Alexandra M. Easson

Understanding and managing cancer cachexia

Mrs MJ is a 56-year-old architect with a husband and two children. You performed a mastectomy and axillary dissection on her after neoadjuvant chemotherapy for locally advanced breast cancer 2 years ago. Unfortunately, she developed widespread disease with metastases to liver, lung, and bone. After several more rounds of chemotherapy, she is currently on antiestrogen therapy. Her disease appears stable. You have continued to follow her and she comes to see you for her routine visit. You notice that she is much thinner than you remember, but otherwise looks well. You ask her about her weight loss. She says: “I don’t really know what it is! I can eat, my bowels are working, but I simply don’t want to. I force myself to swallow food, but I keep losing weight anyway.” On clinical examination, you notice her muscle wasting and recognize the signs of cancer cachexia. You want to know more about how to manage this phenomenon.

Management of malignant bowel obstruction.

Malignant bowel obstruction (MBO) is a common and distressing outcome particularly in patients with bowel or gynaecological cancer. Radiological imaging, particularly with CT, is critical in determining the cause of obstruction and possible therapeutic interventions. Although surgery should be the primary treatment for selected patients with MBO, it should not be undertaken routinely in patients known to have poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A number of treatment options are now available for patients unfit for surgery. Nasogastric drainage should generally only be a temporary measure. Self-expanding metallic stents are an option in malignant obstruction of the gastric outlet, proximal small bowel and colon. Medical measures such as analgesics according to the W.H.O. guidelines provide adequate pain relief. Vomiting may be controlled using anti-secretory drugs or/and anti-emetics. Somatostatin analogues (e.g. octreotide) reduce gastrointestinal secretions very rapidly and have a particularly important role in patients with high obstruction if hyoscine butylbromide fails. A collaborative approach by surgeons and the oncologist and/or palliative care physician as well as an honest discourse between physicians and patients can offer an individualised and appropriate symptom management plan.

Outcomes of Salvage Surgery for Squamous Cell Carcinoma of the Anal Canal

BackgroundFor patients with anal canal cancer who fail combined modality treatment (CMT), salvage surgery (SS) offers the potential for long term survival. The literature regarding SS is limited by small patient numbers and/or heterogeneous treatment protocols. We report on a large series of patients initially treated with chemoradiation at a major referral center.MethodsWe identified 60 patients with persistent or recurrent anal cancer who had undergone SS; 20 were excluded. Overall and disease-free survival (OS, DFS) curves were constructed using the Kaplan Meier method. Univariate analysis was done using the Log-Rank test, and multivariable analysis using Cox proportional hazards.ResultsThe 40 patients (29 women, 11 men, median age 57) underwent curative intent resection. The initial procedure was multivisceral resection (n = 24), abdominoperineal resection alone (n = 14) or local excision (n = 2). Postoperative mortality was 5%. Postoperative complications were seen in 72%. Median follow-up was 18 months overall and 36 months in survivors. Median OS was 41 months; OS and disease free survival at 5 years were 39% and 30%, respectively. Recurrence was present in 21 patients at time of analysis. Failure was locoregional in 86% (18 of 21) and distant in 48% (10 of 21). Independent predictors of poor OS were male gender, Charlson Comorbidity Score and tumor size. Independent predictors of poor disease free survival were positive margins and lymphovascular invasion.ConclusionSS for anal canal cancer was associated with significant morbidity. Long-term survival was achieved in 39% of patients. Comorbidities should guide patient selection, and R0 resection should be the goal.

Discussion of death and dying in surgical textbooks.

BACKGROUND Quality end-of-life care is an increasing concern for the public and the medical profession. Surgical textbooks could serve as an important educational and reference resource to improve this care. METHODS Four general surgical textbooks were scored for helpful information on death and dying for eight surgical diseases. For each disease, nine content domains related to care of the dying patient were evaluated. Three texts included a chapter on cancer that was evaluated separately. RESULTS Disease epidemiology, prognosis/prevention, progression, and medical interventions were generally well discussed in all textbooks. However, little helpful information was provided with regards to breaking bad news/advanced care planning, mode of death, treatment decision-making, effect on family/surgeon, and symptom management. Cancer chapters also addressed only a few of these concerns. CONCLUSION Death and the dying patient are sufficiently frequent in surgical practice that it would be appropriate to increase the amount of information provided.

