Spondylitis caused by Salmonella infantis--case report

Twenty seven Patients with advanced breast cancer were treated with CAC (carboplatin, adriamycin, cyclophosphamide) regimen. Eighteen patients had no prior chemotherapy. Carboplatin was given 300 mg/m2 intravenously (IV), on day 1 or 150 mg/m2 on day 1, 2, adriamycin 40 mg/m2 IV on day 3, cyclophosphamide 500 mg/m2 IV on day 3, 10. The treatment was recycled every 28 days. The overall objective response was 63% (17/27) with a CR rate of 18% (5/27). The median duration of response was 9 months and median survival time was 17 months. The response rate of soft tissue metastasis was 61% (11/18). Lung metastasis responded in 3/5, liver metastasis in 3/3, pleura metastasis in 4/4, bone metastasis in 1/10. The response rate of previously untreated patients was 72% (13/18). The gastrointestinal reaction was mild. No renal toxicity was observed. Leukopenia (WHO grade II, III) was seen in 89%. These results indicate that CAC is an effective regimen for advanced breast cancer.     

Early results of a prospective study of hormone therapy for patients with locally advanced prostate carcinoma

BACKGROUND: Locally advanced prostate carcinoma is usually not curable with surgery or radiation therapy. Primary hormone therapy is an alternative therapeutic option, but contemporary prospective studies of the outcomes of such therapy are not available. METHODS: The authors conducted a prospective, hospital-based study of gonadal androgen ablation with deferred antiandrogen therapy in 103 men with prostate carcinoma clinically classified as T3-4NXM0. The median potential follow-up was 51 months (range, 36-74 months), and the median period of observation was 43 months (range, 6-74 months). RESULTS: Each patient experienced regression of the primary tumor, and none experienced significant morbidity from the primary tumor during the study period. The projected 5-year cause specific, metastasis free, PSA disease free (no PSA elevation > 1.0 ng/mL after the beginning of antiandrogen therapy), and all-cause survival rates were 84%, 84%, 68%, and 58%, respectively. CONCLUSIONS: Primary hormone therapy is a reasonable treatment option for locally advanced prostate carcinoma in elderly men or in men with significant comorbid disease who request therapeutic intervention.     

Skin metastasis as first manifestation of prostatic adenocarcinoma

Incidence of prostate disease has seen a sudden boost over the last few years as a result of an increase in male life expectancy. Prostate carcinoma is the third most common cause of cancer mortality in Spain. Post-mortem studies reveal that this is the most prevalent neoplasia in the elderly. 30% of all males over 50 years could host malignant cells in their prostate, although only 20% of these neoplasias have clinical manifestations. Prostate carcinoma expansion occurs by local spreading, as well as lymph and blood dissemination. Local spreading to the urethra, bladder neck, trigonous and seminal vesicles is frequent. Lymph dissemination to obturating, hypogastric, iliac, presacral and paraaortic nodes is a major path for metastasis. Bone metastasis with increased acid phosphatase is the most illustrative sign of prostate adenocarcinoma expansion. Visceral metastasis occur more frequently in lungs, liver and renal glands. There is a 0.3% likelihood of skin metastasis from prostate adenocarcinoma. Considering the rareness of skin metastasis from prostate adenocarcinoma, the case reported in the present paper, first evidence of a prostate carcinoma, is even more exceptional.     

Selective expression of inducible nitric oxide synthase in human prostate carcinoma

BACKGROUND: Nitric oxide (NO) is synthesized by inducible nitric oxide synthase (iNOS) and plays an important role in tumor growth and angiogenesis. NO generation by iNOS also influences the cytotoxicity of macrophages and tumor-induced immunosuppression. Before now, the expression of iNOS in prostate carcinoma tissue had not been determined. METHODS: In this study, tissue sections from 16 patients with prostate carcinoma were studied immunohistochemically and compared with tissue specimens from 10 patients with benign hyperplasia. RESULTS: Positive iNOS immunostaining was detected in all sections from patients with prostate carcinoma. The malignant epithelial cells were highly positive. The antibody against iNOS also marked round cells, which had the same cell shape as that observed for macrophages. These cells were located in stroma and epithelium adjacent to tumor islets. However, round cells in benign tissue stained negative for iNOS. None of the benign hyperplasia specimens stained positive for iNOS immunohistochemically. CONCLUSIONS: Prostate carcinoma tissue had a high iNOS content, whereas benign tissue did not. The authors suggest that epithelial iNOS expression can be used as a specific immunohistochemical marker for prostate carcinoma. NO generation by iNOS may play multiple roles in the development of this disease.     

