Stem cell treatment for post-prostate cancer surgery incontinence – but note there are potential severe risks associated with it

This is an amazing advance in science – BUT THERE IS A RISK THAT STEM CELL THERAPY MIGHT MULTIPLY ANY RESIDUAL CANCER CELLS THAT ARE LEFT BEHIND AFTER SURGERY.

“Decades ago, researchers discovered that a particular type of stem cell — mesenchymal stem cells — in bone marrow could generate new bone, cartilage, and fat. In 2001 researchers discovered that mesenchymal cells are even more plentiful in body fat…. Injured and inflamed cells send out an SOS signal; new stem cells pick it up. “The stem cells are so smart, all you have to do is turn them loose,” he offers. “They float around to different areas of the body and fix them.”…you’ll find a significant number of unhappy people who’ve paid thousands of dollars at clinics and have not seen any results. ?” [Source]

“Stem cells are able to be derived from a number of sources: embryonic stems cells (ESCs) and mesenchymal stem cells (MSCs) , which include: placental or amniotic fluid stem cells (AFPSCs), muscle-derived stem cells (MDSC) , adipose-derived stem cells (ADSC) , bone-marrow-derived stem cells, and even urinary-derived stem cells (USC).” [Urinary Continence and Sexual Function After Robotic Radical Prostatectomy]

Human trials in stress urinary incontinence have been ongoing for a number of years. Carr et al. reported on a patient population of 38 women with stress urinary incontinence who underwent muscle-derived stem cell injections into the sphincter. The women were also offered a second injection 3 months later. Ninety percent of the treated women had over a 50 % decrease in pad weight and only 50 % reported leaks. Adverse events were essentially absent [ 38 ].

Gotoh treated 11 men with persistent stress urinary incontinence 1 year after prostate surgery and demonstrated a 60 % decrease in urinary leakage volume on pads weighed by the patients. One of the 11 achieved complete return of urinary control. Functional urethral leak and urethral closing pressures were also increased compared to pretreatment levels. No adverse events were reported [39 ].

Currently, there is a large multicenter ongoing trial phase 3 trial in the United States with muscle-derived stem cells in women with stress urinary incontinence and a phase 1, 2 trial using muscle-derived stem cell in postpros-tatectomy incontinence (ClinicalTrials.gov Identifier: NCT01893138 and NCT02291432).

Although stem cells derived from any source are not yet ready for clinical use in men with stress urinary incontinence after radical retropubic prostatectomy, the future appears to hold promise. Nonetheless, ethical and regulatory issues remain of concern and may present hurdles to widespread clinical adoption [40 ].

The early ethical concerns surrounding the use of fetal embryonic stem cells have by and large been resolved by the development of so many other sources for multipotent stem cells. Nonetheless, the recent classification of stem cells as a “drug” places them under the purview of the FDA and now regulatory hurdles may enhance or impede the science and usefulness of these agents.

Finally, the fears of the development of secondary cancers or causing early recurrences/failures of cancers if stems cells are released into the operative field to and in early functional recovery are very real. Well-structured trials need to be carried out to address these questions and the questions of which (if any) of the currently available products might be best used in men undergoing prostatectomy. Nonetheless, the future of stem cells use in our patients undergoing prostatectomy appears bright.  [Urinary Continence and Sexual Function After Robotic Radical Prostatectomy]

Stem cells have been found to fix this issue by regenerating relevant tissue – THIS DOCTOR DOES IT. (Michell Kaye).

Male Incontinence and Cell Surgical Network is using Stromal Vascular Fraction with adipose derived adult mesenchymal stem cells to treat post prostatectomy incontinence. The SVF and a small amount of condensed fat matrix is injected with a telescope directly into a deficient sphincter under local anesthetic. Based on experience from Nagoya University, Japan where Stromal Vascular Fraction has been used successfully for male incontinence, we believe that the external sphincter may be regenerated to some extent to provide bladder control. can provide access to the same technology through our investigatory protocol. [Source]

“In the past five years, the number of U.S. stem cell clinics has mushroomed from 25 to 570, according to a recent report published in the journal Cell Stem Cell…. the costly procedures are still unapproved by the FDA, leaving an open gate for medical charlatans and hucksters.” [Source – including analysis]

“the FDA warns that stem cells can migrate to the wrong site or turn into tumors.” [source]

CLINICAL TRIALS IN AUSTRALIA

http://www.stemcellsaustralia.edu.au/About-Stem-Cells/trials-in-australia.aspx

PAPERS/REPORTS

Stem Cell Injections Ease Incontinence (2007) [“Endoscopic injections of human umbilical cord blood stem cells may be a safe treatment option for women with stress urinary incontinence (SUI), according to findings presented here at the American Urological Association annual meeting.”]

