Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy.

BACKGROUND AND OBJECTIVES: Total mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients. METHODS: A retrospective cohort study of stage 1-3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch-and-wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group. RESULTS: One hundred seventy-one patients (Male 59%) were included with a median surveillance of 43 months. Twenty-nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups. CONCLUSION: A significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging.

Metachronous peritoneal metastases following curative resection for colon cancer: Understanding risk factors and patterns of recurrence.

BACKGROUND: A subset of metachronous colon cancer recurrence manifests as peritoneal metastases (PM). Risk factors for metachronous PM recurrence are not well-defined in patients with stage II or III colon cancers after curative resection and standard adjuvant treatments. METHODS: Population data from the California Cancer Registry for patients with Stage II or III colon cancer were collected between 2004 and 2012. Multivariate analysis was used to identify factors associated with metachronous PM. RESULTS: Of the 2077 patients with stage II or III colon cancer, female patients (odds ratio [OR] = 1.84, p = 0.02), T4 primary tumor (OR = 2.36, p = 0.02), mucinous (OR = 3.97, p < 0.01) or signet-ring histology (OR = 6.01, p = 0.01), and right-sided cancer (OR = 2.2, p < 0.01) were found with increased risk of metachronous isolated PM recurrence after curative resection. Median survival after diagnosis for patients without PM recurrence was 22 months, compared with 12 months for PM recurrence (p < 0.001). CONCLUSION: PM recurrence groups have a worse overall survival than patients with recurrent disease in other sites. A better understanding of the tumor biology and molecular characteristics of colon cancers likely to recur as PM is needed to explain behavior and identify potential targeted therapy.

Health-related quality of life and oncologic outcomes after surgery in older adults with colorectal cancer.

PURPOSE: Data regarding changes in functional status and health-related quality of life (HRQOL) before and after surgery are lacking. We identified colorectal cancer patients from the SEER-Medicare Health Outcomes Survey (MHOS) linked database to evaluate the association between HRQOL and survival. METHODS: HRQOL survey data captured physical/mental health, activities of daily living (ADLs), and medical comorbidities. Patients who underwent surgery with HRQOL surveys prior to cancer diagnosis and ≥ 1 year after diagnosis were selected. Patient, disease, and HRQOL measures were analyzed in regard to overall survival (OS), disease-specific survival (DSS), and non-DSS. RESULTS: Of 590 patients included, 55% were female, 75% were Caucasian, and 83% had colonic primary. Disease extent was localized for 52%, regional for 41%, and distant for 7%. Median OS was 83 months. Decreased OS was independently associated with age ≥ 75 (HR 1.7, p < 0.0001), male sex (HR 1.4, p = 0.011), advanced disease (regional-HR 2.0, p < 0.0001; distant-HR 7.0, p < 0.0001), and decreased mental HRQOL (HR 1.4, p = 0.005). Decreased DSS was independently associated with advanced disease (regional-HR 4.1, p < 0.0001; distant-HR 16.5, p < 0.0001) and rectal primary (HR 1.6, p = 0.047). Decreased non-DSS was independently associated with age ≥ 75 (HR 2.2, p < 0.0001), male sex (HR 1.4, p = 0.03), decreased mental HRQOL (HR 1.4, p = 0.02), and increased comorbidities (HR 1.4, p = 0.04). CONCLUSIONS: The potential overall survival benefit of oncologic surgery is diminished by declines in physical and mental health. Early identification of older surgical patients at risk for functional and HRQOL declines may improve survival following colorectal cancer surgery.

Robotic surgery trends in general surgical oncology from the National Inpatient Sample.

