Tag Archives: all-cause mortality

UPDATE: COLORECTAL CANCER SCREENING IN LOWRISK PATIENTS- NO BENEFIT ON ALL-CAUSE MORTALITY. IS IT ANYTHING BUT A HUGE EXPENSE- AND RISK?

neil.burman@gmail.com

21 Dec 2014 Update: No response has been received from or published by  Annika  Steffens ea  of Australian universities in the past 2 months on the allcause mortality difference by CRC screening in their massive colorectal  cancer CRC screening study in an older population. .

But a number of autopsy studies the past 40 years throw more light on how infrequent CRC actually is elsewhere , Australia apparently having one of the highest rates at 0.125% pa.

As regards apparently undiagnosed cancer found at autopsy: colon cancer is very infrequent, and its import drops with age; and is no more common in sudden death potential organ donors than in others. In Japan over 20 years, the incidence of unsuspected colon cancer in 3600  routine autopsies  was only 0.03%pa. In Singapore in 1000 random autopsies on the other hand, incidental CRC was found in 10 ie a prevalence of 1%. In the Connecticut Cancer registry over 50 years, one cancer trebled the risk of a second cancer- especially  high risk of cancers of lung, larynx, mouth, pharynx; breast;colon, uterus,  ovary, cervix; suggesting a common etiology involving  smoking & HPV? , ie an intriguing link  between female genital tract, breast, airway  and colon but not prostate.. However studies since at least 2005  including from RSA 2007, do indicate a link between HPV and prostate cancer, the latest from Crete University 2014.

So smoking, alcohol and  STDs- especially HPV- are a deadly triad in   male-dominated  permissive countries like South Africa – but  likely worse in strict Islamic countries that keep citizens (subjugated women even more than men) overdressed ie minimize sunshine and thus lifegiving vitamin D3 levels.  .

refs: A  new study   from France asks:  Are suicide rates higher in the cancer population? An investigation using forensic autopsy data.  Med Hypotheses. 2014  de la Grandmaison,  Charlier ea Versailles Saint-Quentin University,    note previous population-based studies have identified increased suicide rates among cancer patients.  In total, 232 cases were included in both the suicide and the control groups.  Cancer was significantly more often found in the suicide group than in the control one (8.6% vs. 3.9%, p=0.03).  the presence of cancer increased the risk of suicide. Moreover, cancer was not known to the deceased in 70% of cases, while the most frequent mental disease found in cancer-related suicide cases was depression (75%). In the 20 cancer-related suicide cases analysed herein, it was difficult to ascertain whether malignancy was the only motive for committing suicide, as cancer could be considered to be either a major causative factor for suicide or an incidental finding.

Crit Rev Oncol Hematol. 2012 Cancer prevalence and mortality in centenarians: a systematic review. Pavlidis ,  Audisio  ea  Univ of Ioannina,Greece.   Data analysis demonstrates how cancer incidence and cause of death present a threefold decrease after age 90 and reach 0-4% above age 100. In addition, the number of metastatic sites are remarkably less and incidental malignant tumours or multiple primary cancers are more frequent, indicating that cancer in centenarians carries a more indolent behaviour. Cancer in the very elderly is relatively uncommon as a disease and as a cause of death. It is characterized by a slow growth and a modest life-threatening potential.

Arch Pathol Lab Med. 2009 Unexpected neoplasia in autopsies: potential implications for donor tissue  safety. Sens, Cooley ea University of North Dakota.-Medical examiner cases are increasingly used as tissue donor referral sources to meet ever-growing need for transplant tissues. Assumption is often made that traumatic and sudden deaths have minimal risk of unsuspected neoplasia.-A retrospective, 5-year review of 412 autopsies from a regional, primarily forensic, autopsy service to determine the incidence of unsuspected neoplasia, potential donor referral suitability. Unsuspected neoplasia rate at autopsy was 7% (29 of 412 patients); cancer was the cause of death in 41% (12 of 29 patients) of these individuals. In patients with a history of cancer, the discordance of cancer diagnosis was 44% (4 of 9 patients [11 patients with known cancer, 2 who refused medical evaluation were excluded from the study]). Nearly 60% (17 of 29 patients) of the unsuspected cancer cases had no apparent reason for deferral of tissue procurement before the autopsy examination.

