Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome

PURPOSE: To evaluate the 10-year outcome of patients with invasive (T2-3N0M0, staged according to the tumor, node, metastasis system) bladder cancer who responded completely to a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery. PATIENTS AND METHODS: Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%) achieved a complete clinical response (T0) on transurethral resection (TUR) of the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a partial cystectomy, and 17 elected a radical cystectomy. The patients were followed up for a median of 10 years (range, 8 to 13 years). RESULTS: Of 43 patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25 (58%) with an intact functioning bladder. Twenty-four patients (56%) developed bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%) and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17 patients who had radical cystectomy, 11 (65%) are alive. CONCLUSION: The majority of patients with invasive bladder tumors who achieve T0 status after neoadjuvant MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages the majority, but not all, of relapsing patients.     

Neoadjuvant treatment for invasive bladder cancer: is it worthwhile?

The clinical relevance of laparoscopy (LS) and laparoscopic echography (LSEG) in diagnosing and staging gastrointestinal carcinomas is assayed in the light of diagnostic methods in current use. The study covers 257 patients undergoing LS, and 23-LSEG. For the purpose a rigid 7.5 MHz echolaparoscopic probe is used. In 16 per cent of the cases LS fails to resolve the basic diagnostic problems faced, whereas in 35 per cent it alters completely the preliminary clinical diagnosis. In over 90 per cent of cases LSEG supplements or modifies the laparoscopic diagnosis. Emphasis is laid on the role played by LSEG in defining the loco-regional stage of gastric and colorectal carcinomas, as well as on the contribution of the method to establish pancreatic carcinomas not lending themselves to resection. What is more, LSEG demonstrates inoperable cases by detecting small, unsuspected metastases, not prominating above the hepatic surface.     

Internal iliac arterial infusion chemotherapy for rabbit invasive bladder cancer

Eleven patients with T4 breast cancer received induction intraarterial chemotherapy (IACT) as the first step in multidisciplinary therapy. The IACT agents (epirubicin and mitomycin C), were delivered weekly in the outpatient department by bolus injection through an implantable port-catheter system. A modified technique of port-catheter system implantation was used. The precise localization of the catheter was dually confirmed by angiography and dye test. The effectiveness of the treatment was evaluated by clinical appearance, image study, and microscopic examination. A 91% response rate was obtained, and the lesions were resectable in < or = 8 weeks. No obvious systemic toxicity resulted from the IACT. Our results show that weekly IACT by bolus injection through a port-catheter system for treating locally advanced T4 breast cancer is feasible and efficacious.     

A case of locally advanced breast cancer successfully treated with intra-arterial infusion chemotherapy of high-dose epirubicin

A case of locally advanced breast cancer was treated with intra-arterial infusion chemotherapy using high-dose epirubicin. The 1st and 2nd cycle consisted of 210 mg (day 1, 4, 7) and 150 mg (day 1, 4, 7), respectively. After completion of 2 cycles of the regimen, remarkable loco-regional control and improved QOL were obtained. Leucopenia (nadir; 1,000/mm3) was the dose limiting factor, but well-tolerated with supportive therapy. The patient underwent salvage surgery and maintenance intra-venous chemotherapy (epirubicin; 30 mg/3 weeks). At this writing, the patient is enjoying favorable QOL. These findings suggested that this modality was effective for cases with exctensive loco-regional involvement.     

Evaluation of intra-arterial infusion chemotherapy for advanced gastric cancer

We evaluated the therapeutic efficacy of intraarterial infusion chemotherapy in advanced gastric cancer, its side effect and patient prognosis, in comparison with systemic infusion. Of 125 cases of advanced gastric cancer, 41 cases received intraarterial chemotherapy (A group) and the rest were given systemic infusion (S group). Protocols of chemotherapy were 5-FU + MTX in 49 cases, 5-FU + cisplatin in 62, and 5-FU + MMC in 14. Location of the disease was the peritoneum in 69 cases, nodes in 59, liver in 38, and other sites, 33. The response rate of A group was significantly higher than that of S group, at 31% and 13% respectively. Although 41% of cases showed side effects (> or = grade 2), there was no significant difference between the 2 groups. The median survival period and 1-year survival rate were 8.4 months and 35%, respectively, and there was no significant difference between the 2 groups. In cases with liver metastasis, the prognosis of A group was better than that of S group. The results suggest that intra-arterial infusion chemotherapy is an effective treatment for liver metastasis from gastric cancer.     

