Acid suppressing therapy as a risk factor for Candida esophagitis.

Studies were reviewed from PubMed for risk factors for the development, recurrence, prevention and therapy of Candida esophagitis, and for mechanisms induced by acid-suppressing therapy potentially influencing these factors. Documented observations included greatly increased Candida populations in the mouth, esophagus, stomach, and upper small intestine induced by acid-suppressing therapy. Among patients without HIV disease, PPI consumers more frequently had developed Candida esophagitis than did non-consumers and had also developed its recurrences more frequently. Similar phenomena associated with H2 -blocker use were less intense, and the possibility of similar phenomena in patients with HIV disease apparently had not yet been examined in spite of their high frequency of this disorder. PPI-induced elimination of the gastric acid barrier is a major mechanism leading to oro-pharyngeal and esophageal candida colonization, while PPI-induced impairment of absorption of most orally administered antifungal agents may limit the prophylactic and therapeutic success of these agents. These observations suggest potential value in limiting PPI use in populations of patients with Candida infections including esophagitis, as well as in patients at risk for their development, and also suggest that post-PPI rebound acid hypersecretion may provide additional anti-Candida benefit. Studies designed to develop the risk-benefit ratios of PPI use in these patients deserve investigation with high priority appropriate for studies in patients with HIV disease.

Osteoporosis due to androgen deprivation therapy in men with prostate cancer.

OBJECTIVES: The frequency of osteoporotic fractures is greatly increased in men receiving androgen deprivation therapy (ADT), but whether the risk of osteoporosis differs between different types of ADT or between continuous and intermittent therapy has not been determined. Techniques for modifying ADT-associated bone loss have not been clearly identified. METHODS: Risk factors for the development of osteoporosis in men receiving ADT will be reviewed. Relations between bone mineral density (BMD) values and the development of osteoporotic fractures, along with methods for preventing both BMD loss and osteoporotic fractures, will be discussed. RESULTS: ADT rapidly accelerates bone loss among men with prostate cancer and multiplies the risk of osteoporotic fractures among them. Factors other than ADT-associated bone loss contributing to this fracture risk include both decreased BMD before ADT and an increased tendency to fall associated with muscle weakness, impaired balance, and postural hypotension. Each of these factors may be associated with poor nutrition, advancing malignant disease, hypogonadism of non-ADT origin, advanced age, and the use of narcotic, antihypertensive, or sedative medications. Although the success of therapy designed to improve BMD values and lower the fracture rate in these patients has not been explored, regular exercise, smoking abstinence, adequate calcium, protein, and vitamin D intake, maintenance of weight, and the use of bisphosphonates or calcitonin may each have a useful therapeutic role. Theoretical considerations suggest that intermittent ADT may decrease the frequency of ADT-associated osteoporosis. CONCLUSIONS: An urgent need exists for the definition of techniques useful in preventing osteoporotic fractures in men receiving ADT for prostate cancer.

Hypogonadism following prostate-bed radiation therapy for prostate carcinoma.

BACKGROUND: The degree of testicular damage resulting from primary treatment of prostate carcinoma by external beam radiation therapy (EBRT) to the prostate bed has not been determined. If significant testicular damage has occurred, the resulting endocrine changes may result in modified tumor behavior, contribute to postradiation impotence, and may aggravate other signs and symptoms of hypogonadism, potentially influencing a patient's choice of primary treatment for his tumor. METHOD: Three to eight years after primary treatment for localized prostate carcinoma, serologic evaluation for hypogonadism was undertaken in 33 men who had received EBRT and in 55 similar men who had received radical prostatectomy (RP). No subjects had developed recognized tumor recurrence, and none had undergone hormonal treatment since primary therapy. RESULTS: Among men of similar age, prior treatment with EBRT was associated with significantly more frequent hypogonadism than prior treatment with RP. In men with EBRT, total testosterone levels averaged 27.3% less, free testosterone levels 31.6% less, dihydrotestosterone levels 33.4% less, luteinizing hormone (LH) levels 52.7% greater, and follicle-stimulating hormone (FSH) levels 100% greater than those values in men who had prior treatment with RP. Differences between postradiation and postsurgical men in LH and FSH levels were most prominent in men older than 70 years. CONCLUSIONS: Three to eight years after primary treatment for prostate carcinoma, striking hormone differences were present between men who had received EBRT to the prostate bed and those with prior RP. These differences strongly suggested that prominent and permanent testicular damage was sustained during EBRT, frequently severe enough to cause hypogonadism.

Progressive osteoporosis during androgen deprivation therapy for prostate cancer.