Ueyama,Tsuneyoshi ea  Kyushu University, Japan.  During the past 20 yr, 17 colorectal carcinomas (0.47%) were incidentally detected among 3,638 autopsied patients without clinically evident colorectal carcinoma, including 2,232 males and 1,406 females, more than 40 yr old. Among the 15 male and two female index subjects, six (0.33%) were detected in the first and 11 (0.60%) in the second decade.

Cancer. 1988 Mar 1;61(5):1059-64.  Incidental carcinoma of the colorectum at autopsy and its effects on the incidence and future trends of colorectal cancers in Singapore.   Lee YS1 Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. It was observed further that incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase.

Natl Cancer Inst Monogr. 1985  Summary: multiple primary cancers in Connecticut, 1935-82.  Curtis,  Fraumeni ea   The risk of developing a second primary cancer was evaluated in over 250,000 persons reported to the Connecticut Tumor Registry (CTR) during 1935-82. The CTR has collected data on cancer incidence longer than any other population-based tumor registry and thus provided researchers with a unique opportunity to investigate the occurrence of second cancers among persons followed for long periods, in some cases for more than 40 years. When compared with the general Connecticut population, cancer patients had a 31% increased risk of developing a subsequent cancer overall and a 23% elevated risk of second cancer at a different site from the first. Little variation in risk was seen for the first 20 years of follow-up, although the risk for females averaged twice that for males (41% vs. 18%). Persons who survived more than 20 years after the diagnosis of their first cancer were at highest risk: 51% for females and 45% for males. Over 1 million person-years of observation were recorded, and the excess risk of developing a new cancer was 3.5 per 1,000 persons per year. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to developing new cancers in the same or contiguous tissue throughout their lifetimes. A notable finding was the high risk of cancers of the lung, larynx, buccal cavity, and pharynx observed among cervical cancer patients, which suggested a common etiology involving cigarette smoking. The intriguing association previously reported among cancers of the colon, uterine corpus, breast, and ovary was confirmed in our data, which indicated the possible influence of hormonal or dietary factors. Incidental autopsy findings were largely responsible for the observed excesses of second cancers of the prostate and kidney, and heightened medical surveillance of cancer patients likely resulted in ascertainment bias and elevated risks for some tumors during the early period of follow-up, most notably cancers of the thyroid. Interestingly, patients with prostate cancer were the only ones found to be at significantly low risk for second cancer development. However, this might be an artifact of case-finding because advanced age at initial diagnosis of prostate cancer was associated with an underascertainment of second cancers.

J Am Geriatr Soc. 1979   Cancer in the aged: an autopsy study of 940 cancer patients.    Ishii, Hosoda ea  In an autopsy study of 940 elderly cancer patients, 1,030 cancers were identified. The prevalence rate for overall cancer declined after age 85 in men and after age 75 in women. The chief sites of major cancers were the stomach, lung, esophagus, liver, and pancreas, in that order. Incidental cancers (chiefly of the prostate, thyroid, and colon) were found more often in patients over 80 years old. For multiple primary cancers, the prevalence rate was relatively constant until the age of 70, when it rose to a peak in the 80–84 age group before declining to the original level

4 Nov 2014  update: a new POSTAL study Colorectal cancer CRC  screening and subsequent incidence of colorectal cancer: results from the 45 and Up Study. by Steffen ea, from Australian universities shows the usual ~50% reduction BY SCREENING  in colorectal cancer occurrence, in a population mean age 60yrs followed for a mean of 3.78yrs in 741 000 screened pts , mean 60yrs at screening, mean BMI 27kg ie a high-risk population . .   But it glaringly omits  mentioning the most important data:     what was the allcause mortality reduction if any in the screened versus the unscreened cohorts after 3.78years? By this strange data omission, it must be assumed that the study showed no such benefit?.

All that the study confirmed is that it detected about 1000 new colon cancers in about 200 000 older people followed for almost 4 years ie an annual incidence of ~ 1 in 400 000 or 0.125% per year . This rate is similar to  the 0.12% cases pa ie per year  of early breast or  prostate cancer   claimed  in USA SEER data;  but the Australian CRC cancer rate reported is strangely almost three times the overall USA CRC incidence rate of about 0.04%pa found in USA men and women combined, similar to the lung cancer incidence reported there. . If the Australian data presented is correct, there must be something colotoxic (Perhaps their high beer and barbeque  intake?)  in the Australian diet compared to the European and USA population, since the great majority of all such citizens are of European “Caucasian”  origin?

