Medical research - what, when, and how?

Bronchial asthma due to small-cell carcinoma is very rare and reports in the literature are few. This paper reports such a case. Asthma was the only noteworthy clinical manifestation of admission. More detailed examination, undertaken because the patient failed to respond to bronchodilator therapy, revealed a pulmonary carcinoma. The bronchoconstriction responded only to octreotide therapy.     

Role of adjuvant chemotherapy in the treatment of invasive carcinoma of the urinary bladder

PURPOSE: The standard treatment for patients with muscle-invasive carcinoma of the urinary bladder is radical cystectomy. While radical cystectomy cures many patients with this tumor, almost 50% of them will develop metastatic disease. Adjuvant chemotherapy has been proposed for these patients in an attempt to reduce the probability of relapse and to improve survival. To assess whether adjuvant chemotherapy does benefit patients with muscle-invasive bladder cancer, we reviewed all phase II and III studies published in the English literature over the last 20 years. METHODS: A review of all published reports was facilitated by the use of Medline computer search and by manual search of the Index Medicus. RESULTS: Several comparative, nonrandomized studies have indicated that adjuvant chemotherapy may prolong disease-free survival. Four randomized studies have been conducted and all had a suboptimal patient accrual. Three studies used a cisplatin-containing combination chemotherapy and included primarily patients with non-organ-confined transitional-cell carcinoma (TCC) of the bladder. All three studies indicated that adjuvant chemotherapy improved disease-free survival and two of them also showed improvement in event-free survival and overall survival, respectively. CONCLUSION: Published series have been unable to establish an undisputed benefit of adjuvant chemotherapy over radical cystectomy alone for muscle-invasive bladder cancer. The interpretation of the available data is compromised by several methodologic and statistical problems. Thus, adjuvant chemotherapy cannot be considered as a standard treatment for all patients with muscle-invasive carcinoma of the bladder. Well-designed prospective randomized studies are needed to clarify the role of adjuvant chemotherapy in this disease. However, outside a protocol setting, there is some evidence that patients with extravesical disease or with lymph node involvement may benefit from adjuvant treatment with cisplatin-based combination chemotherapy. No data support such an approach for patients with muscle-invasive but organ-confined bladder cancer.     

Riedel's thyroiditis: a case report and review of the literature

Riedel's thyroiditis is a very rare disease of unknown aetiology, occasionally associated with retroperitoneal and mediastinal fibrosis. It is a benign condition, but may be confused with an anaplastic carcinoma of the thyroid. The differential diagnosis with anaplastic carcinoma is assured only by intraoperative biopsy. The Authors report a clinical case: symptoms were a progressive enlargement of the thyroid gland, left recurrential palsy, dyspnoea and dysphagia. The surgical treatment was total thyroidectomy, performed with bilateral neurolysis of recurrent nerves. The patient was also under adjuvant corticosteroid treatment.     

Primary, pure, large-cell neuroendocrine carcinoma of the urinary bladder

We report what to our knowledge is the first case in the English-language literature of a primary, pure, undifferentiated large-cell neuroendocrine carcinoma of the urinary bladder. To date, only one case of a large-cell neuroendocrine carcinoma was reported, and it was associated with an adenocarcinoma most likely of urachal origin. On the other hand, slightly more than 100 cases of undifferentiated small-cell carcinoma of the urinary bladder were reported, approximately one-half of which were associated with poorly differentiated transitional-cell carcinoma of the conventional type. The patient in our case was a 73-year-old man with a history of prostatic cancer treated with radiation therapy. He presented with hematuria, leading to the discovery of a solitary tumor on the dorsal wall of the urinary bladder. A diagnosis of large-cell neuroendocrine carcinoma was made, supported by immunohistochemical reactivity for chromogranin, neuron-specific enolase, and synaptophysin; a variety of other hormonal markers of neuroendocrine tumors were negative. The radical cystoprostatectomy and bilateral pelvic lymphadenectomy specimen showed a transmurally invasive tumor, without regional lymph node metastases. The patient died 2 months after surgery, and the autopsy revealed disseminated metastases histologically identical to the urinary bladder neoplasm. Awareness of the occurrence of large-cell neuroendocrine carcinoma of the urinary bladder seems to be important because of the possible aggressive outcome associated with this tumor and because of differential diagnostic considerations, which include malignant lymphoma and metastasis from another primary, especially in tumors occurring in a pure form.     