Neoadjuvant (induction) chemotherapy in advanced bladder carcinoma

Many doctors frequently encounter hirsute patients. Quantification of hair growth may be useful for diagnosis and follow-up. To establish the reference range for distribution and density of hair in females, and to determine the regions yielding the best discrimination between normal and hirsute women, we studied the distribution and density of terminal hair on 12 body regions assessed on a scale of 0-4. Prospectively, 81 healthy female volunteers and 71 hirsute patients of child-bearing age and Dutch ancestry, who were not receiving medication, and who had not had a recent pregnancy were studied. The reference hair pattern was established for each body region, and the threshold value yielding the highest sensitivity and specificity to evaluate hirsutism was calculated. None of the women in the reference population displayed a score of more than 1 for chin, upper back, upper abdomen and upper arm, or more than 2 for upper lip, side-burns, chest, lower back, lower abdomen, thighs or forearm. The best discrimination between the reference and hirsute populations was obtained with the sum of the scores for four regions: upper lip, chin, lower abdomen and thighs. Independent assessment of hair growth by two investigators revealed excellent agreement. We conclude that a score of more than 1 for chin, upper back, upper abdomen and upper arm, or more than 2 for upper lip, side-burns, chest, lower back, lower abdomen, thighs or forearm is abnormal for Dutch women, and that assessment of hair growth on the upper lip, chin, lower abdomen and thighs is the most suitable way to evaluate hirsutism.     

Intra-arterial chemotherapy for muscle-invasive urinary bladder cancer

Mixed cryoglobulinemia is a well-known complication after hepatitis C virus (HCV) infection. We report five cases in which cryoglobulinemia appeared or grossly exacerbated following orthotopic liver transplantation (OLT). Cryoglobulinemia and the associated clinical symptoms resolved or improved in two patients treated with ribavirin after liver transplantation, while plasmapheresis was ineffective in another patient. The mechanism involved in induction of cryoglobulinemia after liver transplantation is unknown. However, the effect of antiviral therapy observed in these patients suggests a correlation between cryoglobulinemia, HCV replication, and possibly hepatocellular disease activity. A larger-scale study is warranted to test the effect of ribavirin on post-OLT HCV-associated cryoglobulinemia.     

The risk of infection associated with intra-arterial catheters for cancer chemotherapy

OBJECTIVE: To determine the frequency of, and risk factors for, infections associated with intra-arterial catheters used for cancer chemotherapy. METHODS: Between September 1992 and September 1995, we conducted a surveillance study of all 807 intra-arterial catheters placed for chemotherapy at our center. The insertion site was disinfected with povidone iodine and alcohol, and the arterial catheter was placed using maximal sterile barrier precautions. Upon removal, all intravascular segments were submitted for semi-quantitative culture. RESULTS: No episodes of catheter-related bloodstream infection (95% confidence interval [CI95], 0%-1.6%) were observed. However, the risk of colonization (>15 colony-forming units) of arterial catheters was 15% (CI95, 12%-17%). Retrospective risk-factor analysis conducted on 224 intra-arterial catheters placed for chemotherapy in 1993 showed that colonization was associated significantly with duration of catheterization (median of 1 day for culture-negative catheters vs median of 4 days for culture-positive catheters, P<.001). Age, gender, prior radiotherapy, underlying cancer, neutropenia, and hypoalbuminemia were not associated with catheter colonization. CONCLUSION: Intra-arterial catheters for cancer chemotherapy placed under maximal sterile barrier precautions for a short period of time are associated with a very low risk of bloodstream infection.     

Electropermeabilization in bladder cancer chemotherapy

PURPOSE: Electropermeabilization has been used for the introduction of genes into cells. Using this technique, we introduced the cytotoxic drug bleomycin (BLM) into cells and examined whether the technique might be useful for the treatment of bladder cancer. MATERIALS AND METHODS: For electropermeabilization in vitro, we used YTS-1 cells, a human transitional cell carcinoma line. Aliquots of cell suspension were mixed with a solution of BLM and immediately exposed to electric pulses. A high-power pulse generator was used to supply square-shaped pulses of 1250 V/cm (100 micros, eight pulses). After a 2-h post-shock incubation, cells were washed and incubated for one further hour. Then the concentration of BLM in the cells was measured using a bioassay. For electropermeabilization of tissue, we used normal male Wistar rats. The bladder was exposed and 10 mg/kg BLM was injected into the caudal vein. A series of eight pulses with a time constant of 100 micros at an electric field intensity of 1000 V/cm was applied. The bladder, liver and lungs were extracted 1 h later and prepared for quantification of the BLM concentration using the bioassay. RESULTS: Electrotreated cells contained significantly higher concentrations of BLM than nonelectrotreated cells. The concentration of BLM 1 h after electrotreatment in bladder tissue was 2.7 times higher than that in nonelectrotreated bladder tissue. CONCLUSION: The electropermeabilization technique has the potential to serve as a new and effective modality for the treatment of bladder cancer.     