This compares to South Africa where the latest stats for the whole population (NRC/CANSA 2007)   (assuming only maybe <1/4 of the population are 45yrs and up) are : prostate or breast 0.05%pa, lung or  CRC 0.01%pa, and cervix (much younger- due to abuse and STD) 0.05%pa. That study reported the lifetime risk of CRC in RSA as 1:115 in men, 1:199 in women, compared to , prostate 1:26 and breast 1:35, cervix 1:42,  uterus 1:176,  lung men 1:91  women  1:250.

There remains  no good evidence of lives saved ie reduction in all-cause mortality by such hugely costly population cancer screening for these commonest cancers. All that it achieves is the knowledge of previously silent cancer,  which would mostly have been buried unknown with the patient dying of other common causes- ie creating the worried well who have become “cancer survivors”.

we await response from the authors  on this primary issue .

Do any   studies show that there is   meaningful survival benefit from  costly mass screening for internal disease  of adults not at high risk, except for hypertension?  Mass CRC screening of people not at increased risk ( from family history, bowel symptoms or disease) is like breast and prostate screening, no apparent benefit on the most crucial issue, all-cause mortality.

19 Sept 2014   .    is there anything to update? CONCLUSION: not really. Conservatism urges avoidance of screening anyway in those with short lifespan from other major disease, or age eg above 75years- UNLESS there is good evidence of meaningful life extension. As we concluded in 2011, is such screening worth perhaps  1 month life extension in old age?

So far there is still no good evidence to support regular mass population screening in apparently well adults without risks for any degenerative disease  EXCEPT for hypertension;  glaucoma;   malignant melanoma; and  women at risk of cervix cancer ie sexually active at a younger age.

Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancerDinh T,  Levin TR  ea 1Archimedes Inc, San Francisco  present a model rationale for FOBT screening from age 50yrs, with a single elective colonoscopy at 66yrs if FOBT remains negative – at a cost of US$10000 per putative QALY gained. .   Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy.   METHODS:  We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials.  RESULTS:   A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50-65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT.    .  CONCLUSIONS:  In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.  Clin Gastroenterol Hepatol. 2013 Sep;:1158-66.

16 Sept 2014: PREVENT INSTEAD OF SCREEN: Dr  Ng  from DANA FABER CANCER INST, BOSTON MASS asks in .  Vitamin D for Prevention and Treatment of Colorectal Cancer: What is the Evidence?   Vitamin D insufficiency is highly prevalent in the U.S, particularly among colorectal cancer (CRC) patients- – studies suggest that higher vitamin D levels are associated with lower risk of incident CRC as well as improved survival in patients with established CRC. There remains a great need to improve prognosis for patients with CRC, and investigating vitamin D as a potential therapeutic modality is an attractive option in regards to safety and cost, particularly in this era of expensive and often toxic anti-neoplastic agents.  Curr Colorectal Cancer Rep. 2014 Sep 1;10:339-345

But as we know well from many studies, conventional “high” doses of vitamins C (eg  hundreds of  mgs/d)  and D (a few hundred to a few thousand iu/d)  have only modest benefit for prevention and against existing disease-  it requires about 10-15fold higher vit D3 ie 80-100iu/kg/day, and 100 to 500 more vit C ie a few to a few score gms vit C a day to have major impact. These must not be in isolation, as they may be limited by conditioned deficiency of other micronutrients especially vits K2. . We know well from eg the ATBC trial of vits A and E that too much and too late may be harmful, especially if these are not in natural balanced forms of all the vits A and E groups.

14 Sept 2014   A colleague is surprised that  at 72yrs I have never had a screening scope.

so I recheck the evidence after 3 years, since my 2011 review. Even The USA National Cancer Institute review of colon cancer screening  (updated to 24 July 2014) agrees  that Based on solid evidence, there is little evidence that screening for colorectal cancer (CRC) reduces all-cause mortality, possibly because of an observed increase in other causes of death, although in some studies it may reduce CRC mortality;   and there is always serious risk of harms. Overall, the NCI concludes that  On initial (prevalence) examinations, from 1% to 5% of unselected persons screened  with stool gFOBT guaiac faecal occult blood test (collected over 3 days, repeated up to yearly )   have positive test results ie 30 per 1000 recalled; of whom on imaging  2% to 10% have cancer and approximately 20% to 30% have adenomas,[26,27] depending on how the test is done.That translates to colon cancer detected in  about 3% of 6%  = 0.18% of the target population screened  – of whom 74% occur between 55 and 84 yrs. .