Normal regional anatomy of the shoulder

Transitional cell carcinoma of the bladder is associated with a high relapse rate, locally and systemically, particularly in patients with nodal or soft-tissue involvement, despite radical cystectomy. The responsiveness of the disease to chemotherapy in the metastatic setting has stimulated the use of systemic therapy in earlier stage disease, either before (neoadjuvant) or after (adjuvant) definitive local therapy. Interpretation of the data is hampered by low patient accrual to randomized trials, lack of standardization of local treatment modalities, and the use of a variety of chemotherapy agents and regimens pointing to the difficulty in reaching a consensus as to what constitutes standard therapy. In this article, we review the use of adjuvant and neoadjuvant chemotherapy, the advantages and disadvantages of both approaches, and the recommendations that can be made based on available data. New approaches to improving survival, potentially with organ preservation, include the development of more effective chemotherapy, and the identification of prognostic features-clinical or biologic-that might be a better guide to patient selection.     

Effect of UFT on treatment of urological cancer--effect of UFT on treatment of invasive bladder cancer and advanced prostate cancer. Ibaraki Urological Cancer Chemotherapy Study Group

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.     

A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.     

A rare case of epidermoid carcinoma of the breast

A case of a 76-year-old woman who seemed to suffer from Paget's disease of the breast, is reported. The patient was submitted to surgical of the breast, is reported. The patient was submitted to surgical treatment of the lesion and histological examination of the specimen showed a rare case of epidermoid carcinoma of the breast.     

Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival

PURPOSE: We assessed the prognostic impact of genitourinary small cell carcinoma tumor and patient characteristics, and therapy. MATERIALS AND METHODS: We retrospectively reviewed the records of 180 patients with genitourinary small cell carcinoma in which patient and tumor characteristics, therapy, followup duration and survival status had been documented. Patient age, sex, primary site, histological features, tumor size, stage, locoregional therapy, systemic chemotherapy and hormonal manipulations were analyzed for association with survival. RESULTS: There were 106 cases of bladder, 60 prostatic, 8 renal and 6 ureteral small cell carcinoma. Median survival was 10.5 months overall, and 7 and 13 months for prostatic and bladder small cell carcinoma, respectively (p <0.0001 log rank analysis). In all cases metastatic disease at presentation (p <0.008, risk ratio 1.9) predicted poor survival on multivariate analysis. Radical surgery (p <0.0001, risk ratio 0.34) and cisplatin chemotherapy (p <0.0001, risk ratio 0.20) were the only factors that predicted improved survival on multivariate analysis. For prostatic small cell carcinoma primary surgical therapy (p <0.012, risk ratio 0.46) was the only parameter that predicted survival on univariate analysis. For bladder small cell carcinoma only cisplatin chemotherapy (p <0.0001, risk ratio 0.15) predicted survival on multivariate analysis. CONCLUSIONS: Genitourinary small cell carcinoma has a poor prognosis, which is worse in prostatic than bladder disease. Patient and tumor characteristics were not determinants of survival when prostatic and bladder small cell carcinoma were analyzed individually. For prostatic disease only primary surgical therapy was associated with prolonged survival, while for bladder disease cisplatin chemotherapy was associated with a favorable prognosis. We recommend considering primary surgical therapy for prostatic and cisplatin based chemotherapy for bladder small cell carcinoma.     

Exposure of macrophage-like cells to titanium particles does not affect bone resorption, but inhibits bone formation

Endocrine tumours of the pancreas, even in case of liver involvement, are generally characterized by a slower evolution and a better prognosis, if compared with ductal carcinoma. This fact gives reason to a radical surgical approach, whenever possible, and to the research of any effective adjuvant treatment. For this purpose, hepatic transarterial chemoembolization (TACE) has been proposed in recent years for the treatment of metastatic endocrine tumours. Out of 80 patients suffering from endocrine tumours of the pancreas, observed between January 1985 and December 1996, 28 (35%) presented liver metastases at the time of diagnosis. Twelve of these patients were submitted to palliative resection of pancreatic tumour and one or more cycles of TACE. Overall survival was 50% (6/12); median survival was 35.4 months (range 4-75). These results suggest that chemoembolization, combined with surgical resection of primary malignancy, appears to be able to control the disease for a certain time and to increase the survival rate.     

