Cancer of the Urinary Bladder

Copyright 2006 Radoslaw Pilarski

Etiology

Above all, occupational exposure to chemical compounds (among others from the group of aromatic amines) is considered to be the factor leading to falling ill with cancer of the urinary bladder. Smoking tobacco is also mentioned (cancerogenic substances found in tobacco smoke such as nitrosamines, as well as tryptophane metabolites excreted in the urine). An additional risk factor, which may contribute to the development of more aggressive forms of cancer of the urinary bladder is a long exposure to foreign bodies and infections (mainly Schistosoma haematobium, it concerns African and Small Asia countries, as well as medicines – cyclofosphamide) and small pelvis irradiation due to another tumors in that area.

Genetic disturbances observed in the case of cancers of the urinary bladder are mainly the mutations within suppressor gene p53, oncogene erbB-2, p21, c-myc.

Symptoms

One of the most frequent symptoms of cancer of the urinary bladder, which forces the patient to visit a doctor is haematuria, sometimes with clots. With the advance of the tumor process disuric symptoms may take place, namely pain, bladder tenesmus, burning sensation during miction, sometimes temporary retention of urine. Pain in the lumbar area as well as features of urinary tracts infection may appear during a stasis of urine in the upper urinary tracts. The pain in pelvis and around groin as well as swelling of the lower extremities usually accompany further symptoms of the disease. The first ‘signaling’ symptoms are the pains caused by metastatic changes in bones.

Diagnosis

Even one haematuria or earlier mentioned pain symptoms are an absolute indication for a patient to be examined in order to exclude the possibility of cancer of the bladder. Ultrasonography should be the first examination in the diagnosis of cancer of the urinary bladder, when the tumor change may be depicted, provided that it is big enough, the bladder is full and the place on the wall accessible during examination.

In contrast examination unevenness of bladder contour, filling defects and rigidity of infiltrated wall may be observed depending on the value and the degree of infiltration.

When a suspicious change is detected in bladder, the character of the change should be explained as soon as possible by the means of histopathologic examination. Having done bimanual examination (in order to find any out of bladder changes) cystoscopy is done. During the examination, segments are taken for histopathologic examination.

The urine cytology examination seems proper, nonetheless the negative result does not exclude the presence of a tumor process.

Apart from the above-mentioned examination, morphology, general urine examination, urography (the evaluation of urethers and kidneys) as well as small pelvis computer tomography (the evaluation of local infiltration and the invading stage of lymph nodes) are done. In the case of pain disorders, radiological examination and bone system scinigraphy seem advisable. Similarly to other tumors, chest RTG, gynecological examination in women and an evaluation of prostate’s state in men are recommended. From the prognosis perspective, determining the degree of histological tumor malignancy (basic prognostic factor apart from the state of primeval tumor determined according to TNM classification) seems vital. The following degrees of differentiation are distinguished: well-differentiated cancer (G1) – about 45% of detected cancers, moderately differentiated (G2), poorly differentiated (G3) and undifferentiated cancer (G4). The diagnostic value of BTA and NMP-22 markers is being checked and their determination does not constitute a norm as far as diagnostic methods are concerned.

Histological Classification

Epithelial tumors:

- transitional cell papilloma - transitional cell papilloma infiltrating the bladder wall - planoepithelial papilloma - transitional cell carcinoma - kinds of transitional cell carcinoma: " with planoepithelial transformation " with adenous transformation " with planoepithelial and adenous transformation - basal cell carcinoma - adenocarcinoma - anaplastic tumor

Non-epithelial tumors:

- adenoma - fibroma - myxoma - myoma - angioma - lipoma - pheochromocytoma - sarcoma

Classification

In order to estimate the level of progression the TNM classification or modified system by Jewett and Marshall are applied.

TNM Classification

Pathological classification pT, pN corresponds to T, N clinical classification.

