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Indian Journal of Cancer, Vol. 48, No. 1, January-March, 2011, pp. 86-93 Review Article Preoperative assessment and optimization in periampullary and pancreatic cancer S Myatra1, JV Divatia1, B Jibhkate1, GS Barreto2, SV Shrikhande3 1 Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Mumbai, India Correspondence Address: Code Number: cn11014
Abstract Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the pancreatic surgeon, anesthesiologist, and the intensive care team. The preoperative surgical evaluation of a pancreatic lesion aims to define the nature of the lesion (malignant or benign), stage the tumor, and to determine resectability or other non-surgical treatment options. Patients are often elderly and may have significant comorbidities and malnutrition. Obstructive jaundice may lead to coagulopathy, infection, renal dysfunction, and adverse outcomes. Routine preoperative biliary drainage can result in higher complication rates, and metal stents may be preferred over plastic stents in selected patients with resectable disease. Judicious use of antibiotics and maintaining fluid volume preoperatively can reduce the incidence of infection and renal dysfunction, respectively. Perioperative fluid therapy with hemodynamic optimization using minimally invasive monitoring may help improve outcomes. Careful patient selection, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome after major pancreatic resections.Keywords: Obstructive jaundice, pancreatic cancer, pancreaticoduodenectomy, preoperative assessment, preoperative evaluation, preoperative optimization, resections, surgery Introduction Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the anesthesiologist, the pancreatic surgeon and the intensive care team. Patients are often elderly, malnourished, with comorbid conditions like chronic obstructive pulmonary disease and diabetes mellitus, which increase the perioperative risk. [1] The only chance for potential cure in pancreatic and periampullary cancer is surgical resection. [2] However, less than 20% of patients present with resectable disease.[3] The two most common resections performed are pancreaticoduodenectomy (PD) for tumors of the head of the pancreas, and distal pancreatectomy (DP) for body and tail tumors. [4] In high-volume centers, the hospital mortality after PD is <5%; postoperative morbidity remains about 20-30%. [5] Major morbidity is often secondary to pancreatic anastomotic leakage and fistula or infection. [6] The anesthesiologist plays a crucial role in the perioperative management of such patients. In the recent past, new information has emerged on many issues including preoperative biliary drainage, nutritional support, cardiovascular assessment, perioperative fluid therapy and hemodynamic optimization. This article attempts to address some of these issues. Methods A literature search was performed with the key words pancreatic cancer, resections, surgery, pancreaticoduodenectomy, preoperative evaluation, preoperative assessment, preoperative optimization and obstructive jaundice. Also, articles dealing specifically with preoperative management strategies were accessed. Moreover, emphasis was placed on respiratory and cardiovascular aspects of evaluation in patients with pancreatic cancer and other major upper gastrointestinal surgeries. A manual search for references from the various articles retrieved was also performed. Surgical Evaluation Patients with pancreatic and periampullary cancer may present with pain in the abdomen, new-onset diabetes, or obstructive jaundice (OJ). An ominous sign is usually the presence of new onset of back pain or deep boring abdominal pain radiating to the back, as this often represents retroperitoneal neural invasion - a sign of inoperability. The first step is to adequately assess the pancreas and, in case a mass is present in the pancreas, to determine the extent of local, regional and distant spread and assess resectability. [7] Diagnosis and Staging While in any cancer of the body the first step is to histologically confirm the diagnosis, in pancreatic cancers, this may not always be possible. Obtaining a precise biopsy may be difficult owing to the location of the tumor. Associated chronic pancreatitis may confound the diagnosis, [8] and also interfere with the ability to obtain a biopsy. Transperitoneal biopsy increases the risk of peritoneal seeding. [9] Hence, failure in obtaining histological confirmation of a suspected malignancy should not delay appropriate surgical treatment. [10] The need for a tissue diagnosis is imperative in patients who are planned for non-operative treatments or when neoadjuvant treatment options are also considered in cases of borderline resectable pancreatic cancer. For more accurate assessment of tumor spread, the surgeon would rely on radiological investigations including computed tomography (CT) scan, magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS) and positron emission tomography (PET) scanning. CT is the modality of choice for evaluating pancreatic neoplasms and to determine resectability. [8] Triphasic