Inflammation-related proteins as biomarkers of treatment-related behavioral symptoms: A longitudinal study of breast cancer patients and age-matched controls.

Background: Behavioral symptoms in breast cancer (BC) survivors have been attributed to cancer treatment and resulting inflammation. However, studies linking behavioral symptoms to BC treatment have observed patients only after some treatment. Our prospective study with pre-treatment baseline investigates post-treatment changes in inflammation-related biomarkers and whether those changes correlate with changes in symptoms. Methods: Participants were postmenopausal women, newly-diagnosed with stage 0-3 BC before any treatment (n = 173 "patients"), and age-matched women without cancer (n = 77 "controls"), who were assessed on plasma markers [soluble tumor necrosis factor receptor type 2 (sTNF-RII), interleukin (IL)-6, IL-1 receptor antagonist (IL-1RA), C-reactive protein (CRP)]) and symptoms (Physical Functioning, Pain, Attention/concentration, Perceived Cognitive Problems, Fatigue, Sleep Insufficiency, Depression). Participants were assessed again 1 month, 1 year, and 2 years after completing primary treatment or similar interval in controls. Generalized linear mixed models tested 4 treatments (surgery alone or with chemotherapy, radiation, or both) for association with change per marker. Joint models tested change per marker for association with change per symptom. Models considered demographic, socioeconomic, and clinical covariates. False Discovery Rate method controlled risk of error from multiple hypotheses. Results: At one month post-completion of treatment, sTNF-RII and IL-6 were elevated by all BC treatments, as were IL-1RA and CRP after surgery alone (all, p < 0.05). By 1 year, markers' average values returned to baseline. Throughout 2-year follow-up, increase-from-baseline in sTNF-RII, IL-1RA, and IL-6 coincided with worsened Physical Functioning, and increase-from-baseline in sTNF-RII coincided with increased Pain (all, p < 0.01). These biomarker-symptom associations (excepting IL-6) were exclusive to patients. No other symptoms worsened, and baseline Fatigue and Depression improved in all participants. Conclusions: BC treatment, even surgery, is associated with transient elevation in inflammatory markers. In patients post-treatment, increase-from-baseline in sTNF-RII accompanies increased Pain and decreased Physical Functioning, suggesting that sTNF-RII merits development as a clinical biomarker in BC patients.

Different Methods of Minimally Invasive Esophagojejunostomy After Total Gastrectomy for Gastric Cancer: Outcomes from Two Experienced Centers.

BACKGROUND: Esophagojejunostomy after minimally invasive total gastrectomy (MITG) for gastric cancer (GC) is technically challenging. Failure of the esophagojejunal anastomosis can lead to significant morbidity, leading to short- and long-term quality of life (QoL) impairment or mortality. The optimal reconstruction method following MITG remains controversial. We evaluated outcomes of minimally invasive esophagojejunostomy after laparoscopic or robotic total gastrectomies. METHODS: We retrospectively reviewed MITG patients between 2015 and 2020 at two high-volume centers in China and the United States. Eligible patients were divided into groups by different reconstruction methods. We compared clinicopathologic characteristics, postoperative outcomes, including complication rates, overall survival rate (OS), disease-free survival rate (DFS), and patient-reported QoL. RESULTS: GC patients (n = 105) were divided into intracorporeal esophagojejunostomy (IEJ, n = 60) and extracorporeal esophagojejunostomy (EEJ, n = 45) groups. EEJ had higher incidence of wound infection (8.3% vs 13.3%, P = 0.044) and pneumonia (21.7% vs 40.0%, P = 0.042) than IEJ. The linear stapler (LS) group was inferior to the circular stapler (CS) group in reflux [50.0 (11.1-77.8) vs 44.4 (0.0-66.7), P = 0.041] and diarrhea [33.3 (0.0-66.7) vs 0.0 (0.0-66.7), P = 0.045] while LS was better than CS for dysphagia [22.2 (0.0-33.3) vs 11.1 (0.0-33.3), P = 0.049] and eating restrictions [33.3 (16.7-58.3) vs 41.7 (16.7-66.7), P = 0.029] at 1 year. OS and DFS did not differ significantly between LS and CS. CONCLUSIONS: IEJ anastomosis generated better results than EEJ. LS was associated with a better patient eating experience, but more diarrhea and reflux compared with CS. Clinical and patient-reported outcomes show the superiority of IEJ with the LS reconstruction method in MITG for GC.

NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

Multimodality management of locally advanced gastric cancer-the timing and extent of surgery.

