Recurrence of breast cancer is usually symptomatic and is often first noticed by the patient rather than at routine follow-up visits to hospital clinics. Women will frequently report the symptoms first to their GP. A study that compared breast cancer follow-up in primary care with specialist care shows that patients were more satisfied with follow-up in general practice and that there was no increase in time to diagnosis of recurrence in primary care compared with specialist care.

‘Guidelines for limited (two or three years) follow-up should be agreed by each network. The aims of follow-up should be to detect and treat local recurrence and adverse effects of therapy, particularly lymphoedema. Intensive follow-up, designed to detect metastatic disease before symptoms develop, is not beneficial and should not be provided.’( NICE: Improving Outcomes in Breast Cancer: Manual Update 2002)

Eva Grunfeld, Sukhbinder Dhesy-Thind, Mark Levine, CLinical Care Guidelines: follow-up after treatment for breast cancer (summary of the 2005 update) CMAJ • May 10, 2005; 172 (10)
.
E. Grunfeld, M. N. Levine, and J. A. Julian
In Reply
J. Clin. Oncol., August 1, 2006; 24(22): 3711 – 3712.

E. Grunfeld, M. N. Levine, J. A. Julian, D. Coyle, B. Szechtman, D. Mirsky, S. Verma, S. Dent, C. Sawka, K. I. Pritchard, D. Ginsburg, M. Wood, and T. Whelan

Randomized Trial of Long-Term Follow-Up for Early-Stage Breast Cancer: A Comparison of Family Physician Versus Specialist Care
J. Clin. Oncol., February 20, 2006; 24(6): 848 – 855.

Hereditary nonpolyposis colorectal cancer (HNPCC) usually occurs in patients younger than age 45 and can result in the development of cancers in a variety of tissues, such as the colon, rectum, endometrium, stomach, ovaries, brain, and skin. A major genetic characteristic of HNPCC tumors is microsatellite instability (MSI). Microsatellites are short repeated sequences of DNA, and MSI results when mutations in genes that are responsible for repairing damaged DNA cause microsatellites to become longer or shorter. Cancers that exhibit MSI account for about 15% of all colorectal cancers. Myriad Genetic’s Colaris test is an MSI test.

Because HNPCC results from inherited mutations, it is possible that family members of patients with HNPCC also have the genetic characteristics that put them at an increased risk for cancers associated with a particular mutation. The Amsterdam criteria were the first diagnostic guidelines to be developed, and the aim of these was to determine whether a family should be classified as having HNPCC. All of the following criteria had to be met to diagnose HNPCC: at least three members of the family should have colorectal cancer and at least one should be a first-degree relative of the other two; at least two generations of the family should have colorectal cancer; and one of the cases of colorectal cancer should have been diagnosed before the individual was age 50 years.

Revised Amsterdam Criteria
In response to criticism that the Amsterdam criteria were too stringent, the revised Amsterdam criteria (Amsterdam II criteria) were developed in 1998 to include extracolonic HNPCC-associated cancers — colorectal cancer or cancer of the endometrium, small bowel, ureter, or renal pelvis — that are also quite common in HNPCC. This revision prevents some individuals and families from being left out of the classification. The original Amsterdam criteria were also modified so that very small families can be considered as having HNPCC. These families must have two diagnosed colorectal cancers in first-degree relatives, which involve at least two generations. One of these individuals must have been diagnosed by the age of 55. The presence of a third relative with an unusual early-onset neoplasm or endometrial cancer is considered sufficient to classify the family as meeting the Amsterdam II criteria.

