David E. Rivadeneira

Nutritional support of the cancer patient

Malnutrition is a common problem in cancer patients that results in devastating quality-of-life, economic, and survival issues. “Cancer cachexia” refers to a complex, multifactorial syndrome characterized by anorexia or the spontaneous and unintended loss of appetite, generalized host tissue wasting, skeletal muscle atrophy, immune dysfunction, and a variety of metabolic alterations. The malnourished cancer patient responds poorly to therapeutic interventions, such as chemotherapy, radiotherapy and surgery, with increased morbidity and mortality compared with well-nourished patients. Many studies have reported the prevalence of malnutrition in cancer patients. In a multicenter cooperative study of more than 3,000 cancer patients, DeWys et al 1 reported substantial weight loss in more than 50% of patients. The highest frequency and severity of weight loss occurred in patients with gastrointestinal malignancies. Weight loss also was identified in 40% of patients with breast cancer and 60% of patients with

Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients.

BACKGROUND Axillary lymph node metastasis (ALNM) represents the single most important prognostic indicator in patients diagnosed with breast cancer. The proportion of < or = 1-cm (T1a, T1b) invasive breast carcinomas is increasing. The incidence and predictive factors associated with ALNM in patients with < or = 1-cm tumors remains unclear and the role of axillary lymph node dissection in these patients has been questioned. The purpose of this study was to determine clinical and pathologic factors predictive of ALNM in patients with < or = 1-cm invasive breast carcinomas by univariate and multivariate analyses. STUDY DESIGN Review analysis from a prospective database identified patients with < or = 1-cm invasive breast cancers treated at our institution between 1990 and 1996. All patients underwent a resection of the primary tumor and axillary lymph node dissections. Routine patient and tumor characteristics evaluated included: age, race, tumor size, histologic grade, estrogen and progesterone receptor status, and lymphatic and vascular invasion. Univariate and multivariate analyses were performed. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS A total of 919 patients were identified in this study with tumors < or = 1 cm. These included 199 patients (21.7%) with T1a tumors and 720 patients (78.3%) with T1b tumors. ALNM was detected in 165 patients with an overall incidence of 18.0%. Of the ALNM group, 32 patients (19.4%) had T1a tumors and 133 patients (80.6%) had T1b tumors. Four variables were found to be significant in univariate analysis. These included: increasing tumor size, poor histologic grade, presence of lymphatic or vascular invasion, and younger age of the patient. An increase in tumor size was associated with a significant risk of ALNM (OR = 2.66, 95% CI = 1.28 to 5.75; p = 0.01). Poor tumor grade and the presence of lymphatic or vascular invasion were also associated with an increased risk of ALNM (OR = 2.69, p = 0.003 and OR = 5.52, p = 0.0001, respectively). Patients with ALNM were more likely to have a tumor grade of 3 (25.0% ALNM versus 12.5% node-negative, p = 0.004) and lymphatic or vascular invasion (16.9% ALNM versus 3.5% node-negative, p < 0.0001). In multivariate analysis, an increased risk of ALNM was demonstrated with increasing tumor size (0.1-cm increments), poor histologic grade, and younger age. CONCLUSIONS This study investigated clinical and pathologic factors influencing ALNM in patients with T1a and T1b breast carcinomas. We have identified three factors by multivariate analysis as significant independent predictors of ALNM in this group of patients. These include increasing tumor size, poor histologic grade, and younger age. Given the significant amount of ALNM demonstrated in this study (overall 18%) and the inability to identify a subgroup of patients that had an acceptable low risk of ALNM, the complete omission of assessing the axilla for metastatic disease in patients with small breast cancers cannot be advocated. Our recommendation for patients diagnosed with T1a and T1b tumors is to have their axilla investigated for metastatic disease either by traditional axillary lymph node dissections or by intraoperative lymphatic mapping and sentinel lymph node biopsy techniques.

