# The Palpable Prostate

Prostate cancer topics, links and more. Now at 200+ posts!

**News:**Health Day, Medical News Today, ScienceDaily, Urol Times, Urotoday, Zero Cancer

**Papers:**Pubmed (all), Pubmed (Free only), Amedeo

Journals: Eur Urol, J Urol, JCO, The Prostate Others Pubmed Central Journals (Free): Adv Urol, BMC Urol, J Endourol, Kor J Urol, Rev Urol, Ther Adv Urol, Urol Ann

Reviews: Cochrane Summaries, PC Infolink Newsletters: PCRI, US Too General Medical Reviews: f1000, Health News Review

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## Monday, August 1, 2016

### Blog updates for July 2016

July 22, 2016. In Metformin and Prostate Cancer we added statin references: Other recent work suggests benefit from combination therapy of metformin with statins [PMC3329836 full free text], [news release], p53 stabilizers [PMID: 26900800], chemotherapy [PMID: 27118574].

## Wednesday, June 22, 2016

### Brachytherapy problem

In a perineal saturation biopsy, a brachytherapy-like grid of rectangular squares is spaced at s = 5mm. Biopsy samples are taken. The cancer will be assumed to be a disc, i.e. circle, of diameter d. It will be detected if the disc intersects a vertex on the grid. What is the probability of detecting the cancer? of missing the cancer?
Consider a disc of diameter d around each of the 4 corners of a particular square in the grid. (See accompanying diagram.)

One quarter of each of those discs lies in the particular square so the total area of those discs within that square divided by the area of the square is the probability of detection. (This assumes a single focus of cancer d mm in diameter, that the probability distribution of its center is uniform and further assumes that the quarter discs shown in the diagram are not so large that they overlap.)

We used the fact that the area within a circle is pi*r^2 where r = d/2 is its radius. In terms of the diamter this can be written as pi * d^2/4. The above only works if the 4 quarter circles do not overlap and that is guaranteed if d is less than s. If d is greater than s then the quarter circles would overlap and adding their areas would represent double counting in the overlapping regions.

To double check we can compare the above formula to a simulation. If the cancer has a diameter of d = 2mm and each side is s = 5mm, then the probability of detecting the cancer, is 0.50265 by the formula and 0.4955 via the simulation below -- these two numbers are equal to two decimal places. We review the formula calculation and then the simulation:

1. Formula. Using the formula above and substituting in d = 2 and s = 5 we find that the probability of detection is 0.50265 (and so the probability of missing the cancer is 1 - 0.50265 = 0.49737).

2. Simulation. Using the R code at the end we create a simulation again assuming d = 2 and s = 5. d as well as s and n (number of iterations) can all be changed as needed by modifying their values near the top of the code. The code generates n = 10,000 points uniformly in an s by s square and then counts the fraction lying within d/2 of a corner as the probability of detection. This approach is more general since it also works even in the case where the discs at the 4 corners of the square overlap. Run it by copying the code below to the clipboard and paste it into the text input box at http://www.r-fiddle.org -- be sure to erase anything already in the r-fiddle text entry box first. Then press Run. (You may need to press Run twice if the answer does not appear the first time.) The code below gives the probability of detection and 1 minus that number is the probability of missing the cancer.

One quarter of each of those discs lies in the particular square so the total area of those discs within that square divided by the area of the square is the probability of detection. (This assumes a single focus of cancer d mm in diameter, that the probability distribution of its center is uniform and further assumes that the quarter discs shown in the diagram are not so large that they overlap.)

```
probability of detection of cancer
```

`= probability that the center of the cancer lies in one of the 4 quarter discs `

`= (sum of 1/4 of the area of 4 discs of diameter d) / (area of one grid square) `

`= 4 * 1/4 * (area of a disc of diameter d) / (area of one grid square) `

`= (area of a circle of diameter d) / (area of one grid square) `

`= (pi * (d^2)/4) / s^2`

` `

We used the fact that the area within a circle is pi*r^2 where r = d/2 is its radius. In terms of the diamter this can be written as pi * d^2/4. The above only works if the 4 quarter circles do not overlap and that is guaranteed if d is less than s. If d is greater than s then the quarter circles would overlap and adding their areas would represent double counting in the overlapping regions.