The optimal treatment for patients with locally advanced gastric adenocarcinoma is multimodal. Surgery is the cornerstone of therapeutic strategies with curative intent. The addition of chemotherapy or chemoradiation decreases rate of recurrence and prolongs survival. Guidelines differ between countries and there is no universal standard of care. Modern studies of patients with locally advanced gastric cancer showed that adjuvant chemotherapy improves survival over surgery alone in Asia. These studies could not be replicated in Europe. Peri-operative chemotherapy strategies, conversely, have been effective in Europe for improving overall and disease free survival. Adjuvant chemoradiation has also demonstrated improved survival when compared to surgery alone, but studies comparing chemotherapy with chemoradiation have not shown significant difference. Trials are ongoing to examine the role of chemoradiation in a neoadjuvant fashion. A D2 extent of lymphadenectomy improves cancer related survival for those who do not undergo distal pancreatectomy/splenectomy. Survival is also associated not only with the extent but also the number of lymph nodes examined. There are ongoing trials related to immunotherapy and targeted therapies, which may also impact or change the treatment paradigm for locally advanced gastric cancer.

Hypothermia Is Associated with Surgical Site Infection in Cytoreductive Surgery with Hyperthermic Intra-Peritoneal Chemotherapy.

BACKGROUND: Maintenance of peri-operative normothermia remains a global quality metric for hospitals. Hypothermia is associated with surgical site infections (SSIs) in colorectal surgery. Patients undergoing cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) can experience multiple complications post-operatively. We sought to investigate the association of peri-operative hypothermia with SSIs in patients undergoing CRS/HIPEC at our institution. PATIENTS AND METHODS: Patients undergoing CRS/HIPEC from 2009-2017 were identified retrospectively from a prospectively collected institutional database. Hypothermia defined as less than 36.0°C in accordance with the Agency for Healthcare Research and Quality metric. Regression analyses were performed with SSIs diagnosed within 30 days post-operatively as the primary outcome. RESULTS: A total of 170 patients were identified, 14 (8.2%) of whom developed an SSI. Patients who developed an SSI experienced lower median temperatures (p = 0.027) and a greater percentage of operative time in hypothermia (p = 0.008). On a multivariable analysis adjusting for known risk factors for SSI, the percentage of operative time in hypothermia (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01-1.07, p = 0.008) was the only parameter associated with SSI within 30 days post-operatively. CONCLUSION: Hypothermia is associated with the development of SSIs in patients undergoing CRS/HIPEC. Our findings suggest that minimizing peri-operative temperatures to less than 36.0°C may decrease peri-operative SSI in this patient population.

Soft Tissue Sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Association of Fluid Administration With Morbidity in Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

IMPORTANCE: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal cancers can be associated with significant complications. Randomized trials have demonstrated increased morbidity with liberal fluid regimens in abdominal surgery. OBJECTIVE: To investigate the association of intraoperative fluid administration and morbidity in patients undergoing CRS/HIPEC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of information from a prospectively collected institutional database was conducted at a National Cancer Institute-designated comprehensive cancer center. A total of 133 patients from April 15, 2009, to June 23, 2016, with primary or secondary peritoneal cancers were included. EXPOSURES: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. MAIN OUTCOMES AND MEASURES: Morbidity associated with intraoperative fluid management calculated by the comprehensive complication index, which uses a formula combining all perioperative complications and their severities into a continuous variable from 0 to 100 in each patient. RESULTS: Of the 133 patients identified, 38% and 37% had diagnoses of metastatic appendiceal and colorectal cancers, respectively. Mean age was 54 (interquartile range [IQR], 47-64) years, and mean peritoneal cancer index was 13 (IQR, 7-18). Mitomycin and platinum-based chemotherapeutic agents were used in 96 (72.2%) and 37 (27.8%) of the patients, respectively. Mean intraoperative fluid (IOF) rate was 15.7 (IQR, 11.3-18.7) mL/kg/h. Mean comprehensive complication index (CCI) was 26.0 (IQR, 8.7-36.2). On multivariate analysis, age (coefficient, 0.32; 95% CI, 0.01-0.64; P = .04), IOF rate (coefficient, 0.97; 95% CI, 0.19-1.75; P = .02), and estimated blood loss (coefficient, 0.02; 95% CI, 0.01-0.03; P = .002) were independent predictors of increased CCI. In particular, patients who received greater than the mean IOF rate experienced a 43% increase in the CCI compared with patients who received less than the mean IOF rate (31.5 vs 22.0; P = .02). CONCLUSIONS AND RELEVANCE: Intraoperative fluid administration is associated with a significant increase in perioperative morbidity in patients undergoing CRS/HIPEC. Fluid administration protocols that include standardized restrictive fluid rates can potentially help to mitigate morbidity in patients undergoing CRS/HIPEC.