Pancreatic anastomotic failure after pancreaticoduodenectomy

BACKGROUND Pancreatic anastomotic failure has historically been regarded as one of the most feared complications after pancreaticoduodenectomy. METHODS We reviewed our recent experience (59 cases), March 1994 to December 1998, with pancreaticoduodenectomy and compared preoperative and intraoperative characteristics as well as outcomes in those patients who experienced (n = 10) versus those who did not experience a postoperative pancreatic leak (n = 49). Information was retrospectively collected from hospital records, office records, and interviews with patients. RESULTS The clinical leak rate in this series was 8.5%. There were no significant differences in preoperative or intraoperative characteristics comparing those with versus those without a postoperative pancreatic leak. Only 1 of 10 patients with a postoperative pancreatic leak required reoperation to manage the leak. Those with a pancreatic leak had more other postoperative complications (median 2 versus 0 complications per patient, P = 0.01) and longer hospital duration compared with those without a leak (median 13 versus 23 days, P<0.01). Overall mortality in the series was 3.4%; no mortalities occurred as a result of a pancreatic leak. CONCLUSIONS In the 1990s pancreatic anastomotic leak remains a potentially lethal problem after pancreaticoduodenectomy. Pancreatic leakage after pancreaticoduodenectomy is associated with other postoperative complications and a longer hospital stay.

Elevation of IL-18 in human sepsis

Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine that shares biochemical features with IL-1β and acts in part by inducing interferon-gamma (IFN-γ). Endotoxic bacterial lipopolysaccharide (LPS) (1 or 2 ng/kg) was insufficient to increase plasma IL-18 in five healthy adults measured 3, 12, and 24 hr following challenge. In contrast, in the first 96 hr of admission to the surgical intensive care unit, mean maximal serum IL-18 was elevated (1122 ± 259 pg/ml) in nine septic patients compared to six healthy adults (191 ± 42 pg/ml), P < 0.01). Serum IL-18 concentrations in septic patients did not correlate with other measured inflammatory mediators: tumor necrosis factor, IL-6, IL-10, or secretory leukocyte protease inhibitor. Therefore, IL-18 circulates in healthy adults and is a component of the human systemic inflammatory response. Further, stimuli other than LPS may induce IL-18 production in vivo in human sepsis.

Comparison of Linear Array Endoscopic Ultrasound and Helical Computed Tomography for the Staging of Periampullary Malignancies

Background: The purpose of this study was to compare linear array endoscopic ultrasound (EUS) and helical computed tomography (CT) scan in the preoperative local staging evaluation of patients with periampullary tumors.Methods: Patients evaluated with EUS and CT for suspected periampullary malignancies from 1996 to 2000 were analyzed. Surgical/pathology staging results were the reference standard.Results: Forty-eight patients (28 men and 20 women; mean age, 62 ± 4.9 years; range, 18–90 years) were identified. Malignancy was histologically confirmed in 44 patients. Parameters evaluated included tumor size, lymph node metastases, and major vascular invasion. EUS was significantly more sensitive (100%), specific (75%), and accurate (98%) than helical CT (68%, 50%, and 67%, respectively) for evaluation of the periampullary mass (P < .05). In addition, EUS detected regional lymph node metastases in more patients than helical CT. Sensitivity, specificity, and accuracy of EUS were 61%, 100%, and 84%, in comparison to 33%, 92%, and 68%, respectively, with CT. Major vascular involvement was noted in 9 of 44 patients. EUS correctly identified vascular involvement in 100% compared with 45% with CT (P < .05).Conclusions: Linear array EUS was consistently superior to helical CT in the preoperative local staging of periampullary malignancies.

Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages.

Macrophage cyclooxygenase‐2 (COX‐2) transcription is mediated through the collaboration of different promoter elements. Here, the role of an overlapping cyclic AMP responsive element (CRE)/E‐box was investigated. Nuclear proteins bound both the CRE and E‐box, which synergized with other promoter elements to induce COX‐2 transcription. Endotoxin induced binding of nuclear proteins to the CRE and E‐box and each element independently induced higher COX‐2 transcription levels than the overlapping CRE/E‐box. Transcription factors associated with the CRE binding complex included c‐Jun and CRE binding protein and with the E‐box binding complex USF‐1; their overexpression significantly induced COX‐2 transcription. Therefore, both CRE and E‐box promoter elements regulate COX‐2 transcription in macrophages.