Stem Cell Therapy for Incontinence: Where Are We Now? (2011) What is the Realistic Potential?
Charuspong Dissaranan, Michelle A. Cruz, Bruna M. Couri, Howard B. Goldman, and Margot S. Damaser [” the future of this therapy looks promising”]

Stem Cells Treatment for the Local Urinary Incontinence After a Radical Prostate Cancer Surgery (2012) – clinical trial.

Stem cell injection successfully treats urinary incontinence (2012) [“The procedure means that today, she can do her strenuous morning exercises of standing broad jumps and stride jumps without having to wear heavy pads to absorb leakage.”

Stem Cell Therapy for Male Urinary Incontinence – Giberti C. · Gallo F. · Schenone M. · Cortese P. · Ninotta G. [“Regarding animal studies, bone marrow-, muscle- and adipose-derived stem cells have been widely studied, showing regeneration of the urethral sphincter and recovery of the damaged pelvic nerves. With regard to human studies, only four papers are available in the literature using muscle- and adipose-derived stem cells which reported a significant improvement in sphincteric function and incontinence with no severe side effects.”]

Pilot Study of Adipose Stem Cells in the Treatment of Urinary Incontinence (2014) [“ASC injection is a viable treatment strategy for female urinary incontinence.”]

Stem Cells May Ease Urinary Incontinence, Study Says (2014) [The study is published online in the July issue of the journal Stem Cells Translational Medicine.]

The potential role of stem cells in the treatment of urinary incontinence (2015) Christine Tran and Margot S. Damas [“Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects.”]

Stem Cell Therapy for Treatment of Stress Urinary Incontinence: The Current Status and Challenges
(2016) Shukui Zhou,1 Kaile Zhang,1 Anthony Atala,2 Oula Khoury,2 Sean V. Murphy,2 Weixin Zhao,2 and Qiang Fu1[“stem cell transplantation as a therapy for SUI has great promise”]

VIDEOS

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Policy issues identified after my experience with prostate surgery

I’ll pursue these after I’m better, but these are initial thoughts:

  1. While it would increase red tape, there should be ongoing regular monitoring of the progress of continence and erectile function for each such surgery. “The NHS – who make surgeons report their success rates these days – regard success after RP as using 1 pad or less per day by 12 months post-op.” – Source]

2. Patients should get a copy of the robotic prostate surgery video.

Doctors do get a copy of their surgery video record:

“I asked my doctor if he understands why some people have more severe incontinence problems and he said there is some correlation with age and fitness but that he’s reviewed the videos and records from his past surgeries and tried to correlate them with the outcomes but he still doesn’t understand the variations in outcome.” [Source].

This does imply, though, that the video might not do any good to an untrained patient. If even experts can’t use videos to predict continence outcomes then giving the videos to the patients may not help.

A full-fledged cost-benefit test should be applied in each case before any change is made to existing policy.

 

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Biopsy results of prostate after removal

The pre-surgery biopsy is available here. Post surgery biopsy below.

MAIN POINT TO NOTE: I have a small positive surgical margin [“To the naked eye, it can look as if all of the cancer has been removed, but when a pathologist examines tissue samples, cancer cells may be lurking right along the edge of the cut tissue. This means that some cancer cells may have been left behind, in what doctors and pathologists term a positive surgical margin.” –Source]

HOWEVER, it is in the para-apical area, which seems to suggest it is less like to cause a problem. [“Positive margins are more common at the apex, where there’s much less surrounding tissue, but they can occur in other areas, such as the bladder neck. A positive margin at the bladder neck probably has the highest likelihood of leading to biochemical recurrence…. The researchers found that patients with a positive margin at the bladder neck were three times more likely to have biochemical recurrence than patients with negative margins. Positive margins at the apex or laterally were equivalent in terms of recurrence, with patients twice as likely to experience biochemical recurrence as those with negative margins.” [Source]  But also see this blog post.

FURTHER, it is the lowest category, i.e. Gleasen pattern 3. Obviously, if that area had Gleasen 4 pattern, the risk would be higher.

INITIAL VIEW: Regular PSA testing is essential in my case.

===RESULTS====

CLINICAL NOTES: HISTOPATHOLOGY

CLINICAL HISTORY

G1 3+4=7 PCA. Radical prostate.

