to be at high risk of developing local recurrences or stage progression. The five and ten years survival in the single tumour group (117 patients) were 86 percent and 72.9 percent as compared to 72.5 percent and 70.7 percent respectively in the multiple tumour group (119 patients). The five and ten year survival rates for grade I tumours were 88.3 percent and 86 percent respectively, for grade II tumours 80.8 percent and 64 percent and for grade III tumours 56.9 percent and 46 percent respectively. The impact of tumour grade on survival was found to be independent of the number of tumours. The response rates to intravesical thiotepa was 54.9 percent mitomycin 60 percent and with BCG 71.5 percent. All the three reduced the local recurrence rates and increase the mean interval to recurrence but the stage progression rate was significantly lowered only with intravesical BCG. In our study, we have used the Danish strain of BCG available to us and have found it to yield response rates comparable to other centres using Tice or Pasteur strains.

Renal cell carcinoma extending to the renal vein and inferior vena cava: results of surgical treatment and prognostic factors.

Forty-seven patients with renal cell carcinoma with tumor thrombus extension to the renal vein or inferior vena cava (IVC) were treated surgically over a 10-year period. There were 41 males and 6 females with a mean age of 45.7 years. Thirty-three patients had right-sided and 14 had left-sided tumors. Patients with renal vein or infrahepatic IVC thrombus were treated with radical nephrectomy with tumor thrombus excision after achieving conventional vascular control over the IVC and the opposite renal vein. Four patients with retrohepatic IVC thrombus were treated with venacavotomy and thrombectomy after achieving vascular control above the thrombus but below the hepatic veins while two other patients with retrohepatic and one with suprahepatic thrombus required a bifemoroatrial partial venous bypass prior to tumor thrombectomy. There was one postoperative death due to pulmonary embolism. The actuarial 5-year survival for all patients with venous extension was 50% and the median survival was 4.35 years. Perinephric spread and lymph node metastases were significant prognostic factors affecting survival. This suggests that it is the locoregional spread of renal cell carcinoma rather than the level of the thrombus which governs the prognosis of patients with tumor thrombus extension to the renal vein or IVC.

Is bladder conservation feasible? An Indian experience.

With the introduction of chemotherapy in the treatment of muscle invasive bladder cancers, endeavors at improving disease-free survival/overall survival are ongoing. As high objective response rates were seen with MVAC/CMV regimens (M-methotrexate, V-vinblastine, A-adriamycin, C-cisplatin) organ conservation is being attempted. A phase II protocol was designed using MVAC as the initial therapy. Based on the response to two cycles all patients were evaluated and where possible the bladder was preserved. Twenty-nine patients completed the protocol and had a median follow-up of 24 months. Complete response (CR) was noted in 7/29 (24.1%) of patients, while 11/29 (38%) had partial response (PR) and 11/29 (38%) showed no response (NR). Bladder conservation was possible in 15/29 (51.7%) patients initially with the use of radiation therapy after the initial chemotherapy. Ten of these patients are presently alive with their bladders intact. Three patients died of distant disease, two with normal bladders and one with local relapse. Two of the other patients required salvage cystectomy and are alive and disease-free. All complete responders 7/7 (100%) and 5/11 (45%) partial responders could have their bladders conserved. Three of 11 partial responders who refused radiotherapy and 11/11 non-responders underwent radical cystectomy after initial chemotherapy. Subset analysis indicates that low stage and grade tumours had the highest likelihood of bladder preservation, and there was no difference in overall survival in the groups according to response criteria. As our study consists of a small number of selected patients, it would be improper to draw firm conclusions. However, it seems that initial chemotherapy selects out a subset of patients with a good prognosis and the chance for bladder conservation.

Do we need to do comprehensive surgical staging in all cases of clinical early ovarian cancer?

Meticulous staging of ovarian cancer has so far been a prerequisite for treatment planning. However, more than 80% of patients operated by non-oncologists all over the world do not under go a complete staging. Recently there have been reports questioning the need for extensive staging from the point of cervical benefit. We have analysed our data of 64 stage ovarian cancer patients to see if clinical staging was adequate or relaparotomy with restaging is necessary. We conclude that though pathological staging is important for proper reporting of results and evaluation of treatment modalities, in the existing circumstances, a judicious use of clinical methods and taking available pathological factors into account, we can still produce comparable results with restricted use of relaparotomy.

Intravesical bacillus Calmette-Guerin for superficial bladder cancer: experience with Danish 1331 strain.