T - primary tumor

Tx - Primary tumour cannot be assessed T0 - No evidence of primary tumour Tis - Carcinoma in situ, preinvasive tumor with focusal anaplasy (G1, G2, G3) within epithelium Ta - Noninvasive papillary carcinoma T1 - Tumor invades subepithelial connective tissue T2 - Tumor invades muscle T3 – Tumor deeply infiltrates a part of muscular coat not exceeding it (T3a) Tumor infiltrates the muscular coat (T3b) Tumor invades perivesical tissue T3a - extracapsular extensions (unilateral) T3b - extracapsular extensions (bilateral) T3c – Seminal vesicles infiltration T4 – Tumor invades other organs T4a - Tumor invades the prostate, uterus, vagina T4b - Tumor invades the pelvic wall, abdominal wall

N – regional lymph nodes

Nx - Regional lymph nodes cannot be assessed N0 - No regional lymph node metastasis N1- Regional lymph node metastasis N2 - Metastasis in a single lymph node, >2 cm but ≤5 cm in greatest dimension; or multiple lymph nodes, ≤5 cm in greatest dimension N3 - Metastasis in a lymph node, >5 cm in greatest dimension

M – distant metastases

MX - Distant metastases cannot be assessed M0 - No distant metastases M1- Distant metastases M1a – lymph nodes other than regional M1b – bone(s) M1c – other organs

In Whitmor-Catalon’s classification A, B, C, D degrees correspond to T1, T2, T3 and T4 respectively in TNM classification.

Classification by Jewett and Marshall

Stage 0: No tumor found in the specimen superficial tumour not invading the submucosa carcinoma in situ Stage A: superficial tumour invading the submucosa Stage B: muscle invasive tumour Stage B1: superficial invasion (less than halfway) Stage B2: deep invasion (more than halfway) Stage C: invasion into the perivesical fat Stage D: Extra vesical disease, further specified in Stage D1: invasion of contiguous organ or regional lymph nodes metastases Stage D2: Extra metastases to distant organs

Treatment

The choice of treatment for patients suffering from urinary bladder cancer depends on the degree of progression according to TNM classification, the level of tumor’s histological malignancy and the general state of the patient.

Surgical treatment

Transurethral resection of tumor (TURT)

This method is used in the case of surface changes (Ta, T1, T2, as well as the multiple ones and when treating preinvasive tumor Tis, if the number of focuses is low and the atypy insignificant). TURT may be done also in the case of T3a tumors if the diameter of the base does not exceed 2 cm. In the case of advanced stages (T3, T4 ) it is sometimes used as paliative treatment.

Partial resection of urinary bladder

It is applied when a 3 cm microscope margin of healthy tissue is possible in big, individual focuses of T2 tumor and in the early period of T3.

Complete resection of urinary bladder (cystectomy)

A two-stage surgery which consists in cutting out a bladder together with lymph nodes and recreating the possibility to drain the urine from the upper urinary tracts.

The operation concerns patients suffering from:

- poorly differentiated cancer (G3) - early recurrence after treatment using other methods - tumors invading the neck of urinary bladder, prostate urethra, bladder triangle when urine flow from kidneys is impeded - extended and multifocal pre-invasive tumors - bleeding from the bladder impossible to control

Cystectomy is also done among patients who underwent unsuccessful partial resection and after recurrences after radiotherapy.

Three ways of urine flow are applicable. One of them, known as the Bricker’s is about creating ileal conduit for the urine to flow to a bag stuck to the skin. The second option is the creation of an intestinal cistern, which when full is emptied by the patient by self catheterization through a skin fistula. The most comfortable way is the creation of a surrogate urinary bladder linked to the urethra (a patient urinates moving his/her stomach muscles).

Radiotherapy

It is applied among patients who do not give their consent to the treatment or when a radical cystectomy is often impossible in their cases. Radiotherapy among patients in T2 to T4 progression stage creates a possibility of attaining a 5-year survival without disease recurrence among 35 to 45% of patients and a 5-year complete survival among 23-40%.

A 45 Gy dose is given for the pelvis and then a boost for bladder tumor is done up to 65 Gy dose. The introduction of conformal radiotherapy which consists in 3-dimensional planning system (3D CRT) into clinical practice in the recent years enables more effective application of radiotherapy in the radical treatment of urinary bladder cancer. Chemotherapy

In the case of urinary bladder cancer it is applied mainly as palliative treatment or together with surgical methods or radiotherapy.

Inductive chemotherapy aims at reducing the size of tumor most often before the radiation.

