Tuesday, July 16, 2013

Human Initiated Therapeutic Vaccine Therapy (HITV)

Dr CK Beh

 Browsing the handouts

Dr Beh answering all the questions from the floor

Engrossed with the new developments in fighting cancer

Mr Dass presented a small momento of appreciationfrom NCSM to Dr Beh

The National Cancer Society Malaysia hosted a talk for the Prostrate Cancer Support Group on Human Initiated Therapeutic Vaccine Therapy (HITV) by Dr CK Beh on Saturday 13 July 2013.
The session was well attended as the topic covered is deemed the latest weapon in the fight against cancer and it is now available in Malaysia. HITV therapy involves Dendritic cells and the immune system in the body.

Dr Beh presented Dr Kenichiro Hasumi's HITVprotocol. Below is the link for further information on the protocol.


Dr Beh also briefly introduced another protocol in gene therapy. Inoculation of the P53 cancer suppressor gene. This protocol is now available only in China, but Dr Beh will be able to facilitate it here in Malaysia if given proper documentation and approval by the Malaysian Ministry of Health.

 Google for Gene P53 tumour suppressor gene therapy for cancer as there are a lot of information about this new protocol.

Dr Beh is from the Mahameru International Medical Centre located in Bangsar Kuala Lumpur.

Allen Lai

Saturday, July 6, 2013

Pain in cancer metastasis

Pain is an imminent symptom with cancer metastasis. Pain is mostly managed with medicinal drugs. But it generally does more harm than good in the long run. It does not solve the underlaying problem, save bringing temporary relief to the patient. All pain killers are toxic and additive. Pain is generally unbearable depending on one's level of pain tolerance.
The only recourse is prevention of cancer metastasis.
I append Dr Stephanie Harman's explanation and descriptions as posted in the popular cancer website GRACE:

Cancer Pain 101

In reviewing posts from GRACE, it’s not surprising to see that pain is major issue for many patients with cancer. Pain is not unique to cancer, but for most patients with cancer, their pain is related to the cancer in some way. In cancer, the causes of pain not only include the disease itself, but also the treatments and procedures involved. There are particular types of pain and pain syndromes that are seen primarily in patients with cancer compared to other illnesses. Within oncology and pain management, cancer pain is so crucial for patient care that it has become essentially its own specialty in recent years. Dr. Janet Abrahm, an oncologist and cancer pain expert at the Dana Farber, has written one of the definitive texts on cancer pain management which is a major reference for this post.

Cancer-related pain can be categorized in several ways into what time course it follows. Patients who have acute cancer-related pain have pain that is expected to improve with cancer-directed therapy or, if it is a treatment-related complication, will resolve after treatment. Chronic cancer-related pain is not expected to resolve or its source cannot be eradicated. This chronic pain is very frustrating; similar to non-cancer patients with chronic pain, treatment focuses on therapies that can help patients function and improve their quality of life.

In considering both the tumor itself and the treatments, there are three major types of pain that are experienced. These types can occur individually or simultaneously.

1. Somatic, body-related: This type of pain involves bone, muscle, skin, and connective tissues. It is usually described as an ache in a particular location and can be constant. As in pain with arthritis, the pain is worsened by movement. An example would be a cancer metastasis to a hip bone.

2. Visceral, organ-related: This type of pain refers to pain involving the organs of the body (like the liver or the intestines) and their linings (“viscera” is a medical term for an organ). It is more difficult to pinpoint a particular location. The pain often is described as a cramping or “squeezing” sensation that is felt deeply—it may also feel like an ache. An example would be a stretched liver due to metastases.

3. Neuropathic, nerve-related: This type of pain involves the nerves of the body, including the spinal cord. This pain is described as burning, sharp and shooting, and electrical—“pins and needles,” or paresthesias can occur as well. Depending on how a nerve is injured, there can be associated numbness or weakness as well. While it may be related to a particular nerve, it can be difficult to pinpoint a specific location. An example of this would be neuropathic pain in the feet and hands from platinum chemotherapy.

A General Approach to Cancer-Related Pain

Having pain is a reflection of having the disease of cancer, not of the patient themselves. Patients often tell me that they don’t bring up pain because they do not want to complain or they perceive that they’re “expected” to handle the pain in order to be “strong.” Physicians 

have also contributed to these barriers as well, as there have been misconceptions in practice about the interpretation of pain and the use of pain medications. I will address misconceptions about pain management further in a later post.