BACKGROUND: Robotic surgery is offered at most major medical institutions. The extent of its use within general surgical oncology, however, is poorly understood. We hypothesized that robotic surgery adoption in surgical oncology is increasing annually, that is occurring in all surgical sites, and all regions of the US. STUDY DESIGN: We identified patients with site-specific malignancies treated with surgical resection from the National Inpatient Sample 2010-2014 databases. Operations were considered robotic if any ICD-9-CM robotic procedure code was used. RESULTS: We identified 147,259 patients representing the following sites: esophageal (3%), stomach (5%), small bowel (5%), pancreas (7%), liver (5%), and colorectal (75%). Most operations were open (71%), followed by laparoscopic (26%), and robotic (3%). In 2010, only 1.1% of operations were robotic; over the 5-year study period, there was a 5.0-fold increase in robotic surgery, compared to 1.1-fold increase in laparoscopy and 1.2-fold decrease in open surgery (< 0.001). These trends were observed for all surgical sites and in all regions of the US, they were strongest for esophageal and colorectal operations, and in the Northeast. Adjusting for age and comorbidities, odds of having a robotic operation increased annually (5.6 times more likely by 2014), with similar length of stay (6.9 ± 6.5 vs 7.0 ± 6.5, p = 0.52) and rate of complications (OR 0.91, 95% CI 0.83-1.01, p = 0.08) compared to laparoscopy. CONCLUSIONS: Robotic surgery as a platform for minimally invasive surgery is increasing over time for oncologic operations. The growing use of robotic surgery will affect surgical oncology practice in the future, warranting further study of its impact on cost, outcomes, and surgical training.

Severe Immune-Mediated Colitis Induced by Checkpoint Inhibitors in an Adolescent With Lynch Syndrome.

Lynch syndrome is a hereditary colorectal cancer caused by mutations in DNA mismatch repair genes. Immune checkpoint therapies have shown promise in treating Lynch syndrome-associated cancers but can lead to immune-related adverse events, such as colitis. In this report, we present a severe case of immune-mediated colitis (IMC) induced by checkpoint inhibitors in a young patient with Lynch syndrome. This 20-year-old male with Lynch syndrome and a history of glioblastoma underwent dual checkpoint therapy, after initial treatment with systemic steroids. Despite this, his condition worsened, resulting in complications, such as toxic megacolon and small bowel obstruction. He was subjected to various treatments, including infliximab and vedolizumab, but ultimately required total abdominal colectomy with J-pouch creation. This case highlights the challenges of managing severe IMC in patients with Lynch syndrome. The patient's suboptimal response to standard treatments and the development of complications emphasizes the need for a better understanding and alternative therapeutic options for IMC. This case also calls into question whether a subset of patients with IMC should be "treated to target," even though the current standard of care for IMC is guided by symptom response, and if so, further research is necessary to identify potential therapeutic targets. Further research is also required to understand the mechanisms of IMC and develop effective treatment strategies tailored to patients with Lynch syndrome and immune-related adverse events.

First-In-Human Pilot PET Immunoimaging Study of 64Cu-Anti-Carcinoembryonic Antigen Monoclonal Antibody (hT84.66-M5A) in Patients with Carcinoembryonic Antigen-Producing Cancers.

Background: PET imaging using radiolabeled immunoconstructs shows promise in cancer detection and in assessing tumor response to therapies. The authors report the first-in-human pilot study evaluating M5A, a humanized anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb), radiolabeled with 64Cu in patients with CEA-expressing malignancies. The purpose of this pilot study was to identify the preferred patient population for further evaluation of this agent in an expanded trial. Methods: Patients with CEA-expressing primary or metastatic cancer received 64Cu-DOTA-hT84.66-M5A with imaging performed at 1 and 2 days postinfusion. 64Cu-DOTA-hT84.66-M5A PET scan findings were correlated with CT, MRI, and/or FDG PET scans and with histopathologic findings from planned surgery or biopsy performed postscan. Results: Twenty patients received 64Cu-DOTA-hT84.66-M5A. Twelve patients demonstrated positive images, which were confirmed in 10 patients as tumor by standard-of-care (SOC) imaging, biopsy, or surgical findings. Four of the 8 patients with negative imaging were confirmed as true negative, with the remaining 4 patients having disease demonstrated by SOC imaging or surgery. All 5 patients with locally advanced rectal cancer underwent planned biopsy or surgery after 64Cu-DOTA-hT84.66-M5A imaging (4 patients imaged 6-8 weeks after completing neoadjuvant chemotherapy and radiation therapy) and demonstrated a high concordance between biopsy findings and 64Cu-DOTA-hT84.66-M5A PET scan results. Three patients demonstrated positive uptake at the primary site later confirmed by biopsy and at surgery as residual disease. Two patients with negative scans each demonstrated complete pathologic response. In 5 patients with medullary thyroid cancer, 64Cu-DOTA-hT84.66-M5A identified disease not seen on initial CT scans in 3 patients, later confirmed to be disease by subsequent surgery or MRI. Conclusions: 64Cu-DOTA-hT84.66-M5A demonstrates promise in tumor detection, particularly in patients with locally advanced rectal cancer and medullary thyroid cancer. A successor trial in locally advanced rectal cancer has been initiated to further evaluate this agent's ability to define tumor extent before and assess disease response after neoadjuvant chemotherapy and radiotherapy. clinical trial.gov (NCT02293954).

