HOW TO OPTIMIZE MANAGEMENT OF HIGH RISK SURGICAL PATIENTS IN GYNAECOLOGICAL CANCER.
Dato' Dr. Mohd Rushdan Md Noor
Consultant Gynaecological Oncologist
Hospital Sultanah Bahiyah
Alor Star, Kedah.
Surgery is one of the important treatment modalities for gynaecological cancer patients. The aim of surgical treament are tumour resection with good surgical margin to achieve cure, to obtain tissue diagnosis, to analyse the histological risk factors in order to select of best treatment modalities and for symptomatic relief. Surgical treatment for Gynaecological cancer often required a specialized skill because not only due to complexity of the surgery but also due to gynaecological cancer patients often an elderly with numerous co-morbid problems. Selection of patients and perioperative optimization of gynaecological cancer patients are extremely important to ensure good surgical outcome and better survival. Unlike benign condition, the success of treatment for Gynecological cancer is judge based on how long the patient can survive without the disease. Surgical skill alone will not guarantee good outcome as knowledge and clinical judgement are equally important and without the latter factors, surgery could do more harm than benefits to the patients. One of the very important factors to ensure gynaecological cancer patient receiving an optimal surgical treatment is to implement an operative risk assessment and to decide the best surgical treatment based on risk-benefit analysis. The choice of surgery should pose minimum perioperative morbidity and mortality. At the same time, this decision is also as much as possible does not compromise the outcome in term of long term survival.
Treatment for Gynaecological Cancer
There are three main modalities of treatment in Gynaecological cancer namely surgery, radiotherapy and chemotherapy. Often patient required more than one modality and it is understanable that multimodality treatment always associated with higher risk of morbidity. However, some combined treatment gives better result than single modality for instance chemoradiation for locally advanced cervical cancer and adjuvant chemotherapy for high risk uterine and ovarian cancer following primary surgical treament.
Surgery for Gynaecological Cancer
Surgery play a major role in the management of patient with Gynaecological Cancer. Surgery is performed not only to resect the tumour completely with the intention to cure the diseases but in some instances, surgery was performed to relief the symptoms. Surgery in Gynaecological cancer has high potential of complications as the primary tumour is arising from the pelvis. There are many vital organs and structures that are bound to be damaged or injured during the pelvic surgery such as bladder, rectum, ureters and also pelvic vessels. Being in a confines space and deep cavity, any complications that have occurred will be difficult to tackle if the surgeon do not have enough experience and skill in dealing with such situation.
Type of surgery perform for the treatment of Gynaecological Cancer ranges from minor surgery such as cervical cone biopsy and adnexectomy , major surgery such as simple or extrafascial hysterectomy, radical hysterectomy, lymphadenectomy ,vulvectomy to a very specialized and complex surgical procedures such as debulking surgery with bowel resection in advanced ovarian cancer, pelvic exenteration in recurrent cervical cancer and recontructive vulvar surgery.
Risk of surgery in Gynaecological Cancer
Surgery in Gynaecological cancer required a specialized skill not only in term of surgical skill but also skill in decision making in term of the best option for each individual patient. The best clinical judgement required experiences and maturity. Different patient may be treated by different approaches based on overall profile including the age, presence of co-morbid medical problem, performance status, nature and the extend of the disease. Surgery in Gynaecological cancer often requires multidiciplanary approaches in particularly when dealing with advanced ovarian cancer and complex pelvic surgery.
Risk of surgery can be divided into anaesthetic risks and surgical risk. Aspiration, failed intubation, hypoxia, thromboembolism, respiratory and cardiovascular complications are among the important anaesthetic risk. While bleeding, internal organs injuries, vascular injury, ureteric injury and sepsis are among the potential surgical risk. In addition of common surgical complications, there are few more potential complications related to specific surgical procedure such as lymphaedema and lymphocoele following lymphadenectomy and chronic bladder dysfunction following radical hysterectomy. Apart from physical complications, psychological and sexual complications such as depression and sexual dysfunction could also be encounterred by women following gynaecological cancer surgery.