As a recent Spanish team review last year says, No strategy, whether alone or combined, has proven definitively more effective than the rest:   Economic evaluation of colorectal cancer (CRC) screening   Cruzado J1Carballo F. ea  1Colorectal Cancer Prevention Program for  Instituto Murciano de Investigación Biosanitaria,  Murcia, Spain Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and (then) studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed.. Best Pract Res Clin Gastroenterol. 2013 ;27:867-80.  

BUT:  Is aging per se a real risk factor for suffering colon cancer? No good evidence yet.  all cancers do increase with aging. But there is still no hard evidence of meaningful life extension from colon, breast or prostate  screening for silent risks in those without other cancer risk factors.

The NCI found four completed  trials of FOBT faecal occult blood testing since 2004 – in Minneapolis(46500), Denmark (31000), Sweden(68000) and UK(151000) – ie 300 000 older lowrisk adults- these   find no benefit in terms of increased length of life. The longest, –  30 year followup in Minneapolis – looks at the longterm mortality benefit of CRC screening– and as with breast and prostate screening for silent cancer in those without significant risk factors.   So organized mass population screening eg every 1  or 10 years from age 50 years does not save lives in the elderly at low risk ie no colon symptoms- at an enormous cost in the scores  of well people  – about 1.2 per 1000- needed to screen, with about 3% of these found positive needing imaging- at major risk of unforseen problems-  to find one cancer, shorten the lead time, save a life from silent cancer. We all die from something eventually. 99.82% of the population screened did not develop colon cancer.

In firstworld people the risk of colon cancer is generally below that of breast and prostate cancer respectively: Wiki sums it up-                                                                    Based on rates from 2007-2009, 5% of US men and women born today will be diagnosed with colorectal cancer during their lifetime.[95] The median age at diagnosis for cancer of the colon and rectum in the US was 69 years of age. Approximately 0.1% were diagnosed under age 20; 1.1% between 20 – 34; 4.0% between 35 – 44; 13.4% between 45 – 54; 20.4% between 55 a-64; 24.0% between 65 – 74;  25.0% between 75- 84; and 12.0% 85+ years. Rates are higher among males (54 per 100,000 c.f. 40 per 100,000 for females). about 20% of such cancer patients have a familial genetic risk.

so faecal screening would be the mass screening method of choice, with about 25% recall rate for costly colon imaging to find the 1.2  cases per 1000 in the target population. But that is supposed to uncover silent colon cancer 2 years earlier, allowing expected drastic reduction in the 75% mortality of clinically presenting colon cancer. So why do no trials of  colon cancer screening show reduction in all-cause mortality? Perhaps its because the lethal colon cancers occur  and present clinically younger in those with lethal genetic risks eg Lynch syndrome, or predisposing colon inflammation eg ulcerative colitis, Crohn’s; or those with multiple polyposis  who are more likely to bleed early.

But we know that real chronic colonic  disease is par excellence a western Saccharine Disease ie of our urban fastfood high sugars,  low fibre diet, inadequate water intake,  and slothful low sunshine ie couch potato  low vitamin D  constipated  lifestyle; with often smoking and alcoholism. . Naturally the Wiki review, written to favour regular screening to find profitable more  silent cancers (like breast and prostate screening) , does not mention this. .

Shaukat A1, Church TR ea  (in N Engl J Med. 2013;369:1106-14  Long-term mortality after screening for colorectal cancer    Minneapolis VA Health Care System USA).  In randomized trials, fecal occult-blood testing FOBT  reduces mortality from colorectal cancer. However, duration of the benefit is unknown, as are the effects specific to age.  METHODS:  In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008.  RESULTS:  Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths 2% were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction).     CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy.