PURPOSE: Hypogonadism is a prominent risk factor for osteoporosis in older men. However, bone loss during androgen ablation therapy for prostate cancer has rarely been quantitated. MATERIALS AND METHODS: Femoral neck bone mineral density was determined in 26 men before orchiectomy or chemical castration as initial hormone therapy for prostate cancer and at 6-month intervals thereafter for 6 to 42 months. Measurements were made in 16 other men at 12 to 24 months beginning 3 to 8 years after the onset of castration. Baseline and post-castration bone loss was related to several host and tumor characteristics, and compared to similar measurements in 12 control subjects. RESULTS: Average age corrected baseline femoral neck bone mineral density was higher in controls than in treated men and remained essentially unchanged for 2 years. Following orchiectomy average bone mineral density decreased 2.4% and 7.6%, respectively, during years 1 and 2 (2-year loss 2.5% to 17.0%), with similar losses documented in men undergoing chemical castration. Average bone mineral density decreased 1.4% to 2.6% per year 3 to 8 years after uninterrupted androgen deprivation. Age corrected baseline bone mineral density was greater in men who were obese, younger than 75 years or participated in regular exercise but the influence of each characteristic could not be isolated. Post-castration bone loss was greater in men who were obese, younger than 75 years without regular exercise. CONCLUSIONS: Chemical or surgical castration in men with prostate cancer is usually followed by greatly accelerated bone loss which may be superimposed on a bone mass already depleted before hormonal therapy. Baseline bone mass and subsequent bone loss may be influenced by host obesity, age and exercise habits.

A worse prognosis for men with testicular atrophy at therapeutic orchiectomy for prostate carcinoma.

BACKGROUND: The significance of testicular atrophy at the time of therapeutic orchiectomy for prostate carcinoma has not been examined even though pretreatment hypogonadism has been associated with poor prognosis during chemical androgen ablation for these tumors. METHODS: Survival after therapeutic orchiectomy was determined for 78 men with prostate carcinoma and related to the histologic severity of testicular atrophy. Included in analysis were the presence or absence of prior radiation therapy, tumor grade and stage at diagnosis, host age, obesity, and smoking habits. RESULTS: Among 35 men who underwent therapeutic orchiectomy for progressive disease after primary radiation therapy to the prostate bed, the 25 men with testicular atrophy had worse 5-year, tumor specific, postorchiectomy survival than the 10 men without testicular atrophy (30% vs. 89%) (P=0.02). These 25 men had tumors of more advanced stage and greater undifferentiation at the time of diagnosis an average of 45 months before orchiectomy, but neither characteristic was related to postorchiectomy survival. Among 25 men with Stage D2 disease (American Urologic Association staging system) with orchiectomy as the primary treatment, the 7 men with testicular atrophy more often had undifferentiated tumors and had lower 2-year tumor specific survival than the 18 men without atrophy (43% vs. 72% ) (P > 0.10). CONCLUSIONS: Testicular atrophy at the time of therapeutic orchiectomy for prostate carcinoma is associated with poor postorchiectomy prognosis in men with prior prostate bed radiation therapy and perhaps in men without prior radiation. The association may reflect a high frequency of inherently more aggressive tumors (often relatively nonandrogen-dependent) among those tumors that are progressing in hypogonadal men.

Testicular atrophy in therapeutic orchiectomy specimens from men with prostate carcinoma: association with prior prostate bed radiation and older age.

BACKGROUND: The significance of testicular atrophy at the time of therapeutic orchiectomy for prostate carcinoma has not been examined even though hypogonadism may occur after prostate bed radiation therapy for these tumors, may itself be symptomatic, and also may be associated with poor tumor prognosis. METHODS: Therapeutic orchiectomy specimens from 78 men with prostate carcinoma and no preceding hormonal therapy were evaluated histologically for atrophy. Observations were related to prior radiation therapy, tumor grade and stage diagnosis, host age, obesity, and smoking habits. RESULTS: Thirty-five men who previously received radiation therapy to the prostate bed had testicular atrophy more frequently than 43 men without prior radiation (71% vs. 28%) (P < 0.001). In men without prior radiation, atrophy was less common in specimens from those age < 70 years than in specimens from men age > 70 years (7% vs. 38%) (P < 0.04). In men with prior radiation, prominent atrophy occurred with similar frequency in specimens from both younger and older men, and was more frequent in specimens obtained within 3 years after radiation therapy than in specimens obtained after longer postradiation intervals (89% vs. 53%) (P < 0.001). CONCLUSIONS: Testicular atrophy at the time of therapeutic orchiectomy for men with prostate carcinoma is much more common in patients with prior prostate bed radiation therapy. Available evidence suggests that this association may reflect both radiation-induced testicular injury and more frequent early tumor recurrence in men with atrophy preceding their radiation therapy.