E-cadherin and associated molecules in the invasion and progression of prostate cancer

Prostatic carcinoma is the most common type of male cancer found in the Western world and its distant metastasis becomes a life threatening event in tumour bearing patients. However, the biology of prostate cancer and metastasis is poorly understood. We review the progress made in the last decade on the molecular and cellular biology of cell-cell adhesion molecules in the invasion and progression of prostate cancer, with emphasis being placed on E-cadherin and its associated molecules.     

Carcinogenic responses of transgenic heterozygous p53 knockout mice to inhaled 239PuO2 or metallic beryllium

BACKGROUND: To investigate if serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of deoxypyridinoline (D-Pyr) are useful markers of bone metastasis in patients with prostate carcinoma, we measured these markers in patients with untreated benign prostatic hyperplasia (BPH) and untreated prostate carcinoma (PCA). METHODS: Serum PICP, ICTP and urinary D-Pyr levels were determined in 53 patients; 16 patients with BPH, 15 patients with PCA without bone metastasis (stage A, B, C and D1) and 22 patients with PCA with bone metastasis (stage D2). At the same time correlations among these markers and serum total alkaline phosphatase (ALP) activity were studied. RESULTS: Serum PICP, ICTP and urinary D-Pyr levels in the PCA patients with bone metastasis were significantly higher than those of BPH. The serum levels of PICP in patients with PCA with bone metastasis group were significantly higher than those of without bone metastasis group. The serum levels of ICTP in patients with PCA without bone metastasis group were significantly higher than those of BPH group, while no significant difference was observed between PCA group with and without bone metastasis. In the PCA patients with bone metastasis, serum PICP and serum total alkaline phosphatase (ALP) activity were significantly correlated (r = 0.80). In these patients, serum ICTP and urinary D-Pyr levels were also significantly correlated (r = 0.70). CONCLUSION: These results suggest that serum PIPC, ICTP and urinary D-Pyr are the useful markers to quantitate bone metastasis in the patients with PCA. Moreover, the determination of serum ICTP levels may be significant for detecting occult bone metastasis in the patients with PCA.     

Clinical significance of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in peripheral blood of patients with gastric carcinoma

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in peripheral blood were measured in 54 patients with gastric carcinoma; 46 were primary and 8 were recurrent cases. There were no significant associations between MMP-9 concentrations and clinicopathological factors. TIMP-1 levels were significantly increased in advanced and recurrent cases, and in cases with peritoneal dissemination and lymph node metastasis, suggesting that TIMP-1 concentration in the peripheral blood could be a new tumor marker for the recurrence of gastric carcinoma.     

Successful multidisciplinary treatment for bladder cancer with priapism. A case report

A 44-year-old man suspected of having transitional cell carcinoma (TCC) of the prostate was referred to our hospital. He had a painful semi-erect penis at his first visit. Then needle biopsy of the corpus cavernosum histologically revealed metastatic TCC. CT of the pelvis showed bilateral ureteral obstruction caused by the advanced tumor but no lymph node swelling was found. Under the diagnosis of prostatic TCC with penile metastasis, bilateral percutaneous nephrostomy followed by two courses of combination chemotherapy (IFEP regimen) was carried out, which resulted in the disappearance of priapism. Radical cystectomy with total penectomy was performed. The final pathological diagnosis was corrected to TCC of the urinary bladder with invasion to the prostate and metastasis of the corpus cavernosum and the right obturator lymph node. Enlargement of the prostate proved to be caused by glandular hyperplasia with atypical hyperplasia of the prostate gland. Three courses of adjvent IFEP chemotherapy was given post-operatively and he has been alive with no evidence of the disease for 10 months.     