For mass Sigmoidoscopy screening,   Five sigmoidoscopy screening RCTs have reported incidence and mortality results.- Norway 2 trials;  and  United Kingdom; Italy; and the U.SA, in 166,000 participants in the screened groups and 250,000 controls. Follow-up ranged from only 6 to 13 years.   There was an overall 28% relative reduction in CRC mortality (RR, 0.72; 95% CI, 0.65–0.80), an 18% relative reduction in CRC incidence (RR, 0.82; 95% CI, 0.73–0.91), and a 33% relative reduction in the incidence of left-sided CRC (RR, 0.67; 95% CI, 0.59–0.76). There was no effect on all-cause mortality.

For mass colonoscopy screening, no trials have been completed to give any evidence of longterm mortality benefit.

One group proposes a screening program based on  periodic stool FIT faecal immunological test , with a single colonoscopy at 66yrs.  Dinh , Levin ea Archimedes Inc, San Francisco,( Clin Gastroenterol Hepatol. 2013 ;11:1158-66   Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancer)  In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.

UPDATE  20 Oct  2011 A chiropracter asks: what is the recommendation regarding screening colonoscopy, mammography, prostate for cancers? would MD’s and DO’s get one and if so in what circumstance?

My answer:

The only link between breast, prostate, bowel, ovary and womb cancers is that these organs (unlike cervix cancer) are genetically linked through common sex hormone influences; and (apart from the breasts) coincidentally abut ..

Prostate cancer associates with higher estrogen and DHT levels. As for usually estrogen-dependent breasts and  breast cancer screening in low-risk breasts discussed previously, the overwhelming evidence favours no screening at all without symptoms  or risk factors. Unlike for breast cancer,  treatment for prostate cancer (as for  colon cancer) seems to make no difference except when there is obstruction or bleeding. For asymptomatic PRCA the rule remains: watchful waiting. Like women and breast cancer, many men have undiagnosed ie asymptomatic prostate cancer at autopsy for other causes of death.

Colon cancer is different.   it is less common in women with estrogen replacement.

But unlike prostate and breast cancer where invasive screening of all lowrisk patients likely causes more harm  (including despondency) than good,  it is hard to find good colon cancer studies of asymptomatic lowrisk people that show no benefit of screening colon imaging. Studies of colon cancer imaging are inevitably by practitioners who have  a major commercial vested interest in such imaging.

But how many studies have been done comparing colon screening with no screening in patients who truly have none of the risk factors –  – heredity, meat diet, smoking, overweight, bleeding,  inflammatory bowel disease, polyps, diabetes?

Few articles are against such colon screening ie rationalize or philosophize against it .

A 2011 Medscape review from a New Jersey University team concludes cautiously: “In particular, education and intervention efforts for colon imaging should be focused on patients that have risk factors eg diabetes, obesity, or are former/current smokers. This population represents a sub-group of patients who are having CRC screening at a rate lower than the average-risk population. Significant reductions in CRC incidence and mortality might be possible by providing targeted screening interventions to increased-risk individuals and by educating physicians on the importance of recommending screening to these patients even in the face of multiple competing demands”. ie it  encourages  colon screening in  increased risk individuals. 

Search of Pubmed for “incidental colon cancer at autopsy” reveals only three  studies, >20 years ago,  two in the orient.

Ueyama ea, Kyushu University, Japan in Am J Gastroenterol.1991    Colorectal carcinomas incidentally detected in 3,638 autopsied cases and inpatients  during the past 20 yr.   17 colorectal carcinomas (0.47%) were incidentally detected among autopsied patients without clinically evident colorectal carcinoma, including 2,232 males and 1,406 females more than 40 yr old. Among the 15 male and two female index subjects, six (0.33%) were detected in the first and 11 (0.60%) in the second decade. During their survival periods, fecal occult blood studies were performed in 14 cases and positive in 12 (86%); however, two of them had gastric ulcers which were responsible for the occult blood. During the recent 11 yr, six cases (0.48%) of colorectal carcinoma (four of them males; two, females) also were detected among 1,249 inpatients who were examined by barium enema and/or colonoscopy, including 816 males and 433 females, 40 yr old, or more, in the Department of Radiology. Fecal occult blood was detected in four cases (67%) before colonic investigation. Compared with 708 surgically resected carcinomas, the incidental lesions from both sources were smaller, consisted of higher percentages of Dukes’ A type, and arose predominantly from the sigmoid colon and, rarely, from the rectum. These results indicate that the prevalence of colorectal carcinoma and its predominance in the sigmoid colon have not only apparently but actually increased in Japan, apart from improved diagnostic capabilities, and that false-negative rates with occult blood tests were surprisingly low in these autopsied cases and inpatients.

