Radical Resection versus Local Excision for Early Rectal Cancer
Julio Garcia-Aguilar, MD, PhD
University of California, San Francisco
Radical resection (RR) of the rectum with total mesorectal excision achieves excellent local control and yields excellent long-term survival in patients with early rectal cancer. Unfortunately, RR is associated with an appreciable risk of mortality and significant morbidity; in many instances, a permanent stoma is required. Accordingly, a less extensive procedure that would spare the rectum without compromising cure would be appealing to many rectal cancer patients. In theory, full-thickness local excision (LE), carried out by means of either standard transanal technique or transanal microscopic microsurgery, should accomplish these goals in cases where rectal cancer is limited to the bowel wall. At present, however, the role of LE as definitive treatment of stage I rectal cancer is controversial.
Solid data are available from prospective studies concerning the results of RR in patients with rectal cancer. In contrast, the current data on LE in this setting derive mostly from retrospective case series, which vary considerably with respect to patient selection criteria, preoperative staging, surgical techniques, use of adjuvant therapy, length and intensity of follow-up, and even end points. The limitations of the data notwithstanding, the experience accumulated over the past few decades clearly indicates that the rate of local recurrence is higher after LE than after RR for tumors that are limited to the submucosa (T1) and that this difference is more apparent in tumors that infiltrate into but not through the muscularis propria (T2).
In comparing RR with LE for the treatment of early rectal cancer, the most relevant end point is survival rather than local recurrence. RR carries a higher perioperative mortality and morbidity than LE does, and the outcome measure should incorporate these differences. Moreover, although some patients in whom LE has failed have unresectable disease at the time when their recurrence is diagnosed, a number of them present with disease that can still be treated by means of salvage RR.
Because of issues with sample size and patient acceptance, a well-designed phase III trial that compares RR and LE with disease-free survival as the end point may not be feasible. Thus, the best information currently available comes from several retrospective reviews of single-institution or population-based case series that evaluated survival in T1 and T2 rectal cancer patients treated with LE or RR. The results of these series indicated that for patients with T1 rectal cancer, RR yielded higher survival rates than LE; however, this trend was not statistically significant. Only two studies reported on T2 tumors, and both found survival rates to be significantly higher for patients treated with RR than for those treated with LE. In the light of these results, curative LE as the sole form of therapy can be recommended (albeit with some reservations) only for patients with T1 rectal cancers; patients with T2 tumors should not be treated with LE alone.
In an effort to extend the potential benefits of LE to patients with T2 tumors without compromising cure, some have proposed administering adjuvant therapy either after or before LE. The best available evidence concerning outcomes after LE combined with postoperative chemoradiation therapy (CRT) comes from two prospective phase II trials. In the Radiation Therapy Oncology Group (RTOG) study, patients with early rectal cancer were assigned to one of three treatment groups after local excision, in accordance with the final pathology. Patients with T1 tumors, negative margins, and favorable histology received no additional therapy after LE; patients with T1 tumors and unfavorable histology and patients with T2 tumors received postoperative CRT. The local recurrence rates were correlated with the T stage: 4% for T1 tumors and 16% for T2 tumors. In the Cancer and Leukemia Group B (CALGB) study, LE was followed by observation in patients with T1 tumors and by CRT in patients with T2 tumors. The local recurrence rates at 48 months were 7% for T1 tumors and 14% for T2 tumors. The actuarial 6-year disease-free survival rates were 85% for T1 tumors and 71% for T2 tumors. These results were comparable with the survival data reported for stage I disease by the National Cancer Database. Unfortunately, surgical compliance was very poor in the RTOG study, and almost one third of the patients originally registered in the CALGB study were excluded after surgery because of larger tumor sizes, questionable resection margins, or both.
Preoperative adjuvant CRT induces tumor regression in a substantial proportion of patients with locally advanced rectal cancer, and it achieves better local tumor control than postoperative CRT does. It would therefore seem logical to try to take advantage of this downstaging effect of neoadjuvant CRT in patients with early rectal cancer who may be candidates for LE. The results of several retrospective studies and one small prospective study suggest that CRT followed by LE is comparable to RR alone with respect to local tumor control and patient survival.
