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The role of surgeons in cancer management
CANCER TREATMENT
The role of surgeons in cancer management
causes of cancer deaths are lung (18.2% of the total), stomach (9.7%) and liver (9.2%). In the last 20 years UK cancer management has changed, with the introduction of multidisciplinary teams (MDT). The diagnosis and treatment of cancer patients is coordinated by a team of experts including surgeons, radiologists, pathologists, oncologists and specialist nurses, that improves consistency in the standard of care offered.3 The MDT usually meets weekly to discuss the diagnosis and multidisciplinary management plan for each patient. The decision-making process is helped by an increasing number of national guidelines which help to standardize and optimize the care of cancer patients. The role of surgeons in cancer treatment has evolved. Historically, cancer patients were subjected to surgery in order to achieve a diagnosis, remove the cancer or manage complications. The role of surgery in cancer management has expanded to include screening, prevention, diagnosis and staging, reconstruction and palliation.
Valentina Lefemine Helen Sweetland
Abstract The incidence of cancer continues to rise in western countries, although slower than in previous decades. In the UK 24% of all deaths are caused by cancer. The role of surgery in cancer management has expanded over the last few decades to include screening, prevention, diagnosis and staging, reconstruction and palliation. In UK, the breast, bowel and cervical national screening programmes rely on surgeons to perform invasive diagnostic procedures. Genetic testing enables identification of carriers of pathological genetic mutations who are at high risk of developing cancer and might benefit from ‘risk-reducing’ surgery. Advances in surgical technology have led to a variety of new techniques being available to surgeons and cancer patients for diagnostic and therapeutic purposes, including vacuum-assisted devices, photodynamic therapy, radio frequency ablation, cryosurgery and microwave ablation. Oncological surgical procedures often result in disfigurement, mutilation or functional loss, and restorative surgery has become an integral part in the management of cancer patients with the ultimate aim of improving their quality of life. In incurable cancer patients, palliative surgery can be justified to reduce the severity of symptoms and improve the quality of life, where conservative strategies or less invasive interventions have failed or are not appropriate.
Keywords Cancer screening; palliation; reconstructive risk-reducing surgery; staging; surgical technique advances
Screening In UK there are three NHS cancer screening programmes (www. cancerscreening.nhs.uk) which include breast, colorectal and cervical cancer. Surgeons play an active role in each programme. The breast screening programme performs mammography, 3-yearly on women aged 50e70 years, with plans to extend the screening age to 73 years by 2016. Surgeons perform diagnostic excision biopsies where cancer cannot be excluded by imaging and core biopsies, and operate on those diagnosed with cancer. The colorectal screening programme offers screening, 2-yearly to men and women, aged 60e69 years, by faecal occult blood (FOB) tests. It relies on endoscopists (surgeons or gastroenterologists) to perform screening colonoscopy in those patients who have an abnormal result from the FOB test. Surgeons then perform open or laparoscopic colonic resections when required. Women between the ages of 25 and 64 years are eligible for a cervical smear test every 3e5 years. The programme is generally run by specialist nurses, but gynaecologists will be involved if a colposcopy is needed for patients who are found to have abnormal epithelial cells on a smear.
surgery;
Introduction
Prevention through surgery
The incidence of cancer continues to rise in western countries, although slower than in previous decades. The Office for National Statistics report in 2011,1 showed that in the UK (2006e2008) breast, lung and colorectal cancers accounted for around 41% of cases and 40% of cancer deaths. In the UK 24% of all deaths are caused by cancer. A different trend has been reported worldwide: cancer accounts for 12% of all deaths each year and data retrieved from the GLOBOCAN2 cancer database have shown that the common
Some people have a higher risk of developing cancer due to inherited pathological mutations of certain genes. Common hereditary cancer syndromes include: type 2 multiple endocrine neoplasia syndrome (RET proto-oncogene mutation), hereditary breast ovarian cancer (BRCA1/2 gene mutation), diffuse gastric cancer (CDH1 gene mutation) and polyposis and non-polyposis colorectal cancer syndromes (APC and mismatch-repair genes mutation). For these genetic mutation carriers, the lifetime risk of developing the corresponding cancer is approximately 70e80%, and often associated with high mortality. Genetic testing can identify high-risk patients so that an effective preventive strategy can be agreed between the patient, geneticist, surgeon and radiologist. The role of surgery in cancer prevention has increased as these genetic mutations have been discovered and ‘risk-reducing’ surgery is used more frequently in clinical practice; however decision-making remains complex and multifactorial. There are
Valentina Lefemine MRCS is a Specialist Registrar in General and Breast Surgery at Cardiff and Vale Breast Centre, University Hospital of Llandough, Cardiff, UK. Conflicts of interest: none declared. Helen Sweetland FRCS is a Consultant Breast Surgeon at Cardiff and Vale Breast Centre, University Hospital of Llandough, Cardiff, UK. Conflicts of interest: none declared.
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Ó 2012 Elsevier Ltd. All rights reserved.