 Lee YS in Cancer 1988 studied Incidental carcinoma of the colorectum at autopsy in Singapore. . . Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. Incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase. The current underdiagnosis of ascending colon carcinomas has to be taken into consideration when any future increase in right-sided cancers of the large bowel is observed. 

Suen ea Cancer. 1974 studied Cancer and old age – autopsy study of 3,535 patients over 65 years old, in New York from 1960 to 1970 ie a decade earlier than the above oriental studies; they showed that men had cancer nearly twice as frequently as women (40% vs. 24%); and more incidental ie less aggressive neoplasms as age advanced. The most frequent cancers were those of the prostate (12% of men), gyne (7.5% of women- breast 3%) , kidney 3.5%, and colon 5.6%.. 70% of the cancers were already diagnosed in life ie 30% were incidental findings. Cancer tended to metastasize less frequently in the elderly.  The most common sites of latent asymptomatic cancer reported by Berg et al The prevalence of latent cancers in cancer patients. Arch. Pathol 1971. in their study of 5636 cancer patients with ages ranging from the teens to over 80,were prostate, thyroid, colon, and kidney. They further emphasized that cancer of the colon and kidney were the ones most easily missed clinically. In our study, the most frequent sites of incidental cancer, among the common cancers, were prostate (incidental 67%), kidney (51%), colon (31.5%), and breast 16.6%.

And  researchers from the Universities of California, North Carolina and Harvard –  Walter ea show in 2005  Screening for colorectal, breast, and cervical cancer in the elderly: Am J Medicine  that “characteristics of individual patients that go beyond age should be the driving factors in screening decisions… in one study -Selby ea A case-control study of screening sigmoidoscopy and mortality from colorectal cancer . N Engl J Med . 1992; .”For colorectal cancer screening, fecal occult blood testing has the strongest evidence of benefit in elderly patients, while flexible sigmoidoscopy reduces mortality from colorectal cancer by 59% .Flexible sigmoidoscopy has fewer complications than colonoscopy, with perforations occurring in less than 0.1 of 1000 examinations; .” But they did not report data on benefit of colorectal screening of lowrisk adults in terms of actual overall life extension ie reduction in all-cause mortality- which benefit has not been shown in rigorous analysis of xray screening mammography or screening blood and digital exams of lowrisk men for prostate cancer. .

Lack of significant life extension by breast and colon screening was shown by Rich and Black from Vermont USA in Clin Pract. 2000 When should we stop screening? Given a starting age of 50 years, screening throughout life has a maximum potential life expectancy benefit of 43 days for breast cancer and 28 days for colon cancer.

These 1 month extensions in life expectancy do not justify screening the entire population of older persons- surely only those of us with significant risk factors need be screened.

CONCLUSION: from the above references from autopsy series, the prevalence  of   incidental ie asymptomatic colon cancer at routine autopsy  in older deaths varies between about 0.5% and 3% in oriental and New York patients. So since I dont have any symptoms or risk factors listed, after 50 years in medicine I havent had colon or prostate imaging for a potential 4 week gain in life expectancy. I will do so promptly if I get colon symptoms.

I tell my older lowrisk patients the dubious potential benefit of cancer screening, and the serious risks, from overdiagnosis- polyps and lowgrade cancers that might never present in lifetime, to perforation ; while explaining to them that well-patient  breast, prostate  and colon cancer screening is hugely profitable universal policy.

For non-emergency consultations and especially costly and invasive procedures, doctors and patients need reminding that it’s the patient’s choice, not the doctors’..

This brings us to one of the ethical dilemmas of medicine: when our experience, and careful sifting of the hard evidence, conflicts with conventional wisdom- which is often based on belief and vested interests- evidence slanted hy bias- surely we practitioners have both a right to express our evidence-based personal conviction, and a duty to do so. Thus we surely have a duty  to give the patient the hard evidence both for and against- be it about the power of prayer and belief, about contraception and abortion, for and against statins for mild-moderate lipidemia, or in the low-risk patient, screening mammography, prostate or colon screening.