CT allows visualization of the pancreas not only in the conventional arterial and venous phases but also in the pancreas phase at which time the parenchyma is maximally enhanced. Multidetector CT (MDCT) scanners have even shown high accuracy for detecting vascular involvement and predicting resectability in pancreatic neoplasms. [11],[12] MRCP also provides excellent information on the pancreatic and bile duct anatomy, the vascular relations, parenchymal disease as well as peripancreatic extension and may even be more accurate than CT. [13],[14] EUS has been shown to be superior to CT, MR, or PET in the detection of small tumors (especially submucosal lesions) and lymph nodal involvement. [9] It also has the highest accuracy in predicting tumor resectability by being able to demonstrate invasion of vascular structures, viz, portal and superior mesenteric veins. [15],[16],[17] Laparoscopy and laparoscopic ultrasound may help detect occult metastatic lesions in the liver and peritoneal cavity undetected by previous imaging modalities. [10],[18] They are able to detect metastasis in up to 37% of patients with locally advanced lesions, confirming unresectability. [9],[19] Common Bile Duct Stenting In patients with periampullary cancers in whom an obstruction of the common bile duct (CBD) has resulted in biliary stasis and cholangitis or in poorly nourished patients, preoperative stenting of the CBD has been recommended to decompress the duct and to allow time to build-up the nutritional level of the patient. Preoperative biliary drainage by endoscopic retrograde cholangiopancreatography (ERCP) and stenting is associated with bacteribilia. [20] More adverse outcomes were observed when surgery was attempted prior to the completion of 6 weeks of stenting when the results of bile cultures were positive. [21] Thus, surgery should be performed at least 6 weeks after CBD stenting. A recent randomized controlled trial reported that routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increased the complication rates. According to this study, poor results were obtained with plastic stents. Hence, preoperative biliary drainage, when used in the period of neoadjuvant treatment for borderline resectable pancreatic cancer, might be best achieved with metal stents, which have a higher patency rate than plastic stents and do not affect the outcome of surgery. [22] Preoperative Anesthetic Evaluation and Optimization The symptoms of pancreatic cancer are generally vague. Malaise, anorexia, weight loss, or abdominal pain make patients seek medical advice. [23] Painless OJ is the most characteristic sign of carcinoma involving head of the pancreas. Nausea and vomiting may be present in case of gastric outlet obstruction and may result in dehydration. [24],[25] A careful history may reveal smoking, long-standing chronic pancreatitis, recent onset diabetes, a sedentary lifestyle, and even a hereditary predisposition. [23] The American Society of Anesthesiologists physical status score (ASA score) and age do not predict morbidity, mortality, and survival after PD. [26] Routine biochemical markers including preoperative blood urea nitrogen ≥18 mg/dl and an albumin ≤3.5 g/dl was a significant multivariate predictors of a postoperative complication after PD. [27] Anemia and Malnutrition Patients are often anemic and malnourished on presentation. Anemia is either due to the disease process itself or to bleeding. Anemia imposes a stress on the cardiovascular system that may exacerbate myocardial ischemia and aggravate heart failure. [28] In asymptomatic patients without cardiovascular disease, a transfusion trigger of 7 g/dl should be used. In patients with ongoing bleeding, signs of inadequate systemic oxygen delivery (tachycardia, tachypnea) and, in patients with cardiovascular disease, a higher transfusion threshold such as 9-10 g/dl may be used. [29] Weight loss may be related to malabsorption from exocrine pancreatic insufficiency, anorexia or nausea, vomiting, and early satiety from gastric outlet obstruction. [25] Enteral nutrition is the preferred route of nutrition. If enteral nutrition is withheld due to gastric dilatation, feeding through a nasojejunal tube should be considered. Only if there is evidence of severe malnutrition (recent weight loss of >10-15% or actual body weight <90% of ideal body weight) and enteral nutrition is not feasible, parenteral nutrition can be started 5-7 days preoperatively and continued in the postoperative period. Parenteral nutrition should be continued till the night prior to surgery. After surgery, it is stopped and patients are started on 10% dextrose intravascularly, and a close watch is kept on blood glucose level, as patients may become hypoglycemic after stopping total parental nutrition. Parenteral nutrition should not be initiated in the immediate postoperative period but delayed for 5-7 days. It is started only if the duration of therapy is expected to be more than 7 days. [30],[31] Obstructive Jaundice Tumors of the head of the pancreas cause OJ due to the obstruction of the passage of conjugated bilirubin from liver cells to