Most often applied treatment schemes are:

M-VAC

Metotreksat 30 mg/m2 im Doksorubicine 30 mg/m2 iv Cisplatine 70mg/m2 iv Vinblastine 3mg/m2 iv The pause between the cycles 28 days

M-VC

Metotreksat 30 mg/m2 im Cisplatine 70mg/m2 iv Vinblastine 3mg/m2 iv The pause between the cycles 28 days

CISCA

Cyklofosfamide 650 mg/m2 iv Doksorubicine 50 mg/m2 iv Cisplatine 100mg/m2 iv The pause between the cycles 21 - 28 days

Paclitaxel (monotherapy)

Paclitaxel 250 mg/m2 iv 1 day, the cycles repeated every 21 days

Direct bladder treatment

Such a method is recommended in the cases of:

- tumors of T1 degree (multiple) - multifocal changes of Ta type - lesions of Tis character

Most often used drugs are: thipotepa, BCG vaccine, mitomycine, doksorubicine.

BCG therapy of the surface tumor has been more effective so far than direct bladder chemotherapy, as it decreases the risk of regional recurrence and, what is more, decreases probability of undergoing the disease process at invasive cancer stage.

Prognosis

In the case of urinary bladder cancer the prognosis depends on the level of progression as well as the choice of optimal treatment and the internal state of patients. A percentage of 5-year cure most often oscillates around 50-70% as for the I and the II degree, and 20-30% as for the III degree. Longer survival periods are rarely reported in the IV degree.

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Lower Your Risk For Breast Cancer & Heart Disease

Many postmenopausal women are looking for alternatives to hormone therapy, especially in light of the recent Women's Health Initiative research findings concerning the risks of combined estrogen and progestin therapy. Of particular interest are phytoestrogens, which have been gaining popularity due to their "natural" status, alleged health claims, and availability in a wide range of foods and supplements.

What are Phytoestrogens?

Phytoestrogens are naturally occurring plant compounds that have some similarities to estradiol, the most potent naturally occurring estrogen. However, phytoestrogens tend to have weaker effects than most estrogens, are not stored in the body, and can be easily broken down and eliminated.

Observational studies have found a lower prevalence of breast cancer, heart disease and hip fracture rates among people living in places like Southeast Asia, where diets are typically high in phytoestrogens. In North America, knowledge of these reported health effects has stimulated great interest in the health benefits of phytoestrogens. According to the Food and Drug Administration, the sale of soy foods, a major source of phytoestrogens, has increased dramatically in the past decade.

Dietary Sources of Phytoestrogens

Phytoestrogens consist of more than 20 compounds and can be found in more than 300 plants, such as herbs, grains and fruits. The three main classes of dietary phytoestrogens are isoflavones, lignans and coumestans:

1. Isoflavones (genistein, daidzein, glycitein and equol) are primarily found in soy beans and soy products, chickpeas and other legumes.

2. Lignans (enterolactone and enterodiol) are found in seeds (primarily flaxseed), cereal bran, legumes, and alcohol (beer and bourbon).

3. Coumestans (coumestrol) can be found in alfalfa and clover. Most food sources containing these compounds typically include more than one class of phytoestrogens.

The Skeletal Effects of Phytoestrogens

Much of the evidence concerning the potential role of phytoestrogens in bone health is based on animal studies. In fact, soybean protein, soy isoflavones, genistein, daidzein and coumestrol have all been shown to have a protective effect on bone in animals who had their ovaries surgically removed.

In humans, however, the evidence is conflicting. Compared to Caucasian populations, documented hip fracture rates are lower in countries such as Hong Kong, China and Japan where dietary phytoestrogen intakes are high. Yet reports suggest that Japanese women have a greater risk of sustaining a vertebral fracture than Caucasian women.

Several studies have explored the effects of soy isoflavones on bone health, but results have been mixed, ranging from a modest impact to no effect. Most of these studies have serious limitations, including their short duration and small sample size, making it difficult to fully evaluate the impact of these compounds on bone health.

Ipriflavone Supplements

Ipriflavone, a synthetic isoflavone, has shown some promise in its ability to conserve bone in postmenopausal women. Ipriflavone has also been shown to have a protective effect on bone density in pre-menopausal women taking gonadotropin-releasing hormone (GnRH), a treatment for endometriosis that triggers bone loss.

However, a definitive three-year study of more than 400 postmenopausal women concluded that ipriflavone did not prevent bone loss. Additionally, the compound was linked to lymphocytopenia (a reduction in lymphocytes) in a significant number of study participants. Lymphocytes are a type of white blood cell that helps the body fight infection.