Long-term followup of all patients with muscle invasive (stages T2, T3 and T4) bladder carcinoma in a geographical region

PURPOSE: We studied the relationship between long-term survival and treatment of stages T2, T3 and T4 bladder carcinoma in an unselected patient population. MATERIALS AND METHODS: A total of 680 patients with the initial diagnosis of bladder carcinoma in 1987 to 1988 in Western Sweden was prospectively registered and followed until 1994. Of these patients 107 had stage T2 to T3 and 41 had stage T4 disease. RESULTS: Of the patients with stage T2 to T3 disease 30 (mean age 66) underwent radical cystectomy, 33 (mean age 75) full dose radiotherapy and 44 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). The 5-year crude survival rates were 33, 15 and 14%, respectively. Of the patients with stage T4 disease 6 (mean age 61) underwent radical cystectomy, 9 (mean age 73) full dose radiotherapy and 26 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). All except 1 patient died of disease within 4 years. CONCLUSIONS: More than 60% of the patients in the cohort were considered unsuitable for radical cystectomy and their survival was poor, whether treated with full dose radiotherapy or transurethral resection of the bladder alone.     

Adjuvant therapy for stage II colon cancer after complete resection. Provincial Gastrointestinal Disease Site Group

GUIDELINE QUESTION: Should patients with resected stage II colon cancer receive adjuvant therapy? OBJECTIVE: To make recommendations regarding the use of adjuvant therapy in the treatment of resected stage II colon cancer. OUTCOMES: Overall survival is the primary outcome of interest. Secondary outcomes are disease-free survival and adverse effects of the treatment regimens. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 2 members of the Provincial Gastrointestinal Disease Site Group (GI DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The recommendations resulting from this review have been approved by the GI DSG, which comprise medical and radiation oncologists, surgeons and epidemiologists. Community representatives did not participate in the development of this practice guideline but will do so in future guidelines development. QUALITY OF EVIDENCE: There are 25 published randomized controlled trials (RCTs) and 1 meta-analysis. The GI DSG pooled data from 11 of the 25 RCTs that provided adequate data. BENEFITS: The 25 RCTs are grouped according to the type of therapy and whether the control patients received no treatment (observation) or other adjuvant therapy after resection. Because the trials usually included patients with stage II and III cancer, the complete trial results and those for a subset of patients with stage II disease were analysed. Although the overall trial results showed a survival benefit for adjuvant treatments, the benefit was not significant for stage II patients. A meta-analysis of 11 trials comparing adjuvant treatment with observation in patients with stage II cancer indicated no significant reduction in the odds ratio (OR) for death (OR 0.83; 95% confidence interval [CI] 0.62 to 1.10). The OR for death among patients receiving chemotherapy by portal vein infusion (PVI) was 0.62 (95% CI 0.35 to 1.11). HARMS: The toxic effects of 5-fluorouracil (5-FU) with either levamisole or leucovorin, or both, were mild to moderate and consisted mostly of stomatitis, diarrhea and myelosuppression; 5% of patients required hospital admission. 5-FU plus levamisole was associated with transient neurotoxic effects in 18% of patients. Toxic effects associated with PVI were mild, rare and mostly consisted of leukopenia and diarrhea; 1% of patients experienced bowel perforation. PRACTICE GUIDELINE: Adjuvant therapy is not recommended at this time for the routine management of patients with resected stage II colon cancer. Patients with stage II disease and high-risk factors (bowel obstruction, tumour adhesion, invasion, perforation or aneuploidy) have a poorer prognosis, similar to that of patients with stage III colon cancer. For individual management, these patients should be made aware of their prognosis; treatment can be considered after the uncertainty of the value of adjuvant therapy has been explained to the patient. The enrolment of patients with high-risk stage II disease in clinical trials is encouraged. Trials comparing adjuvant therapy with observation are needed and are ethically acceptable in stage II colon cancer.     

