A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk.

BACKGROUND: Animal models suggest that n-3 fatty acids inhibit prostate cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies do not uniformly support these findings. METHODS: A nested case-control study was conducted among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Conditional logistic regression was used to estimate the relative risks (RR) and 95% confidence intervals (95% CI) of total, non-aggressive (stage A/B and Gleason < 7) and aggressive (stage C/D, Gleason >or= 7, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific fatty acids expressed as percentages of total fatty acids. RESULTS: Whole blood levels of all long-chain n-3 fatty acids examined and of linoleic acid were inversely related to overall prostate cancer risk (RR(Q5vs.Q1), 0.59; 95% CI, 0.38-0.93; P(trend) = 0.01 for total long-chain n-3 fatty acids and RR(Q5vs.Q1), 0.62; 95% CI, 0.41-0.95; P(trend) = 0.03 for linoleic). Blood levels of gamma-linolenic and dihomo-gamma-linolenic acids, fatty acids resulting from the metabolism of linoleic acid, were directly associated with prostate cancer (RR, 1.41; 95% CI, 0.94-2.12; P(trend) = 0.05 for gamma-linolenic and RR, 1.54; 95% CI, 1.03-2.30; P(trend) = 0.02 for dihomo-gamma-linolenic acid). Levels of arachidonic and alpha-linolenic acids were unrelated to prostate cancer. CONCLUSIONS: Higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer. The direct associations of linoleic acid metabolites with prostate cancer risk deserve further investigation.     

Dose escalation in locally advanced carcinoma of the prostate

Radiotherapeutic management of advanced prostate cancer is challenging. Several retrospective analyses showed a dose response for local tumor control before the availability of conformal radiation therapy. Attempts to escalate dose without the benefit of modern treatment planning was commonly fraught with high rates of bowel or bladder complications. The advent of image-guided or computed tomography-based treatment planning has allowed safe delivery of high-dose radiation therapy in men with prostate cancer with an acceptable rate of side effects and complications. Several prospective clinical trials have been conducted both at single institutions and in the cooperative group setting. Early evidence suggests that patients with high-risk factors such as advanced clinical stage, high initial prostate-specific antigen, or poorly differentiated tumors may benefit from high-dose 3-dimensional conformal radiation therapy with improved biochemical and local tumor control. A published randomized trial with conformal radiation therapy shows that a modest escalation of radiation dose leads to improved biochemical disease-free survival for a select group of patients. A confirmatory trial within the Radiation Therapy Oncology Group is underway to determine if dose escalation will improve overall survival in men without compromising quality of life. Copyright Elsevier Inc. All rights reserved.     

Inverse association between nonsteroidal anti-inflammatory drugs and prostate cancer.

BACKGROUND: Prostate cancer is considered a major health problem in western countries. Promising results from observational studies on cancer at other sites fuelled the publication of several studies assessing the association between nonsteroidal anti-inflammatory drug (NSAID) use and prostate cancer. However, these studies show conflicting results. METHODS: We conducted a cohort study with a nested case-control analysis to further study the association between NSAIDs and prostate cancer. We used data from the General Practice Research Database in United Kingdom. RESULTS: Aspirin use was associated with a reduced risk of prostate cancer [odds ratio (OR) = 0.70, 95% confidence interval (95% CI) = 0.61-0.79]. We also found that paracetamol use with a treatment duration longer than 1 year was associated with a decreased risk (OR = 0.65, 95% CI = 0.54-0.78). Non-aspirin-NSAID (NA-NSAID) and paracetamol short-term use was associated with a small increased risk whereas long-term users of NA-NSAIDs presented an OR of 0.89 (95% CI = 0.73-1.08). DISCUSSION: Our findings support a protective effect of aspirin and paracetamol against prostate cancer. The transient elevated risk observed among newly started users of NA-NSAIDs and paracetamol is most likely explained by prothopathic bias. We found some suggestion of a reduced risk with long-term use of NA-NSAID.     