How to assess the operative risk
The most universally used classification system is the one developed by the American Society of Anesthesiologists (ASA) since 1963, which is based on the patient's functional status and comorbid conditions (e.g., diabetes mellitus, peripheral vascular disease, renal dysfunction, and chronic pulmonary disease) [see Table 1 ](1) . The ASA index generally associates poorer overall health with increased postoperative complications, longer hospital stay, and higher mortality. ASA classes I and II correspond to low risk, class III to moderate risk, and classes IV and V to high risk.
Besides functional capacity and comorbid conditions, age has also been shown in some study to be a determinant of operative risk, as has the type of operation being performed (with vascular procedures and prolonged, complicated thoracic, abdominal, and head and neck procedures carrying higher levels of risk).
Table 1 : American Society of Anesthesiologists Physical Status Classification : Non-Emergency Surgery (Dripps RD, Echenhoff JE, Vandom D: Introduction to Anesthesia: The Principles of Safe Practice. WB Saunders Co, Philadelphia, 1988 , p 17)
Normal, Healthy patient
Uterine fibroid in a healthy women
Patient with mild to moderate systemic disorder related to the condition to be treated or to some other, unrelated process
Moderate obesity, extremes of age, diet-controlled diabetes, mild hypertension, chronic obstructive pulmonary disease.
Patient with severe systemic disease that limits activity but is not incapacitating
Morbid obesity, severely limiting heart disease, angina pectoris, healed myocardial infaction, insulin-dependent diabetes, moderate to severe pulmonary insufficiency
Patient with incapacitating systemic disease that is life threatening
Organic heart disease with signs of cardiac insufficiencey, unstable angina , refractory arrhythmia, advanced pulmonary, renal, hepatic or endocrine disease
Moribund patient not expected to survive 24 hours without an operation
Ruptured aortic aneurysm with profound shock, massive pulmonary embolus, major cerebral trauma with increasing intracranial pressure
The most important parameter in preoperative assessment is cardiovascular and pulmonary function. While the other important parameters are presence of renal impairment and endocrine dysfunction in particularly insulin dependent diabetes mellitus. In some study, age alone was found to be less significant predictive factor for operative morbidity and postoperative hospital stay if proper perioperative assessment and optimization are being carried out. However age with coexisting medical illnesses will definitely carries much higher operative risk and longer postoperative hospital stay if compared to younger age group(2,3). In the other study, patient aged between 80-89 years old undergoing abdominal surgery carries a mortality rate ranging from 3-9% while the risk of death significantly increased to 25% for women aged more than 90 years old. This finding is self explainatory as many studies have shown that patient in elderly age group (>70 years old) has higher proportion having ASA Class III and IV. Furthermore analyzing the comorbidities by ASA class groups, cardiovascular diseases, severe pulmonary diseases, diabetes,and vascular diseases were significantly more frequent in ASA III and IV patients in comparison with ASA I and II patients (Giannice et al).
ASA Classification and Risk of surgery
Until recently, there are only few studies on gynecological cancer surgery analizing the perioperative morbidity and mortality in relation to the ASA Classification especially in elderly patients. Study by Giannice et al on elderly gynaecological oncological patients aged more than 70 years old had found a significant higher rate of postoperative morbidity in ASA Class III and IV (48%) as compared to Class I and II (28%). The incidence of severe postoperative complications was statistically significantly higher in ASA III and IV patients compared with ASA class I and II patients (17% vs. 5%; P= .000). Overall severe cardiovascular and pulmonary complications were significantly more frequent in ASA III and IV patients than in ASA I and II patients. The mortality rate in this group of patients was 2-4%.
Studies on younger age women undergoing gynaecological oncology surgery were conducted by few for instance Fuchtner et al.(4) showed, in a series of 90 patients with a median age of 41 years who were submitted to gynecological oncological surgery, intraoperative and postoperative complication rate was 10% and 38% respectively while 4% developed severe postoperative complication rate. While Kirschner et al.(5) reported a severe morbidity rate of 9% among 77 patients with a median age of 42 years undergoing surgery for gynecological cancer.
How to optimize management of high risk surgical patients undergoing gynaecological cancer surgery.
A. Informed consent and counseling. Postoperative misunderstandings can often be prevented by educating a woman and her family preoperatively. A thorough and well-documented consent helps to insure that the patient's expectations for her surgery, recovery, and final outcome are realistic and appropriate.