Endoscopy and polyps-diagnostic and therapeutic advances in management

Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.

Glucocorticoid blockade does not abrogate tumor-induced cachexia.

Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.

The impact of Model for End-Stage Liver Disease-Na in predicting morbidity and mortality following elective colon cancer surgery irrespective of underlying liver disease.

BACKGROUND The Model for End-Stage Liver Disease Sodium Model (MELD-Na) is a validated scoring system that uses bilirubin, international normalized ratio, serum creatinine, and sodium to predict mortality in cirrhotic patients awaiting liver transplantation. The aim of this study was to identify the utility of MELD-Na to predict patient outcomes, with and without liver disease, after elective colon cancer surgery. METHODS A review of the American College of Surgeons National Surgical Quality Improvement Program database (2005 to 2010) was conducted to calculate risk-adjusted 30-day outcomes using regression modeling. RESULTS A total of 10,842 patients (mean age, 68 years; 51% women) were included. MELD-Na scores were higher in men (10.2 vs 9.1, P < .001) and in open procedures (9.9 vs 9.1, P < .001). The overall complication and mortality rates were 26.3% and 3.3%, respectively. Incremental increases in MELD-Na score correlated with a 1.2% increase in mortality and a 1.1% increase in complications. On multivariate analysis, complications increased with MELD-Na score (odds ratio [OR], 1.05 per 1 point increase; 95% confidence interval [CI], 1.038 to 1.066). MELD-Na score was also associated with increased mortality (OR, 1.13; 95% CI, 1.1 to 1.16), along with ascites (OR, 5.7; 95% CI, 3.7 to 8.8) and corticosteroids (OR, 2.1; 95% CI, 1.3 to 3.3). CONCLUSIONS Elevated preoperative MELD-Na score is significantly associated with worse outcomes after elective resection for colon cancer.

Prophylactic antibiotics for hemorrhoidectomy: are they really needed?

BACKGROUND: Hemorrhoidectomy is considered by many to be a contaminated operation that requires antibiotic prophylaxis to lower the incidence of surgical site infection. In reality, little evidence exists to either support or refute the use of antibiotic prophylaxis in this setting. OBJECTIVE: This study aimed to determine if antibiotic prophylaxis is associated with reduced incidence of postoperative surgical site infection following hemorrhoidectomy. DESIGN: This is a retrospective database review. SETTING: This study was conducted at multiple institutions. PATIENTS: All patients undergoing hemorrhoidectomy with minimum 3-month follow-up were included. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence of postoperative surgical site infection. RESULTS: Eight hundred fifty-two patients met the inclusion criteria (50.1% female; mean age, 50.0 ± 13.7 years). The prevalence of preoperative risk factors for surgical site infection included 7.7% with a smoking history, 2.5% with diabetes mellitus, 0.8% receiving steroids, and 0.2% with Crohn’s disease. Surgery was performed predominately for 3-column prolapsed internal and mixed internal/external hemorrhoidal disease. All surgeries performed were closed hemorrhoidectomies. Antibiotic prophylaxis was used in a fewer number of cases (41.3% vs 58.7%). Overall, there were only 12 documented postoperative infections identified, producing an overall incidence of 1.4%. Of those patients who developed postoperative surgical site infections, 9 (75%) did not receive antibiotic prophylaxis (p = 0.25). On multivariate regression analysis, no perioperative risk factor was associated with an increased risk of developing a posthemorrhoidectomy surgical site infection. Conversely, there were no adverse antibiotic-related complications such as Clostridium difficile colitis or antibiotic-associated diarrhea in those receiving antibiotic prophylaxis. LIMITATIONS: This study was limited by the retrospective nature of the analysis. CONCLUSIONS: Postoperative surgical site infection is an exceedingly rare event following hemorrhoidectomy. Antibiotic prophylaxis does not reduce the incidence of postoperative surgical site infection, and its routine use appears unnecessary.