Dynamics of cardiac and skeletal muscle lactate dehydrogenase activity following a single exposure to an alternating magnetic field]

Analysis of records of microscopic slides from 33 patients with pure squamous carcinoma of the bladder who underwent radical cystectomy and lymphadenectomy disclosed a 5-year survival rate of 48 per cent. This survival rate correlated closely with pathologic stage and histologic grade of tumor and was significantly better than for each corresponding stage of transitional cell carcinoma of the bladder. The favorable survival rate and reasonably low operative mortality rate support aggressive therapy of this uncommon lesion.     

Adrenocortical carcinoma. Current approaches in diagnosis and treatment

Adrenocortical carcinoma is a rare malignant tumor. The survival rate is related to a radical tumor resection. However, adrenocortical carcinomas are usually diagnosed in advanced stage. Although some cases of long-term regressions of metastases under op'-DDD (Mitotane) therapy have been sometimes reported the overall efficiency of mitotane in prolonging life remains controversial. Between May 1975 and January 1994, 9 patients were surgically treated for adrenocortical carcinoma at our institution. There were 6 females and 3 males, mean age 40.8 years (median 40 years). Five (55.6%) patients presented with abdominal pain, whereas 4 (44.4%) patients had symptoms of hormone secretion (cortisol). One patient was lost at follow-up. Overall survival rate was 16.8 +/- 5.9 months, the survival rates according to tumor stage were: stage I. 58 months (1 case), stage II. 6 and 16 (2 cases; mean 11 months), stage III. 7, 15.17 and 22 (4 cases, mean 15 months) and stage IV. 9 months (1 case). The progression of the disease is not controlled by the administration of op'-DDD and the best treatment is represented by surgery.     

Small cell carcinoma of the uterine cervix: a clinicopathological review

Small cell carcinoma of the cervix is rare, with an aggressive natural history. We report on a series of 11 patients treated at the Christie Hospital, Manchester and examine their treatment and survival. Eleven patients with small cell carcinoma of the cervix were identified retrospectively from patient case notes. Treatment was individualised and included a variety of combinations of surgery radiotherapy and chemotherapy. Four patients were disease-free between 21 and 108 months (crude disease-free survival 36%). They presented with earlier disease and were older than the average for the group. They were all initially treated with radical radiotherapy. 7 patients died between 7 and 25 months. Despite combination chemotherapy, survival with advanced disease was poor. Published studies are small and fail to provide definitive answers on the best management of small cell carcinoma of the cervix. Drawing on the experience of small cell carcinoma of the lung however, combination therapy with radiotherapy, chemotherapy and possibly surgery requires careful assessment by an oncologist.     

Paraneoplastic opsoclonus

Opsoclonus occurs in a number of clinical settings, but its association with carcinomas in adult patients is rare. We present a case of paraneoplastic opsoclonus in a 63 year-old male who had a small-cell lung cancer. Even though paraneoplastic opsoclonus may be associated with an immunological response, there was no elevation of blood parameters associated with inflammation. The patient was treated with prednisolon without any clinical effect, and died only a few months after opsoclonus was diagnosed.     

Self-concept and self-esteem: a clarification of terms

Primary malignant non-Hodgkin lymphoma is rare. The mammographic appearance is unspecific. The final diagnosis can usually be made after examination of paraffin-embedded tissue only. There exists no therapeutic standard for this disease. In the case of 3 patients treated at our institution, tumorectomy only and adjuvant therapy have been performed because there is no survival advantage for patients who underwent radical surgery.     