To explore this treatment strategy, the American College of Surgeons Oncology Group (ACOSOG) has initiated the Z6041 study [see Figure below], a phase II trial aimed at determining the disease-free survival rate at 3 years in patients with T2N0 rectal cancer (as staged by endorectal ultrasonography or endorectal coil magnetic resonance imaging) after treatment with neoadjuvant CRT and LE. This study should also provide valuable information about the response rate of early rectal cancer to preoperative CRT, about the potential complications of LE after CRT, and about the impact of CRT and LE on anorectal function and quality of life. We hypothesize that the combination of neoadjuvant CRT and LE will result in higher rates of tumor control than the combination of LE and postoperative CRT examined in other protocols. In addition, we hypothesize that the reduced tumor size and the downstaging that result from the cytoreductive effects of preoperative CRT will increase the number of patients who are candidates for this type of therapy and will reduce the percentage who have positive margins after LE. The main limitations of the Z6041 study are (1) the tumor staging and patient selection based on imaging studies and (2) the potential increase in morbidity associated with performing LE in an irradiated rectum. The study was opened to accrual in June 2006; to date, it has accrued 60 out of a total sample size of 82 patients. Physicians wishing to enter patients into the Z6041 trial may contact ACOSOG via the Group's Web site: http://www.acosog.org.
In summary, the role of LE in the treatment of early rectal cancer remains to be determined. LE may be an option for patients with T1 tumors of the distal rectum who want to avoid a permanent colostomy or the sequelae of a coloanal anastomosis. For patients with T2 rectal cancer, RR provides the best chance of cure, and LE as the only form of therapy cannot be recommended. Patients seeking an alternative to RR should be entered into a prospective study such as the ACOSOG Z6041 protocol.
9 Care in Special Situations
2 The Elderly Surgical Patient
Sylvia S. Kim, MD
Michael E. Zenilman, MD, FACS
State University of New York Downstate College of Medicine
The elderly portion of the U.S. population uses a substantial share of total health care resources, and physicians must take into account this population's physiologic changes, assessments that help determine their preoperative candidacy, and the surgical procedures common to this population.
Older persons are the fastest-growing demographic group in the United States. It is estimated that by 2020, Americans older than 65 years will account for more than 20% of the total population. By 2030, their numbers will have doubled to 70 million, one fourth of whom will be 85 years of age or older. This segment of the U.S. population uses a substantial share of total health care resources.
Aging is a multifactorial process. In dealing with older patients, physiologic factors are undoubtedly significant and must always be taken into account. Additionally, chronologic age alone is a poor predictor of performance status and advanced age is not considered an acceptable contraindication to surgery. Therefore, adequate assessment of functional age and physiologic reserve are of paramount importance in the elderly surgical patient.
A solid understanding of the physiologic changes associated with aging can facilitate preoperative assessment of the elderly patient's functional reserve and thus, ultimately, help ensure a more accurate assessment of the operative risk and likelihood of potential complications.
Physiologic Changes Associated with Aging
Changes in cardiac function are particularly significant, and cardiac complications remain a leading cause of perioperative morbidity and mortality. A 2007 report from an American College of Cardiology (ACC)/American Heart Association (AHA) task force for perioperative cardiovascular evaluation recognized the utility and efficacy of the Revised Cardiac Risk Index (RCRI) and delineated a stepwise approach to perioperative cardiac assessment. The first step is a basic clinical evaluation. The patient is assessed for any active cardiac conditions or clinical risk factors that might have to be treated before surgery. Active cardiac conditions include unstable coronary syndromes, decompensated heart failure, significant dysrhythmias, and severe valvular disease. If any of these conditions are present, the surgical procedure should be postponed until further testing and treatment are complete. If no active cardiac conditions demanding immediate attention are present, the patient's functional status should be evaluated.
Also with aging comes a significant decline in respiratory function, and pulmonary complications account for nearly 50% of postoperative complications in the total population of surgical patients. The renal system of the elderly population also sees its share of morphologic and histologic changes. These physiologic changes place elderly surgical patients at increased risk for dehydration and prerenal azotemia. Acute renal failure can increase postoperative mortality substantially in these patients. Fluids and electrolytes should be carefully monitored, exposure to nephrotoxic drugs should be minimized, and oliguria should be addressed promptly and aggressively.