Osteoporosis after orchiectomy for prostate cancer.

PURPOSE: The possibility of increased osteoporosis and osteoporotic fractures following therapeutic orchiectomy in men with prostate cancer was investigated. MATERIALS AND METHODS: A total of 235 men with nonstage A prostate cancer diagnosed between 1983 and 1990 was analyzed for therapeutic orchiectomy, other osteoporotic risk factors and subsequent hospital treatment for osteoporotic fractures. The 17 castrated men alive in 1995 were interviewed, and femoral neck bone mineral density was compared to that of 23 controls of similar age. RESULTS: Risk factors for osteoporosis, including smoking, slender habitus and atrophic testes, were common among men treated with orchiectomy. Of the men in the study cohort 10 had osteoporotic fractures: 8 of 59 treated with and 2 of 176 without orchiectomy (13.6 versus 1.1%, p < 0.001). First fracture cumulative incidence rates 7 years after castration or diagnosis were 28 and 1%, respectively (p < 0.001). Osteoporotic fractures were much more common than pathological fractures or those due to major trauma (1 each). Bone mineral density averaged 0.91, 0.84, 0.79 and 0.66 gm./cm.2 in 9 controls without prostate cancer, 14 men with prostate cancer before orchiectomy, 9 men at 9 to 60 and 8 men at 60 to 115 months after orchiectomy, respectively. Of the 16 men surviving for longer than 60 months after orchiectomy 6 had osteoporotic fractures, as did 5 of 6 and 5 of 7 with a bone mineral density of less than 0.70 gm./cm.2 and less than 75% of normal for age, respectively. CONCLUSIONS: Orchiectomy for prostate cancer is frequently followed by severe osteoporosis, some of which had developed before castration. Appropriate therapy should be identified that does not diminish the antitumorigenic effectiveness of androgen ablation.

A better prognosis for obese men with prostate cancer.

PURPOSE: The possibility was investigated whether obesity is associated with a favorable prognosis in men with nonstage A prostatic cancer independent of other risk factors. MATERIALS AND METHODS: A total of 235 men with nonstage A prostatic cancer diagnosed between 1983 and 1990 at a community hospital was evaluated by tumor grade and stage, degree of obesity, smoking habits, age, year of diagnosis and survival. RESULTS: In comparison to tumors of less obese men those in men who were at least 10% overweight were more often stage B or C than D (odds ratio 2.3, 95% confidence interval 1.4 to 4.9). Smoking abstinence, patient age older than 70 years and low Gleason scores were also independently associated with less advanced tumors. The lower frequency of advanced stage tumors among those of obese men was most prominent for stage D2 disease in nonsmokers, progressively decreasing from 24% of 29 nonsmokers who had been underweight for many years before diagnosis to 8% of 24 who had been greatly overweight for many years (p < 0.05). Tumor specific mortality was also lower in obese men and nonsmokers independent of tumor stage and grade with 5-year tumor specific mortality rates of 10% in obese nonsmokers, 27% in nonobese nonsmokers, 36% in obese smokers and 43% in nonobese smokers. These differences reflected a combination of obesity related differences in stage distribution and a more favorable prognosis for obese men among patients with tumors of similar stages. CONCLUSIONS: These observations suggest inhibition of prostate cancer growth and metastasis by increased endogenous estrogen, decreased endogenous testosterone or other systemic changes characteristic of obesity.

A worse prognosis for smokers with prostate cancer.

To identify phenomena that might explain a higher mortality-to-incidence ratio for prostate cancer among smokers, 359 patients with newly diagnosed tumors at a community hospital were analyzed by tumor stage and grade, host age, obesity, smoking habits and survival. Among the 235 men with nonstage A tumors, stage D disease was independently related to host smoking (odds ratio 2.1, 95% confidence interval 1.3 to 4.3, p = 0.015), as well as to higher tumor grade, younger host age and lack of obesity. Stage D disease was present in 69% of 16 heavy smokers, 41% of 44 other smokers and 31% of nonsmokers. The 5-year tumor-specific mortality rate was greater among smokers than nonsmokers with stage D2 disease (88% versus 63%, p < 0.05) or with nonstage A disease (39% versus 17%, p < 0.001). These observations are compatible with earlier metastasis and more aggressive subsequent tumor advancement in smokers, and indicate that smoking habits may contribute to differences in prostate cancer prognosis between populations.