Laparoscopy Can Safely Be Performed in Frail Patients Undergoing Colon Resection for Cancer.

The present study aims to evaluate the role of laparoscopy in frail patients undergoing colorectal surgery for colorectal cancer. A review of the 2011 to 2014 American College of Surgeons National Surgical Quality Improvement Program database was performed to identify frail patients (using a frailty index), who underwent resection for colorectal cancer. Univariable and multivariable analyses were performed to evaluate 30-day mortality and Clavien-Dindo grade IV (CD-IV) complications. A total of 52,087 patients with colorectal cancer were identified, of which frailty accounted for 2.63 per cent (index score ≥5). Patients above the age 85 were considered frail 6.8 per cent of the time and accounted for 24.5 per cent of patients with frailty. Laparoscopic surgery was performed in 32.9 and 53.1 per cent of patients with and without frailty (P < 0.001). Patients with frailty were less likely to die within 30 days of surgery if younger (P = 0.004), performed electively (P < 0.001), or laparoscopically (P < 0.001). On multivariate analysis, laparoscopy and elective surgery were associated with better perioperative survival; whereas, older age, male sex, and tobacco use were associated with 30-day mortality. Laparoscopy and lower body mass index were associated with fewer Clavien-Dindo grade IV complications. Although laparoscopy is performed less commonly in the frail, this study indicated better perioperative outcomes for patients undergoing elective surgery who were <85 years old.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

Inflammatory Biomarkers, Comorbidity, and Neurocognition in Women With Newly Diagnosed Breast Cancer.

BACKGROUND: Neurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by pro-inflammatory cytokines. METHODS: One hundred seventy-four postmenopausal patients with newly diagnosed breast cancer underwent a comprehensive neuropsychological evaluation (assessment of cognitive function, mood, and fatigue) and measurement of key cytokine levels prior to surgery. Age-matched control participants without cancer were evaluated concurrently. Multivariable regression analyses examined the contribution of circulating Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type two (sTNF-RII) in predicting neurocognitive performance in patients after controlling for key factors thought to impact functioning. All tests of statistical significance were two-sided. RESULTS: Memory performance was statistically significantly reduced, in patients compared with controls (P = .02). Of the three cytokines measured, only IL-1ra was statistically significantly elevated in cancer patients when compared with control participants (mean ± SD, 375 ± 239 pg/mL vs 291 ± 169 pg/mL, P = .007). After controlling for age, education, race, mood, fatigue, body mass index, and comorbidity, cytokines independently explained 6.0% of the total variance in memory performance (P = .01) in cancer patients but not control participants, with higher sTNF-RII associated with worse functioning. Exploratory analyses found that comorbidity statistically significantly explained variance in processing speed and executive functioning (P = .03 and P = .03, respectively). CONCLUSION: An association of TNF with memory, previously reported in patients after exposure to chemotherapy, was found prior to initiation of any treatment, including surgery. This association requires further investigation as sTNF-RII was not higher in cancer patients relative to control participants.

Gastrointestinal stromal tumors, version 2.2014.

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

Soft tissue sarcoma, version 2.2014.

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

Evaluation of expert criteria for preoperative magnetic resonance imaging of newly diagnosed breast cancer.

Despite 2 randomized trials reporting no reduction in operations or local recurrence at 1 year, preoperative magnetic resonance imaging (MRI) is increasingly used in diagnostic workup of breast cancer. We evaluated 5 utilization criteria recently proposed by experts. Of women (n = 340) newly diagnosed with unilateral breast cancer who underwent bilateral MRI, most (69.4%) met at least 1 criterion before MRI: mammographic density (44.4%), under consideration for partial breast irradiation (PBI) (19.7%), genetic-familial risk (12.9%), invasive lobular carcinoma (11.8%), and multifocal/multicentric disease (10.6%). MRI detected occult malignant lesion or extension of index lesion in 21.2% of index, 3.3% of contralateral, breasts. No expert criterion was associated with MRI-detected malignant lesion, which associated instead with pre-MRI plan of lumpectomy without PBI (48.2% of subjects): Odds Ratio 3.05, 95% CI 1.57-5.91 (p adjusted for multiple hypothesis testing = 0.007, adjusted for index-vs-contralateral breast and covariates). The expert guidelines were not confirmed by clinical evidence.

Prediction of the adequacy of lymph node retrieval in colon cancer by hospital type.