Gastrointestinal changes associated with aging include decreased basal and stimulated salivary flow rates (which can lead to impaired swallowing), reduced mucosal protection of the stomach, and prolonged intestinal motility. Clinicians should be aware of the risk of potentially important cytochrome P-450“mediated drug interactions, particularly in the setting of polypharmacy.
Aging is associated with disruption of thermoregulation. Maintaining normothermia during surgical procedures is of particular importance in elderly patients. The elderly also see their share of structural and functional changes in the musculoskeletal system. Muscle mass is lost, muscle strength declines, and body fat mass increases. To counter this, early ambulation in the postoperative period, with assistance as necessary, should be encouraged. One should also take extra care when positioning patients in the OR, ensuring that appropriate padding and joint protection are provided.
In 1987, the National Institutes of Health (NIH) Consensus Conference on Geriatric Assessment Methods for Clinical Decision-making defined the Comprehensive Geriatric Assessment (CGA) as a 'multidisciplinary evaluation in which the multiple problems of older persons are uncovered, described, and explained, if possible, and in which the resources and strengths of the person are catalogued, need for services assessed, and a coordinated care plan developed to focus interventions on the persons problems.' The CGA differs from a standard preoperative evaluation in that it is a truly multidimensional evaluation of the elderly patient. In addition to assessing comorbid conditions, cognitive ability, mental function, socioenvironmental factors, and nutrition status, it also scrutinizes medications and functional ability.
The CGA may be used both to identify at-risk individuals and to guide interventions. When evaluated as a screening tool in the geriatric community, it has been shown to detect new and unsuspected problems in 76% of elderly persons living at home. It has been found to be potentially beneficial in reducing the incidence of hospitalization, falls, delirium, and readmission in geriatric medical studies. It is predictive of both morbidity and mortality in older patients. In addition to the CGA, various additional preoperative assessments exist to evaluate elderly individuals [see Table 2].
Functional status may be measured in several different ways. In geriatric medicine, evaluation of functional status typically includes assessment of the patient's ability to perform activities of daily living (ADLs) (personal care tasks) and instrumental activities of daily living (IADLs) (everyday tasks). The performance status scores commonly used in oncology include the Eastern Cooperative Oncology Group (ECOG) grade and the Karnofsky score. Both of these are essentially global indicators of overall functional status. Studies involving older cancer patients have shown that adding assessment of ADLs and IADLs substantially enhances the functional status evaluation provided by Karnofsky scores or ECOG grades alone.
Comorbid conditions are common in elderly surgical patients and frequently translate into adverse outcomes. The scoring system that is almost universally employed for assessing comorbidity in surgical patients is the American Society of Anesthesiologists physical status classification. Additional measures of comorbidity include the Cumulative Illness Rating Scale“Geriatrics and the Charlson Comorbidity Index.
Impaired nutritional status is highly prevalent among the elderly. As many as 12% of men and 8% of women in the healthy geriatric population are undernourished. Higher rates of surgical complications and increased postoperative mortality have been observed in patients with poor nutritional status, as determined by a low body mass index, weight loss, a low preoperative serum albumin level, or a low Mini Nutritional Assessment score.
Preoperative cognitive dysfunction has been associated with increased postoperative complications and worse survival in elderly surgical patients. Cognitive ability can be assessed with the Mini-Mental State examination.
Depression and the lack of social support are also linked to adverse outcomes in older surgical patients. A tool that is commonly employed in screening for depression in the elderly is the Geriatric Depression Scale. Several tools are available for quantifying social support resources in elderly patients. One such tool is the Medical Outcome Study Social Support Survey, which yields a score on a scale of 0 to 100 and includes 'emotional' and 'tangible' subscales. Another commonly used measure of social support is the Seeman and Berkman Social Ties Score, which measures social ties in four different areas.
The physiologic changes associated with aging lead to alterations in pharmacokinetics, and these alterations, in conjunction with polypharmacy, leave the older patient susceptible to adverse drug interactions. Review of the patient's medication list is an integral component of the CGA.