The surgical team should discuss the planned procedure with the woman, and encourage her to include family or friends. The discussion is not limited to one encounter; a second appointment is scheduled before hospitalization and the woman is encouraged to write down any questions arising between the initial and subsequent encounter. Women should be approached in an open, direct, and detailed fashion; statements such as "Don't worry, I am competent enough to take care of this," or "Everything will be fine," may later lead to serious allegations if complications arise during or after surgery; no surgical outcome can be guaranteed.
B. Preoperative evaluation and optimization.
a. History and physical examination. A thorough history and physical examination are extremely important as in most instances , majority of risk factors were discovered through good history and complete physical examination. Recent myocardial infaction (< 6 months), unstable angina, symptomatic cardiac arrhytmias, recent stroke, pulmonary problem, uncontrolled diabetes and renal insufficiencies are very important high risk factors. Patient who smoke carries a higher risk of cardiovascular , pulmonary complications and surgical sites infection (6). Patients on Aspirin should stop the medication at least a week prior to surgery in order to reduce the risk of bleeding. Physical examination can also provides the informations on the extend of the disease in term of operability. Hard and fixed pelvi-abdominal mass suported with the signs of bowel or bladder invasion as well as ureteric dilatation on imaging technique always indicate difficult surgery with potentially high risk of operative morbidity.
b. Pre-operative investigations. Basic blood investigations and urinalysis are mandatory in all patients. Chest xray, ECG and coagulation profiles almost always required by all women undergoing major gynaecological oncology surgery. Specific investigations such as echocardiogram, lung function test etc are indicated in selected patients.
c. Optimization of co-morbid illnesses.
i. Endocrine-related conditions. The most relevant endocrine disorders in the perioperative period are hypothyroidism, hyperthryroidism, diabetes mellitus, pheochromocytoma, and adrenal insufficiency (in particular, iatrogenic adrenocortical insufficiency secondary to steroid use within the preceding 6 months). All of these conditions should be normalized to the extent possible before elective surgery, whether by hormone replacement, by adrenergic blockade, or by administration of stress-dose steroids. Diabetes is a very common disease and can potentially impose a higher risk of cardiovascular complication (due to angiopathy) and sepsis. Study have shown that with good control of diabetes, exercise therapy and preventive medical management can reduced the risk of cardiovascular and microvascular complications in diabetic patient. Patient undergoing surgery following chemotherapy should be thoroughly evaluated not only the effect of antineoplastic drugs to their blood count but also the use of steroid during and after chemotherapy. This patient required parenteral steroid treatment intraoperatively.
ii. Cardiac disease . Cardiac patient should be referred to Cardiologist for full cardiac assessment and optimization before undergoing surgery. Significant cardiovascular risk factors include angina pectoris, dyspnea and evidence of right-side or left-side heart failure, any cardiac rhythm other than sinus rhythm, more than five ectopic ventricular beats per minute, aortic stenosis with left ventricular hypertrophy, mitral regurgitation, and previous MI. The risk of intraoperative or postoperative MI is much higher in patients who have suffered heart muscle damage within the preceding 6 months. In large retrospective reviews, 37% of patients experienced reinfarction when they underwent operation within 3 months of an infarction; however, the incidence of reinfarction decreased to 16% when the operation was performed between 3 and 6 months after the first infarction and to 4.5% when the operation was performed more than 6 months afterward (7). A number of trials have indicated that perioperative beta blockade can reduce the risk of perioperative cardiac complications in patients with known or suspected CAD who are undergoing major noncardiac procedures. (8,9)
iii. Respiratory disease. The incidence of postoperative pulmonary complication after laparotomy was reported to be 14% but in patients with high risk factors such as COPD, prolonged procedures and other co-morbid problem, the risk increased to 47%. (10) .Patient with respiratory disease should be referred to respiratory physician and they may benefits from preoperative optimizing program such us smoking ceaseation, use of bronchodilators, chest physiotherapy and antibiotics.
iv. Renal disease . Thirty percent of the elderly surgical patients have a pre-existing renal disturbance causing perioperative stress-related decompensation. Approximately 20% of perioperative deaths in elderly patients are caused by acute renal failure.To prevent renal failure , it is important to ensure adequate hydration.