A critical review of the role of definitive radiation therapy in bladder cancer

The role of radiation therapy in the management of bladder cancer continues to be controversial. Attention to the issue of response to treatment, instead of overall survival, ultimate local control and quality of life, has hampered progress in determining the optimal-treatment strategy for patients with bladder cancer. Although the heterogeneity of bladder cancer has been recognized for some time now, the trend has been to seek one cure for all, rather than to use the available modalities selectively and optimally. The use of continent urinary diversion has made cystectomy more acceptable, but no form of diversion is as satisfying as a natural, well functioning bladder. The case against definitive XRT has been built on the lack of total radiosensitivity of transitional cell carcinoma. It is interesting that the lack of total chemosensitivity of bladder cancer and total curability with surgery has not prevented those modalities from being widely used. The recognition of the systemic nature of invasive bladder cancer has appropriately led to increased attention to the control of systemic disease. However, this has led to, at times, compromised local therapy. The use of primary or adjuvant chemotherapy should not impede the pursuit of optimal local therapy in patients with bladder cancer with the emphasis on the optimal quality of life. In parallel, the goal of bladder preservation and improved quality of life should not overshadow the importance of local tumor control. Because metastatic bladder cancer currently is an almost universally lethal disease, we should optimize the use of effective treatment modalities to achieve modest improvements in cure rate. The idea that definitive radiation therapy has no role in the management of bladder cancer exists in the minds of those who hold strong convictions and see an alternative view to their own as being controversial. We believe that attention should not focus on this controversy but on the recognition of the reality that the best management of bladder cancer is a shared responsibility among the oncologists of all disciplines. With this recognition, clinical research toward improving outcome for patients with bladder cancer will move forward.     

Glutamate release in the nucleus tractus solitarius induced by peripheral lipopolysaccharide and interleukin-1 beta

PURPOSE: The selection of therapy for stage T1 bladder cancer is controversial, and reliable biomarkers that identify patients likely to require cystectomy for local disease control have not been established. We evaluated our experience with T1 bladder cancer to determine whether early cystectomy improves prognosis, and whether microvessel density has prognostic value for T1 lesions and could be used for patient selection. MATERIALS AND METHODS: We retrospectively reviewed the records of 88 patients with T1 transitional cell carcinoma of the bladder. Patient outcome was correlated with therapeutic intervention. Paraffin embedded tissue from 54 patients was available for factor VIII immunohistochemical staining for microvessel density quantification. RESULTS: Median followup was 48 months (range 12 to 239). Of the patients 34% had no tumor recurrence. The rates of recurrence only and progression to higher stage disease were 41 and 25%, respectively. The survival of patients in whom disease progressed was diminished (p = 0.0002). Grade did not predict recurrence or progression nor did cystectomy provide a survival advantage. Microvessel density did not correlate with recurrence or progression. CONCLUSIONS: Patients with T1 bladder cancer have a high risk of recurrence and progression. Tumor progression has a significant negative impact on survival. Neither grade nor early tumor recurrence predicted disease progression. Because early cystectomy did not improve patient outcome, we suggest reserving cystectomy for patients with progression or disease refractory to local therapy. Microvessel density is not a prognostic marker for T1 bladder cancer and has no value in selecting patients with T1 disease for cystectomy.     

Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning. II. Instrumental conditioning

BACKGROUND: Recurrence of rectal and colonic carcinoma remains substantial despite apparently curative surgery. Adjuvant therapy has been applied to improve prognosis. METHODS: This review evaluates the use of adjuvant therapy in the management of resectable rectal and colonic carcinoma. It assesses critically the evidence supporting the addition of radiotherapy, chemotherapy, chemoradiotherapy and other treatment modalities to optimal surgery. RESULTS: In the case of rectal tumours, preoperative is more effective than postoperative radiotherapy; It can significantly reduce the incidence of local tumour recurrence. A number of trials have tended towards showing a survival advantage and a recent large randomized trial has shown a significant improvement in survival in patients with Dukes C tumours. Postoperative chemoradiotherapy is associated with a survival benefit and is standard therapy in the USA, although it is associated with increased toxicity. The effectiveness of preoperative chemoradiotherapy is currently being investigated. Postoperative fluorouracil-containing chemotherapy has resulted in a survival advantage in patients with Dukes C colonic tumours; such therapy may be administered either systemically or intraportally. The evidence of benefit with rectal tumours is more limited. Immunotherapy has been studied to a limited extent and the use of a tumour-directed monoclonal antibody has produced a survival advantage in a single trial. CONCLUSION: Preoperative radiotherapy and postoperative chemoradiotherapy can produce a survival advantage in patients with Dukes C rectal carcinoma and reduce local recurrence. Postoperative fluorouracil-containing chemotherapy can produce a survival advantage in those with Dukes C colonic cancer. The optimal use and combination of adjuvant therapy remains uncertain.