Special Surgical Considerations in the Elderly
The elderly account for the majority of cancer patients. Fifty-six percent of all newly diagnosed cancers and 70% of cancer deaths are found within the group of patients aged 65 years and older. The increased incidence and prevalence of cancer in older patients, coupled with the increased project longevity within the geriatric population, make cancer treatment in the elderly a common concern. Not surprisingly, cancer treatment plans employed in elderly patients differ from those employed in younger patients. Nevertheless, surgical intervention is generally accepted to be part of the standard of care for elderly patients with some of the more commonly seen cancers.
The incidence of breast cancer is six times higher in older patients than in younger ones. Many elderly breast cancer patients may be undertreated: studies have shown that such patients are less likely to undergo radiation treatment, chemotherapy, or axillary dissection. However, there is evidence to suggest that the biologic behavior of breast tumors differs in the elderly. Older women with breast cancer are more likely to have estrogen receptor“positive tumors that are amenable to hormonal therapy. In addition, they are more likely to have a lower rate of tumor cell proliferation. Physicians must take into account these potential differences in tumor biology seen in older patients, the common comorbid conditions, and the typical functional impairments when planning treatment, along with the understanding that undertreatment is associated with higher recurrence rates and increased mortality.
Lung cancer is the leading cause of cancer-related death in Western nations. More than 50% of persons diagnosed with lung cancer are older than 65 years. For patients with early non“small cell lung carcinoma, surgery affords the best chance of a cure. Lobectomy is currently the surgical standard of care for these patients.
Colorectal cancer is the second most common cancer in the United States, with over 150,000 new cases and 50,000 deaths estimated for 2007. The mainstay of curative treatment for colorectal cancer is surgery: segmental resection for colon cancer and additional total mesorectal excision for rectal cancer. In selected elderly patients, functional outcomes after low anterior resection may be as good as those in younger patients, with similar subjective findings of satisfaction with bowel function and similar objective findings from manometry data. However, there is a growing body of evidence supporting the idea that elderly patients are capable of tolerating adjuvant chemotherapy and deriving a demonstrable survival benefit comparable to that observed in younger patients.
9 Care in Special Situations
6 Organ Procurement
Talia B. Baker, MD, FACS
Anton I. Skaro, MD, PhD, FRCSC
Paul Alvord, MD
Prosanto Chaudhury, MD, CM, MSc (Oxon), FRCSC
Northwestern University Feinberg School of Medicine, Naval Medical Center, and McGill University Faculty of Medicine
As a result of organ procurement from both cadaveric and living donors, and even non“heart-beating donors, more patients than ever benefit from organ transplantation.
Improvements in immunosuppression, organ preservation, surgical technique, and recipient management have led to the widespread adoption of transplantation as a viable therapeutic option for end-stage organ disease. Consequently, more patients than ever benefit from organ transplantation. Unfortunately, the rate of organ donation has not kept pace with the increase in the number of recipients awaiting transplantation.
The relative shortage of organs has necessitated an increasing reliance on creative strategies aimed at broadening or expanding the limits of the donor pool. For instance, organs now are frequently obtained from so-called extended-criteria donors (i.e., donors who are elderly or who have significant comorbid conditions) or from non“heart-beating donors. A particularly important strategy for alleviating the organ shortage has been the broader application of living donor transplantation.
This chapter outlines the current state of organ procurement from both cadaveric and living donors, including donor evaluation and various donor procedures. Cadaveric and living donors are discussed separately because these two groups differ vastly, both from a technical or surgical standpoint and from a medical standpoint.
Organ Procurement from Cadaveric Donors
A patient does not become a potential donor until all lifesaving efforts have failed. Once the patient has been declared brain dead and the decision has been made to proceed with organ donation, management of the donor is redirected toward optimizing potentially salvageable organs. After a potential donor has been identified, the donor coordinator from the local organ procurement organization (OPO) obtains a detailed medical and social history. The OPO coordinator then contacts local and regional transplant programs about their needs. Sharing of all organs is based on the principle that organs should be offered first to patients in the local area and then to patients within a larger geographic region. However, specific medical criteria for prioritizing patients on the waiting lists for various organs are constantly being reevaluated.
Once organs are matched to specific recipients, the local OPO procurement coordinator arranges an operating room time for the donor procedure and organizes transportation of the participating surgical teams. The decision to use an organ is ultimately based on an experienced transplant surgeon's judgment at the time of the procurement. Careful evaluation of the donor, the prospective recipient's medical history, and any pertinent laboratory data is essential for ensuring the best outcome.