NDPK/nm23 expression and its correlation with lymph node metastasis in human lung cancer

Using labelled streptavidin-biotin (LSAB) method, we examined the expression of nucleoside diphosphate kinase(NDPK), the product of metastasis suppressor gene nm23, in human lung cancer. Of 88 patients tested, 48 (54.5%) showed positive staining. The positive staining rate was higher in adenocarcinoma (28/42, 66.7%) than in squamous cell carcinoma (20/46, 43.5%; P < 0.05). Higher incidence of positive staining was also found in squamous cell carcinoma without hilar or mediastinal lymph node metastasis (16/27, 59.3%) than in that with hilar or mediastinal lymph node involvement (4/19, 21.1%; P < 0.05). NDPK/nm23 was equally expressed in adenocarcinoma irrespective of lymph node status. In both cell types of carcinoma, expression of NDPK/nm23 was not correlated with tumor cell differentiation, nor was it correlated with the P-TNM staging. Our results suggest that NDPK/nm23 may play different roles in the pathogenesis and metastasis of human pulmonary squamous cell carcinoma and adenocarcinoma. Its expression levels are inversely correlated with lymph node metastasis in squamous cell carcinoma.     

Extremity soft tissue sarcoma with metastases to abdominopelvic surfaces

BACKGROUND: In a majority of patients with extremity soft tissue sarcoma, the lungs are the first site at which recurrent disease is detected. Other common sites of recurrence are the resection site, bone metastasis, and liver metastasis. Although abdomino pelvic sarcomatosis is common as a site of recurrence for visceral and retroperitoneal sarcoma, it has not been previously reported for extremity sarcoma. METHOD: We present three patients in whom extremity soft tissue sarcoma metastasized to the peritoneal surfaces, and in all three patients this was symptomatically the dominant site for recurrence. All of them underwent a palliative surgical cytoreduction and were then treated with intraperitoneal chemotherapy. RESULTS: In two of the three patients, isolated progression of peritoneal sarcomatosis has again occurred: one patient remains disease free at 14 months. CONCLUSIONS: Metastasis to peritoneal surfaces within the abdomen and pelvis must be considered a possible site for systemic dissemination of extremity soft tissue sarcomas. Effective treatments for sarcoma spread to peritoneal surfaces would benefit this small but symptomatic group of patients.     

Predictors of survival for prostate carcinoma patients treated with salvage radical prostatectomy after radiation therapy

BACKGROUND: Salvage radical prostatectomy is a treatment option for patients with recurrent cancer following radiation therapy. This study was conducted to identify predictors of survival for patients treated with salvage radical prostatectomy. METHODS: The authors studied 86 prostate carcinoma patients who underwent salvage radical prostatectomy for locally persistent or recurrent prostate carcinoma at Mayo Clinic between 1967 and 1996. The mean interval from radiation therapy to biopsy-proven recurrence was 3.7 years (range, 6 months to 17 years). Patient age at surgery ranged from 51 to 78 years (median, 66 years). The mean follow-up after surgery was 5.8 years (range, 1.0-15.2 years). Cox proportional hazards models were used to identify clinical and pathologic factors associated with distant metastasis free survival and cancer specific survival. RESULTS: Actuarial distant metastasis free survival, cancer specific survival, and overall survival were 83%, 91%, and 85% at 5 years and 69%, 64%, and 54% at 10 years, respectively. In multivariate analysis, radical prostatectomy Gleason score and DNA ploidy were independent predictors of distant metastasis free survival and cancer specific survival. CONCLUSIONS: Postirradiation Gleason score and DNA ploidy were highly predictive of the clinical outcomes of patients treated by salvage radical prostatectomy after radiation therapy.     

Systemic interleukin 2 therapy for human prostate tumors in a nude mouse model

Once the regional lymph nodes become involved in prostate carcinoma, 85% of patients develop distant metastases within 5 years, and metastatic disease is difficult to treat. We have investigated the effect of systemic interleukin 2 (IL-2) treatment on metastatic prostate carcinoma using a xenograft tumor model. Cells from a PC-3/IF cell line, produced by intrafemoral injection of human PC-3 prostate carcinoma cells, were injected in the prostate of Balb/c nude mice. Prostate tumors and para-aortic lymph nodes were resected, and tumor cells were recultured and passaged in the prostate in vivo to produce new cell lines. On day 6 following prostatic injection of these cell lines, mice were treated with i.p. injections of IL-2 at 25,000-50,000 units/ day for 5 consecutive days. The effect of IL-2 on tumor progression was assessed, and histological studies were performed on prostate tumor and lymph node sections. The tumor cell lines generated by serial prostate injection were tumorigenic and metastasized to regional para-aortic lymph nodes. Tumors of 0.4 cm were obtained by day 16 and grew to 1-1.5 cm by day 40 with metastasis to para-aortic lymph nodes. Following two to three weekly courses of 5 days of 25,000-40,000 units/day of IL-2, the growth of prostate tumors was inhibited by 94%. Higher doses of 50,000 units/ day were toxic. Histologically, prostate sections showed vascular damage manifested by multifocal hemorrhages and an influx of lymphocytes and polymorphonuclear cells into disintegrating tumors and areas of necrosis containing numerous apoptotic cells. In contrast to control mice, para-aortic lymph nodes were not enlarged in responding mice. These findings suggest that systemic IL-2 therapy can induce an antitumor response in prostate tumors and control their growth and metastasis.     