the intestine. A liver function test is essential, with testing for direct and indirect bilirubin and coagulation profile. The presence of coagulopathy, sepsis and renal failure may pose major problems in these patients. [32] Patients with OJ are susceptible to develop sepsis. In the absence of biliary intervention, this may be due to a combination of gut failure with increased bacterial translocation via the portal system or significant biliary colonization. [33],[34] About two-thirds of patients with malignant OJ have positive bile cultures at initial ERCP. Rates of colonization approach almost 100% in patients who have had a biliary intervention, and these infections tend to be polymicrobial. Infections in patients without biliary intervention tend to be monomicrobial, with the most common organisms isolated being Gram-negative Escherichia coli, Klebsiella spp., and Proteus spp. [35],[36],[37],[38] A beta-lactam inhibitor in combination with aminoglycoside can be used empirically. Quinolones, third-generation cephalosporins, and carbapenams are generally effective monotherapy in the treatment of cholangitis and are excreted in the bile. [39],[40],[41] Antibiotics targeting enterococci and anaerobes may be added in sicker patients, those who do not respond, and in those with previous biliary intervention and elderly patients. [42],[43] However, antibiotics alone are unlikely to be effective in the absence of effective biliary drainage. Coagulopathies are common because malabsorption of vitamin K and liver dysfunction result in hypoprothrombinemia and a prolonged prothrombin time. [32] Sepsis may precipitate disseminated intravascular coagulation. Essential preventative strategies include reversal of coagulopathy by parenteral vitamin K and the replacement of clotting factors. Patients with evidence of liver disease or a prolonged partial thromboplastin time (PTT) or active hemorrhage require the administration of freeze-dried plasma to replace clotting factors. [44] Correction of coagulopathy is essential not only in the context of intraoperative bleeding but also for the insertion of an epidural catheter preoperatively. Renal failure in patients with OJ may be a life-threatening complication. This risk is increased in patients with decreased intravascular volume, especially when they are starved for various investigations and procedures. A number of prophylactic interventions, including administration of preoperative bile salts and mannitol to ensure adequate diuresis, [45],[46] were advocated in the past. Mannitol may have an adverse effect by producing a forced diuresis in an inadequately volume-loaded patient. The single most important preventative measure to reduce the risk of postoperative renal dysfunction is overnight intravenous fluid therapy to maintain an adequate intravascular volume. [47] Diabetes Mellitus New-onset diabetes mellitus (within the preceding two years) has been observed in 6-68% of patients with pancreatic cancer. [3],[48] It has been proposed that a higher islet amyloid polypeptide (amylin) secretion by the tumor rather than endocrine insufficiency due to destruction of the pancreas alone is responsible for the diabetogenic state. Glucose tolerance often improves in patients after surgical resection. [49] Presence of diabetes increases risk of atherosclerosis and silent ischemia. Diabetic patients should also be evaluated for associated microvascular and macrovascular complications such as nephropathy, peripheral neuropathy, retinopathy, diabetic autonomic neuropathy, and cardiovascular disease. [50] Long-term glycemic control can be assessed by the glycosylated hemoglobin (HbA1c) level. A level below 7 is adequate to prevent microvascular complications. [51] End-organ damage and associated comorbidities are responsible to a great extent for perioperative complications and mortality in diabetic patients undergoing surgery. Patients scheduled for major pancreatic surgery must receive insulin for glycemic control. Oral hypoglycemic agents must be stopped 24-48 hours before surgery and switched to insulin. In the perioperative period, blood sugar level should be maintained between 110 and 150 mg/dl. Aiming for a strict glucose control, with blood sugar level at 80-110 mg/dL increases the risk of severe hypoglycemia. [52],[53],[54] Cardiac Assessment Cardiac complications are a leading cause of intraoperative and postoperative morbidity and mortality, [1] in patients undergoing major thoracic, abdominal, or vascular surgery, especially in patients of age 70 years or older. [55],[56],[57],[58] Pancreatic surgery comes in the intermediate risk stratification with a reported cardiac risk of 1-5%. Associated comorbidities like pulmonary disease, diabetes, anemia, and renal impairment increases the perioperative cardiac risk. [59] Cardiovascular assessment of patients scheduled for major pancreatic resections should be based on the presence of clinical risk factors, presence of active cardiac conditions, and the patient′s functional capacity, as recommended by the American College of Cardiology and American Heart Association. [59] Hypertension