When the Sun Can Set on an Unoperated Bowel Obstruction: Management of Malignant Bowel Obstruction

Mr XY is a 75-year-old man with known recurrent rectosigmoid adenocarcinoma in the pelvis. He had an emergency Hartmann’s procedure 2 years earlier for a bowel perforation caused by tumor. The patient had been offered a surgical intervention 3 months earlier for the recurrent pelvic mass visualized on CT, but he declined any additional surgical intervention. No metastatic disease was noted at that time. He had no symptoms of bowel obstruction at the time, although there were signs of minimal proximal bowel dilatation. He presented to the Emergency Department on three separate occasions in a 3-week period with nausea, vomiting, abdominal cramping, and no colostomy output. A partial small bowel obstruction was confirmed on plain film x-rays. Clinically, the patient was in good condition and had no physical inhibitions. He was treated with nasogastric decompression on each occasion and the symptoms quickly resolved and bowel function resumed. On the first two occasions, he was able to eat a regular diet and return home within 3 to 5 days of being admitted to the hospital. He had a small bowel follow-through after the second obstruction episode, which was nondiagnostic. After the third episode, a lengthy conversation was undertaken with the patient about his goals and concerns related to an operation. This revealed fears of the pain related to surgery. After discussion about the likelihood of continued episodes of bowel obstruction and the assurance that diligent perioperative pain management would be practiced, including the possible use of an epidural catheter, he agreed to have an operation. The goals of restoring his capacity to eat, and the hope of allowing him to remain home without multiple readmissions to the hospital, were clearly delineated. We believed that the obstruction was most likely from a single site at his pelvic recurrence, and we were likely to achieve these goals. It was made clear to the patient that he could have more disease or adhesions than expected, making a definitive surgical approach difficult or impossible, and necessitating alternative therapies. He was told that even with surgery, bowel obstruction and wound complications could occur in the future. At operation, there were extremely dense adhesions throughout his entire peritoneal cavity, especially in the pelvis. He did not have peritoneal carcinomatosis, although he did have tumor nodules throughout his liver. The source of the bowel obstruction was difficult to locate because no area of decompressed bowel was found, and extensive adhesiolysis was required. The colostomy site was closely inspected to ensure that it was not the site of obstruction. Ultimately, a loop of very distal small bowel was adherent to a pelvic tumor mass overlaying the iliac vessels and ureter. The small bowel was folded on itself, creating a small blind loop. The decision was made to do a small resection instead of a bypass.This was accomplished with a primary anastamosis without complication. Postoperatively, the patient’s bowel function was slow to resume. Otherwise, he recovered uneventfully and went home 8 days after the operation. One month after operation he remains at home without symptoms or signs of recurrent bowel obstruction.

Clinical research for surgeons in palliative care: challenges and opportunities

Symptom management and palliative medicine have gained growing interest among physicians and other health care providers. One reason might be the profound shift in patient demographics and associated diseases. What was once a formidable condition, such as an acute coronary occlusion, for the most part follows a straightforward clinical protocol today with interventional cardiology and cardiac procedures. Sudden death from acute myocardial events among people in their sixth or seventh decade has become relatively uncommon. Instead, the elderly population is chronically plagued by heart failure, a condition present in nearly every other person more than 85 years of age. In the younger population of 65 to 74 years of age, advanced cancer has surpassed heart disease as the most frequently cited cause of death. We live in a rapidly aging society; 78% of people in the United States will live past their 65th birthday. Congestive heart failure, advanced cancer, stroke, and dementia—the four formidable chronic morbidities—all share one common characteristic. There is no cure for their underlying disease process. Most current treatment modalities aim for disease control and symptom palliation rather than cure in the strict sense. Surgeons might wonder how palliative care fits into their surgical practice. This might be because of the surgical myth that the principal role of the surgeon is to cure the patient and the business of palliation is deemed best relegated to the nonsurgeons. But the presumed delineation between cure and palliation is becoming increasingly blurred because of the underlying patient demographics and associated disease processes that are fundamentally incurable, at least from today’s vantage point. In the end, it might be more constructive to consider the role of palliative care in surgery in terms of specific patient-oriented clinical outcomes, rather than in terms of the elusive cure versus palliation. In addition to survival, examples of patient-oriented clinical outcomes include functional status; relief from symptoms such as pain, dyspnea, and cachexia; and emotional and psychological well-being—all of which contribute to quality of life. In the aforementioned context, there is a need to define what palliative surgery is, and what a palliative surgeon is. Palliative surgery is not to be construed as a type of surgery exclusive of any intent to cure. When cure is possible, palliative surgery is inclusive of curative intervention. In addition, palliative surgery does not connote any degree of diminishment or retrenchment of care. If anything, palliative surgery might provide more aggressive care, recognizing the value of medical, procedural, or other interventions leading to symptom relief and enhanced quality of life. Symptom palliation might even result in increased patient survival, whether or not cure is possible in the traditional sense. What distinguishes palliative surgery is the palliative surgeon’s expansion of clinical outcomes beyond surgical morbidity or mortality outcomes and recurrence of disease to include outcomes that are meaningful to the patient. Palliative surgeons acknowledge that death can be a natural and expected outcome of an advanced disease process, such as cancer and systemic atherosclerotic disease. They aim to set appropriate goals of care and to offer other clinical services for the total care of the patient and family. For most patients with advancing atherosclerotic disease, malignancy, and dementia, relief from debilitating symptoms and quality of life might be just as or more important than the number of years lived. A concenNo competing interests declared.

Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

PURPOSE A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. METHODS AND MATERIALS From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicity was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. RESULTS Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus-positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were significantly better at 12 months than at baseline. Multiple dose-volume parameters correlated moderately with diarrhea, skin, and hematologic toxicity scores. CONCLUSION IMRT reduces acute grade 3 + hematologic and gastrointestinal toxicities compared with reports from non-IMRT series, without compromising locoregional control. The reported QOL scores most relevant to acute toxicities returned to baseline by 3 months after treatment.

The Ability of Existing Questionnaires to Measure Symptom Change After Paracentesis for Symptomatic Ascites

BackgroundSymptomatic malignant ascites is a problem for patients with advanced intra-abdominal malignancy. Although the goal of paracentesis, the most common therapeutic intervention, is symptom palliation, the best method of assessing symptom improvement is unknown. The aim of this study was to assess the ability of existing symptom and quality-of-life questionnaires to detect change in symptoms after paracentesis.MethodsPatients with symptomatic ascites completed four questionnaires before and 24 hours after paracentesis. These tests were Edmonton Symptom Assessment System–Ascites Modification (ESAS:AM), Memorial Symptom Assessment Scale–Short Form, European Organization for the Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), and the EORTC Core Quality of Life Questionnaire, 26-item pancreatic cancer module (QLQ-PAN26). Sensitivity, validity, reliability, and responsiveness of the questionnaires were evaluated.ResultsSixty-one patients completed the baseline and 44 the follow-up questionnaire. Most patients had ovarian (41%) or gastrointestinal cancer (25%); Eastern Cooperative Oncology Group performance status was 2 (26%) and 3 (49%). Patients reported major symptoms at baseline; symptom scores were highest for the clinically recognized symptoms of ascites. Most patients (78%) reported that their symptoms improved after paracentesis. All questionnaires showed strong sensitivity, validity, and reliability. Subscales that included the most distressing symptoms were most responsive; great improvement was seen in abdominal bloating (42% to 54%), anorexia (20% to 37%), dyspnea (33% to 43%), insomnia (29% to 31%), fatigue (14% to 17%), and mobility (25%). The amount of fluid removed (median, 3.5 L; range, .3% to 9.7 L) did not correlate with symptom improvement (r = .29, P = −.10).ConclusionsParacentesis provides symptom relief that can be measured by existing questionnaires. For future clinical trials of symptomatic ascites, the QLQ-C30 and the ESAS:AM together, or the QLQ-C30 with the addition of the QLQ-PAN26 ascites and abdominal pain subscales could be used.

Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs).

Background Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution. Principal Findings TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×107 TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day “rapid expansion protocol” (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/− 1034-fold) after 14 days. Conclusions TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT.

Ethical considerations and barriers to research in surgical palliative care.

There are many distinctive ethical characteristics, dilemmas, and potential barriers for surgeons involved in palliative care research. Although some of these issues might not be unique to patients facing the end of life, they are often magnified in this population. Because of the inherent stresses for patients, families, and caregivers in treating terminally ill patients, many ethical concerns are magnified in this patient group. These concerns compound the potential ethical issues present in all clinical research trials. In addition, when considering surgical interventions, the risk-benefit analyses warranted in all clinical research require special attention. Ethical dilemmas and barriers to research for surgeons might be similar to those noted for palliative care in general, but there are several distinctive characteristics that must be considered.