Bethesda Guidelines
The need for a set of guidelines for genetic diagnosis of HNPCC became obvious in the mid-1990s. The use of the Amsterdam criteria was achieving their original purpose; however, their limited sensitivity hampered decisions of choosing which patients should undergo genetic testing. The Bethesda guidelines (or criteria) were therefore developed with a different objective to the Amsterdam criteria[31] — they mainly aid in the decision process for whether individuals with cancer in families that do not fulfill Amsterdam criteria should undergo genetic testing. The Bethesda guidelines include additional criteria such as pathological evaluation of the Amsterdam-criteria-positive individuals (BOX 3), which allows less stringent criteria. Individuals with two HNPCC-related cancers — including synchronous (two or more tumours are present at the same time) and metachronous (first tumour is followed by a second one at a later date) cancers — or associated extracolonic cancers, or individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or colorectal adenoma are considered to fulfill the Bethesda criteria. Alternatively, individuals are considered to fulfill the Bethesda guidelines if one of the cancers is diagnosed by 45 years and the adenoma is diagnosed by 40 years; if colorectal cancer or endometrial cancer is diagnosed by 45 years; if right-sided colorectal cancer with an undifferentiated pattern (solid/cribiform) on histopathology is diagnosed by 45 years; or if signet-ring-cell-type colorectal cancer is diagnosed by 45 years.

Revised Bethesda Guidelines
Although the Bethesda guidelines are considered to be a useful tool for making decisions about whether genetic testing and/or MSI testing of the tumours from individuals with HNPCC should be performed, data that has been accumulated over the past five years on both genetics and IHC characterization indicate that these criteria should be updated. An international group of HNPCC researchers and clinicians unanimously decided to revise these guidelines. In the revised Bethesda guidelines, changes were undertaken for several reasons: to identify patients who were at risk for hereditary cancer, to include a complete spectrum of colonic and extracolonic cancers, and to identify MSH2 and MLH1 germline-mutation carriers in patients with cancers who might or might not fulfill the Amsterdam II criteria. First, the Amsterdam and then the Amsterdam II criteria can be used to assess cases that can be subjected to the revised Bethesda guidelines. Next, cancers from these cases can be analysed for MSI or the absence of MSH2 or MLH1 — by IHC — based on the availability of either test or the cost effectiveness in a particular situation. The final decision is whether genetic testing of the main HNPCC genes, MSH2 and MLH1, should be performed. If individuals are found to have disease-related mutations, they are confirmed as having HNPCC.

It was decided that individuals who meet one of the following criteria fulfilled the revised Bethesda guidelines and should be recommended to undergo genetic testing. Those diagnosed with colorectal cancer before the age of 50 years; who had synchronous or metachronous colorectal or other HNPCC-associated tumours, regardless of age; who had MSI-H under the age of 60 years; who had one or more first-degree relatives with colorectal cancer or other HNPCC-related tumour, with one of the cancers diagnosed by the age of 50 years (including adenoma by the age of 40 years); or who had colorectal cancer with two or more relatives with colorectal cancer or other HNPCC-related tumours, regardless of age.

Although Bethesda criteria differ in their original purpose to the Amsterdam criteria, several studies show that the Bethesda criteria are the most sensitive (94%), followed by the Amsterdam II criteria (72%) and then the Amsterdam criteria (61%). Now, with further refinements in the Bethesda guidelines (revised Bethesda guidelines), it is hoped that the clinical-research community will accept these new guidelines to make decisions in patients with familial cancer and to decide whether determination of precise gene mutation in MMR genes should be performed.

In summary, the revised criteria suggest that tumors from patients with colorectal cancer should be tested for MSI and subsequent genetic testing to confirm a mutation in one of the genes responsible for HNPCC in the following situations:

1. The patient is younger than age 50.
2. The patient has multiple HNPCC-associated tumors in the colon or in other areas known to be caused by the same mutations, either at the same time or occurring over a period of time.
3. A patient younger than age 60 has colorectal cancer that has microscopic characteristics that are often indicative of MSI.
4. A patient has one or more first-degree relatives who had an HNPCC-related tumor at age 50 or younger.
5. A patient has two or more first- or second-degree relatives who had HNPCC-related tumors at any age.

Syngal, S., Fox, E. A., Eng, C., Kolodner, R. D. & Garber, J. E. Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1. J. Med. Genet. 37, 641-645 (2000).

Cai, S. J. et al. Clinical characteristics and diagnosis of patients with hereditary nonpolyposis colorectal cancer. World J. Gastroenterol. 9, 284-287 (2003).

Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96;2004:261-8.