CANCER TREATMENT
no randomized controlled trials addressing the efficacy of prophylactic surgery in these high-risk individuals or to support the role of prophylactic surgery over chemoprevention or surveillance, so its full impact is not completely understood. Prophylactic surgery is defined as the pre-emptive removal of an organ prior to its malignant transformation. You et al.4 proposed five rational criteria that should be met for prophylactic surgery to be considered: the genetic mutation must have a very high penetrance there must be a highly reliable test to identify genetic mutation carriers the organ must be removed with minimal morbidity and mortality there must be a suitable replacement for the function of the removed organ there must be a reliable method to prove that the patient has been cured by ‘prophylactic surgery’. The authors conclude that only type 2 multiple endocrine neoplasia syndromes meet all these criteria. Medullary thyroid cancer occurs in virtually 100% of affected patients and it is the most common cause of death, therefore prophylactic thyroidectomy is recommended. Phaeochromocytoma, neurogangliomas and hyperparathyroidism are other common associated manifestations of the syndrome but which much lower penetrance. There is, however, evidence5 that preventive surgery has a fundamental role in other cancer hereditary syndromes. BRCA1/2 mutation carriers have a lifetime risk of between 60 and 80% of developing breast cancer and a 20e40% risk of developing ovarian cancer. Prevention strategies for these patients include screening (MRI, mammography, clinical examination), chemoprevention (tamoxifen) and prophylactic surgery. Riskreducing salpingo-oophorectomy (RRSO) and bilateral mastectomy (RRBM) have been shown to be highly effective in cancer risk reduction.6 RRSO will reduce the risk of ovarian and breast cancer by 90% and 50% respectively whilst RRBM will reduce the risk of breast cancer by 90e95%. Both types of surgery have proved to be more effective than tamoxifen combined with surveillance7 and the majority8 of patients who opt for this type of surgery report substantial relief of emotional concern regarding cancer risk despite its significant psycho-emotional impact. Familial adenomatous polyposis (FAP) is an autosomaldominant form of hereditary colon cancer with 100% penetrance; it is secondary to a genetic mutation of the APC gene. Surgical intervention for FAP should always be prophylactic whenever possible, given the considerable risk for malignant transformation of adenomatous polyps. Surgical options include sub-total colectomy and ileorectal anastomosis (in the presence of relative rectal sparing), pan proctocolectomy with end ileostomy or restorative proctocolectomy with ileoanal pouch anastomosis. Overall survival has been shown to improve significantly when surgery is performed before the diagnosis of cancer is made. Hereditary non-polyposis colon cancer (HNPCC), also known as Lynch syndrome, is also an autosomal-dominant condition caused by a mutation in the DNA mismatch-repair genes. HNPCC surveillance,9,10 with colonoscopy, should be biennial from the age of 25 years (or 5 years younger than the incidence in the youngest family member) till the age of 75 years. Defining a clear role for prophylactic colon resection remains difficult as there is
SURGERY 30:4
not enough evidence to support it. For those patients who opt for surgical intervention, a sub-total colectomy with ileorectal anastomosis is the operation of choice. Hereditary diffuse gastric cancer (DGC) tends to presents late. Patients carrying the CDH1 germ line mutations have a 70% lifetime risk of developing DGC, hence they should be considered for prophylactic total gastrectomy.11 The risks and benefits of undergoing surgery need to be carefully balanced: a total gastrectomy carries a 2e4% mortality risk and a significant risk of long-term morbidity such as weight loss, reflux, dumping, diarrhoea and metabolic derangements. However the lack of effective screening and the high number of patients who have metastatic disease at their first presentation justify the role of prophylactic surgery. Although the use of prophylactic surgery is now a common component of clinical practice, there is a need for further highquality studies to evaluate the role of surgery in cancer prevention and its impact on the patients’ quality of life.
Diagnostic and staging techniques Cancer diagnosis can be difficult; it requires a combination of history, physical examination, imaging, laboratory tests (including tumour markers), tumour biopsy and occasionally endoscopic examination, surgery, or genetic testing. The definitive diagnosis of cancer is made on histological or cytological confirmation. Surgeons play an important role in cancer diagnosis, often being involved in the initial assessment of the patient, in requesting appropriate investigations and in obtaining tissue samples for histological or cytological examination. The following are examples of techniques used: Fine-needle aspiration cytology (FNAC): a 22e25-gauge needle is inserted into the suspicious area and a syringe is used to aspirate fluid and cells (with suction) for analysis. The advantages of the procedure are that it is minimally invasive and generally safe, it is cheaper than an open biopsy and the results can be obtained rapidly if a trained cytologist is available. The disadvantage is that the tissue architecture is absent so cytological analysis only is obtained. Core needle biopsy: automated Tru-CutÒ needle biopsy is an alternative to FNAC. Biopsies are performed using a 14- or 18-gauge needle mounted in an automated firing device employing a spring-loaded mechanism. After local anaesthetic infiltration of the skin the needle is inserted into the tissue, and as it penetrates, it also ‘cuts’, allowing a small core to remain embedded within the needle channel. The advantages are that there is tissue for analysis, and the tissue architecture is preserved so a histological diagnosis can usually be made. Both biopsies can be done clinically or image guided for impalpable abnormalities. Imaging techniques that are used include stereotactic mammography, computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasound. Vacuum-assisted biopsy devices (VAD): such as the ‘Mammotome’ device (Ethicon Endo-Surgery, Inc, Cincinnati, Ohio) have become popular recently and can be used for diagnostic and occasionally therapeutic purposes in breast pathologies. These devices couple a disposable
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Ó 2012 Elsevier Ltd. All rights reserved.
