Jukes P. Namm

Quantitating the impact of stage migration on staging accuracy in colorectal cancer.

BACKGROUND The number of nodes retrieved is a powerful predictor of survival in node-negative colorectal cancer (CRC). Whether this is because of improved staging or improved surgery, or both, is unclear. We sought to quantitate the impact of stage migration in node-negative colorectal cancer. STUDY DESIGN Between January 1994 and December 2003, 7,192 patients in Region 5 of the California Cancer Registry, diagnosed with node-negative or node-positive colorectal cancer, were reviewed. The number of nodes examined, node-positive rate, and disease-specific survival (DSS) were analyzed. RESULTS The mean number of nodes examined was 9.3 (range 0 to 89 nodes). The 5-year DSS was 84.5% for N0, 65.2% for N1, and 46.8% for N2 disease. The 5-year DSS difference for those who had more than 12 nodes retrieved was 87.3% (95% CI, 85.2% to 89.3%) and for those with 0 to 3 nodes retrieved, 83.7% (95% CI, 80.6% to 86.82%; p = 0.0009). As the number of retrieved nodes increased, the risk of understaging patients decreased. For 0 to 3 nodes, 78.3% of patients were N0; for 4 to 7 nodes, 67.6%; 8 to 9 nodes, 62.1%; 10 to 12 nodes, 59.5%; and only 57.2% for more than 12 nodes examined. Using more than 12 nodes as the definition of an adequate lymphadenectomy and staging, for apparently N0 patients with 0 to 3 nodes retrieved, DSS survival would be affected by approximately 5%. CONCLUSIONS Differences in outcomes between CRC patients with limited numbers of nodes harvested and those with more than 12 nodes harvested are substantial. Stage migration alone can explain the entire DSS difference between patients with more than 12 nodes retrieved and those with smaller numbers of nodes retrieved.

Is a Level III Dissection Necessary for a Positive Sentinel Lymph Node in Melanoma

For melanoma patients with a positive axillary SLN, the extent of ALND remains controversial, with debate over whether a level III dissection is needed.

Combination of radiotherapy and vaccination overcomes checkpoint blockade resistance

The majority of cancer patients respond poorly to either vaccine or checkpoint blockade, and even to the combination of both. They are often resistant to high doses of radiation therapy as well. We examined prognostic markers of immune cell infiltration in pancreatic cancer. Patients with low CD8+ T cell infiltration and high PD-L1 expression (CD8+ TloPD-L1hi) experienced poor outcomes. We developed a mouse tumor fragment model with a trackable model antigen (SIYRYYGL or SIY) to mimic CD8+ TloPD-L1hi cancers. Tumors arising from fragments contained few T cells, even after vaccination. Fragment tumors responded poorly to PD-L1 blockade, SIY vaccination or radiation individually. By contrast, local ionizing radiation coupled with vaccination increased CD8+ T cell infiltration that was associated with upregulation of CXCL10 and CCL5 chemokines in the tumor, but demonstrated modest inhibition of tumor growth. The addition of an anti-PD-L1 antibody enhanced the effector function of tumor-infiltrating T cells, leading to significantly improved tumor regression and increased survival compared to vaccination and radiation. These results indicate that sequential combination of radiation, vaccination and checkpoint blockade converts non-T cell-inflamed cancers to T cell-inflamed cancers, and mediates regression of established pancreatic tumors with an initial CD8+ TloPD-L1hi phenotype. This study has opened a new strategy for shifting “cold” to hot tumors that will respond to immunotherapy.

Postoperative management after hepatic resection

Hepatic resection has become the mainstay of treatment for both primary and certain secondary malignancies. Outcomes after hepatic resection have significantly improved with advances in surgical and anesthetic techniques and perioperative care. Metabolic and functional changes after hepatic resection are unique and cause significant challenges in management. In-depth understanding of hepatic physiology is essential to properly address the postoperative issues. Strategies implemented in the postoperative period to improve outcomes include adequate nutritional support, proper glycemic control, and interventions to reduce postoperative infectious complications among several others. This review article focuses on the major postoperative issues after hepatic resection and presents the current management.

B lymphocytes as effector cells in the immunotherapy of cancer.

Over the years, the role of B cells in the host immune response to malignancy has been overshadowed by our focus on T cells. Nevertheless, B cells play important roles as antigen‐presenting cells and in the production of antibodies. Furthermore, B cells can function as effector cells that mediate tumor destruction on their own. This review will highlight the various functions of B cells that are involved in the host response to tumor. J. Surg. Oncol. 2012;105:431–435.

Is multimodality therapy necessary for the management of pure myxoid liposarcomas? A multi-institutional series of pure myxoid liposarcomas of the extremities and torso.

The treatment of patients with pure (<5% round cell component) myxoid liposarcomas (pMLS) has not been well characterized. We hypothesized that multimodality therapy (oncological resection with radiation therapy) may not be necessary for pMLS.