To double check we can compare the above formula to a simulation. If the cancer has a diameter of d = 2mm and each side is s = 5mm, then the probability of detecting the cancer, is 0.50265 by the formula and 0.4955 via the simulation below -- these two numbers are equal to two decimal places. We review the formula calculation and then the simulation:

1. Formula. Using the formula above and substituting in d = 2 and s = 5 we find that the probability of detection is 0.50265 (and so the probability of missing the cancer is 1 - 0.50265 = 0.49737).

`(pi * (d^2)/4) / s^2 = (3.1415926 * 4^2/4) / 5^2 = 0.50265`

2. Simulation. Using the R code at the end we create a simulation again assuming d = 2 and s = 5. d as well as s and n (number of iterations) can all be changed as needed by modifying their values near the top of the code. The code generates n = 10,000 points uniformly in an s by s square and then counts the fraction lying within d/2 of a corner as the probability of detection. This approach is more general since it also works even in the case where the discs at the 4 corners of the square overlap. Run it by copying the code below to the clipboard and paste it into the text input box at http://www.r-fiddle.org -- be sure to erase anything already in the r-fiddle text entry box first. Then press Run. (You may need to press Run twice if the answer does not appear the first time.) The code below gives the probability of detection and 1 minus that number is the probability of missing the cancer.

Thanks to Don Morris for raising this problem.set.seed(123) n <- 10000 # number of iterations in simulation s <- 5 # length of side of a grid square d <- 4 # diameter of each of the 4 discs centred at the 4 corners r <- d/2 x <- runif(n, 0, s) y <- runif(n, 0, s) mean(x^2 + y^2 < r^2 | (s - x)^2 + y^2 < r^2 | x^2 + (s-y)^2 < r^2 | (s-x)^2 + (s-y)^2 < r^2)

## Friday, June 3, 2016

### Blog Updates for May 2016

June 3, 2016. In Metformin and Prostate Cancer we added: A May 2016 update by Sayyid and Fleshner [PMID: 27195314] [Full Free Text] reviews studies that show a decreased prostate cancer risk with metformin as well as beneficial effects for prostate cancer patients after treatment. Other recent work suggests benefit of combination therapy of metformin with statins, p53 stabilizers [PMID: 26900800], chemotherapy [PMID: 27118574].

## Saturday, April 30, 2016

### Blog Updates for April 2016

Note to readers. The Palpable Prostate Blog has now published over 200 blog posts -- this post is number 201.

April 30, 2016 in Metformin and protate cancer we added: A number of investigations have concluded that metformin acts by blocking the glucose cancer cells need and in the absence of glucose they will turn to glutamanine and leucine. They hypothesize that interfering with glutamine and leucine uptake might synergistically work with metformin. Note that glutamine is a non-essential amino acid (i.e. the body can produce it itself) so simply lowering the intake of glutamine-containing foods might not be effective. [PMID: 23687346] [Free full text] [PMID: 26550231] [Full free text] [PMID: 24052625] [Full free text]

April 30, 2016 in Metformin and protate cancer we added: A number of investigations have concluded that metformin acts by blocking the glucose cancer cells need and in the absence of glucose they will turn to glutamanine and leucine. They hypothesize that interfering with glutamine and leucine uptake might synergistically work with metformin. Note that glutamine is a non-essential amino acid (i.e. the body can produce it itself) so simply lowering the intake of glutamine-containing foods might not be effective. [PMID: 23687346] [Free full text] [PMID: 26550231] [Full free text] [PMID: 24052625] [Full free text]

## Thursday, March 31, 2016

### Blog Updates for March 2016

March 31. In Choosing a Surgeon - Part I. Considerations, Choosing a Surgeon - Part I we added: Incidentally it has also been found that it is also true that radiation at high volume centers have better outcomes. See [PMID: 26972640] .