CANCER TREATMENT
probe with a reusable probe driver. Vacuum is applied to the probe, which pulls the tissue into the cutting window and then transports the tissue outside of the breast where it can be collected while the probe stays in place. The advantages of these devices are: single insertion of the probe into the breast, larger samples and faster retrieval of a number of specimens. The major disadvantage of the VAD is the cost. Excisional and incisional biopsy: an incisional biopsy consists of removing only a portion of the tumour and is only used when all other methods of obtaining tissue have failed to make a diagnosis. Excisional biopsies are performed when it has not been possible to make a tissue diagnosis by other methods and it is possible to remove the whole tumour without significant risk to the patient. This is sometimes the case in breast screening. The patient may however need definitive surgery, such as re-excision of margins when the diagnosis of cancer is confirmed. Sentinel lymphnode (SLN) biopsy: over the last decade surgical oncologists have been trained in performing a sentinel node biopsy as a staging procedure. This technique is routinely used in patients with breast cancer or melanoma: a combination of radioactive isotope and blue dye are injected near the tumour in order to identify the firste or ‘sentinel’ e node to receive lymph from the cancer, the sentinel node (SLN) is then excised and sent for histological examination. A positive SLN carries valuable prognostic information for both types of cancer. In patients with primary cutaneous melanoma the histological status of the SLN accurately reflects12 the presence or absence of metastatic disease in the relevant regional lymph node basin. In breast cancer, a negative sentinel node indicates more than a 95% chance that the remaining lymph nodes in the axilla are also cancer free. The use of this technique has eliminated the need for unnecessary lymph node clearances and their associated morbidity if the SLN is negative for cancer cells. Sentinel node biopsy is being studied with other cancer types13 including colorectal cancer, gastric cancer, oesophageal cancer, head and neck cancer, thyroid cancer, nonsmall cell lung cancer, penile, vulval and anal cancers. Endoscopic biopsy: biopsy can be obtained during upper or lower gastrointestinal endoscopy, cystoscopy, colposcopy, mediastinoscopy, etc. A fibreoptic endoscope is inserted either through a natural body orifice or a small surgical incision and allows direct visualization of the suspicious areas and accurate tissue sampling. Diagnostic and staging laparoscopy: minimally invasive surgery has significantly changed the management of cancer patients with regards to diagnosis, staging and treatment. Laparoscopy enables the direct inspection of intra-abdominal organs and facilitates obtaining biopsy specimens. In experienced hands laparoscopic ultrasound is also an important adjunct that helps in the evaluation of deep organs that are not amenable to inspection. Laparoscopic surgery has been beneficial for the staging of upper gastrointestinal and hepato-biliary malignancies as it is the only reliable method to detect peritoneal dissemination in patients with apparently localized disease.
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Pancreatic and oesophageal cancers carry a very poor prognosis even after curative resection; hence it is important not only to identify patients with resectable disease but also to spare patients with incurable disease the psychological and physical morbidity of an unnecessary operation. Thus, accurate staging is of paramount importance. Up to 48% of patients with pancreatic cancer are found to have unresectable disease during laparotomy, even after appropriate preoperative imaging. For this reason, staging laparoscopy has been introduced in the treatment algorithm of pancreatic adenocarcinoma in an effort to decrease unnecessary laparotomies. In patients with oesophageal cancer, staging laparoscopy should be utilized to discriminate between patients with an early stage tumour who are candidates for immediate curative resection from those with a more advanced stage who need neo-adjuvant therapy. Patients who have liver metastases from a primary colorectal cancer, may be candidates for curative resection provided that the liver disease is resectable. In this context laparoscopy is occasionally performed by hepato-biliary surgeons prior to embarking on liver resection. Laparoscopic ultrasound can provide more accurate identification of hepatic lesions, including size, number, and location, than non-invasive imaging and can help differentiate patients with resectable disease from non-curable patients. The incidental finding, on imaging, of intra-abdominal lymphadenopathy, quite often poses a diagnostic challenge as, even for non-malignant conditions, a definitive diagnosis is needed before embarking on treatment. In the absence of palpable peripheral nodes, tissue has to be obtained from intra-abdominal lymph nodes either by image-guided biopsy or through surgery. Image guided biopsy is less invasive then surgery and avoids the need for a general anaesthetic, however in patients in whom the nodes are small or present in locations unsuitable for imageguided biopsy, a laparoscopic biopsy is an invaluable alternative. It avoids the morbidity of a laparotomy and provides a safe and effective means of obtaining biopsy.
Surgical treatments The location and extent of the tumour defines whether a cancer is amenable to surgical treatment, and in this context it is important to differentiate between palliative and curative resections. A curative resection is reserved for tumours which can be entirely removed with the aim of leaving no microscopic cancer behind. This corresponds to an R0 resection, a microscopically negative resection margin, in which no microscopic tumour remains in the tumour bed. R1 resection indicates the removal of all macroscopic disease, but microscopic margins are positive for tumour. Complete macroscopic resection with negative margins is the gold standard in the surgical treatment of cancer; however there is emerging evidence14 that in this era of increasingly efficient chemotherapy and radiotherapy regimes, the long-term outcome after R1 resection matches that of R0 resection in terms of overall survival. R2 resection indicates gross residual disease after surgical intervention where the tumour mass is debulked but not
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Ó 2012 Elsevier Ltd. All rights reserved.