A total of 95 patients with stage Ta/T1 superficial bladder cancer was eligible for intravesical bacillus Calmette-Guerin (BCG) immunoprophylaxis according to the standard high risk criteria for tumor recurrence and progression. Of these patients 50 agreed to undergo treatment while the remaining 45 refused any intravesical therapy and served as concurrent nonrandomized controls. The patient and tumor characteristics in the 2 groups of patients were identical. All patients underwent complete transurethral resection of the bladder tumor. Therapy consisted of 120 mg. weekly instillations of BCG (Danish 1331 strain) for 6 weeks. Among the 50 patients 33 received BCG initially while 17 received it after failure of intravesical chemotherapy. Responses were evaluated according to standard criteria. Recurrence was noted in 24 patients (48%) in the BCG group compared to 38 (84.4%) in the control group. The recurrence rates per year and per 100 patient-months were significantly reduced in the BCG arm compared to the control arm. The mean interval to first recurrence and the mean recurrence interval were significantly increased in the BCG arm compared to the control arm. The relative risk of recurrence in the BCG group was 0.62 versus 1.63 in the control group. Subgroup analysis showed significant benefit of BCG for patients with single as well as multiple, stages Ta and T1, and grades II and III tumors. Comparison with pretreatment controls in the BCG group revealed a significant reduction in the recurrence rate in those patients after treatment with BCG, which was not seen in the control group. The benefit of BCG was seen in those who received BCG initially as well as in those who received it after failure of intravesical chemotherapy. Multivariate analysis of prognostic factors showed that this benefit in the BCG group was related only to the treatment, while other prognostic parameters, such as tumor stage, grade, number and so forth were not independent prognostic variables. The rate of progression to muscle invasion was not significantly different in the 2 treatment groups. The relapse-free survival in the BCG group was 35.4% at 60 months compared to 11.2% in the control group (p < 0.001). The side effects of BCG therapy were mild, brief and easily controlled with conservative measures.

Bilateral renal angiomyolipoma.

Bilateral renal angiomyolipoma is a rare entity, usually associated with tuberous sclerosis. Five cases of bilateral renal angiomyolipoma, all females, with a mean age of 34.6 years, are reported. All patients had symptoms attributable to lesions only on one side, with flank pain and mass the commonest symptoms encountered. Only one case had clinical evidence of stigmata of tuberous sclerosis. The mean size of the lesions on the symptomatic side was 17 cm, while that on the asymptomatic side was 2 cm. Three patients were diagnosed correctly as having angiomyolipomas preoperatively with the use of ultrasonography and computed tomography (CT); two of these were treated with total nephrectomy and the third with partial nephrectomy. The other two cases were seen before the availability of CT and were only diagnosed intraoperatively. Both patients were treated with total nephrectomy. The lesions on the asymptomatic side were kept on close surveillance. Two patients developed an increase in the size of the lesions in the contralateral kidney 1 year and 3 1/2 years after the first surgery. Both patients were treated with partial nephrectomy. All patients are alive at 3-14 years (mean 6.6 years) after operation.

Prophylactic bilateral groin node dissection versus prophylactic radiotherapy and surveillance in patients with N0 and N1-2A carcinoma of the penis.

Sixty-four patients with carcinoma of the penis and clinically negative nodes (N0, N1-2a) had either bilateral groin node dissection (BGND), radiotherapy (RT) to the groin or surveillance in a prospective nonrandomized study on a sequential basis. The tumors were classified according to TNM staging and showed T1, T2 and T3 lesions in 24, 20, 20 patients, respectively, while their node status was N0 in 37 and N1-2A in 27 patients. The tumor grade was G1, G2 and G3 in 10, 30 and 24 patients, respectively. Of these patients 27 had BGND, 18 RT and 19 surveillance. The BGND group showed positive nodes in 4 (14%) patients: 1 with T2 and 3 with T3, and 2 each with N0 and N1-2A status. The 5-year survival was analyzed in terms of primary (T), node status (N), and grade (G) of the tumor and showed 79, 75 and 50% in G1, G2 and G3 tumors, respectively. The overall 5-year survival rate was 74, 66 and 63%, in the BGND, RT and surveillance groups, respectively. Furthermore, analysis of the survival rates in relation to the T and N status in the 3 treatment groups showed identical survival rates for the T category, but for the N category N0 patients had a significantly higher survival rate in the BGND group when compared with the others. In the follow-up relapses occurred in 10 (15%) patients: 7, 2 and 1 in the surveillance, RT and BGND groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor cytotoxicity and production of interleukin-1 and tumor necrosis factor from blood monocytes of cervical carcinoma patients.