Pain is experienced differently by each patient. For example, pain from the same bone marrow biopsy can be experienced differently by different patients. While it may be rated differently amongst patients, what is recognized is that if the pain is not treated, that rating will remain the same or worsen. Pain is measured based on what a patient reports–that is central to how physicians can assess and treat cancer-related pain. Physicians use assessment tools like numeric scales to measure pain for severity as well as other factors to guide the evaluation and treatment of pain, including the quality of the pain, exacerbating factors such as activity or position, relieving factors such as medications or resting, and timing of the pain. When pain is particularly difficult to control, a pain “diary” can be very helpful in determining patterns of pain—one example would be to track episodes of pain with the date/time, severity, duration, use of medications, and response to medications. I see pain as an area where physicians and patients have the opportunity to collaborate closely to tailor treatment regimens, so that physicians are asking about pain on a regular basis and patients are equipped to better control their pain.

Pain is a complex experience that involves and affects other dimensions beyond the physical, including emotional and psychological well-being, cognition, and spirituality. These are all intricately intertwined. Consider that both anxiety and depression are exacerbated by pain. Pain can affect cognitive functioning, even to the point of causing delirium. The non-physical aspects of pain constitute a vast area of therapy and study—I will review this in a later post.

This is the first in a series of posts on cancer-related pain—while they will by no means be exhaustive, I hope to address common and challenging topics for patients. 

Link to dr Harman's post in GRACE

Monday, July 1, 2013

Perineural Invasion (PNI)

PNI as detected in the nerves within the prostrate gland

I append an interesting post about PNI findings in biopsies for prostrate cancer. This is generally not discussed by the Urulogist/Oncologist when deciding the best course of treatments. Read below a detail explaination to PNI and its impact to treatment decisions. Discuss PNI with your Oncologist.

Perineural Invasion On Prostate Biopsy: How It May Change The Game Plan

A reader recently asked me to share my thoughts on perineural invasion found on a prostate biopsy. In formulating my response to this question, I was surprised that I did not cover this topic sooner. After all, perineural invasion (PNI) is found in approximately 30% of biopsies. The presence of PNI on a prostate biopsy can sometimes be a sign that the prostate cancer found on the biopsy may be just the tip of the iceberg in terms of the cancer within the prostate. As such, PNI can change both the prognosis and treatment course for men with newly diagnosed prostate cancer. In this post, I will describe PNI and explain its impact on treatment plans and prognosis.

Defining Perineural Invasion

Before I explain the importance of perineural invasion, we must first be on the same page as to what this finding on a prostate biopsy actually means. The presence of PNI means that the pathologist has seen prostate cancer cells surrounding or tracking along a nerve fiber within the prostate. The importance of this finding becomes apparent when you realize that nerves within the prostate travel outside of the gland through microscopic holes within the prostate capsule. The capsule, as you may remember from my previous post about positive margins, is the outer covering of the prostate. This covering serves as a barrier preventing the spread of cancer outside of the prostate, at least for a while. Because nerves travel through holes in the capsule, prostate cancer growing around these nerves can follow them all the way out of the prostate without needing to overcome the resistance of the capsule. As a result, the presence of PNI on a biopsy portends a higher likelihood of prostate cancer that has or will escape the prostate gland. Studies have, indeed, validated this theory while also demonstrating other negative impacts of PNI.

The Impact of Perineural Invasion on Final Pathology

Numerous clinical studies have compared the final pathologic findings (after radical prostatectomy) of those patients with and without PNI on initial biopsy. The results are very striking. Large studies have demonstrated that men with PNI have a 2-3 times higher rate of extracapsular extension (prostate cancer outside of the gland) and nearly twice the likelihood of positive margins after prostatectomy when compared to men without PNI on their prostate biopsy. That means that the presence of PNI at least doubles the chance of T3 disease in a man undergoing treatment for what is clinically localized, T2 disease. In addition, numerous studies have demonstrated that PNI on biopsy is associated with higher grade disease (Gleason 8-10) on final pathology even when only low grade disease (Gleason <7) is found on biopsy. In fact, one study demonstrated that over 40% of men with PNI and low grade disease on biopsy are subsequently found to have high grade disease on final pathology after prostatectomy. The reason for this disparity appears to be sampling error, with high grade disease not caught in the original biopsy specimens. Hence when a prostate biopsy demonstrates Gleason 6 disease and PNI, there is a high likelihood that higher grade, more aggressive cancer is present in the prostate but was not detected. Other studies have also demonstrated a higher risk of seminal vesicle invasion and lymph node metastases in men found to have PNI.