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physical, psychological and social well being of the patient. The aim of reconstructive surgery is to improve and restore, whenever possible, the anatomy, function and cosmetic appearance of cancer patients, with the ultimate goal of improving their quality of life. Breast cancer treatment has radically changed over the past decade. The reconstructive and cosmetic aspects of breast cancer surgery have merged with the concept of oncological clearance to create a new branch of breast surgery, oncoplastic breast surgery. A recent national audit15 has testified to the success of such a merger. Breast reconstruction in UK is now an integral part and an essential phase of breast cancer care, which should be considered from the time of diagnosis as part of a complete and comprehensive treatment plan. Similarly, reconstructive surgery is an essential component in the care of head and neck cancer patients. The primary objective of rehabilitation in these cases is the restoration of appearance and functions such as speech, swallowing, control of saliva, and mastication. Restorative surgery has become an integral part in the management of cancer patients, and the role of surgical oncologists has expanded to embrace this change. Achieving oncological clearance and good cosmesis can be challenging, however the oncological principles of curative cancer surgery should never be jeopardized in the attempt to achieve better cosmetic outcomes as this would defeat the role of surgery in cancer management.
amenable to complete resection. Surgery is in this case is performed with a palliative intent. Advances in surgical technology have lead to several new techniques being available to surgeons and cancer patients. Examples of new techniques include: Photodynamic therapy: relies on a photosensitizing agent which is activated by a light of a specific wavelength. The photosensitizing agent is injected intravenously and systemically absorbed. Cancerous cells will selectively retain this agent at 24/72 hours, when irradiated the light interacts with the photosensitizers causing them to emit free radicals which destroy the targeted abnormal cells. NICE has licensed its use for the treatment of bronchial carcinoma, oesophageal cancer, bile duct cancer, head and neck cancer, parotid carcinoma and variety of benign and malignant skin conditions. Radio frequency ablation therapy: uses a needle-shaped electrode which is directed into the tumour and can be placed percutaneously under CT scan guidance, laparoscopically or at open surgery. A radiofrequency current is passed via the needle to increase the temperature in the tumour that results in destruction of the cancer tissue whilst causing a fibrous reaction in the surrounding tissue. It is used for the treatment of primary or secondary liver, lung and kidney cancers. Gamma knife radio surgery: is a technique that aims concentrated beams of high-intensity gamma radiation on the tumour, without damaging the surrounding healthy tissue. Gamma knife radiosurgery has proven effective for patients with small benign or malignant brain tumours and vascular malformations such as arterio-venous malformations. Cryosurgery: is the use of extreme cold produced by liquid nitrogen or argon gas to destroy abnormal tissue. For external tumours, liquid nitrogen is applied directly to the cancer cells with a cotton swab or spraying device. For an internal tumour a cryoprobe is placed in direct contact with the tumour during surgery or percutaneously. After cryosurgery, the frozen tissue is either naturally absorbed by the body or forms a scab in case of external tumours. Cryosurgery is used in the management of liver and prostate cancer, precancerous conditions of the cervix, early stage skin cancers and bone tumours. Microwave ablation: is an alternative means of thermal coagulation of tissue which uses microwaves. It is used for hepatic tumour ablation as an alternative to radio frequency ablation. High-intensity focused ultrasound (HIFU): uses an endorectal probe incorporating an ultrasound scanner and a HIFU treatment applicator which emits an ultrasound beam, focused to reach a high intensity in the target area. Absorption of the ultrasound energy creates an increase in temperature, which destroys the tissue within the focal area. This technique is only available in the UK in the context of clinical trials for the treatment of prostate carcinoma.
Surgery in palliative care In incurable cancer patients, palliative surgery can be justified to reduce the severity of symptoms and improve the quality of life, where conservative strategies or less invasive interventions have failed or are not appropriate. By-pass procedures, formation of stomas or stent insertion are performed to relieve symptoms of intestinal obstruction caused by primary gastrointestinal cancer or by extrinsic compression from other intra-abdominal malignancies such as ovarian cancer or lymphoma. The primary goal of palliation in patients with locally advanced and metastatic hepato-biliary-pancreatic cancers is to relieve jaundice, control pain and relieve or prevent gastric outlet obstruction and this is achieved by mean of surgical bypass or stent insertion. Cystectomy for bleeding or obstructing bladder cancer is another palliative procedure. Hospital and community palliative care teams play an important role in caring for the physical, psychological, emotional and spiritual aspects of these patients and their families. They should be included in discussions with the MDT regarding the care of the palliative cancer patient. A
REFERENCES 1 Office for National Statistics. Cancer incidence and mortality in the UK, 2006e2008. Stat Bull 2011 June 1. http://www.ons.gov.uk/ons/ publications/index.html. 2 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893e917. €rlimann B, Nicoll JJ. The multidisciplinary 3 Ruhstaller T, Roe H, Thu meeting: an indispensable aid to communication between different specialities. Eur J Cancer 2006; 42: 2459e62.