Valérie Bonadona, Bernard Bonaïti, Sylviane Olschwang, Sophie Grandjouan, Laetitia Huiart, Michel Longy, Rosine Guimbaud, Bruno Buecher, Yves-Jean Bignon, Olivier Caron, Chrystelle Colas, Catherine Noguès, Sophie Lejeune-Dumoulin, Laurence Olivier-Faivre, Florence Polycarpe-Osaer, Tan Dat Nguyen, Françoise Desseigne, Jean-Christophe Saurin, Pascaline Berthet, Dominique Leroux, Jacqueline Duffour, Sylvie Manouvrier, Thierry Frébourg, Hagay Sobol, Christine Lasset, Catherine Bonaïti-Pellié, for the French Cancer Genetics Network Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch Syndrome  JAMA. 2011;305(22):2304-2310.

Cancer Risks Are Lower in Lynch Syndrome Families with MSH6 Mutations
JWatch Gastroenterology. 2011;2011(624):1.

A 2001 BlueCross BlueShield Association Technology Evaluation Center (TEC) Assessment, which offered the following observations and conclusions:

For acute GVHD or chronic GVHD in previously untreated patients, or in those responding to conventional therapy, there were no studies that met selection criteria and reported results of extracorporeal photopheresis, alone or in combination with other therapies. Therefore, it was not possible to draw conclusions concerning the effects of this therapy on health outcomes in previously untreated or responsive patients.
In acute GVHD, a phase II study by Greinix et al. involving 38 patients reported complete remission in 86%, 55%, and 30% of patients with grades 2, 3, and 4 agvhd respectively. The best results were obtained in 82%, 61%, and 61% of patients with skin, liver, and gut agvhd respectively.
Studies focusing on patients with chronic GVHD unresponsive to other therapies reported resolution or marked improvement of lesions in about 50% of patients. The one phase II study by Flowers et al.  reported on a multicentre prospective phase II randomized study in 23 transplant centres in North and South America, Europe, and Australia. The 95 enrolled patients were randomized either to ECP plus standard therapy or to standard therapy alone. The conclusion reached was that ECP had a steroid-sparing effect in the treatment of chronic GVHD.
Three studies reported outcomes for 38 patients with acute GVHD that was refractory to standard treatment with steroids and other immunosuppressive drugs. Patients with Grade IV disease were generally unresponsive to photopheresis. While a single study of 21 patients reported responses in a majority of patients with Grade III disease, the small number of patients in this study was not sufficient to permit conclusions concerning the outcomes of photopheresis for treatment-refractory acute GVHD. SInce then there ahd been a nubmer of otehr reprots but no studies. A 2008 workshop convcded: “The evidence for the efficacy of ECP has been appraised by a combined British Photodermatology Group and U.K. Skin Lymphoma Group workshop on the basis of evidence published up to the end of 2001 and on the consensus of best practice. There is fair evidence for the use of ECP in erythrodermic CTCL and steroid-refractory GVHD, but randomized controlled studies are needed.” National Institute for Health and Clinical Excellence in the UK endorsed the use of ECP for CTCL and because of the complexity of treatment supported its use in specialized centres and also suggested the need for expansion of this service.

A 2012 guideline(Dinghan et al) recommends it as second line treatment.

Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN, on behalf of the Haemato-oncology Task Force of the British Committee [trunc]. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol 2012 Jul;158(1):46-61. [125 references]

Greinix HT, Knobler RM, Worel N. The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica. 2006;91:405–8.

Scarisbrick JJ, Taylor P, Holtick U, et al. U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol. 2008;158:659–678.

J. Klassen, The role of photopheresis in the treatment of graft-versus-host disease Curr Oncol. 2010 April; 17(2): 55–58.

Halle P, Paillard C, D’Incan M et al. Successful extracorporeal photochemotherapy for chronic graft-versus-host disease in pediatric patients. J Hematother Stem Cell Res 2002;11(3):501-12

Salvaneschi L, Perotti C, Zecca M et al. Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood. Transfusion 2001;41(10):1299-305

Flowers ME, Apperley JF, van Besien K. A multi-center prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood. 2008;112:2667–74. [Erratum in: Blood 2009;113:4478]

Clinical Summary:
71 year-old man s/p reduced intensisty allogeneic transplant from sister after AML diagnosed and induced in May 2010. He developed Graft vs Host Disease and was treated with tacrolimus but now received photopheresis.

