Correlation between lymph node size on pathology and metastatic disease in right-sided colon cancer: A retrospective review.

BACKGROUND: Identification of positive lymph nodes in colon cancer can significantly impact treatment. Few studies have examined the role of lymph node size in staging and prognosis. This study evaluated the relationship between lymph node size and lymph node metastases in right-sided colon cancer. METHODS: Retrospective chart review was performed for patients undergoing colectomy for right-sided colon cancer from 2015 to 2020 across a single multi-hospital health system. Patients under age 18 or who did not have invasive adenocarcinoma upon pathological examination were excluded. Primary endpoints assessed lymph node size and lymph node metastases. 572 patients were stratified by lymph node size; lymph nodes ≥5 mm (n = 308) were characterized as enlarged. RESULTS: All surgical specimens examined had adequate number of lymph nodes for staging. 33.9% of all specimens examined contained lymph node metastases. Patients with enlarged lymph nodes were significantly more likely to have lymph node metastases than those with normal-sized lymph nodes (p < 0.001). Enlarged lymph nodes were associated with advanced nodal staging. CONCLUSIONS: Patients with enlarged nodes were significantly more likely to have lymph node metastases than those with normal-sized lymph nodes. Further research to analyze these enlarged lymph nodes on radiologic imaging is warranted to determine the role of radiographic assessment of lymph node size during pre-operative staging.

Effect of Body Mass Index on Outcomes After Surgery for Perforated Diverticulitis.

BACKGROUND: Despite the increased adoption of minimally invasive techniques in colorectal surgery, an open resection with ostomy creation remains an accepted operation for perforated diverticulitis. In the United States, there is an increase in the rates of both morbid obesity and diverticular disease. Therefore, we wanted to explore whether outcomes for morbidly obese patients with diverticulitis are worse than nonmorbidly obese patients after open colectomy for diverticulitis. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2015, we identified adults with emergent admission for diverticulitis (International Classification of Diseases, Ninth Revision, code 562.11) with evidence of preoperative sepsis and intraoperative contaminated/dirty wound classification, in which a resection with ostomy (Current Procedural Terminology codes 44141, 44143, or 44144) was performed. We excluded cases with age >90 y, ventilator dependence, evidence of disseminated cancer and missing sex, race, body mass index, functional status, American Society of Anesthesiologists class, length of stay (LOS), or operative time data. Morbid obesity was defined as body mass index >35 kg/m2. Risk variables of interest included age, sex, race, medical comorbidities, requirement for preoperative transfusion, preoperative sepsis, and operative time. Outcomes of interest included LOS, 30-d postoperative complications, and mortality. Univariate and propensity scores with postmatching analyses were performed. RESULTS: A total of 2019 patients met inclusion and exclusion criteria, of which 413 (20.5%) were morbidly obese. Morbidly obese patients tended to be younger (mean 57.2 versus 62.6 y) and female (54.5% versus 45.5%). Morbidly obese patients also had higher rates of insulin-dependent diabetes (8.0% versus 4.2%), hypertension (60.1% versus 51.3%), renal failure (3.4% versus 1.5%), and higher American Society of Anesthesiologists class (class 4: 23.5% versus 19.6% and class 5: 1.45% versus 0.87%). Morbidly obese patient had no increase in 30-d mortality or LOS, but they had higher rates of superficial wound infection (9.0% versus 5.8%; P = 0.0259), deep wound infection (4.4% versus 1.9%; P = 0.0073), acute renal failure (4.8% versus 2.4%; P = 0.0189), postoperative septic shock (17.7% versus 12.1%; P = 0.0040), and return to the operating room (11.1% versus 6.4%; P = 0.0015). We identified 397 morbidly obese patients well matched by propensity score to 397 nonmorbidly obese patients. Conditional logistic regression showed no difference in LOS (median 12.9 versus 12.4 d; P = 0.4648) and no increased risk of 30-d mortality (P = 0.947), but morbid obesity was an independent predictor for return to the operating room (adjusted odds ratio: 27.09 [95% confidence interval: 2.68-274.20]; P = 0.005). CONCLUSIONS: This analysis of a large national clinical database demonstrates that morbidly obese patients presenting with perforated diverticulitis undergoing a Hartmann's procedure do not have increased mortality or LOS compared with nonobese patients. After adjusting for the effects of morbid obesity, morbidly obese patients had increased risk of return to operating room. Despite literature describing the many perioperative risks of obesity, our analysis showed only increased reoperation for obese patients with diverticulitis.

Venous thromboembolism in patients with cancer undergoing surgical exploration.