Reconstructive surgery Oncological surgical procedures often result in disfigurement, mutilation or functional loss, with a significant impact on the
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4 You YN, Lakhani VT, Wells SA. The role of prophylactic surgery in cancer prevention. World J Surg 2007; 31: 450e64. 5 Jatoi I, Benson JR, Liau SS, et al. The role of surgery in cancer prevention. Curr Probl Surg 2010 Oct; 47: 750e830. 6 Kauff ND, Barakat RR. Risk-reducing salpingo-oophorectomy in patients with germline mutations in BRCA1 or BRCA2. J Clin Oncol 2007; 10: 2921e7. 7 Agnantis NJ, Paraskevaidis E, Roukos D. Preventing breast, ovarian cancer in BRCA carriers: rational of prophylactic surgery and promises of surveillance. Ann Surg Oncol 2004; 11: 1030e4. 8 Lostumbo L, Carbine NE, Wallace J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database of Syst Rev 2010; (11). Art. No.: CD002748. 9 The Association of Coloproctology of Great Britain and Ireland. Guidelines for the management of colorectal cancer, www.acpgbi.org. uk/assets/documents/COLO_guides.pdf; 2007. 10 Dunlop MG, British Society for Gastroenterology, Association of Coloproctology for Great Britain and Ireland. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer,
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11
12
13
14
15
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familial adenomatous polyposis, juvenile polyposis, and PeutzJeghers syndrome. Gut 2002 Oct; 51(suppl 5): V21e7. Norton JA, Ham CM, Van Dam J, et al. CDH1 truncating mutations in the E-cadherin gene: an indication for total gastrectomy to treat hereditary diffuse gastric cancer. Ann Surg 2007; 245: 873e9. Carcoforo P, Soliani G, Bergossi L, et al. Reliability and accuracy of sentinel node biopsy in cutaneous malignant melanoma. Tumori 2002 MayeJun; 88: S14e6. Chen SL, Iddings DM, Scheri RP, Bilchik AJ. Lymphatic mapping and sentinel node analysis: current concepts and applications. Cancer J Clin 2006; 56: 292e309. de Haas RJ, Wicherts DA, Flores E, Azoulay D, Castaing D, Adam R. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg 2008 Oct; 248: 626e37. The NHS Information Centre. National mastectomy and reconstruction audit e Fourth annual report 2011. www.ic.nhs.uk. Document reference: IC20010111.
Ó 2012 Elsevier Ltd. All rights reserved.
The role of surgeons in cancer management
causes of cancer deaths are lung (18.2% of the total), stomach (9.7%) and liver (9.2%). In the last 20 years UK cancer management has changed, with the introduction of multidisciplinary teams (MDT). The diagnosis and treatment of cancer patients is coordinated by a team of experts including surgeons, radiologists, pathologists, oncologists and specialist nurses, that improves consistency in the standard of care offered.3 The MDT usually meets weekly to discuss the diagnosis and multidisciplinary management plan for each patient. The decision-making process is helped by an increasing number of national guidelines which help to standardize and optimize the care of cancer patients. The role of surgeons in cancer treatment has evolved. Historically, cancer patients were subjected to surgery in order to achieve a diagnosis, remove the cancer or manage complications. The role of surgery in cancer management has expanded to include screening, prevention, diagnosis and staging, reconstruction and palliation.
Valentina Lefemine Helen Sweetland
Abstract The incidence of cancer continues to rise in western countries, although slower than in previous decades. In the UK 24% of all deaths are caused by cancer. The role of surgery in cancer management has expanded over the last few decades to include screening, prevention, diagnosis and staging, reconstruction and palliation. In UK, the breast, bowel and cervical national screening programmes rely on surgeons to perform invasive diagnostic procedures. Genetic testing enables identification of carriers of pathological genetic mutations who are at high risk of developing cancer and might benefit from ‘risk-reducing’ surgery. Advances in surgical technology have led to a variety of new techniques being available to surgeons and cancer patients for diagnostic and therapeutic purposes, including vacuum-assisted devices, photodynamic therapy, radio frequency ablation, cryosurgery and microwave ablation. Oncological surgical procedures often result in disfigurement, mutilation or functional loss, and restorative surgery has become an integral part in the management of cancer patients with the ultimate aim of improving their quality of life. In incurable cancer patients, palliative surgery can be justified to reduce the severity of symptoms and improve the quality of life, where conservative strategies or less invasive interventions have failed or are not appropriate.
Keywords Cancer screening; palliation; reconstructive risk-reducing surgery; staging; surgical technique advances
Screening In UK there are three NHS cancer screening programmes (www. cancerscreening.nhs.uk) which include breast, colorectal and cervical cancer. Surgeons play an active role in each programme. The breast screening programme performs mammography, 3-yearly on women aged 50e70 years, with plans to extend the screening age to 73 years by 2016. Surgeons perform diagnostic excision biopsies where cancer cannot be excluded by imaging and core biopsies, and operate on those diagnosed with cancer. The colorectal screening programme offers screening, 2-yearly to men and women, aged 60e69 years, by faecal occult blood (FOB) tests. It relies on endoscopists (surgeons or gastroenterologists) to perform screening colonoscopy in those patients who have an abnormal result from the FOB test. Surgeons then perform open or laparoscopic colonic resections when required. Women between the ages of 25 and 64 years are eligible for a cervical smear test every 3e5 years. The programme is generally run by specialist nurses, but gynaecologists will be involved if a colposcopy is needed for patients who are found to have abnormal epithelial cells on a smear.
surgery;
Introduction
Prevention through surgery
The incidence of cancer continues to rise in western countries, although slower than in previous decades. The Office for National Statistics report in 2011,1 showed that in the UK (2006e2008) breast, lung and colorectal cancers accounted for around 41% of cases and 40% of cancer deaths. In the UK 24% of all deaths are caused by cancer. A different trend has been reported worldwide: cancer accounts for 12% of all deaths each year and data retrieved from the GLOBOCAN2 cancer database have shown that the common
Some people have a higher risk of developing cancer due to inherited pathological mutations of certain genes. Common hereditary cancer syndromes include: type 2 multiple endocrine neoplasia syndrome (RET proto-oncogene mutation), hereditary breast ovarian cancer (BRCA1/2 gene mutation), diffuse gastric cancer (CDH1 gene mutation) and polyposis and non-polyposis colorectal cancer syndromes (APC and mismatch-repair genes mutation). For these genetic mutation carriers, the lifetime risk of developing the corresponding cancer is approximately 70e80%, and often associated with high mortality. Genetic testing can identify high-risk patients so that an effective preventive strategy can be agreed between the patient, geneticist, surgeon and radiologist. The role of surgery in cancer prevention has increased as these genetic mutations have been discovered and ‘risk-reducing’ surgery is used more frequently in clinical practice; however decision-making remains complex and multifactorial. There are
Valentina Lefemine MRCS is a Specialist Registrar in General and Breast Surgery at Cardiff and Vale Breast Centre, University Hospital of Llandough, Cardiff, UK. Conflicts of interest: none declared. Helen Sweetland FRCS is a Consultant Breast Surgeon at Cardiff and Vale Breast Centre, University Hospital of Llandough, Cardiff, UK. Conflicts of interest: none declared.