Risks and Benefits Are Unclear

Some studies suggest that, unlike estrogen, phytoestrogens do not appear to target breast or uterine tissue. This suggests that they may act more like SERMS (selective estrogen receptor modulators such as raloxifene and tamoxifen) than actual estrogens. However, in other studies high isoflavone levels have been linked to an increased risk of breast cancer.

Clearly, additional research is needed to further evaluate the effects of phytoestrogens before judgments regarding their safety and usefulness can be made.

Key Points

Based on information available at this time, it is reasonable to make the following conclusions concerning phytoestrogens and bone health in postmenopausal women:

1. Moderate amounts of foods containing phytoestrogens can be safely included in the diet but do not expect it to help build bone. Keep to the basic rule - eat the least processed forms.

2. Due to a lack of evidence and concerns about safety, supplementation with synthetic isoflavones (ipriflavone) is in question.

3. Postmenopausal women are encouraged to view evidence concerning phytoestrogens and bone health as conflicting and incomplete. For women who are estrogen dominant increasing their phytoestrogen intake may not improve their bone position.

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Sunburn, UV Overexposure & Skin Cancer: Prevention or Cure?

Overexposure to the sun and UV rays is rarely obvious at the time, -- and on many occasions, probably quite unintentional. However repeated exposure has rather more adverse long-term implications for our bodies and our health.

We’re all well aware of the more obvious and painful symptoms of sunburn including hot, red, tender skin – which in the case of a more heavy burn can also include blistering, peeling and dehydration.

The damage that occurs beneath the skin as a result of sunburn is considerably ‘less obvious’ at the time of exposure, and may in fact take years to produce symptoms visible to the naked eye.

The fact that damage caused to skin cells during sunburn can not only accelerate the aging process, but also increase the risk of cataracts and skin cancer, should certainly demand our attention.

When faced with the potential risk of having to treat more than just the temporary symptoms and pain of sunburn, doesn’t it make more sense to avoid the risk in the first place?

Seek prevention rather than cure!

So before you venture out into the sun again, remember these important tips to protect yourself from overexposure of UV rays and sunburn, and its associated risks:

1. Wear protective clothing, including a long-sleeve shirt and a hat. Consider the ‘additional’ protection of an umbrella or shade where appropriate.

2. Avoid sun exposure between 10 am and 3 pm if at all possible.

3. Remember that UV rays are present even on cloudy days.

4. Remember that sunlight is strongly reflected from sand, snow, ice, water and concrete, which can intensify your direct sunlight exposure.

5. Apply sunscreen containing a sun protection factor (SPF) of at least 15, at least 15 minutes before going out into the sun.

6. Reapply sunscreen at regular intervals while out in the sun, especially if you are perspiring heavily or swimming.

7. Remember that UV overexposure is not limited to ‘sun exposure’. Sunburn can also occur as a result of UV exposure from other sources including tanning beds/lamps, welding arcs etc.

Prevention is a far better treatment than cure. In the event however, that you discover any unusual moles or growths on your skin – (particularly if they’re irregular in shape, bleed, itch, or appear to be changing) - consult your healthcare provider as soon as possible.

When it comes to overexposure of UV rays and sunburn that result in skin cancer, early detection will certainly assist in providing you with more effective treatment. But considering your options beforehand – what will provide the best outcome for your health? Prevention or Cure? I know which one I’d choose...!

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Breast Cancer; Its Causes

Breast cancer is a malignant tumor developed from cells of the breast, and it is one of the most common cancers affecting females, at time has not been established what is the exact cause of this one, but last researches clearly pointing that there are several risks factors;
These are the most probably breast cancer risk factors;

- Last researches have established that in the age group above 50 years there is a high incidence; on the other hand, in the age group below 25 years the incidence is very low. It is very important to say that this disease is very aggressive in patient 25-50 years old.

- Menstrual cycle is other factor that should be considered; common in the ladies who have a longer menstrual life, i.e. the onset of menarche is earlier and cessation of menstruation is late.

- The women that smoke and drink alcohol increase the risk of developing breast cancer.

- Breast cancer is developed more frequently in spinsters and married woman that have not given birth to children, or if given birth then have not breast fed their offspring.