Several biochemical parameters are considered in the evaluation of liver grafts. With ideal donors, these parameters normally include the serum aspartate aminotransferase, serum alanine aminotransferase, and bilirubin levels. However, even with donors in whom the injurious event leading to death results in abnormal transaminase levels (which may be reversible), livers suitable for transplantation can often be salvaged after appropriate resuscitation. Livers from donors with viral hepatitis or alcoholism can also be successfully used for transplantation if an acceptable biopsy is performed.
When kidney transplantation is performed in a sensitized recipient, a negative crossmatch is essential for avoiding accelerated rejection. For the kidney graft itself, anoxia time and hypoperfusion time correlate with graft dysfunction. Donor-related factors contribute to native renal disease, which may prevent use of the kidneys for transplantation. Biochemical parameters are also important indicators of kidney function. If the donor is elderly and has multiple comorbid conditions, a renal biopsy is helpful in determining suitability for transplantation.
The criteria for heart and lung donors are strict. Donors are usually young, with no cardiac disease and a normal chest x-ray and electrocardiogram. Donors are also closely matched to recipients with respect to size.
Pancreas transplantation is not lifesaving, and therefore, pancreas donors tend to be chosen more selectively than donors of other organs. Clearly, diabetes is an absolute contraindication to donation. Less commonly, fibrotic or fatty infiltration resulting from alcohol use and obesity may render pancreata unsuitable for transplantation.
Intestinal transplantation poses substantial challenges to surgeons because of the problems faced by patients with intestinal failure: frequent line infections, difficult access, and cirrhosis arising from total parenteral nutrition“related liver disease. Consequently, intestinal donors are chosen very carefully.
Procurement of Cadaveric Organs
Every effort is made to sustain the donor in a normal physiologic state up to the organ procurement procedure. Aggressive monitoring of blood pressure, arterial oxygenation, central venous pressure, and urine output are key to donor management. Before the procurement procedure, the donor's chart is carefully reviewed by the transplant surgeon to confirm satisfactory completion of the declaration of brain death and the consent for organ donation. In addition, the blood type, the serologic assays, and the laboratory test results should be confirmed.
There are as many ways to perform donor operations as there are surgeons performing them. In general, however, regardless of which organs are to be procured, the operation includes a preliminary dissection of the great vessels of the abdomen and the chest. The aorta is isolated at preplanned levels to allow cross-clamping, so that the organs to be removed can be core-cooled in situ with intra-aortic and intraportal infusions, thereby avoiding warm ischemia. This technique has been adopted as an international standard.
The procurement procedure begins with a generous incision from the sternal notch to pubis with an electrocautery device. The abdominal and thoracic contents are grossly examined and palpated and a cursory examination of the abdominal and thoracic contents is made. The organs are evaluated for their quality. It is critical that all occult pathologic conditions be fully investigated and that biopsies be obtained when indicated. The order in which the steps of the procurement procedure are done varies from surgeon to surgeon, as does the ratio of 'warm dissection' to 'cold dissection.' The approach described here is only one of the many viable methods.
Often, different teams work at different paces, on different organs, and in different body cavities, and cross-clamping must be coordinated across all of the participating teams. Once the surgeon communicates with the other teams to coordinate the cross-clamping in the chest and the abdomen, the surgeon should ensure that adequate amounts of cold preservation solution and sterile ice are available to minimize potential injury to the organs during the ischemic time.
The preservation solutions are designed to maintain the organs' cellular integrity. The impermeants and colloids they include prevent cell swelling, which is the major mechanism of organ injury. At present, University of Wisconsin solution (Belzer solution) is still the gold standard for preservation of the kidney, the liver, the pancreas, and the small bowel.
Static cold storage is the preferred organ preservation method in most centers. However, every effort must be made to minimize cold ischemia time so as to maximize organ function in the recipient. Cold ischemia sets the stage for a complex cascade of inflammatory events occurring upon reperfusion that result in early graft injury and dysfunction. The various organs differ in their ability to tolerate cold ischemia. Kidneys can be preserved for as long as 72 hours¤often longer when hypothermic machine storage is employed. Pancreas and liver grafts may be safely preserved for as long as 20 hours; however, the risk of primary liver graft nonfunction increases substantially when cold ischemic time exceeds 12 hours. The intestine may be preserved for as long as 12 hours, but it should be implanted as soon as possible. Time constraints are more rigid for the heart and the lungs: these organs should be transplanted within 6 hours.