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Ó 2012 Elsevier Ltd. All rights reserved.
CANCER TREATMENT
no randomized controlled trials addressing the efficacy of prophylactic surgery in these high-risk individuals or to support the role of prophylactic surgery over chemoprevention or surveillance, so its full impact is not completely understood. Prophylactic surgery is defined as the pre-emptive removal of an organ prior to its malignant transformation. You et al.4 proposed five rational criteria that should be met for prophylactic surgery to be considered: the genetic mutation must have a very high penetrance there must be a highly reliable test to identify genetic mutation carriers the organ must be removed with minimal morbidity and mortality there must be a suitable replacement for the function of the removed organ there must be a reliable method to prove that the patient has been cured by ‘prophylactic surgery’. The authors conclude that only type 2 multiple endocrine neoplasia syndromes meet all these criteria. Medullary thyroid cancer occurs in virtually 100% of affected patients and it is the most common cause of death, therefore prophylactic thyroidectomy is recommended. Phaeochromocytoma, neurogangliomas and hyperparathyroidism are other common associated manifestations of the syndrome but which much lower penetrance. There is, however, evidence5 that preventive surgery has a fundamental role in other cancer hereditary syndromes. BRCA1/2 mutation carriers have a lifetime risk of between 60 and 80% of developing breast cancer and a 20e40% risk of developing ovarian cancer. Prevention strategies for these patients include screening (MRI, mammography, clinical examination), chemoprevention (tamoxifen) and prophylactic surgery. Riskreducing salpingo-oophorectomy (RRSO) and bilateral mastectomy (RRBM) have been shown to be highly effective in cancer risk reduction.6 RRSO will reduce the risk of ovarian and breast cancer by 90% and 50% respectively whilst RRBM will reduce the risk of breast cancer by 90e95%. Both types of surgery have proved to be more effective than tamoxifen combined with surveillance7 and the majority8 of patients who opt for this type of surgery report substantial relief of emotional concern regarding cancer risk despite its significant psycho-emotional impact. Familial adenomatous polyposis (FAP) is an autosomaldominant form of hereditary colon cancer with 100% penetrance; it is secondary to a genetic mutation of the APC gene. Surgical intervention for FAP should always be prophylactic whenever possible, given the considerable risk for malignant transformation of adenomatous polyps. Surgical options include sub-total colectomy and ileorectal anastomosis (in the presence of relative rectal sparing), pan proctocolectomy with end ileostomy or restorative proctocolectomy with ileoanal pouch anastomosis. Overall survival has been shown to improve significantly when surgery is performed before the diagnosis of cancer is made. Hereditary non-polyposis colon cancer (HNPCC), also known as Lynch syndrome, is also an autosomal-dominant condition caused by a mutation in the DNA mismatch-repair genes. HNPCC surveillance,9,10 with colonoscopy, should be biennial from the age of 25 years (or 5 years younger than the incidence in the youngest family member) till the age of 75 years. Defining a clear role for prophylactic colon resection remains difficult as there is
SURGERY 30:4
not enough evidence to support it. For those patients who opt for surgical intervention, a sub-total colectomy with ileorectal anastomosis is the operation of choice. Hereditary diffuse gastric cancer (DGC) tends to presents late. Patients carrying the CDH1 germ line mutations have a 70% lifetime risk of developing DGC, hence they should be considered for prophylactic total gastrectomy.11 The risks and benefits of undergoing surgery need to be carefully balanced: a total gastrectomy carries a 2e4% mortality risk and a significant risk of long-term morbidity such as weight loss, reflux, dumping, diarrhoea and metabolic derangements. However the lack of effective screening and the high number of patients who have metastatic disease at their first presentation justify the role of prophylactic surgery. Although the use of prophylactic surgery is now a common component of clinical practice, there is a need for further highquality studies to evaluate the role of surgery in cancer prevention and its impact on the patients’ quality of life.