- The women that have had a breast cancer on one side have greater risk to develop cancer on the opposite side, and if there are antecedents of breast cancer in their families (mother, sisters and daughters), there are greatest risks too.

- Breast cancer is linked with obesity and higher intake of saturated fatty acids

- Breast cancer is linked too, with the continuous or sequential uses of combined oestrogen plus progestin hormone therapy (CHT)

- Women that have been using oral anti contraceptives for more than ten years are more vulnerable to the development of this disease.

On the other hand, women doing 4-5 hours of exercises per week reduce their risk of developing breast cancer.

In short, these facts derive from the statistical analysis; they should not be taken as causative or predisposing factors.

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Cancer Information and Support Can Hasten Healing and Save Lives

It's the word that no one ever wants to hear: cancer. Although our parents or grandparents might have heard that word and considered it an automatic death sentence, today's focus on prevention, early detection, and treatment means that people who are diagnosed with cancer often have a very good chance of beating the disease.

The Latest Statistics

According to the National Cancer Institute (NCI), death rates from cancer have been decreasing since the early 1990s. In a recently published report on cancer from the years 1975 through 2004 (the latest year for which statistics are available), the NCI noted that, "Death rates decreased on average 2.1 percent per year from 2002 through 2004, nearly twice the annual decrease of 1.1 percent per year from 1993 through 2002."

The NCI emphasized that, "Death rates are the best indicator of progress against cancer." This is because the diagnosis rates of cancer can often be viewed in a positive light. For example, an increase in the diagnosis of prostate cancer (a typically non-fatal cancer) may be the result of a greater number of men obtaining PSA tests. Similarly, an increase in mammography may lead to an increase in the diagnosis of breast cancer, but early detection almost always leads to better outcomes. In other words, more women may be diagnosed with early stage breast cancer, but fewer will die from the disease.

According to the NCI report, mortality rates "decreased for 12 of the 15 most common causes of cancer death in men (i.e., cancers of the lung, prostate, colon and rectum, bladder, kidney, stomach, brain, and oral cavity as well as leukemia, non-Hodgkin lymphoma and myeloma)." Among women, mortality rates "decreased for 10 of the 15 most common cancers (i.e., breast, colon and rectum, stomach, kidney, cervix, brain and bladder cancers as well as non-Hodgkin lymphoma, leukemia, and myeloma)." Unfortunately, while deaths from blood and cervical cancers decreased, those from liver cancer and lung cancer increased for women.

When the Unthinkable Happens

If you or a loved one are diagnosed with cancer - whether bone cancer, skin cancer, ovarian cancer, or some other form - it's natural to jump to conclusions. That is why it is imperative to gather all of the information possible on the form of cancer and its treatments. Thankfully, the Internet can provide a wealth of information on cancer and cancer treatments. Becoming education about the disease your fighting may well be your best weapon in beating the disease. Information gives you the power to ask the right questions of health care providers, better understand your options, and pave the way to making an informed decision about cancer treatment.

Everyone Needs Support

The Internet is also a critical tool for finding the support you need while battling cancer. If you've received the diagnosis, it's extraordinarily helpful to connect with a network of people who share your experience. If a loved one has received the diagnosis, you need to get a grasp of what lies on the road ahead, and get the support you need in order to support the one you love.

Remember, cancer isn't necessarily a death sentence, and information and support are two of the most potent weapons you can have in your arsenal to battle the disease.

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Abdominal Chemo Increases Ovarian Cancer Survival Rate

A large clinical test shows that giving chemotherapy directly into the stomach, as well as into a vein, can improve survival of women with advanced ovarian cancer by about sixteen months. The results of the study, which pop up in this week's issue of the New England Journal of Medicine, prompted the National Cancer Institute to issue a statement supporting doctors to employ this plan of attack for appropriate patients.

Why is this new treatment reigmine so important? Ovarian cancer is the fourth greatest reason of cancer demises in women, affecting more than 22,000 women and killing more than 16,000 in 2005. Although this disease is super treatable when saw ahead of time, virtually all cases are not noticed until they have dispersed beyond the ovaries. Because so many ovarian cancer patients are diagnosed at a later stage, it is crucial to find ways to better treatments for further progressed disease.