 

 

SPECIALIST CHRONIC DISEASES CLINIC OF EXCELLENCE

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IS IT ELECTROLYTE- OR VITAMIN- OR PROTEIN- OR FAT- OR STARCH- OR ACID- LOAD, THAT MATTERS? OF COURSE ALL DO.

neil.burman@gmail.com

Discussing the controversy about phosphate load in soda drinks,  Fenton’s Calgary University metaanalysis  discounts adverse effect of  soda-drink -based phosphate load and balance –  but  apparently does not dispute the acid-diet hypothesis of osteoporosis.

Their focus exclusively on calcium, phosphate and hydroxyproline  balance apparently studiously omits mention of hydrogen/bicarbonate/ pH/ other electrolyte  balance. The significance of calcium-phosphate intake and balance without correcting for pH and potassium-magnesium  balance is debatable. They found that “All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low .

The concept of pH and H+ balance has been established for at least  a century, so to avoid it in discussion of osteoporosis pathogenesis as Fenton ea do   is puzzling, considering especially that theirs  is a cost-free meta-analysis- not a trial or even an observational study. Thus their netanalysis  carries less weight compared to clinical studies like Wynn’s  EVANIBUSStudy.
Selye’s 1949 Textbook of Endocrinology mentions acidosis only in the context of  terminal diabetic or kidney failure – when clinical acidosis was obvious; but after the landmark first paper on Pubmed of Poul Astrup  in 1954 measuring blood acid-base balance (pH) in humans, Guyton’s 1961 Textbook of Physiology when we were students already detailed the crucial importance of pH maintenance by kidney and lung function- known  since the late 19th century from the work of Arrhenius, Henderson, Hasselbach, Beckman,  Sorensen ea ..

Wynn’s University of Lausanne EVANIBUSStudy published this month confirms that “There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods”.

so if people wont reduce their high meat intake (which damages bones brain and heart as well as kidneys),
– quite apart from discouraging commercial unhealthy ‘sodas’ and “fruit juice” due to adverse sugar, phosphate and aspartame intake –
at least we  can and must  protect people  against all major chronic degenerative diseases, we must reduce all-cause mortality by encouraging a potassium -magnesium (calcium) -zinc-boron  -high vits  (especially D+K+B+C) and fish oil  supplement . . especially in eg Asians who take a phosphate-rich (eg chapati) diet.

Naturally the FDA – (read  Food and Drug Antihealth Agency)  industry mafia for whom Only Disease Pays- are determined to suppress such evidence-based prevention and supplements  so as to maximize their profits from  the nefarious processed drink and food chain (soda drinks) and designer drug industry interests (eg bisphosphonates – which may reduce osteoporotic  fractures by half but have major adverse effects and do nothing to reduce the global burden of degenerative -frailty-  diseases and thus non-fracture mortality) .

It will be interesting to see what food and drug companies support Fenton’s Calgary Alberta   impeccable nutritional study  that denies adverse effect of soda-drink phosphate loading.  Their paper does not specifically state where the concept of the study originated, and that there was no indirect  support or input from the food and drug industry for the University or for  their study.

FIFTY+ YEAR OLD TREATMENTS OF OVERWEIGHT, HYPERTENSION & DIABETES ARE STILL BEST

Eight major new studies (below)  published this year confirm that old is best, and give the lie to costly marketing-hype trials trying to promote newer anti-hypertensive ( beta-, calcium channel- and angiotensin blockers), anticholesterol (statin), antidiabetic and antithrombotic blockbuster drugs. 

So the Veterans, MRC, TOMHS, SHEP, ALLHAT, German Reserpine, Cache County, USA, UK, Indian, Chinese and now Turkish, POISE, Australian and the Eniwa antidiabetes, antihypertension and cardiovascular studies. show that one can achieve unsurpassed prevention and treatment of a range of conditions –

overweight or already diabetic, hypertension, stroke, heart-failure, thrombosis, arrhythmia, lipidemia, diabetes, dementia and all-cause premature death –

using low-dose diuretic – ideally co-amiloretic 7 to 13.5mg/d, (or a buchu-dandelion-calmag-potassium equivalent) plus low-dose reserpine 0.05 to 0.1mg (or the herbal parent rauwolfia extract), plus metformin (or the herbal parent galega with other highly effective insulin sensitizer / appetitie regulators), including fish oil 3 – 4gm/day.