v. Haematological disorders. Both hypercoagulable and hypocoagulable state are equally harzadous and should be reconized and treated early before surgery. Coagulation profile should be done prior to surgery and corrected. Thromboprophylaxis either in form of drug such as heparin or by using mechanical method such as TED stocking and Pneumatic compression are mandatory in cancer patient undergoing major pelvic and abdominal surgery. Hypercoagalable state can be due to disease such as Polycytaemia rubra vera, blood dyscrasia and paraneoplastic phenomena. It can also be due to physiological state such as dehydration and this can be easily overcome by providing an adequate hydration before, during and after surgery.
vi. Nutritional status. Nutritional status is a known risk factor for operative complication and cancer patient in particularly patient with advanced ovarian cancer often sufferred from malnutrition. Loss of more than 15% body weight during the previous 6 months is associated with an increased incidence of postoperative complications, including delayed wound healing, decreased immunologic competence, and inability to meet the metabolic demand for respiratory effort. Peripheral edema and signs of specific vitamin deficiencies are suggestive of severe malnutrition. Serum Albumin is one of the important parameter for nutritional status and and also a very important predictor for operative morbidity and mortality. Study have shown that a decrease in serum albumin concentration from greater than 4.6 g/dl to less than 2.1 g/dl was associated with an increase in mortality from less than 1% to 29% and an increase in morbidity rate from 10% to 65% (11). Patient with severe malnutrition should be referred to dietician and received nutritional therapy before and after surgery. Patient with poor bowel functions and unable to consume food orally for more than 5 days should be subjected for parenteral nutrition. A trial done by a study group from the Veteran Affairs determined that preoperative nutritional intervention was necessary found that this intervention was able to decrease the operative risk in patient with malnutrition especially those who lost more than 15% of their body weight.(12)
What is the best treatment option for high risk surgical patients in Gynaecological Cancer.
In all Gynaecological cancer patients, thorough disease evaluation in term of the primary site, histology and the extend of the disease both clinically as well as radiologically must be performed before deciding the most appropriate treatment.
Following a thorough preoperative evaluation and operative risk assessment, surgeon and the other member of the team should analyse the entire situation taking the consideration of the type and stage of cancer, surgical risk (based on ASA classification) and not to forget the patients mental and psychological status as well as the patient’s wishes. The attending surgeon should be a trained Gynaecological Oncologist or senior Gynaecologist with enough experienced in treatment of Gynaecology cancer . The final decision should be aim for the best interest of patient i.e improves in overall survival and minimizing the operative morbidity. This will required good clinical judgement according to the result from risk-benefits analysis based on the integration of surgical skill, knowledge, experieced and maturity on behalf of deciding Surgeon/s. Following are the 3 scenarios related to high risk surgical patients with Gynaecological cancer that commonly encountered by Gynaecologist in their daily practise.
a. Patient with ASA III and ASA IV suffering ovarian cancer
Majority of patient with ovarian cancer presented at an advanced stage of disease. The possibility of bowel, bladder and ureteric involvement should always be considered and referral to colorectal surgeon and the urologist is a wise decision to make. Couple with advancing age and preoperative immorbility, primary surgical treatment in this group of patient will carry a significant risk of morbidity and mortality, very likely surgical option may be more harm than good to this patient. Patient and her relative should be extensively counseled on the risk of primary surgical treatment and the counseling should be directive toward the alternative to surgical treatment. The alternative to surgical treatment is neoadjuvant chemotherapy. Tissue diagnosis is mandatory prior to the chemotherapy. Tissue diagnosis can be made through imaging guided true-cut or FNAC and this is important to determine the histology and subsequently the choice of chemotherapy regimen. Study have shown that primary chemotherapy followed by interval debulking surgery in select group of patients doesn't appear to worsen the prognosis, but it permits a less aggressive surgery to be performed subsequently(13). Chemotherapy should be administered by an experienced or trained oncology team and less toxic antineoplastic drug/s such as Carboplatin should be the first line of treatment. Single agent carboplatin has been shown to be equally effective as compared to combination therapy in selected patient in ICON 3 trial (14). If patient responded well to chemotherapy, she should be re-evaluated and interval surgery can be considered once the size of tumour has been significantly reduced. If surgery is contempleted, a thorough preoperative optimization, close monitoring (preferably invasive monitoring) intra and postoperatively and postoperative intensive care should be provided. Surgical team should consist at least a Gynae Oncologist or Senior Gynaecologist experienced in Gynaecology Oncology surgery and Senior Anaesthesiologist. Surgery should be perform as shorter time as possible best if taking place less than 2 hours.