Diagnostic and staging techniques Cancer diagnosis can be difficult; it requires a combination of history, physical examination, imaging, laboratory tests (including tumour markers), tumour biopsy and occasionally endoscopic examination, surgery, or genetic testing. The definitive diagnosis of cancer is made on histological or cytological confirmation. Surgeons play an important role in cancer diagnosis, often being involved in the initial assessment of the patient, in requesting appropriate investigations and in obtaining tissue samples for histological or cytological examination. The following are examples of techniques used: Fine-needle aspiration cytology (FNAC): a 22e25-gauge needle is inserted into the suspicious area and a syringe is used to aspirate fluid and cells (with suction) for analysis. The advantages of the procedure are that it is minimally invasive and generally safe, it is cheaper than an open biopsy and the results can be obtained rapidly if a trained cytologist is available. The disadvantage is that the tissue architecture is absent so cytological analysis only is obtained. Core needle biopsy: automated Tru-CutÒ needle biopsy is an alternative to FNAC. Biopsies are performed using a 14- or 18-gauge needle mounted in an automated firing device employing a spring-loaded mechanism. After local anaesthetic infiltration of the skin the needle is inserted into the tissue, and as it penetrates, it also ‘cuts’, allowing a small core to remain embedded within the needle channel. The advantages are that there is tissue for analysis, and the tissue architecture is preserved so a histological diagnosis can usually be made. Both biopsies can be done clinically or image guided for impalpable abnormalities. Imaging techniques that are used include stereotactic mammography, computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasound. Vacuum-assisted biopsy devices (VAD): such as the ‘Mammotome’ device (Ethicon Endo-Surgery, Inc, Cincinnati, Ohio) have become popular recently and can be used for diagnostic and occasionally therapeutic purposes in breast pathologies. These devices couple a disposable
182
Ó 2012 Elsevier Ltd. All rights reserved.
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probe with a reusable probe driver. Vacuum is applied to the probe, which pulls the tissue into the cutting window and then transports the tissue outside of the breast where it can be collected while the probe stays in place. The advantages of these devices are: single insertion of the probe into the breast, larger samples and faster retrieval of a number of specimens. The major disadvantage of the VAD is the cost. Excisional and incisional biopsy: an incisional biopsy consists of removing only a portion of the tumour and is only used when all other methods of obtaining tissue have failed to make a diagnosis. Excisional biopsies are performed when it has not been possible to make a tissue diagnosis by other methods and it is possible to remove the whole tumour without significant risk to the patient. This is sometimes the case in breast screening. The patient may however need definitive surgery, such as re-excision of margins when the diagnosis of cancer is confirmed. Sentinel lymphnode (SLN) biopsy: over the last decade surgical oncologists have been trained in performing a sentinel node biopsy as a staging procedure. This technique is routinely used in patients with breast cancer or melanoma: a combination of radioactive isotope and blue dye are injected near the tumour in order to identify the firste or ‘sentinel’ e node to receive lymph from the cancer, the sentinel node (SLN) is then excised and sent for histological examination. A positive SLN carries valuable prognostic information for both types of cancer. In patients with primary cutaneous melanoma the histological status of the SLN accurately reflects12 the presence or absence of metastatic disease in the relevant regional lymph node basin. In breast cancer, a negative sentinel node indicates more than a 95% chance that the remaining lymph nodes in the axilla are also cancer free. The use of this technique has eliminated the need for unnecessary lymph node clearances and their associated morbidity if the SLN is negative for cancer cells. Sentinel node biopsy is being studied with other cancer types13 including colorectal cancer, gastric cancer, oesophageal cancer, head and neck cancer, thyroid cancer, nonsmall cell lung cancer, penile, vulval and anal cancers. Endoscopic biopsy: biopsy can be obtained during upper or lower gastrointestinal endoscopy, cystoscopy, colposcopy, mediastinoscopy, etc. A fibreoptic endoscope is inserted either through a natural body orifice or a small surgical incision and allows direct visualization of the suspicious areas and accurate tissue sampling. Diagnostic and staging laparoscopy: minimally invasive surgery has significantly changed the management of cancer patients with regards to diagnosis, staging and treatment. Laparoscopy enables the direct inspection of intra-abdominal organs and facilitates obtaining biopsy specimens. In experienced hands laparoscopic ultrasound is also an important adjunct that helps in the evaluation of deep organs that are not amenable to inspection. Laparoscopic surgery has been beneficial for the staging of upper gastrointestinal and hepato-biliary malignancies as it is the only reliable method to detect peritoneal dissemination in patients with apparently localized disease.
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Pancreatic and oesophageal cancers carry a very poor prognosis even after curative resection; hence it is important not only to identify patients with resectable disease but also to spare patients with incurable disease the psychological and physical morbidity of an unnecessary operation. Thus, accurate staging is of paramount importance. Up to 48% of patients with pancreatic cancer are found to have unresectable disease during laparotomy, even after appropriate preoperative imaging. For this reason, staging laparoscopy has been introduced in the treatment algorithm of pancreatic adenocarcinoma in an effort to decrease unnecessary laparotomies. In patients with oesophageal cancer, staging laparoscopy should be utilized to discriminate between patients with an early stage tumour who are candidates for immediate curative resection from those with a more advanced stage who need neo-adjuvant therapy. Patients who have liver metastases from a primary colorectal cancer, may be candidates for curative resection provided that the liver disease is resectable. In this context laparoscopy is occasionally performed by hepato-biliary surgeons prior to embarking on liver resection. Laparoscopic ultrasound can provide more accurate identification of hepatic lesions, including size, number, and location, than non-invasive imaging and can help differentiate patients with resectable disease from non-curable patients. The incidental finding, on imaging, of intra-abdominal lymphadenopathy, quite often poses a diagnostic challenge as, even for non-malignant conditions, a definitive diagnosis is needed before embarking on treatment. In the absence of palpable peripheral nodes, tissue has to be obtained from intra-abdominal lymph nodes either by image-guided biopsy or through surgery. Image guided biopsy is less invasive then surgery and avoids the need for a general anaesthetic, however in patients in whom the nodes are small or present in locations unsuitable for imageguided biopsy, a laparoscopic biopsy is an invaluable alternative. It avoids the morbidity of a laparotomy and provides a safe and effective means of obtaining biopsy.