Trials for 30 years have shown that only the plant extract metformin reduces all deaths in type 2 diabetes

–         In the 20year UKPDS (Holman ea) only metformin lowered all major diseases and deaths by 36%;

–         In a Canadian Medicaid Program (Johnson ea), metformin halved deaths in diabetics over 5 years.

Now Servier’s ten-thousand patient ACCORD trial (in North America) confirms that, in contrast to the parallel  but less aggressive ten thousand patient ADVANCE trial in the rest of the world, RELATIVE TO METFORMIN, multiple drugs to lower HBA1c intensively below 6.5% increase deaths by 22% by the 2nd yr, from heart attack, hypoglycemia etc. 

The higher death rate in ACCORD was associated, inter alia, with much higher use (than in ADVANCE) of insulin; glitazone; incretins; sulphonylurea; statin – none of which prevented a mean of 3kg weight gain. (There was no such weight gain in ADVANCE).

Since humans first became aware of the dangers of human indolence and overeating, observation has shown an inexorable link between increasing overweight and morbidity and premature mortality.

Drug companies (and their paid armies of researchers and lay / academic lobbyists) will not or cannot accept the obvious, that lipidemia and hyperglycemia are not the prime causes of disease that need to be suppressed, but are simply manifestations of disturbed metabolism due to excess calorie (and often salt) intake, leading to insulin resistance.

So they keep churning out new data promoting new antihypertensives, statins and hypoglycaemic agents – which massive studies like TOMHS, SHEP, ALLHAT, UKPDS, PROactive and now ACCORD and the Australian antihypertensive metanalysis debunk.

“Authorities” (which as in South Africa, UK and the EU, downplay metformin or lowdose reserpine / rauwolfia and lowdose diuretics) are mostly (it seems) paid panderers to Big Pharma’s (the drug industry’s) zeal to sell newer blockbusters at any cost. They thereby deny the overweight public the best anti-lipidemia, weight-limiting and antihypertensive agents available.

For the Disease Industry, only disease pays – cheap effective prevention does not.

References / Abstracts: Continue reading

METFORMIN AS PRIMARY PREVENTION OF OBESITY, DIABETES AND THE OTHER MAJOR COMMON DEGENERATIVE DISEASES OF AGING

This column (see below) has repeatedly pointed out that metformin (aet 1922), a plant derivative, is the only designer drug ever that has both been tested in a real longterm RCT – 20yrs (the UKPDS 1998)- and shown to halve both all-cause mortality in type 2 diabetics, and the incidence of new diabetics when used preventatively in those at risk at all ages with increasing body fat.

This has now been confirmed by a new analysis by Sally Salpeter’s prolific group – whose 2006 metanalysis showed almost as good results for appropriate HRT. Metformin is simply a variant of appropriate HRT, since metformin, like fish oil, and appropriate testosterone and estradiol replacement, is effectively a prohormone that reduces insulin resistance and thus allows insulin to work and glucose to be metabolised as energy by muscle (including the heart) and brain, instead of being accumulated as fat (triglyceride) everywhere.

But while metformin is the only ‘synthetic’ panacea ever invented that remotely matches fish oil, appropriate HRT and all the other natural therapeutic food micronutrients in combination, it should not be forgotten that there are scores  of natural insulin sensitizers listed on the internet; of which the freely available two dozen are easily combined into a potent lowcost combination that, with simple avoidance of sugar and cooked fats – at least halves all disease.

This makes the prescription metformin largely unnecessary- the combination just has to be used with discretion, and sensible regular meals , exercise and the routine supplements, to avoid causing hypoglcemia.

ndb

Am J Med. 2008 Feb;121(2):149-157.e2.
Meta-analysis: Metformin treatment in persons at risk for diabetes mellitus.
Sally Salpeter ea Santa Clara Valley Medical Center, CA USA.
PURPOSE: We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes. METHODS: We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. RESULTS: Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7–4.0), fasting glucose (-4.5%, CI, -6.0–3.0), fasting insulin (-14.4%, CI, -19.9–8.9), calculated insulin resistance (-22.6%, CI, -27.3–18.0), triglycerides (-5.3%, CI, -10.5–0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3–3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. CONCLUSION: Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.