Malignancy and surgery are both independent risk factors for venous thromboembolism (VTE) events. The current NCCN guidelines recommend VTE prophylaxis for up to 28 days after major abdominal or pelvic surgery for malignancy. We set out to evaluate the rate and timing of VTEs among patients with gastric, pancreatic, colorectal, and gynecologic malignancies who underwent surgery. We performed a retrospective review of the NSQIP database (2005-2013) focusing on patients with gastric, colorectal, pancreatic, and gynecologic malignancies. Our primary endpoint was a diagnosis of VTE within 30 days of surgery. We analyzed 128,864 patients in this study. On multivariable analysis, patients with pre-operative sepsis (OR 2.36, CI 2.04-2.76, p < 0.001), disseminated cancer (OR 1.73, CI 1.55-1.92, p < 0.001), congestive heart failure (OR 1.69, CI 1.25-2.28, p = 0.001), gastric cancer (OR 1.3, CI 1.09-1.56, p = 0.004), and pancreatic cancer (OR 1.2, CI 1.03-1.30, p = 0.021) were more likely to have a VTE. Of patients who had a VTE event, 34% occurred after discharge from surgery (gastric: 25%, colorectal 34%, pancreatic 31%, gynecologic malignancy 42%). Our study demonstrates that patients who undergo an operation for malignancy with pre-operative sepsis, disseminated cancer, congestive heart failure, gastric cancer, or pancreatic cancer are more likely to develop a VTE within 30 days of their operation. Of those patients who developed a VTE, approximately one-third occurred after discharge during a 30 day post-operative period. This data supports that further studies are needed to determine the appropriate length of post-operative VTE chemoprophylaxis in patients with cancer.

High mobility group box-1 induces pro-inflammatory signaling in human nucleus pulposus cells via toll-like receptor 4-dependent pathway.

Intervertebral disc (IVD) degeneration (DD) is associated with low back pain, the leading cause of disability worldwide. Damage-associated molecular patterns (DAMPs) that contribute to inflammation and trigger DD have not been well characterized. Extracellular high mobility group box-1 (HMGB1) protein has been implicated as a potent DAMP and pro-inflammatory stimulus in the immune system. In this study, we show that HMGB1 and IL-6 levels increase in patients with advanced DD in comparison to early DD. This study further tested the hypothesis that HMGB1 promotes inflammatory signaling driving DD in human nucleus pulposus (NP) cells and tissue. Immunofluorescence and western blot analysis confirmed the expression of HMGB1 and its extracellular release by NP cells under cell stress. Gene expression and protein quantification indicate that HMGB1 stimulates the expression IL-6 and MMP-1 in a dose-dependent manner. The contributions of toll-like receptor (TLR) -2, -4 and receptor for advanced glycation end products (RAGE) as receptors mediating HMGB1 signaling was examined using small molecule inhibitors. Inhibition of TLR-4 signaling, with TAK-242, completely abrogated HMGB1 induced IL-6 and MMP-1 expression, whereas inhibition of TLR-2, with O-vanillin, or RAGE, with FPS-ZM1, had mild inhibitory effects. HMGB1 stimulation activated NF-ĸB signaling while TAK-242 co-treatment abrogated it. Lastly, effects of HMGB1 on matrix deposition was evaluated in a 3D culture system of human NP cells. These results implicate HMGB1 as a potent DAMP that promotes inflammation in NP cells and degradation of NP tissues. TLR4-HMGB1 axis is a potential major pathway to alleviate disc inflammation and mitigate DD. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Serum levels of the proinflammatory cytokine interleukin-6 vary based on diagnoses in individuals with lumbar intervertebral disc diseases.

BACKGROUND: Many intervertebral disc diseases cause low back pain (LBP). Proinflammatory cytokines and matrix metalloproteinases (MMPs) participate in disc pathology. In this study, we examined levels of serum cytokines and MMPs in human subjects with diagnoses of disc herniation (DH), spinal stenosis (SS), or degenerative disc disease (DDD) relative to levels in control subjects. Comparison between subjects with DH and those with other diagnoses (Other Dx, grouped from SS and DDD) was performed to elaborate a pathological mechanism based on circulating cytokine levels. METHODS: Study participants were recruited from a spine neurosurgery practice (n = 80), a back pain management practice (n = 27), or a control cohort (n = 26). Serum samples were collected before treatment and were assayed by multiplex assays for levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor-α, MMP-1, MMP-3, and MMP-9. Inflammatory and degradative mediator levels were compared for subjects with LBP and control subjects, by diagnosis and by treatment groups, controlling for effects of sex, age, and reported history of osteoarthritis. Spearman's correlation coefficient was used to examine relationships with age, body mass index (BMI), symptom duration, and smoking history. RESULTS: Serum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects. Participants with LBP due to Other Dx had significantly higher levels of IL-6 than DH and controls. Serum levels of MMP-1 were significantly lower in LBP subjects, specifically those with DH, than in control subjects. Positive correlations were found between IL-6 levels and BMI, symptom duration, and age. MMP-1 levels were positively correlated with age. CONCLUSIONS: The findings of the present clinical study are the results of the first examination of circulating cytokine levels in DDD and SS and provide evidence for a more extensive role of IL-6 in disc diseases, where patients with DDD or SS have higher serum cytokine levels than those with DH or control subjects. These findings suggest that LBP subjects have low-grade systemic inflammation, and biochemical profiling of circulating cytokines may assist in refining personalized diagnoses of disc diseases.

Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics.

Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repair, biomaterials, and tissue engineering. Findings on the effects of the omega-6 fatty acid, linoleic acid, on nucleus pulposus tissue engineering are presented. Studies described in this review provide greater insights into the pathogenesis of disc degeneration and may define new paradigms for early or differential diagnostics of degeneration using new techniques such as systemic biomarkers. In addition, research on the mechanobiology of disease enriches the development of therapeutics for disc repair, with potential to diminish pain and disability associated with disc degeneration.