The cardiac team proceeds first, removing the heart, the lungs, or both as expeditiously as possible while the abdominal organs are covered with ice slush and perfused with the preservation solution. Thereafter, the process of removing the liver and pancreas begins. The last organs to be procured are the kidneys. The two organs may be removed either individually or en bloc.
Organ Procurement after Cardiac Death
Since the mid-1970s, when the U.S. adopted the legal definition of brain death, the majority of cadaveric organs have been obtained from brain-dead donors. A brain-dead donor is fully supported with medication and mechanical ventilation throughout the donation process until the organs are flushed with cold preservation solution; thus, warm ischemia is eliminated entirely. However, the ever-increasing disparity between the number of organs available and the number of patients awaiting transplantation has stimulated renewed interest in the procurement of organs from non“heart-beating donors (donation after cardiac death, or DCD). Donation from non“heart-beating donors begins after cardiopulmonary function has ceased and the prescribed additional amount of time (2 to 5 minutes) has passed before death can be declared and organ retrieval initiated. Accumulating data suggest that despite the warm ischemia, kidneys, livers, lungs, whole pancreata, and pancreatic islet cells from non“heart-beating donors can be used for transplantation in selected situations.
In a 10-year analysis of DCD published in 2005, the average number of organs transplanted from each DCD donor was 2.02, compared with 3.18 from each brain-dead donor. In terms of long-term graft survival, outcomes with kidneys from DCD donors appear to be equivalent to those with kidneys from brain-dead donors. The results of liver transplantation from controlled DCD donors are not as high as for kidney transplantation but are encouraging. To date, experience with transplantation of whole pancreata and islet preparations from DCD donors has been limited.
Organ Procurement from Living Donors
Living donor transplantation is not a new concept. However, with living donors, even more than with cadaveric donors, good judgment and a high degree of technical skill are crucial for successful recipient and donor outcomes. Regardless of which organ is considered for donation, donor safety must be paramount. Evaluation of a living donor must be careful and comprehensive. Practice guideline recommendations regarding living donors have been outlined by the Live Organ Donor Consensus Group.
Any healthy adult (age >18 years) can be considered as a potential living liver donor. Many programs have upper age limits; virtually all would be reluctant to consider donors older than 60 years. In general, liver donation is the most rigorous, including comprehensive blood testing, ECG and chest x-ray, imaging studies, liver biopsies in some cases, and a host of additional tests that may be clinically indicated on an individual basis. Living donor liver transplantation (LDLT) has been performed since the late 1980s. Preliminary results from a current U.S. study document a 1-year graft survival rate of 81%, which is consistent with other registry data worldwide. Operative techniques include open left lateral sectionectomy and open donor right hepatectomy. One of the major impediments to more widespread adoption of LDLT has been donor morbidity. The application of minimally invasive techniques to this operation, such as laparoscopic-assisted donor right hepatectomy, has the potential to reduce this impediment and thereby broaden the pool of willing donors.
Kidney donation from a live donor may be accomplished either via an open approach or laparoscopically. Although open donor nephrectomy has historically been the standard, the laparoscopic alternative is now the procedure of choice, particularly for left kidneys.
Single-lung transplantation from a living donor has been performed with some success. Procurement of the pancreas and the small intestine from living donors has been shown to be technically possible; however, serious concerns remain about the adequacy of partial grafts for correcting diabetes or short-gut syndrome. Such procedures are currently considered experimental.
Management of Diabetic Foot Ulcers
A lower-extremity ulcer presents a unique window into a patient's health. The term ulcer implies a nonhealing wound, meaning that an ulcer is most likely to be present in a patient with an underlying pathophysiologic derangement. There is no standard protocol that encompasses the care of all diabetic foot ulcers. Treatment of such wounds must be individualized, which is why it is best undertaken in a multidisciplinary fashion. The following are the general steps that should be taken to address the major causative variables, though, as noted, their relative importance will vary from patient to patient