Perineural Invasion and Prognosis After Prostatectomy
Given the significant adverse impact of PNI on final pathology, it is not surprising that PNI has also been demonstrated to negatively affect prognosis after surgery. One study out of Johns Hopkins followed 1256 men with prostate cancer for an average of 3 years after radical prostatectomy. Out of this patient population, 188 men (15%) were found to have PNI on prostate biopsy. Even over this relatively short follow up period, men with PNI on biopsy were found to have three times the likelihood of PSA recurrence as compared to those men without PNI. Similar findings were reported in 6 out of 10 studies of the impact of PNI on men undergoing radical prostatectomy for prostate cancer. Not surprisingly, men with low risk prostate cancer (Gleason 6, T1-T2a, and PSA<1O) and PNI are three times more likely to require salvage radiation than their low risk counterparts without PNI.

Perineural Invasion and Prognosis After Radiation Therapy

The prognosis after radiation therapy, as well, appears to be negatively impacted by the presence of PNI on prostate biopsy. One study followed 381 men undergoing radiation therapy for localized prostate cancer, 86(23%) of whom were found to have PNI on prostate biopsy. After 5 years of follow up, 69% of men without PNI were free of cancer as compared to only 47% of men with PNI. When dividing men into risk categories, the study demonstrated that only 50% of men with low risk prostate cancer (Gleason 6, T1a-T2a, PSA <10) and PNI were free of cancer at 5 years of follow up. This rate of cancer free survival was lower than the 53% rate achieved by men with high risk prostate cancer (Gleason 8-10 or T2c-T4 or PSA >20) but without PNI. Hence, the presence of PNI could instantly transform an otherwise low risk prostate cancer into a high risk disease. Such findings were validated in 5 out of 10 large studies of men treated with radiation therapy. Interestingly, one large study of men undergoing brachytherapy for prostate cancer did not demonstrate a difference in treatment outcomes of men with and without PNI. Of note, however, is that men selected for brachytherapy generally have lower risk disease than those who undergo external beam radiation.

How Perineural Invasion Can Change the Treatment Plan

Given the significant impact of PNI on final pathology and prognosis, it seems obvious that the presence of PNI can influence the treatment course chosen by patients and their doctors. A study of surgical approaches in men with PNI demonstrated that removing the nerves on the side of the prostate with PNI on biopsy led to a positive margin rate of 11%. In contrast, the positive margin rate was 100% when the nerves were spared on the side of PNI. Of note, a recent study from Johns Hopkins reported that nerve sparing did not impact positive margin rates or prognosis in men with PNI. This data needs to be taken with an enormous grain of salt however in that all men in the study were operated on by Dr Patrick Walsh, the urologist credited for the development of the modern day open radical prostatectomy. It would see unlikely (at best) that such outcomes could be replicated by the typical urologist performing the surgery. As a result, most urologists will sacrifice nerve sparing in order to assure negative margins in men with PNI. In addition, given the high likelihood of positive margins and T3 disease, urologists often counsel patients with PNI on biopsy that they may likely need to undergo radiation therapy following radical prostatectomy. Similarly, radiation oncologists treating men with PNI often approach them as high risk patients regardless of clinical stage, PSA, or Gleason score. As a result, they often treat men with PNI with a combination of radiation and hormonal therapy rather than radiation therapy alone. In addition, they may also use dose escalation as part of their radiation protocol.

Take Home Message

Perineural invasion is a very significant finding on a prostate biopsy. It often indicates high risk prostate cancer, even in men with seemingly low risk disease. PNI is also usually associated with a poorer prognosis, leading to a higher risk of recurrent disease. As a result, men with prostate cancer that are found to have PNI on prostate biopsy are often provided with more aggressive therapy, whether it be in the form of surgery or radiation. Understanding the significance of PNI on prostate biopsy is crucial to formulating a successful battle plan against prostate cancer.

Link to the post above:

Take care

Allen Lai