BACKGROUND: Examination of 12 or more regional lymph nodes (LNs) is the accepted minimum for nodal staging in colon cancer and serves as a surrogate for adequate resection. OBJECTIVE: To determine the contributing role of the hospital in the number of LNs retrieved. Design/ SETTING: We retrospectively reviewed colon resections in 83 patients by 2 surgical oncologists at a National Comprehensive Cancer Network (NCCN) hospital or at community-based hospitals from January 1, 2002, through December 31, 2007. PATIENTS: We included all patients undergoing colectomy for primary colon cancer and excluded patients with recurrence, rectal cancer, or preoperative chemotherapy. MAIN OUTCOME MEASURES: Total number of LNs retrieved. We also analyzed clinical factors accounting for differences. RESULTS: The median number of LNs examined at the NCCN hospital (42 patients) vs the community hospitals (41 patients) were 17.8 vs 7.0 (P < .001), and the frequency of an inadequate number of LNs examined (<12) was 11 of 42 cases (26%) vs 35 of 41 cases (85%) (P < .001). Potential predictive factors for LNs retrieved were grouped into modifiable (hospital type, surgeon, and surgical approach [laparoscopic vs open]) and nonmodifiable (age, sex, and tumor location). On multivariate analysis of the factors, hospital type was the only modifiable factor predictive of LNs reported (P < .001). CONCLUSIONS: Our study is the first, to our knowledge, to demonstrate that the number of LNs removed in colectomies performed by the same 2 surgeons depends on the hospital type (NCCN vs community) in which the resection occurred. We postulate that the number of LNs retrieved may be related to the institution's pathological review in addition to the extent of surgical resection.

Effectiveness of decentralized community-based screening, detection, and treatment of breast cancer in low-income, uninsured women.

Different systems exist currently in the provision of breast care to low-income, uninsured women. We assessed the efficacy of screening, diagnosis, and treatment of breast cancer in this patient population through a decentralized network of providers. We retrospectively reviewed charts of all patients referred for evaluation and treatment under the Cancer Detection Program: Every Woman Counts (CDP:EWC), the California equivalent of the National Breast and Cervical Cancer Detection and Prevention Program, in a suburban area of Los Angeles County. A total of 972 CDP:EWC screening mammograms was performed in the Antelope Valley during a 7-year study period (2000 to 2007). Sixty-two screened women aged 40 to 64 years were referred for further evaluation. Breast cancer detection rate per screening mammogram was 0.8 per cent; 80 per cent were early-stage breast cancer. The majority of the women (nine of 15) underwent breast conservation surgery. The axilla was staged using sentinel lymph node dissection and/or axillary lymph node dissection. Adjuvant chemotherapy and radiation were administered to all eligible patients. Compliance with published practice guidelines was high. This suggests that a decentralized community-based network of providers may be an effective model to deliver breast care to a low-income, uninsured patient population.

Malignant phyllodes tumor of the breast: local control rates with surgery alone.

PURPOSE: Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. METHODS AND MATERIALS: We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. RESULTS: Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). CONCLUSIONS: Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.

Impact of a full-time preceptor on the institutional outcome of laparoscopic colectomy.

BACKGROUND: Laparoscopic assisted colectomy (LAC) is a difficult operation with long learning curves and conversion rates inversely proportional to the surgeon's experience. Methods to help train surgeons outside of residency or fellowship programs have been poorly analyzed. This study was undertaken to assess the impact of an experienced laparoscopic surgeon preceptor on the outcome of LAC in a single institution METHODS: In September 2004, a fellowship-trained laparoscopic surgeon joined our department of surgery. This surgeon served as a LAC preceptor for six inexperienced staff surgeons and four surgical oncology fellows. Clinical and pathologic data from all attempted LAC for the 22 months preceding the arrival of the trained laparoscopic surgeon were compared with those for the 18 months following the recruitment. RESULTS: Before the addition of the expert surgeon, 28 LAC were performed in our institution, compared with 63 during the preceptor program. These represented 59% and 95% of eligible operations for each time period, respectively (P = 0.005). Overall conversion rates before and after the preceptor's arrival decreased from 44% to 14%, respectively (P < 0.05). The chances of conversion were strongly affected by the presence or absence of the preceptor in the operating room (7% vs. 30%, respectively, P = 0.003). Overall complication rates, hospital stay, blood loss, operative time and number of lymph nodes retrieved were not affected by the presence of the preceptor. Operations completed laparoscopically resulted in significantly lower blood loss and length of stay compared with converted ones. CONCLUSIONS: A shared departmental preceptor can positively affect the institutional outcome of laparoscopic colectomy. This model may help improve training and patient care in inexperienced centers.