Although erectile dysfunction is more commonly caused by diabetes, prostate cancer surgery, especially retroperitoneal dissection, often causes it as well. It can be considered a complication of prostate cancer treatment.

1. Gresser U, Gleiter CH. Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil: review of the literature. Eur J Med Res.2002;7:435-446.Montague DK, Jarow JP, Broderick GA, et al, and the Erectile Dysfunction Guideline Update Panel. The management of erectile dysfunction: an AUA update.
   J Urol. 2005;174:230-239.

RICE (Rest, Ice, Compression, Elevation) hasbeen used to treat acute and chronic injury and assist in orthopedic surgery rehabilitation.  Game Ready System simultaneously delivers both adjustable cold therapy and intermittent compression, to apply the two  aspects of the RICE regimen. Cold compression therapy combines two of the principles of R.I.C.E. (Rest, Ice, Compression, Elevation) to reduce pain and swelling from a sports or activity injury to soft tissues. The therapy is especially useful for sprains, strains, pulled muscles and pulled ligaments.

ON general, cold compression wraps should be used for 20 minutes every two hours the first day a soft tissue injury occurs. Thereafter they should be used 2 to 3 times a day until pain and swelling diminishes.

While the theoretical basis for this technology is sound and anecdotal evidence appear reasonable, I have not been able to find sufficient credible medical literaure of this specific device to consider this therapy medically necessary and to justify the cost of $3800.00 purchase price or
$1600.00 rental price cost for 2 wks  .

Cameron MH. Physical agents in rehabilitation from research to practice. 1999. W.B. Saunders Company, Philadelphia, PA.

http://www.gameready.com/

C. Kunisaki, H. Akiyama, M. Nomura, G. Matsuda, Y. Otsuka, H. Ono, Y. Nagahori, H. Hosoi, M. Takahashi, F. Kito, et al.
Significance of Long-Term Follow-Up of Early Gastric Cancer
Ann. Surg. Oncol., March 1, 2006; 13(3): 363 – 369.

Yasuhiro Kodera, MD, Seiji Ito, MD, Yoshitaka Yamamura, MD, Yoshinari Mochizuki, MD, Michitaka Fujiwara, MD, Kenji Hibi, MD, Katsuki Ito, MD, Seiji Akiyama, MD and Akimasa Nakao, Follow-Up Surveillance for Recurrence After Curative Gastric Cancer Surgery Lacks Survival Benefit Annals of Surgical Oncology 10:898-902 (2003)

Kodera Y, Ito S, Yamamura Y, et al. A follow-up surveillance for recurrence after curative gastric cancer surgery lacks survival benefit. Ann Surg Oncol 2003; 10:898–902.[

Biphopshonates are approved for treatment of osteoporosis and to prevent skeltal related events (fractures) in certain cancer patients with bone or other metastases. Clodronate, or ibandronate may delay or prevent bone metastases in patients with nonmetastatic breast cancer and are being studied for adjuvant therapy. In addition to the ABCSG-012 trial, which is reported below, the parallel-design Zometa®/Femara® Adjuvant Synergy Trials (Z-FAST and ZO-FAST in the U.S. and Europe, respectively) are investigating the benefit of immediate and delayed treatment with zoledronic acid (4 mg every 6 months) in postmenopausal women receiving adjuvant therapy with letrozole (2.5 mg/day) for early-stage hormone-receptor-positive breast cancer. Those trials will also enroll women in whom menopause has been induced by chemotherapy. The poposed trial is ongoing. Based on the results from early clinical trials, bisphosphonates appear to be effective for the prevention of fractures. Current consensus guidelines from the American Society of Clinical Oncology recommend the use of i.v. or oral bisphosphonate therapy in patients who develop T scores below -2.5 standard deviations from normal (osteoporosis) during adjuvant therapy for breast cancer.