Chylous ascites following heart transplantation

BACKGROUND: Hepatocellular carcinoma is highly refractory to most chemotherapeutic agents. Clofazimine, a riminophenazine compound used to treat leprosy since 1962, inhibits various cancer cell lines, including hepatocellular carcinoma cell lines, via phospholipase A2 dependant processes. Clofazimine also inhibits p170-glycoprotein, the mdr1 gene product. PATIENTS AND METHODS: Thirty patients (26 males and four females) with unresectable (25) or metastatic (5) hepatocellular carcinoma received oral clofazimine 600 mg daily for two weeks, followed by 400 mg daily until progression or death. RESULTS: There were three responses (10%)--one of a soft tissue metastasis, and two of local disease, with 13 patients disease stabilizing for up to 20 months. The overall median survival was 13 weeks. Adverse events included hyperpigmentation, eczematous skin rashes and palpitations. CONCLUSIONS: Although only three patients had an objective response (10%), the 13 patients with stable disease for up to 20 months, and an overall median survival of 13 weeks, suggest that clofazimine, or other riminophenazine compounds may prove to be of value in hepatocellular carcinoma.     

Preoperative assessment of advanced gastric carcinoma using computed tomography

OBJECTIVES: The role of computed tomography (CT) for the staging of gastric carcinoma is controversial. The purpose of this study was to evaluate the utility of CT in assessing the perigastric spread of advanced gastric carcinoma. METHODS: The study included 56 patients who underwent dynamic CT and laparotomy for the treatment of node-positive gastric adenocarcinoma. Preoperative CT findings were compared with surgical findings, and diagnostic accuracy was estimated. RESULTS: Sensitivity, specificity, and accuracy of preoperative CT in determining the perigastric tumor spreads were 33, 97, and 73% in pancreatic invasion, 36, 97, and 70% in level III lymph node involvement, and 89, 98, and 96% in liver metastasis. Peritoneal dissemination was not detected in 15 of 56 patients (27%), and stage IV disease was not diagnosed correctly in 18 of 40 patients (45%). CONCLUSIONS: Radiologists and surgeons must remember that pancreatic invasion, extended lymph node metastasis, and peritoneal dissemination are sometimes overlooked in CT examination in patients with advanced gastric carcinoma.     

Statistical analysis of 1186 cases of gastric carcinoma: with special reference to advanced lesion (author's transl)

750 cases of advanced gastric carcinoma were macroscopically and microscopically studied in relation with the 10 year survival rate. Most of the patients, 59.3% in female and 68.8% in male, belonged to the 5th and 6th decades. Macroscopically 44.1% of the cases were grouped in Borrmann III type, and secondly Early-Cancer Like Lesion, 26,6%. Histologically, in 510 cases out of 750 (68.0%) serosa was definitely broken by carcinoma cell nests and in 500 cases (66.7%) lymphnode metastasis was observed. The most frequent histological type was diffuse type, 44.9%, and secondly papillotubular type, 21.2%. 10 year survival rate of 516 cases, in which no residual cancer tissue was ascertained and the favorite prognosis could be expected was studied on various factors: Early-Cancer-Like-Lesion and Borrmann I & II types carcinoma, those cases in which the muscularis propria or serosa was preserved, those cases without lymphnode metastasis, and papillotubular or medullary tubular carcinomas showed a favorite prognosis in comparison with other types.     

Is there a role for cryoablation of the prostate in the management of localized prostate carcinoma?