History and Evolution of Surgical Ethics: John Gregory to the Twenty-first Century

As surgery grew to become a respected medical profession in the eighteenth century, medical ethics emerged as a response to the growing need to protect patients and maintain the public’s trust in physicians. The early influences of John Gregory and Thomas Percival were instrumental in the formulation of patient-centered medical ethics. In the late nineteenth century, the modern surgical advances of anesthesia and antisepsis created the need for a discipline of ethics specific to surgery in order to confront new and evolving ethical issues. One of the founding initiatives of the American College of Surgeons in 1913 was to eliminate unethical practices such as fee-splitting and itinerant surgery. As surgery continued to advance in the era of solid organ transplantation and minimally invasive surgery in the latter half of the twentieth century, surgical innovation and conflict of interest have emerged as important ethical issues moving forward into the twenty-first century. Surgical ethics has evolved into a distinct branch of medical ethics, and the core of surgical ethics is the surgeon–patient relationship and the surgeon’s responsibility to advance and protect the well-being of the patient.

A semi-automated assessment of sarcopenia using psoas area and density predicts outcomes after pancreaticoduodenectomy for pancreatic malignancy

Background Sarcopenia has been associated with increased adverse outcomes after major abdominal surgery. Sarcopenia defined as decreased muscle volume or increased fatty infiltration may be a proxy for frailty. In conjunction with other preoperative clinical risk factors, radiographic measures of sarcopenia using both muscle size and density may enhance prediction of outcomes after pancreaticoduodenectomy (PD) for malignancy. Methods Preoperative computed tomography (CT) scans of patients undergoing PD for malignancy were analyzed from a prospective pancreatic surgery database. Sarcopenia was assessed both manually and with a semi-automated technique by measuring the total psoas area index (TPAI) and average Hounsfield units (HU) at the L3 lumbar level to estimate psoas muscle volume and density, respectively. Adjusting for known pre-operative risk factors, preoperative sarcopenia measurements were analyzed relative to perioperative outcomes. Results Sarcopenia assessments of 116 subjects demonstrated good correlation between the semi-automated and the manual techniques (P<0.0001). Lower TPAI (OR 0.34, P=0.009) and HU (OR 0.84, P=0.002) measurements were predictive of discharge to skilled nursing facility (SNF), but not major complications, length of stay, readmissions or recurrence on univariate analysis. Lower TPAI was protective against the risk of organ/space surgical site infection (SSI) including pancreatic fistula (OR 3.12, P=0.019). On multivariate analysis, the semi-automated measurements of TPAI and HU remained as independent predictors of organ/space SSI including pancreatic fistula (OR 4.23, P=0.014) and discharge to SNF (OR 0.79, P=0.019) respectively. Conclusions When combined with preoperative clinical assessments in patients with pancreatic malignancy, semi-automated sarcopenia metrics are a simple, reproducible method that may enhance prediction of outcomes after PD and help guide clinical management.

Factors Associated With Underestimation of Invasive Cancer in Patients With Ductal Carcinoma In Situ: Precautions for Active Surveillance

Importance Recent recognition of the overdiagnosis and overtreatment of ductal carcinoma in situ (DCIS) detected by mammography has led to the development of clinical trials randomizing women with non–high-grade DCIS to active surveillance, defined as imaging surveillance with or without endocrine therapy, vs standard surgical care. Objective To determine the factors associated with underestimation of invasive cancer in patients with a clinical diagnosis of non–high-grade DCIS that would preclude active surveillance. Design, Setting, and Participants A retrospective cohort study was conducted using records from the National Cancer Database from January 1, 1998, to December 31, 2012, of female patients 40 to 99 years of age with a clinical diagnosis of non–high-grade DCIS who underwent definitive surgical treatment. Data analysis was conducted from November 1, 2015, to February 4, 2017. Exposures Patients with an upgraded diagnosis of invasive carcinoma vs those with a diagnosis of DCIS based on final surgical pathologic findings. Main Outcomes and Measures The proportions of cases with an upgraded diagnosis of invasive carcinoma from final surgical pathologic findings were compared by tumor, host, and system characteristics. Results Of 37 544 women (mean [SD] age, 59.3 [12.4] years) presenting with a clinical diagnosis of non–high-grade DCIS, 8320 (22.2%) had invasive carcinoma based on final pathologic findings. Invasive carcinomas were more likely to be smaller (>0.5 to ⩽1.0 cm vs ⩽0.5 cm: odds ratio [OR], 0.73; 95% CI, 0.67-0.79; >1.0 to ⩽2.0 cm vs ⩽0.5 cm: OR, 0.42; 95% CI, 0.39-0.46; >2.0 to ⩽5.0 cm vs ⩽0.5 cm: OR, 0.19; 95% CI, 0.17-0.22; and >5.0 cm vs ⩽0.5 cm: OR, 0.11; 95% CI, 0.08-0.15) and lower grade (intermediate vs low: OR, 0.75; 95% CI, 0.69-0.80). Multivariate logistic regression analysis demonstrated that younger age (60-79 vs 40-49 years: OR, 0.84; 95% CI, 0.77-0.92; and ≥80 vs 40 to 49 years: OR, 0.76; 95% CI, 0.64-0.91), negative estrogen receptor status (positive vs negative: OR, 0.39; 95% CI, 0.34-0.43), treatment at an academic facility (academic vs community: OR, 2.08; 95% CI, 1.82-2.38), and higher annual income (>

Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

63 000 vs <