MACROSCOPY

1) “Prostate gland” – A prostate gland with attached seminal vesicles and vasa deferentia, 35mm apex to base, 45mm right to left lateral and 43mm anterior to posterior. Prostate weight without attached seminal vesicles and vasa deferentia is 39.7g. The attached right seminal vesicle is 25mm and the right attached vas deferens is up to 10mm. A possible detached left vas deferens is 25mm in length and a short stump of seminal vesicle is 5mm in maximum dimension. Specimen serially sliced from base to apex into 9 slices, with slice 1 being the base and slice 9 the apex. Within all slices are multilobulated circumscribed creamy nodules, predominantly in the anterior right and left lateral quadrants which appear to be closely abutting the anterior margin. Inking: anterior yellow, posterior black, left lateral green and false resection margin post seminal vesicle and vasa deferentia resection orange. RS, part processed. 36 blocks.

1A-1G – LS base slice 1:

1A-4, 1B-2, 1C-2, 1D-1, 1E-1, 1F-2, 1G-3LS

1H-1K – composite slice 2:

1H-1 left posterior slice, 1I-1 left anterior slice, 1J-1 right anterior slice, 1K-1 right posterior slice.

1L-1Q – composite slice 4:

1L-1 left posterior slice, 1M-1 left middle slice, 1N-1 left anterior slice, 10-1 right anterior slice, 1P-1 right middle slice, 1Q-1 right posterior slice.

1R-1W – composite slice 5:

1R-1 left posterior slice, 1S-1 left middle slice, 1T-1 left anterior slice, 1U-1 right anterior slice, 1V-1 right middle slice, 1W-1 right posterior slice.

1X-1AA – composite slice 6:

1X-1 left posterior slice, 1Y-1 left anterior slice, 1Z-1 right anterior slice, lAA-1 right posterior slice.

1AB-1AE – composite slice 7:

1AB-1 left posterior slice, lAC-1 left anterior slice, 1AD-1 right anterior slice, 1AE-1 right posterior slice.

1AF-1AG – composite slice 8:

1AF-1 left lateral half, 1AG-1 right lateral half, 1AH-1AJ-LS slice 9 apex.

lAH-3, lAI-2, lAJ-4LS.

1AK-1 – shave of right seminal vesicle and vas deferens

1AL-1 – shave of left seminal vesicle and vas deferens.

2) “Anterior prostate fat” – Multiple pieces of fatty tissue in aggregate 30 x 25 x 5mm. All in. 2 blocks. kp

MICROSCOPY

1-2) The sections from this extensively sampled radical prostatectomy confirm acinar adenocarcinoma, predominantly characterised by separate well-formed infiltrative glands, with a minute component (<5%) represented by poorly-formed glands with ill-defined lumina, evoking modified Gleason score 3+4=7. Tumour is centred in the right anterior quadrant, and extends into both sides of the organ from apex to base in a patchy infiltrative pattern (estimated span 30mm). Tumour reveals no extraprostatic extension and there is no invasion of sampled seminal vesicles. The bladder neck shows unremarkable smooth muscle, and lymphovascular invasion is not identified. The tumour involves one anterior surgical margin over 1 mm span (Gleason pattern 3 disease, block 1AD), and 2 separately sampled lymph nodes within the preprostatic fat are free of tumour (specimen 2, 0/2). Background prostatic parenchyma exhibits nodular hyperplasia.

SUMMARY DIAGNOSIS

SYNOPTIC REPORT FOR PROSTATE CANCER

1-2) RADICAL PROSTATECTOMY (39.7g) AND PRE-PROSTATIC FAT

–              ACINAR ADENOCARCINOMA,

–              GLEASON SCORE 3+4=7 (ISUP GRADE GROUP 2),

–              TUMOUR LOCATION: CENTRED IN RIGHT ANTERIOR QUADRANT,

–              MAXIMUM SIZE OF DOMINANT NODULE: 30mm,

–              OTHER TUMOUR NODULES >10MM: ABSENT,

–              EXTRA-PROSTATIC EXTENSION: ABSENT,

–              MARGIN STATUS: INVOLVED,

-> LOCATION: ANTERIOR, PARA-APICAL,

-> EXTENT OF INVOLVED MARGIN: 1mm,

-> TYPE OF INVOLVED MARGIN: SURGICAL,

-> GLEASON PATTERN AT MARGIN: PATTERN 3,

–              SEMINAL VESICLES: NOT INVOLVED,

–              BLADDER NECK: NOT INVOLVED,

–              LYMPH NODE STATUS: IDENTIFIED IN ANTERIOR PROSTATIC FAT, NOT INVOLVED (0/2),

–              AJCC TUMOUR STAGE (8TH EDITION, 2017): pT2 NO.

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