NCT00127205, is a study of Zoledronate, Clodronate, or Ibandronate in Treating Women Who Have Undergone Surgery for Stage I, Stage II, or Stage III Breast Cancer. It is not yet known whether zoledronate is more effective than clodronate or ibandronate in treating breast cancer.

However,the Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-21)reported that the addition of adjuvant Zometa® (zoledronic acid) to endocrine therapy for the treatment of hormone-positive, early breast cancer significantly improved progression-free and recurrence-free survival beyond the effects of endocrine therapy alone among premenopausal women. These results were recently presented as a late-breaking abstract at the 2008 annual American Society for Clinical Oncology (ASCO) meeting in Chicago, Illinois May 30 to June 2, 2008.

This was a multicenter, open-label Phase III study that included 1,803 premenopausal women with Stages I-II, hormone-positive breast cancer. Compared with hormone therapy alone, the addition of Zometa improved disease-free survival by 36% (p=0.01) and recurrence-free survival by 35% (p=0.015).

Researchers affiliated with the Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-21) have reported that the addition of adjuvant Zometa® (zoledronic acid) to endocrine therapy for the treatment of hormone-positive, early breast cancer significantly improved progression-free and recurrence-free survival beyond the effects of endocrine therapy alone among premenopausal women. These results were recently presented as a late-breaking abstract at the 2008 annual American Society for Clinical Oncology (ASCO) meeting in Chicago, Illinois May 30 to June 2.

The current study, the Austrian Breast & Colorectal Cancer Study Group Trial 12 (ABCSG-21), was a multicenter, open-label Phase III study that included 1,803 premenopausal women with Stages I-II, hormone-positive breast cancer. Patients had fewer than 10 involved axillary lymph nodes. Following curative surgery and initiation of the gonadotropin-releasing hormone analog goserelin for ovarian suppression, patients were enrolled and randomized into one of four treatment groups: 1) Arimidex® (anastrozole) plus Zometa; 2) Arimidex alone; 3) Nolvadex® (tamoxifen) plus Zometa; 4) Nolvadex alone. Treatment was continued for three years; the median follow-up of the trial was five years. Disease-free survival in all treatment groups was the primary endpoint; recurrence-free survival, overall survival and safety were secondary endpoints. Bone-metastases-free survival was an exploratory endpoint of the trial.

Compared with hormone therapy alone, the addition of Zometa improved disease-free survival by 36% (p=0.01) and recurrence-free survival by 35% (p=0.015).

Patients treated with Zometa had a survival of 98% compared with 94% for the control group (p=0.10).
Patients treated with Zometa had a trend toward a lower risk of developing bone metastases (p>0.05).
Longer follow-up and a larger number of events are necessary to truly determine significance of overall survival and the risk of the development of bone metastases.

There were no reported cases of osteonecrosis of the jaw (ONJ); side effects were consistent with the known drug safety profile. These are among the first data to suggest that there is a specific anti-tumor effect of bisphosphonates in anadjuvant setting.

It is recommended that, if available, zoledronic acid (4 mg intravenously [over 15 minutes or longer] every 6 months [for 3 to 5 years]) or clodronate (1,600 mg/d orally [for 2 to 3 years]) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy.
Sukhbinder Dhesy-Thind et al, Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology 35, no. 18 (June 2017) 2062-2081.

Reid IR, Brown JP, Burckhardt P et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 2002;346:653–661

Gnant M, Hausmaninger H, Samonigg H et al. Changes in bone mineral density caused by anastrozole or tamoxifen in combination with goserelin (± zoledronate) as adjuvant treatment for hormone receptor-positive premenopausal breast cancer: results of a randomized multicenter trial. Presented at the 25th Annual San Antonio Breast Cancer Symposium, December 11–14, 2002, San Antonio, TX.

Saarto T, Blomqvist C, Valimaki M et al. Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens. Br J Cancer 1997;75:602–605

Allan Lipton Toward New Horizons: The Future of Bisphosphonate Therapy The Oncologist, Vol. 9, Suppl 4, 38–47, September 2004