## Thursday, February 25, 2016

### Blog Updates for Feburary 2016

Feb 25, 2016. In Prostate Cancer Calculators we added this calculator:

Feb 25, 2016. In Prostate Cancer Calculators we added this calculator in the Memorial Sloan Kettering section:

*Probability of Recurrence, Potency and Continence after Laprascopic (LRP) Surgery*Based on 500 LRP surgery patients of Christopher Eden this calculator accepts PSA and stage and displays the percentage of patients who were cancer-free, the percentage who regained potency and the percentage who regained continence after surgery. It also displays a table of data for all patients fitting the input parameters. The data is based on a follow up of 12 - 36 months with an average follow up of 13.5 months. The site links to a paper that provides more background detail. See theprostateclinic .Feb 25, 2016. In Prostate Cancer Calculators we added this calculator in the Memorial Sloan Kettering section:

*Life Expectancy:*As described and linked to in this prostatecancerinfo review "to use the tool, you will first be asked a number of questions about your health, your age, and your diagnosis with prostate cancer, and then those data are used to project your risk of death from prostate cancer and from other causes at 10 and 15 years after diagnosis.## Tuesday, January 5, 2016

### Metformin and prostate cancer

[Updated July 22, 2016]

A 2014 article in the Journal of the National Cancer Institute by Azvolinksy [PMID: 24511112] [Full Free Text] and a 2014 article by Fleshner in the Canadian Urological Association Journal [PMID: 25243043] [Full Free Text] discuss observational studies on diabetic prostate cancer patients which have shown reduced risk of death from prostate cancer as well as reduced all cause mortality among those taking the widely used inexpensive diabetes drug, metformin. A May 2016 update by Sayyid and Fleshner [PMID: 27195314] [Full Free Text] reviews studies that show a decreased prostate cancer risk with metformin as well as beneficial effects for prostate cancer patients after treatment. Other recent work suggests benefit from combination therapy of metformin with statins [PMC3329836 full free text], [news release], p53 stabilizers [PMID: 26900800], chemotherapy [PMID: 27118574].

An undated overview by Peter Wehrwein speculates that the biological mechanism may be the lowering of insulin, lowering of blood sugar output of the liver or via interruption of signalling pathways. A number of investigations have concluded that metformin acts by blocking the glucose cancer cells need and in the absence of glucose they will turn to glutamanine and leucine. They hypothesize that interfering with glutamine and leucine might synergistically work with metformin. Note that glutamine is a non-essential amino acid (i.e. the body can produce it itself) so simply lowering the intake of glutamine-containing foods might not be effective. [PMID: 23687346] [Free full text] [PMID: 26550231] [Full free text] [PMID: 24052625] [Full free text].

A 2015 meta-analysis by Wu et al found that the risk of developing prostate cancer (as opposed to the risk of death for those who have prostate cancer) is unaffected by metformin.

Confirmation of these results in diabetics and non-diabetics through randomized clinical trails is underway. See: [ClincialTrials.gov]

A video on metformin and prostate cancer by oncologist Dr. Charles (Snuffy) Myers can be viewed here: How + When to Use Metformin.

A 2014 article in the Journal of the National Cancer Institute by Azvolinksy [PMID: 24511112] [Full Free Text] and a 2014 article by Fleshner in the Canadian Urological Association Journal [PMID: 25243043] [Full Free Text] discuss observational studies on diabetic prostate cancer patients which have shown reduced risk of death from prostate cancer as well as reduced all cause mortality among those taking the widely used inexpensive diabetes drug, metformin. A May 2016 update by Sayyid and Fleshner [PMID: 27195314] [Full Free Text] reviews studies that show a decreased prostate cancer risk with metformin as well as beneficial effects for prostate cancer patients after treatment. Other recent work suggests benefit from combination therapy of metformin with statins [PMC3329836 full free text], [news release], p53 stabilizers [PMID: 26900800], chemotherapy [PMID: 27118574].

An undated overview by Peter Wehrwein speculates that the biological mechanism may be the lowering of insulin, lowering of blood sugar output of the liver or via interruption of signalling pathways. A number of investigations have concluded that metformin acts by blocking the glucose cancer cells need and in the absence of glucose they will turn to glutamanine and leucine. They hypothesize that interfering with glutamine and leucine might synergistically work with metformin. Note that glutamine is a non-essential amino acid (i.e. the body can produce it itself) so simply lowering the intake of glutamine-containing foods might not be effective. [PMID: 23687346] [Free full text] [PMID: 26550231] [Full free text] [PMID: 24052625] [Full free text].

A 2015 meta-analysis by Wu et al found that the risk of developing prostate cancer (as opposed to the risk of death for those who have prostate cancer) is unaffected by metformin.

Confirmation of these results in diabetics and non-diabetics through randomized clinical trails is underway. See: [ClincialTrials.gov]

A video on metformin and prostate cancer by oncologist Dr. Charles (Snuffy) Myers can be viewed here: How + When to Use Metformin.

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