n-3 polyunsaturated fatty acid intake and cancer risk in Italy and Switzerland

Data from a series of case-control studies, conducted in Italy and Switzerland between 1991 and 2001, have been analyzed to evaluate the role of n-3 polyunsaturated fatty acid (PUFA) intake in the etiology of cancer of oral cavity and pharynx (736 cases, 1772 controls), esophagus (395 cases, 1066 controls), large bowel (1394 colon, 886 rectum, 4765 controls), breast (2900 cases, 3122 controls) and ovary (1031 cases, 2411 controls). Controls were patients admitted to hospital for acute, non-neoplastic conditions, unrelated to modifications in diet. The multivariate odds ratios (OR) for the highest quintile of n-3 PUFAs compared to the lowest one were 0.5 for oral and pharyngeal cancer, 0.5 for oesophageal cancer, 0.7 for colon cancer, 0.8 for rectal and breast cancer and 0.6 for ovarian cancer; the estimates and the trends in risk were significant for all cancer sites, excluding rectal and breast cancer. The estimates for an increase in n-3 PUFAs of 1 g/week were 0.70 for oral and pharyngeal cancer, 0.71 for oesophageal, 0.88 for colon, 0.91 for rectal, 0.90 for breast and 0.85 for ovarian cancer. All the estimates were statistically significant, excluding that for rectal cancer, and consistent across strata of age and gender. These results suggest that n-3 PUFAs decrease the risk of several cancers.     

Inverse association between coffee drinking and the risk of hepatocellular carcinoma: a case-control study in Japan

Coffee use has consistently been associated with lower serum liver enzyme levels and a reduced risk of liver cirrhosis. A limited number of cohort and case-control studies also suggest a decreased risk of hepatocellular carcinoma (HCC) among coffee drinkers, but mostly without consideration of hepatitis virus infection. In the present case-control study, we recruited 209 incident HCC cases and three different controls (1308 community controls, 275 hospital controls, and 381 patients with chronic liver disease [CLD] without HCC), all of whom were aged 40-79 years and residents of Saga Prefecture, Japan. A questionnaire survey elicited information on coffee use during the last 1-2 years and 10 years before, and plasma hepatitis B surface antigen and antibodies to hepatitis C virus were tested for all but community controls. After adjustment for sex, age, heavy alcohol use, smoking status and hepatitis virus markers (except for community controls), coffee use during the last 1-2 years was associated with a decreased risk against any control group. For coffee use 10 years before, comparison between HCC cases and either community controls or CLD patients revealed a decreased risk; adjusted odds ratios for occasional use, 1-2 cups/day and > or =3 cups/day compared with no use were 0.33, 0.27 and 0.22 (P trend < 0.001), respectively, against community controls, and 0.86, 0.62 and 0.53 (P trend = 0.05), respectively, against CLD patients. These results suggest that coffee may protect against the development of HCC, yet further elaborate studies (hopefully, intervention studies) are warranted to corroborate these findings.     

Chemotherapy of advanced prostatic carcinoma

Metastatic prostate cancer remains incurable. Historically, therapy options for patients with nonlocalized disease have been limited to hormonal therapy and palliative radiation therapy. The use of cytotoxic chemotherapy has not been routine, and is still not rigorously demonstrated to alter the natural history of androgen-independent prostate cancer. Nonetheless, there is an established, if not universally accepted, role for chemotherapy in symptom palliation, and several combinations have been described that produce response rates in the range that are associated with alteration of disease progression and improved survival in other cancers. The further refinement of such combination regimens, and their application to patients much earlier in the course of the disease, are the most important immediate challenges for medical oncologists who treat prostate cancer. At present, the curative potential of all local therapies remains disappointing; it is expected that the advent of truly effective systemic therapy will bring much improved prospects for cure by the application of combined modality treatment.     

The challenge of locally advanced prostate cancer

Locally advanced prostate cancer can be reliably identified and has a disease-specific death rate of approximately 75%. Monotherapy treatment options have limited efficacy for locally advanced disease. Multimodality therapy may improve survival. This article reviews the current results of multimodality therapy, including hormonal therapy plus radiation therapy, hormonal therapy plus radical prostatectomy, and brachytherapy plus external-beam radiation therapy (EBRT), and presents current ideas for novel multimodality approaches.     

局部进展期前列腺癌的治疗进展

The standard treatment mode of locally advanced prostate cancer is still controversial. With the progress of medical technology, treatments of prostate cancer achieve different progresses in surgical treatment, radiotherapy and endocrine therapy. The three treatment modes have diverse tumor growth control rate and survival period, which have different complications and different influences on the quality of life.     