What is already known about ovarian cancer? virtually all women with advanced ovarian cancer get chemotherapy after surgery to get rid of the tumor. That chemotherapy is usually given into a vein and moves through the bloodstream to reach tumor cells in the stomach. Doctors have also experimented with rendering the chemotherapy straight into the abdomen through a catheter, a system called intraperitoneal (IP) chemotherapy. Eight clinical trials of this approach have been done, and most showed a gain to IP chemotherapy. But this technique is not widely wore, according to the study's author, Deborah Armstrong, MD.

"There has been a prejudice against IP therapy in ovarian cancer because it's an old idea, it requires skill and experience for the surgery and for the chemotherapy, and it's additional complicated than IV chemotherapy," said Armstrong, who is a medical oncologist and associate professor at the John Hopkins Kimmel Cancer Center in Baltimore.

How this study was done: Women with stage III ovarian cancer were randomly assigned to get either standard chemotherapy in a vein (210 women), or a combination of chemotherapy in a vein and IP chemotherapy (205 women). The women had already had surgery that successfully removed all or most of the tumor; none had tumors remaining that were larger than 1 cm in diameter. All the women were treated with the same drugs, cisplatin and paclitaxel. Six cycles of chemotherapy were planned for both groups.

What was found? Women who had IP chemo operated long without their cancer coming back and lived longest overall. Women who had traditional chemotherapy in a vein survived about 4 years after treatment, while those who got chemotherapy in the stomach as well as a vein stomach an median of nearly 5 ½ years after treatment.

That improvement is "one of the largest benefits ever observed for a new therapy in gynecologic oncology," based on data from Stephen A. Cannistra, MD, who composed an editorial published with the study. He is a professor at Harvard Medical School and managing director of the division of gynecologic medical oncology at Beth Israel Deaconess Medical Center in Boston.

Nonetheless, the IP treatment was very much more difficult on the patients. Women who had this treatment had many additional terrible or life-threatening side effects, including low white blood cell counts, infection, tiredness, and anguish. Many side effects were associated to the catheters that must be introduced into the stomach to deliver the chemotherapy. These problems were so serious that fewer than half of the women designated to undergo IP chemotherapy finished all six designed treatment cycles. That makes the survival advance that good deal supplementary noteworthy, Cannistra composed.

Women who got IP therapy also reported significantly worse caliber of life during and just after treatment. By one year out, nonetheless, both groups described similar quality of life.


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Recognizing And Battling Breast Cancer

Breast cancer occurs due to the irrepressible growth of cells in the breast that invades the nearby tissues and spreads throughout the body. These collections of irrepressible growth of tissue are called tumors or malignant tumors. However, not all tumors are cancerous.

Breast cancer has been diagnosed in large numbers in North America and Europe. In 2001, about 200,000 cases of breast cancer were diagnosed in the United States alone. Every woman has a 1 in 8 risk of developing breast cancer, but the risk of dying from breast cancer is much lower, barely 1 in 28.

The risk of getting breast cancer is generally higher among older women, women with a family history or previous history of breast cancer, women who had radiation therapy in the chest region, women who started their periods before 12 years old, women who had menopause after 50 years old, women who never had children or had them age 30 or older, or women with genetic mutation. In recent times genetic mutations for breast cancer have become a hot topic of research.

The breast cancer tumor has the following symptoms: lump or thickening that appears on the breast or underarm, changes in the breast's shape, nipple turned inwards followed by colorless discharge, red or scaled skin or nipple, or ridges on the breast skin.

If a woman experiences any of these symptoms, it does not necessarily mean she has breast cancer. In such a case she should undergo a breast cancer personal check-up. It is estimated that 95% of breast cancer is detected through personal check-up. The breast cancer personal check-up includes checking for lumps in the breasts after each menstrual period, puckering the skin, and checking for nipple retraction or discharge. For consistent result, every woman should do a breast cancer personal check-up at the same time every month. Various other techniques such as mammography, thermography, ultrasonography, computerized tomography scan etc, can also help detect breast cancer.

Breast cancer treatments include surgery that removes cancerous tissues, with breast conservation therapy (BCT) being one such surgery. Other breast cancer treatments include chemotherapy, radiotherapy, hormonal therapy and biologic therapy. Radiotherapy is a common breast cancer treatment, and radiation treatment and chemotherapy may follow surgery to ensure the destruction of the stray cancer cells.

Even after undergoing many or all of these breast cancer treatment measures, unfortunately almost half the women suffer from a recurrence of the disease.

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