Surgical treatments The location and extent of the tumour defines whether a cancer is amenable to surgical treatment, and in this context it is important to differentiate between palliative and curative resections. A curative resection is reserved for tumours which can be entirely removed with the aim of leaving no microscopic cancer behind. This corresponds to an R0 resection, a microscopically negative resection margin, in which no microscopic tumour remains in the tumour bed. R1 resection indicates the removal of all macroscopic disease, but microscopic margins are positive for tumour. Complete macroscopic resection with negative margins is the gold standard in the surgical treatment of cancer; however there is emerging evidence14 that in this era of increasingly efficient chemotherapy and radiotherapy regimes, the long-term outcome after R1 resection matches that of R0 resection in terms of overall survival. R2 resection indicates gross residual disease after surgical intervention where the tumour mass is debulked but not
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physical, psychological and social well being of the patient. The aim of reconstructive surgery is to improve and restore, whenever possible, the anatomy, function and cosmetic appearance of cancer patients, with the ultimate goal of improving their quality of life. Breast cancer treatment has radically changed over the past decade. The reconstructive and cosmetic aspects of breast cancer surgery have merged with the concept of oncological clearance to create a new branch of breast surgery, oncoplastic breast surgery. A recent national audit15 has testified to the success of such a merger. Breast reconstruction in UK is now an integral part and an essential phase of breast cancer care, which should be considered from the time of diagnosis as part of a complete and comprehensive treatment plan. Similarly, reconstructive surgery is an essential component in the care of head and neck cancer patients. The primary objective of rehabilitation in these cases is the restoration of appearance and functions such as speech, swallowing, control of saliva, and mastication. Restorative surgery has become an integral part in the management of cancer patients, and the role of surgical oncologists has expanded to embrace this change. Achieving oncological clearance and good cosmesis can be challenging, however the oncological principles of curative cancer surgery should never be jeopardized in the attempt to achieve better cosmetic outcomes as this would defeat the role of surgery in cancer management.
amenable to complete resection. Surgery is in this case is performed with a palliative intent. Advances in surgical technology have lead to several new techniques being available to surgeons and cancer patients. Examples of new techniques include: Photodynamic therapy: relies on a photosensitizing agent which is activated by a light of a specific wavelength. The photosensitizing agent is injected intravenously and systemically absorbed. Cancerous cells will selectively retain this agent at 24/72 hours, when irradiated the light interacts with the photosensitizers causing them to emit free radicals which destroy the targeted abnormal cells. NICE has licensed its use for the treatment of bronchial carcinoma, oesophageal cancer, bile duct cancer, head and neck cancer, parotid carcinoma and variety of benign and malignant skin conditions. Radio frequency ablation therapy: uses a needle-shaped electrode which is directed into the tumour and can be placed percutaneously under CT scan guidance, laparoscopically or at open surgery. A radiofrequency current is passed via the needle to increase the temperature in the tumour that results in destruction of the cancer tissue whilst causing a fibrous reaction in the surrounding tissue. It is used for the treatment of primary or secondary liver, lung and kidney cancers. Gamma knife radio surgery: is a technique that aims concentrated beams of high-intensity gamma radiation on the tumour, without damaging the surrounding healthy tissue. Gamma knife radiosurgery has proven effective for patients with small benign or malignant brain tumours and vascular malformations such as arterio-venous malformations. Cryosurgery: is the use of extreme cold produced by liquid nitrogen or argon gas to destroy abnormal tissue. For external tumours, liquid nitrogen is applied directly to the cancer cells with a cotton swab or spraying device. For an internal tumour a cryoprobe is placed in direct contact with the tumour during surgery or percutaneously. After cryosurgery, the frozen tissue is either naturally absorbed by the body or forms a scab in case of external tumours. Cryosurgery is used in the management of liver and prostate cancer, precancerous conditions of the cervix, early stage skin cancers and bone tumours. Microwave ablation: is an alternative means of thermal coagulation of tissue which uses microwaves. It is used for hepatic tumour ablation as an alternative to radio frequency ablation. High-intensity focused ultrasound (HIFU): uses an endorectal probe incorporating an ultrasound scanner and a HIFU treatment applicator which emits an ultrasound beam, focused to reach a high intensity in the target area. Absorption of the ultrasound energy creates an increase in temperature, which destroys the tissue within the focal area. This technique is only available in the UK in the context of clinical trials for the treatment of prostate carcinoma.
Surgery in palliative care In incurable cancer patients, palliative surgery can be justified to reduce the severity of symptoms and improve the quality of life, where conservative strategies or less invasive interventions have failed or are not appropriate. By-pass procedures, formation of stomas or stent insertion are performed to relieve symptoms of intestinal obstruction caused by primary gastrointestinal cancer or by extrinsic compression from other intra-abdominal malignancies such as ovarian cancer or lymphoma. The primary goal of palliation in patients with locally advanced and metastatic hepato-biliary-pancreatic cancers is to relieve jaundice, control pain and relieve or prevent gastric outlet obstruction and this is achieved by mean of surgical bypass or stent insertion. Cystectomy for bleeding or obstructing bladder cancer is another palliative procedure. Hospital and community palliative care teams play an important role in caring for the physical, psychological, emotional and spiritual aspects of these patients and their families. They should be included in discussions with the MDT regarding the care of the palliative cancer patient. A
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Reconstructive surgery Oncological surgical procedures often result in disfigurement, mutilation or functional loss, with a significant impact on the
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