Patient with early stage ovarian cancer may be offerred a similar approach but primary surgical treatment may be reasonable option in selected patient with ASA III. If primary surgical treatment is decided, after thorough discussion with patient and her familiy surgery should be performed in the similar manner. The extend of surgical treatment will be very much depend on the expertise and judgement of the surgeon. To reduce operative risk , minimal but optimum surgery such as adnexaectomy or simple hysterectomy, random peritoneal biopsy and infracolic omentectomy are sufficient if the disease appeared to confine to ovary, more so if the tumour has ruptured intraoperatively as any other added procedure will not altered the subsequent treatment. Lymphadenectomy in ovarian cancer is still debatable, furthermore lymphadenectomy in ovarian cancer should be both systematic bilateral pelvic and para-aortic lymphadenectomy at least up to the level of inferior mesenteric artery. Performing pelvic lymphadenectomy alone without para-aortic lymphadenectomy is considered as inadequate staging procedures as the risk of pelvic and para-aortic lymph node metastasis in ovarian carcinoma are almost similar (15) . This surgical procedure required skill and not without major complication such as vascular injury and sepsis. In patient with ASA III and ASA IV, this surgical procedure may carry more harm then benefits.
b. Patient with ASA III and ASA IV suffering early cervical cancer.
Patient with ASA III and IV and suffering from early stage cervical cancer should be offerred primary radiotherapy similar with more advanced disease. In patient who refuses radiotherapy despite of extensive counseling may benefit from chemotherapy either as primary treatment of as an neoadjuvant treatment followed by less radical surgery (Class II RH). The basic principle of surgery is similar with what has been discussing in ovarian cancer (Shorter time and less radical). Landoni F et al have shown in his randomized trial that Class II and Class III Radical Hysterectomy in patient with small volume stage 1B cervical cancer carries a comparable outcome in term of recurrent rate as well as 5 years survival. (16) In selected patient with stage 1A1, cone biopsy or simple hysterectomy is sufficient.
c. Patient with ASA III and IV suffering endometrial cancer
Primary treatment for early stage (stage 1 and 2) endometrial cancer is Extrafascial hysterectomy with or without pelvic lymphadenectomy. Pelvic lymphadenectomy in stage 1 endometrial cancer is still debatable. Patient with stage 1 and 2 disease and medically inoperable (ASA III and ASA IV) should be counselled for primary radiotherapy. Study by Fishmen DA on medically inoperable stage 1 and 2 endometrial cancer treated with primary radiotherapy have shown an acceptable survival as compared with standard treatment (17) .The Radiation oncologist should familiar with the technique of primary radiotherapy in endometrial cancer. If patient refuse radiotherapy despite of extensive counseling, hormonal treatment can be offerred in form of high dose progestogen (if no contraindication) in Stage 1, grade 1 and type 1 endometrial cancer after thorough pre-treatment radiological assessment. Hormonal treatment is not suitable for type 2 endometrial cancer as well as higher grade and higher stage of type 1 endometrial cancer. If surgery is the only option available, simple hysterectomy is sufficient. Vaginal hysterectomy has an advantages as there will be no abdominal wound , less intraabdominal manipulation, less painful and faster recovery. Laparoscopic hysterectomy by trained laparoscopist is the other acceptable option after discussion with anaesthetist to determine the risk of pneumoperitoneum on cardiopulmonary system and therefore risk-benefits assesment can be calculated.
Apart from all above options, palliative care should always be a reasonable choice in patient who is ill and medically unfit for any form of interventions. This is true for instance in patient with recent myocardial infaction or stroke with multiorgan dysfunction and at the same time suffering an advanced stage gynaecological cancer. This is also apply for patient who remain medically inoperable despite of initial measures taken as highlighted above either the tumour do not respond or the disease is progressing.
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