Inverse association between prostate cancer and the use of calcium channel blockers.

Calcium channel blockers block calcium signal-mediated apoptosis. It is hypothesized that the use of these drugs may be associated with the development of cancer. This study investigated the association between daily use of calcium channel blockers and prostate cancer in a community-based cohort of men who participated in a longitudinal study of lower urinary tract symptoms. Study subjects were men ages 40 to 79 years by January 1, 1990, and were randomly selected from Olmsted County in Minnesota. At baseline, participants underwent an interview to determine all medications taken on a daily basis, including calcium channel blockers and to elicit a family history of prostate cancer. During follow-up, all men with a histological diagnosis of prostate cancer were identified through patient self-report and by a review of the complete medical record. Over 12,668 person years of follow-up, 15 (6.8%) of 220 calcium channel blocker users and 120 (10.5%) of 1142 nonusers developed prostate cancer (P = 0.09; odds ratio, 0.62; 95% confidence interval, 0.36-1.10). With adjustment for age and family history of prostate cancer, the risk (odds ratio, 95% confidence interval) of prostate cancer was 0.55 (0.31-0.97) in calcium channel blocker users compared with nonusers. In analyses stratified by family history of prostate cancer, the risk of prostate cancer was 0.45 (0.23-0.88) in men without a family history and 2.64 (0.82-8.47) in men with a family history of prostate cancer (P = 0.006). These findings suggest an association between prostate cancer and daily use of calcium channel blockers that varies by family history of prostate cancer.     

Long-term hormone therapy and radiation is cost-effective for patients with locally advanced prostate carcinoma

BACKGROUND: In Radiation Therapy Oncology Group (RTOG) trial 92-02, after men received neoadjuvant hormone cytoreduction and radiotherapy for locally advanced prostate carcinoma, they were randomized to receive either 2 years of long-term androgen-deprivation (LTAD) or no further treatment (short-term androgen-deprivation [STAD]). The specific objective of the current study was to determine whether LTAD was a cost-effective treatment for patients with locally advanced prostate carcinoma. METHODS: The cost-effectiveness of LTAD was tested using a Markov model that was designed using proprietary software. The analysis took a payor's perspective. Unit costs were obtained by estimation using a global Medicare fee schedule. Costs and outcomes were discounted by 3%. Distributions were sampled at random from the treatment utilities, transition probabilities, and costs using a second-order Monte Carlo simulation technique. RESULTS: The expected mean cost was 32,564 dollars for LTAD compared with 33,039 dollars for STAD after accounting for the additional cost of salvage treatment for men who were treated with STAD. The mean number of quality-adjusted life years (QALYs) for men who received LTAD was 4.13 QALYs compared with a mean of 3.68 QALYs for men who received STAD. The cost-effectiveness acceptability curve analysis showed a 91% probability that LTAD was cost-effective compared with STAD. Although overall survival was similar in the LTAD and STAD groups, the patients who received LTAD experienced gains in QALYs and had lower costs, because LTAD prevented biochemical failure and the necessitating salvage hormone therapy. CONCLUSIONS: The current analysis showed that LTAD was cost-effective for the entire population studied in RTOG trial 92-02.     

The association between metabolic syndrome and the risk of prostate cancer,high-grade prostate cancer,advanced prostate cancer,prostate cancer-specific mortality and biochemical recurrence

Background

Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association.

Methods

We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs).

Results

The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96).

Conclusions

The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required.     

Sero-epidemiologal association between human-papillomavirus infection and risk of prostate cancer

Some epidemiological studies of prostate cancer have suggested the existence of a sexually transmitted risk factor, and some studies have reported the presence of human papillomavirus (HPV) DNA in prostate-cancer tissue. To perform a sero-epidemiological evaluation of whether HPV infection is associated with increased risk for prostate cancer, we performed a nested case-control study within a serum bank containing samples from 20,243 healthy Finnish men. We identified 165 cases of prostate cancer that were diagnosed up to 24 years after donation of the serum sample. Two control subjects per case were selected, matched for gender, age and municipality of residence. Serum samples were analyzed for the presence of IgG antibodies against 4 HPV types and against Chlamydia. The presence of antibodies against HPV type 18 was associated with a 2.6-fold increased risk of developing prostate cancer during follow-up (p < 0.005). HPV type 16 tended to be associated with subsequent prostate-cancer occurrence (relative risk: 2.4, p = 0.06), whereas seropositivity for HPV type 11 or type 33 or for Chlamydia was not associated with risk. The results suggest that infection with oncogenic HPV might be involved in the etiology of a minority of prostate cancers. Int. J. Cancer 75:564–567, 1998. © 1998 Wiley-Liss, Inc.     