serves as a useful marker for potential ischemic heart disease (IHD). [60] In addition, several investigators have demonstrated exaggerated intraoperative blood pressure fluctuation with associated electrocardiographic (ECG) evidence of myocardial ischemia in patients with hypertension. [61],[62],[63],[64] This effect can be modified by treatment. [62],[63],[64],[65],[66],[67] Preoperative control of blood pressure may thus reduce perioperative ischemia and cardiac morbidity. In patients with known IHD, or new-onset signs or symptoms suggestive of IHD, further cardiac assessment like echocardiography and stress cardiac imaging should be performed. Echocardiography can be used to assess static function or can be combined with exercise or pharmacologic stress to assess dynamic function. Identification of asymptomatic left ventricular dysfunction by preoperative echocardiography can alert the physician about potential problems of fluid management to avoid postoperative pulmonary edema. Stress cardiac imaging should be considered in patients with important abnormalities on their resting ECG (eg, left bundle-branch block, LV hypertrophy with "strain" pattern, or digitalis effect). Exercise ECG testing can provide an estimate of functional capacity as well as detect myocardial ischemia through changes in the ECG and hemodynamic response. In patients who cannot exercise, myocardial oxygen demand can be increased using pharmacological agents. [59] Routine prophylactic coronary revascularization is not recommended to be performed in patients with stable CAD before non-cardiac surgery. [59] Indications for preoperative coronary angiography are similar to those identified for the non-operative setting. Accurate recording of current medications used and dosages is essential. Intraoperative hypotension can occur in patients taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. Many authors have suggested withholding ACE inhibitors and angiotensin receptor antagonists the day before surgery. ACE inhibitors should be restarted in the postoperative period only after the patient is euvolemic. Beta-blockers should be continued in patients undergoing surgery who are receiving beta-blockers to treat angina, symptomatic arrhythmias, and hypertension. The usefulness of starting beta-blockers is uncertain in patients undergoing PD (intermediate-risk procedures) in whom preoperative assessment identifies a single clinical risk factor. [59] Such patients may also be on drugs like Aspirin and Clopidogrel. Venous thrombosis and migratory thrombophlebitis, and often occur in patients with pancreatic cancer and also, at times, these may be their first presentation. All patients should receive prophylaxis for venous thrombosis in perioperative period. [25] Low molecular weight heparin and heparin should be stopped 12 and 4 hours prior to surgery, respectively, and can be restarted after hemostasis is adequate. [68] Clopidogrel bisulfate should be stopped 5 days prior to elective surgery, though aspirin may be continued unless the risk of bleeding exceeds the thrombotic risk from withholding the drug.[69] The usage of these drugs besides having implications on bleeding can also affect the decision to insert an epidural catheter. Respiratory Perioperative pulmonary complications occur frequently and lead to significant morbidity following major upper abdominal surgeries. Patients with compromised pulmonary function are at a higher risk of developing significant postoperative pulmonary complications such as bronchospasm, atelectasis, and pneumonia as well as postoperative ventilation. There is 2- to 5-fold increase in risk for pancreatic cancer in patients who smoke more than 40 packs per year.[24] Acute cessation of smoking for 24 hours reduces the quantity of methemoglobin and can improve oxygenation. However, cessation between 24 hours and 6 weeks is associated with an increased incidence of morbidity, presumably secondary to decreased mucociliary clearance. Cessation greater than 6 weeks returns oxygenation and mucociliary clearance to baseline, though not necessarily to normal. [70],[71] Reactive airways and reversible air flow obstruction are common features. The use of medications to establish and sustain normal airway function like bronchodilators is important. Performing a preoperative chest X-ray can identify abnormalities that may lead to modification of care and also delay in surgery. Preoperative chest X-ray is indicated in patients with a history or clinical evidence of pulmonary disease. [72] Pulmonary function testing may be required in case of active pulmonary disease, wheezing or dyspnea on exertion, in heavy smokers with active cough, in elderly (age > 70), and morbidly obese patients. However, for non-pulmonary surgery, rarely, additional information is available beyond that obtained from history and clinical examination. Treatment of lung infections with antibiotics is essential prior to surgery. Preoperative therapeutic measures to improve lung function prior to surgery will reduce the likelihood of postoperative complications. Usually, the therapy is carried out for 48-72 hours before surgery and should be continued after surgery as well. The treatment regimen is aimed largely at four modalities:
Hemodynamic Optimization Major surgery generates a strong systemic inflammatory response and an overall substantial increase in oxygen demand. Physiological compensatory responses maintain cardiovascular function at a higher than normal level after surgery. [74] Organ failure occurs when these responses do not compensate adequately. It is therefore essential to avoid hypovolemia to optimize cardiovascular function in the perioperative period. A strategy of achieving supranormal cardiac output using fluid loading and inotropes in the perioperative period results in better outcomes after major surgery in high-risk patients. [75] However, excessive fluid loading can have deleterious effects on gastrointestinal function, including splanchnic edema, intraabdominal hypertension, splanchnic hypoperfusion, intramucosal acidosis, ileus, increased gut permeability, delayed wound healing, and anastomotic dehiscence. [76] Postoperative gastrointestinal function recovered faster in patients receiving restricted fluid therapy. [77],[78],[79] However, in a small randomized trial of 32 patients undergoing colonic surgery, total number of complications in restrictive fluid therapy group increased (18 vs 1, P < 0.01), and a trend was seen toward increased anastomotic dehiscence and in the number of patients with complications. [80] Thus, both excessive liberal therapy and excessive restriction of fluid and hypovolemia may lead to worse outcomes. Titration of fluid administration to hemodynamic goals may allow correction of hypovolemia and restoration of tissue perfusion and oxygenation, while avoiding complications due to fluid overload. However, the traditional hemodynamic goals of achieving prespecified filling pressures central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) are flawed, as both of them have been shown to correlate poorly with left ventricular preload. [81] It is now possible using minimally invasive cardiac output monitoring, such as the esophageal Doppler and arterial waveform analysis, to determine the stroke volume on a beat-to-beat basis. This allows for individualized fluid therapy as follows: Fluid can be administered while stroke volume (SV) is monitored continuously: if SV increases in response to fluid loading, the patient is a fluid responder; if SV does not increase, the patient is not a fluid responder; hence, another therapeutic approach (eg, inotropic support) must be selected to increase SV. Fluid boluses are administered until SV increases by less than 10% in response to 250 ml colloid rapid (10-20 minutes) infusion. Numerous studies have been performed using the esophageal Doppler, and meta-analyses [82],[83] of these studies suggest that goal-directed fluid therapy, using stroke volume optimization as the goal, leads to shorter hospital stay, reduced complications, fewer intensive care unit (ICU) admissions and the need for inotropes, as well as faster return to normal gastrointestinal function (defined as tolerating solid diet). However, no reduction in mortality has been noted when employing such a strategy. Another recent meta-analysis [84] concluded that goal-directed fluid therapy rather than fluid therapy guided by conventional hemodynamic variables, reduces morbidity after colorectal resection. Pain Management Mid-epigastric pain, with radiation to the mid- or lower-back region suggests retroperitoneal invasion and infiltration of the splanchnic nerves. [85] The patient may be on multiple analgesic medications, which may interact with anesthetic medications. [86] Opioid analgesics should be used early and may be combined with antidepressants and other psychotropic medications to augment analgesia. [87] In cases with severe pain, intravenous patient-controlled analgesia with morphine or fentanyl may be required prior to surgery. If surgery is to be performed within 24-48 hours, epidural analgesia may be provided using a combination of opioids and local anesthetics. Some patients may experience pain, which significantly worsens after eating. This usually occurs due to obstruction in the pancreatic or biliary ducts. These patients may benefit from endoscopic decompression with stents. Our experience has shown that neurolytic celiac plexus block is an effective tool to reduce opioid requirement and the drug-related adverse effects in locally advanced and metastatic pancreatic cancer. [88] However, this block does not have much role in the preoperative period. The block may also be considered intraoperatively when assessing the patient′s potential for resection. Conclusion A team approach (pancreatic surgeon, anesthesiologist, and the intensivist) plays a crucial role in the perioperative management of pancreatic and periampullary cancer. Careful patient selection, individualized preoperative evaluation and optimization go a long way in improving the short-term and long-term outcomes of these patients. References
Copyright 2011 - Indian Journal of Cancer |
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