To assess the functional integrity of monocytes in patients with cervical carcinoma, cytotoxic potential of peripheral blood monocytes and their ability to secrete interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) after activation with different stimulating agents were studied. Comparable levels of monocyte-mediated cytotoxicity were observed in healthy donors and patients. The production of IL-1 and TNF-alpha by monocytes of healthy donors and patients was similar indicating no defect in monocyte functions in these patients.

Growing teratoma syndrome.

Growing teratoma syndrome is the term applied to enlarging retroperitoneal or other metastatic masses containing mature teratoma during chemotherapy for nonseminomatous germ cell tumors. Four cases of the growing teratoma syndrome are presented, the metastatic masses being in the retroperitoneal in all the cases. All these patients had enlarging retroperitoneal masses in the presence of normal serum biomarkers following chemotherapy for nonseminomatous tumors. Surgical excision was carried out in all four patients, with disease free survivals ranging from 6 to 24 months after surgery.

Urethral recurrences following radical cystectomy for invasive transitional cell carcinoma of the bladder.

A total of 177 patients with invasive transitional cell carcinoma of the bladder underwent radical cystoprostatectomy, of whom 13 underwent simultaneous urethrectomy. The remaining 164 patients were followed up regularly with urethroscopy and urethral cytology. Fifteen patients developed urethral recurrences, 4 of which were associated with relapses at other sites (recurrence rate 9%), with a mean recurrence-free interval of 13.5 months. Nine of the 11 patients with isolated urethral recurrences underwent total urethrectomy and all except 1 are alive and disease-free 2 to 8 years later. One patient was salvaged by radiation therapy and refused further treatment. The 4 patients with other associated relapses died within 18 months. The urethral recurrence rate was correlated to different risk groups defined on the basis of tumour characteristics in the cystectomy specimen. This revealed a 70% urethral recurrence rate in the high risk group, 9.6% in the moderate risk group and 1.2% in the low risk group. However, no conclusion could be drawn regarding the influence of prostatic involvement on the urethral recurrence rate.

Stage I testicular tumours: the Tata Memorial Hospital experience.

One hundred and fifty-six patients with stage I testicular germ cell tumours--81 seminomas and 75 nonseminomatous tumours--were treated at the Tata Memorial Hospital, Bombay over a 5 year period. Among the seminomas, 71 were treated with post-orchidectomy prophylactic radiation therapy to the retroperitoneum and/or mediastinum, while 10 patients refused radiation therapy and were put on surveillance. The disease-free and total survival in seminomas were 92.6% and 100%, respectively. Among the patients with nonseminomatous tumours, 58 had normal levels of serum biomarkers while 17 had raised biomarkers. In the normal marker group, 20 patients underwent retroperitoneal lymph node dissection (RPLND) with a nodal positivity of 30%, while the other 38 patients refused surgery and were either placed on unplanned surveillance (33 patients) or chemotherapy (5 patients). In this group, the patients undergoing RPLND had a survival rate of 100% as compared to 93.9% in those with surveillance. The overall disease-free and total survival rates in patients with normal markers were 86.2% and 96.6%, respectively. In the raised marker group, 6 patients underwent RPLND with a survival rate of 100% and 11 patients received chemotherapy with a survival of 90%, with the overall survival for patients with raised markers being 94.1%. The overall disease-free and total survival rates for all patients with stage I nonseminomatous tumours were 88% and 96%, respectively.

Neobladder after cystectomy: an Indian experience.

A continent urinary reservoir was constructed from an ileocolonic segment and anastomosed to the urethra in 30 males after radical cystectomy for infiltrating bladder cancer. A small cuff of the prostate was retained for anastomosis with the reservoir and ureteric anastomosis was done from within the reservoir by the "pull through" method. Complete continence was achieved in 29 patients, all of whom had an adequate reservoir capacity exceeding 400 ml; they were able to empty the reservoirs satisfactorily as judged by the residual urine (< 50 ml). Urodynamic study revealed an intra-abdominal pressure < 30 cm of water at rest and at reservoir capacity of 500 ml. Early post-operative complications included urinary leaks in 3 patients, intestinal obstruction in 3 and a faecal fistula in 1. Deterioration of the upper tracts was noted in 5 cases. Twenty-seven patients are alive after a mean follow-up of 36 months.