More advanced-stage tumors among smokers with endometrial cancer.

To determine whether endometrial cancer is unusually aggressive in smokers, smokers were compared with nonsmokers among 157 women who had undergone hysterectomy for these tumors between 1979 and 1988. The following factors were analyzed: tumor stage and grade, duration of tumor-related symptoms, host age, degree of obesity, use of estrogen supplementation, and smoking habits. Multivariate analysis indicated that women with advanced-stage disease (stages II-IV) more often had been smokers than women with early-stage disease (stages 0-I; 12 of 30 [40%] versus 14 of 127 [11%], respectively; odds ratio, 5.38; confidence interval, 2.23-11.31). Smokers and nonsmokers were similar in age, parity, degree of obesity, use of estrogen supplementation, tumor grade, and duration of symptoms. Advanced-stage disease also was associated with a high tumor grade (odds ratio, 3.16). Among women with early-stage tumors, a trend toward more frequent myometrial invasion in smokers was not significant by conventional criteria. These observations apparently reflect a smoking-related decrease in the incidence of early-stage tumors, plus smoking-related increases in tumor invasiveness and metastasis.

Larger prostatic adenomas in obese men with no associated increase in obstructive uropathy.

In 379 men less than age 75 years who underwent initial transurethral prostatectomy for benign prostatic hypertrophy specimen weights were compared with host ages, obesity, smoking habits and the presence of incidental cancer. Among 334 men 60 to 74 years old average specimen weights increased with increasing obesity from 20.3 to 36.6 gm. Underweight men in comparison with men at least 30% overweight demonstrated more small specimens (10 gm. or less, 24% versus 2%, p < 0.001) and fewer large specimens (50 gm. or more, 5% versus 26%, p < 0.005). This pattern was present in smokers and nonsmokers. Adenoma weights increased with increasing host age and were larger in nonsmokers of all age groups. Body habitus was similar in the prostatectomy patients and 290 office patients of similar age, suggesting no increase in obstructive uropathy among obese men despite the larger adenomas. These observations are compatible with different risk factors for the obstructing and nonobstructing components of benign prostatic enlargement.

More stage A prostatic cancers, less surgery for benign hypertrophy in smokers.

Records were reviewed of 396 men less than 75 years old with a history of transurethral prostatectomies, known smoking habits, height, weight and no prostate malignancy more advanced than stage A. The 51 men with stage A cancer included more current smokers than the 345 without malignancy (45.1% versus 22.3%, odds ratio 2.9, confidence interval 1.6 to 4.5, p < 0.001). Prostatectomy specimens from smokers were smaller than those from nonsmokers (21.4 versus 26.9 gm., p < 0.005) and those from cancer patients were smaller than those from men without cancer. Small adenomas included more cancers per kilogram than large adenomas in smokers and nonsmokers. Men with a history of prostatectomy were less often current smokers than 128 men with newly diagnosed colon cancer (22.3% versus 42.2%, odds ratio 0.49, confidence interval 0.27 to 0.77), and less often ever smokers than 325 men from a general internist's office (46.5% versus 55.4%, odds ratio 0.70, confidence interval 0.52 to 0.94). These data suggest smoking as a risk factor for stage A prostatic cancer and confirm smoking abstinence as a risk factor for prostatic hypertrophy requiring surgery.

Larger axillary metastases in obese women and smokers with breast cancer--an influence by host factors on early tumor behavior.

To better define the influence by host factors on very early breast cancer behavior, we retrospectively analyzed nodal status, diameter of the largest axillary metastasis (M), diameter of the primary tumor (P), the M/P ratio, tumor estrogen receptor status, age, obesity, and smoking habits in 176 women with node-positive breast cancer. Both M/P ratios and M were larger in the 72 obese women and in the 40 nonobese smokers than in the 64 nonobese nonsmokers after control for other factors. Step-wise regression analysis demonstrated independent associations between M/P ratios and obesity (p = 0.0002), larger primary tumors (p < 0.0001), more positive nodes (p < 0.0001), and smoking (p = 0.0268), as well as between M and obesity (p = 0.0201), larger primary tumors (p = 0.0093), and more positive nodes (p = 0.0001). Among the 104 nonobese women, smoking was associated both with larger M (p = 0.0257) and larger M/P (p = 0.0055). Our observations suggest more rapid growth by metastases in obese women and smokers with breast cancer, as well as earlier metastasis from their primary tumors.