It is impossible to adequately answer the question of whether there is a role for CSAP in the management of localized prostate carcinoma without considering the relative advantages and limitations of using other therapies to manage this disease (radical prostatectomy, radiation therapy, hormonal therapy, brachytherapy, expectant observation, and so on). Obviously, this is beyond the scope of this article. It is probably fair to point out, however, that the management of localized prostate carcinoma in the United States is generally quite controversial at the present time, and that despite a considerable amount of data pertaining to these therapeutic alternatives, it is difficult to discern a standard approach that can be broadly applied for all men with this disease. Therefore, if an absence of consensus on the management of localized prostate carcinoma does exist, it seems evident that investigations into alternative therapies are justified, and the preliminary results and efforts investigating CSAP fall well into this paradigm. In this context, several points can be made based on the available information. Significant numbers of patients who undergo CSAP can sustain undetectable levels of PSA for durable periods of time (more than 24 months). Thus, on a clinical level it seems possible to ablate the entire prostate with percutaneous CSAP, although rates of achieving this may be lower than originally anticipated. The reasons for persistence of carcinoma post CSAP are likely technical and related to the difficulties in determining the effective probe placements, number of probes to be used, number of freeze-thaw-freeze cycles to be used, and so on. Previous radiation exposure appears to confer an increased risk of CSAP-related morbidity, with incontinence, tissue sloughing, and rectal injury most prominent. Among nonradiated patients, incontinence is rare, and the most prominent postoperative concern involves BOO/tissue sloughing in a minority of patients. The longest follow-up data available on CSAP suggests that for patients with nonmetastatic prostate carcinoma, CSAP is associated with persistence of carcinoma in only 25% of patients. This compares favorably with the available biopsy data following external beam radiotherapy, in which most reports document positive biopsy results ranging between 30% and 100%, with the majority in the 40% to 50% range. Notably, the positive biopsy rate among patients with stage T3 disease following CSAP at 2 years can be less than 30%, which compares very favorably with previously reported positive biopsy result for these patients following external beam radiation therapy, which ranged between 40% and 100%. The management of patients with persistent carcinoma following CSAP poses fewer concerns to physicians than for those with persistent carcinoma following radiation therapy. Given the number of patients with prostate carcinoma who currently undergo radiotherapy as primary management, these data indicate that CSAP can now be considered a very viable therapeutic alternative for selected patients. With standardizations of technique as well as improved modifications in equipment, these preliminary CSAP results may well improve steadily in the near future. In the absence of randomized, comparative trials, it is difficult to draw meaningful comparisons between CSAP and radical prostatectomy. Based on available information, CSAP appears to be associated with a much lower incidence of stress and total incontinence than is radical prostatectomy. The rates of impotence following CSAP are somewhat comparable to those seen after radical prostatectomy, with wide variation among individual series. For patients who would be ideal candidates for radical prostatectomy (for example, less than stage T2c disease, PSA less than 10 ng/mL, and Gleason score of 7 or less), several authors have noted that the positive biopsy rate between 6 and 12 months is less than 10%.     

Association of p53 mutations with metastatic prostate cancer

In prostate cancer, mutation of the p53 tumor suppressor gene has been associated with locally advanced disease and hormone-resistant disease that is predominantly localized to bone. However, little is known regarding the status of the p53 gene in metastatic prostate cancer that has not been treated with hormonal manipulation. We evaluated formalin-fixed, paraffin-embedded malignant tissues from 86 patients with various stages of prostate cancer, including pathologically confined, locally advanced, and metastatic disease, to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. No abnormal p53 immunostaining was detected in 18 patients with prostate cancer confined to the gland. Two tumors from 21 patients with locally advanced disease (extracapsular extension and/or seminal vesicle invasion) had abnormal nuclear p53 accumulation, and a mutation in exon 7 of the p53 gene was detected in tumor DNA from one patient using single-strand conformation polymorphism-direct sequencing analysis. Of the remaining 47 patients studied in whom tissues from the prostate gland and a metastatic site (44 lymph node, 2 bone, and 1 lung) were available, only 3 had received hormonal therapy prior to obtaining metastatic tissue. In four patients both primary and metastatic tumors demonstrated accumulation of p53 protein, whereas seven additional patients exhibited p53 accumulation only at the metastatic site. In three patients the metastatic tumors harbored missense single-base substitutions in exon 5, as detected using single-strand conformation polymorphism-direct sequencing. These results indicate that p53 abnormalities are associated with lymph node metastases derived from prostate cancer patients that had not undergone hormonal therapy.