External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma

BACKGROUND: The current study was conducted to evaluate the combination of external beam radiation therapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. METHODS: Twenty-six patients were treated on a Phase I/II protocol between June 1990 and April 1993. The median age of the patients was 69 years. Nine patients had well differentiated adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and six patients had poorly differentiated adenocarcinoma. All patients had American Urologic Society Stage C2-D1 adenocarcinoma. The median pretreatment prostate specific antigen (PSA) level was 29 ng/mL (range, 6-104 ng/mL). All patients received external beam radiation therapy using a four-field technique. The median radiation dose was 6,800 centigrays (cGy) given in 200-cGy fractions. Hyperthermia was administered concurrently with radiation therapy to temperatures of 42.5 degrees C for 30 minutes using a transrectal ultrasound applicator with 3 thermometry probes, given as either a single treatment (9 patients) or as two treatments (17 patients). Overall survival (OS) and biochemical no evidence of disease (bNED) status were calculated using Kaplan-Meier analysis. A consensus conference definition of PSA failure was used. The Cox proportional hazards model was used for multivariate analysis. The median follow-up for all patients was 71 months. RESULTS: The median time to PSA nadir was 15 months with a median PSA nadir value of 1.0 ng/mL. The median and 5-year OS was 88 months and 73%, respectively, and the median and 5-year bNED survival was 36 months and 35%, respectively. Multivariate analysis revealed only the pretreatment PSA level (P = 0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED survival. The duration of hyperthermia therapy showed a trend toward significance for OS (P = 0.06). CONCLUSIONS: The current Phase I/II protocol evaluating the combination of prostate hyperthermia and external beam radiation therapy for the treatment of patients with locally advanced prostate carcinoma suggests prostate hyperthermia to be feasible with no apparent significant increased toxicity, although there was no significant improvement in treatment outcome when compared with other studies reported in the literature evaluating external beam radiation therapy with or without androgen suppression. However, further investigation into the duration as well as the temperature of the hyperthermia with a greater number of patients is warranted.     

Neoadjuvant radiotherapy for locally advanced and high-risk prostate cancer

Men presenting with high-risk or locally advanced prostate cancer may benefit from a combination of radiotherapy and surgery to maximize local control. Adjuvant radiotherapy following surgery has improved biochemical progression-free survival, metastasis-free survival, lengthened the time to hormone therapy use and improved overall survival in three randomized-phase III trials. One surprising result of the Southwest Oncology Group (SWOG) 8794 trial and the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial is that treatment failure was mainly a result of lack of local control. This finding has led to a new appreciation of local control as a determinant of survival and the role for combined modality approaches within a multidisciplinary team in the treatment of high-risk and locally advanced prostate cancer. One emerging novel approach is the use of preoperative or intraoperative radiotherapy in addition to best surgical and systemic treatments. Preliminary results from clinical trials indicate low rates of intraoperative toxic effects, an advantage of short treatment times and smaller image-guided radiotherapy treatment volumes when compared with postoperative radiotherapy. Potential disadvantages include over-treatment of patients and lack of data on long-term toxic effects. We present the published treatment approaches and rational for preoperative and intraoperative radiotherapy and compare these methods to the utility of postoperative radiotherapy.     

Modern management of locally advanced cervical carcinoma

Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.     

局部晚期鼻咽癌的综合治疗

随着诊断和治疗技术不断进步,鼻咽癌的疗效已大幅提升,但局部晚期患者远处转移控制尚不理想,是影响患者生存的主要问题。化疗在鼻咽癌综合治疗中具有重要地位,适当的化疗强度及其与放疗结合的模式一直是研究热点。同期放化疗（concurrent chemora diotherapy,CCRT）虽已成为目前标准治疗模式,但在调强放疗时代,其价值再次受到挑战。本文就近年局部晚期鼻咽癌综合治疗的研究进展作一论述。     

Clinical and biological effects of neoadjuvant sargramostim and thalidomide in patients with locally advanced prostate carcinoma.