Selective bladder preservation by combination treatment of invasive bladder cancer

BACKGROUND: For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. We sought to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured. METHODS: We enrolled 53 consecutive patients with muscle-invading bladder cancer (stages T2 through T4, NXM0) in a trial of transurethral surgery, combination chemotherapy, and irradiation (4000 cGy) with concurrent cisplatin administration. Urologic evaluation of the tumor response directed further therapy: radical cystectomy in the 8 patients who had incomplete responses, additional chemotherapy and radiotherapy (6480 cGy) in the 34 patients who had complete responses or who were unsuited for cystectomy, and alternative care in the 11 patients who could not tolerate either irradiation or chemotherapy. RESULTS: After a median follow-up of 48 months, 24 of the 53 patients (45 percent) were alive and free of detectable tumor. In 31 patients (58 percent) the bladder was free of invasive tumor and functioning well, even though in 9 (17 percent) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 28 patients who had complete responses after initial treatment, 89 percent had functioning tumor-free bladders. CONCLUSIONS: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial that included a group for simultaneous comparison would be required to produce definitive results.     

Eosinophilic cystitis masquerading as invasive bladder cancer

Bilateral torsion of testicular appendages is extremely uncommon. We present a rare clinical case of bilateral synchronous torsion of the hydatids of Morgagni. Clinical management was dictated by the clinical findings.     

Late invasive recurrence despite long-term surveillance for superficial bladder cancer

Superficial transitional cell carcinoma of the bladder is associated with a 15 to 70% recurrence rate within 2 years. Most recurrences are superficial. A recurrence after 2 disease-free years is unusual. A review of the tumor registry revealed 124 patients followed for superficial disease at the Veterans Administration Center in Baltimore. Of the patients 20 were identified with either stage Ta (7) or stage T1 (13) papillary transitional cell carcinoma who had completed at least 5 years of surveillance without tumor recurrence. Invasive transitional cell carcinoma of the bladder requiring cystectomy developed in 7 of these 20 patients after remaining tumor-free for 5 years (stage Ta in 4 and stage T1 in 3). All 7 patients had organ-confined disease and were alive with no evidence of disease at 18 months to 5 years after cystectomy. These results demonstrate that superficial, low grade transitional cell carcinoma of the bladder can become muscle invasive despite careful surveillance and a long dormant period. In our series yearly cystoscopy and urine cytology identified tumor recurrence before metastases developed, suggesting that long-term surveillance is required in patients with superficial bladder cancer.     

Neoadjuvant intraarterial chemotherapy for ten cases of inflammatory breast cancer by Seldinger's methods

The conventional methods (CM) of intraarterial (IA) chemotherapy for inflammatory breast cancer were catheterizations from superior epigastric and brachial artery under general anesthesia. Since 1997, we selected the Seldinger's methods (SM) for ten cases of the disease to control local effects and simplify the technique. Complications of the SM were slight, and side effects were equal to those with CM. The postoperative pathological findings of the SM showed the direct effects of chemotherapy to tumor cells (degenerative and necrotic changes) as compared with the embolism-like effects of CM. But the overall histological effects of chemotherapy by SM were almost equal to those for CM. The strong points of the SM were as follows: 1) More selective IA chemotherapy is available, 2) one can find the passage of the aim vessels and no trouble related to catheter, 3) general anesthesia is not necessary, and the techniques are simple, 4) the wounds are not remarkable. The disadvantages are as follows: 1) Patients must rest the day of IA chemotherapy, 2) in 20% of the procedures, one can not search the vessels, and 3) in 4 cases complications of stiffness of Mj or Mn pectral muscles were found. In future, we expect more effective results by dose escalation or combination chemotherapy.     

Organ preservation with radiochemotherapy in locally advanced bladder cancer

Bladder cancer is frequent in Western countries and predominantly affects males (ratio: 3:1). In 15-25% of cases there is muscular wall invasion. Treatment of > T1 tumors is radical cystectomy with or without preoperative radiotherapy. In T2 there is 60% survival at 5 years, 40% in T3. Exclusive radiotherapy used to prevent radical cystectomy has lower survival rates in T2 (30-40% at 5 years) as well as in T3 (20% at 5 years). Recently, concomitant radiotherapy and chemotherapy has been introduced again to prevent demolitive surgery. Results are similar or slightly superior than those of surgery alone. In our experience with radiotherapy 180 cGy daily for a total dose of 64 Gy in combination with fluorouracil in locally advanced tumors 40% bladder preservation was achieved.     

Neoadjuvant chemotherapy and radiotherapy for inoperable head and neck cancer: the LSU-Shreveport experience

A retrospective review of 8 years of treatment in 2 hospitals in Shreveport showed that neoadjuvant chemotherapy with radiotherapy was performed in 39 patients with inoperable, locally advanced head and neck cancer. Twenty-two individuals treated by definitive radiotherapy alone served as historical controls. The cumulative survival rate at 4 years was 34% in patients managed by neoadjuvant chemotherapy with radiotherapy and 7% in patients treated by radiotherapy only. With the exception of greater acute toxicity seen in patients receiving neoadjuvant chemotherapy with radiotherapy, differences in locoregional failure, distant metastasis, and late complication rates were not observed between the patient groups.