PURPOSE: Granulocyte macrophage colony-stimulating factor (GM-CSF) and thalidomide are active agents in prostate cancer. This study assessed the biological effects and safety of GM-CSF and thalidomide in patients with localized prostate cancer before radical prostatectomy. EXPERIMENTAL DESIGN: Locally advanced prostate cancer patients undergoing radical prostatectomy were recruited for this study. Treatment consisted of two 28-day cycles of GM-CSF (250 microg, s.c., thrice weekly) and thalidomide (200 mg, orally, daily) on days 1 to 28 of each cycle. Radical prostatectomy occurred within 7 to 10 days after completion of therapy. Pretreatment and posttreatment specimens were used to assess the expression of CD3, CD68, Ki-67, S100, PTEN, and CD31. Peripheral blood was examined for dendritic cells, regulatory T cells, and cytokines. RESULTS: Twenty-eight patients were enrolled. No pathologic responses (P0) were observed and no unexpected toxicities or surgical complications occurred. Eighty-one percent of patients had a prostate-specific antigen decline (mean +/- SD decrease was 21.1 +/- 15.4%; median, 18.0%). With a median follow-up of 32 months, five patients have experienced progression. Radical prostatectomy tumor tissue specimens showed significant CD3 and S100 overexpression when compared with pretreatment biopsies. No significant changes in tumor macrophage infiltration were observed. Increased number of serum dendritic cell, as well as high serum levels of interleukin-8, basic fibroblast growth factor, and vascular endothelial growth factor, was also observed. CONCLUSIONS: Neoadjuvant GM-CSF and thalidomide was safe and feasible and did not affect the perioperative morbidity of radical prostatectomy. Although no pathologic complete responses were observed, significant posttreatment tumor T-cell and dendritic cell infiltration was noted. No significant changes in serum cytokines, dendritic cells, or regulatory T cells were induced.     

局部晚期喉癌颈部淋巴结转移规律及相关因素分析

目的 分析局部晚期(T3、T4期)喉癌颈部淋巴结转移(LNM)规律,为喉癌放疗颈部靶区勾画提供参考。方法 回顾分析2000-2017年中国医学科学院肿瘤医院初治局部晚期喉癌患者,所有患者至少行双颈Ⅱ-Ⅳ区淋巴结清扫,计算颈部各区LNM率。采用Logistic回归分析LNM相关因素。结果 共272例患者纳入研究,全组患者LNM率为57.1%(156/272)。根据原发病变部位分3个组:A组(72例),原发灶局限于一侧;B组(86例),原发灶主体偏于一侧但侵犯过中线;C组(114例),原发灶为巨大或中央型病变。各组不同颈部分区LNM率:A组同侧颈部Ⅱ区36.3%、Ⅲ区26.4%、Ⅳ区6.9%,对侧分别为13.9%、8.3%、1.4%;B组:同侧颈部Ⅱ区41.9%、Ⅲ区29.1%、Ⅳ区11.6%,对侧分别为18.6%、14.0%、1.2%;C组:左侧Ⅱ区24.6%、Ⅲ区 23.7%、Ⅳ区2.6%,右侧分别为21.9%、26.3%、6.1%。局限单侧(A组)与中线受侵(B、C组)双侧LNM率相近(15.3%、25.0%,P=0.093)。同侧Ⅲ区是否转移和临床淋巴结分期与对侧颈是否LNM相关(OR=2.929,95%CI为1.041~8.245,P=0.042)和OR=0.082,95%CI为0.018~0.373,P=0.001)。同侧Ⅱ区、Ⅲ区转移是同侧Ⅳ区转移的危险因素(P=0.043、0.009)。结论 双侧颈部Ⅱ、Ⅲ区是高危LNM区,Ⅳ、Ⅴ区转移较少见;同侧Ⅱ、Ⅲ区转移是同侧Ⅳ区及对侧颈LNM的相关因素,cN0期患者少见对侧颈LNM。