Separation of color channels from conventional colonoscopy images improves deep neural network detection of polyps.

SIGNIFICANCE: Colorectal cancer incidence has decreased largely due to detection and removal of polyps. Computer-aided diagnosis development may improve on polyp detection and discrimination. AIM: To advance detection and discrimination using currently available commercial colonoscopy systems, we developed a deep neural network (DNN) separating the color channels from images acquired under narrow-band imaging (NBI) and white-light endoscopy (WLE). APPROACH: Images of normal colon mucosa and polyps from colonoscopies were studied. Each color image was extracted based on the color channel: red/green/blue. A multilayer DNN was trained using one-channel, two-channel, and full-color images. The trained DNN was then tested for performance in detection of polyps. RESULTS: The DNN performed better using full-colored NBI over WLE images in the detection of polyps. Furthermore, the DNN performed better using the two-channel red + green images when compared to full-color WLE images. CONCLUSIONS: The separation of color channels from full-color NBI and WLE images taken from commercially available colonoscopes may improve the ability of the DNN to detect and discriminate polyps. Further studies are needed to better determine the color channels and combination of channels to include and exclude in DNN development for clinical use.

Role of minimally invasive surgery for rectal cancer.

Rectal cancer is one of the most common malignancies worldwide. Surgical resection for rectal cancer usually requires a proctectomy with respective lymphadenectomy (total mesorectal excision). This has traditionally been performed transabdominally through an open incision. Over the last thirty years, minimally invasive surgery platforms have rapidly evolved with the goal to accomplish the same quality rectal resection through a less invasive approach. There are currently three resective modalities that complement the traditional open operation: (1) Laparoscopic surgery; (2) Robotic surgery; and (3) Transanal total mesorectal excision. In addition, there are several platforms to carry out transluminal local excisions (without lymphadenectomy). Evidence on the various modalities is of mixed to moderate quality. It is unreasonable to expect a randomized comparison of all options in a single trial. This review aims at reviewing in detail the various techniques in regard to intra-/perioperative benchmarks, recovery and complications, oncological and functional outcomes.

Surgical Smoke Exposure in Operating Room Personnel: A Review.

Importance: Smoke generated during surgical procedures has long been thought to be hazardous to hospital personnel; however, the degree of danger has yet to be determined. Observations: The dangers of surgical smoke are associated with the composition of the plume. Small-particulate matter is found in the smoke that is easily inhaled. Particulates deposit in the lungs, circulatory system, and other organs, which may cause numerous health problems. The smoke also contains many gaseous compounds known to cause cancer. The type of tissue and the form of cautery have been shown to alter the composition of the surgical smoke. Well-cited articles have asserted that daily inhaled surgical smoke could be equivalent to smoking dozens of cigarettes. Unsafe levels of cancer-causing compounds have been found in the smoke. However, there is no firm evidence that operating room personnel show increased cancer rates compared with the general population. Data implicating other forms of passively inhaled smoke, such as fumes associated with cooking and wood burning, are likely comparable to the smoke issued during surgical procedures. Most operating rooms do not require smoke evacuation, and the elimination techniques are variable. Most systems rely on dispersion and, possibly, mechanical evacuation and filtration. Newer electric filters show promise but require more development. Conclusions and Relevance: Surgical smoke is dangerous, but the severity of the risk has yet to be determined. Therefore, no safe level is known at this point. Efforts should be made to reduce and possibly eliminate smoke from the operating room. Research into cost-effective forms of smoke evacuation is necessary. Studies of respiratory and cancer sequelae of exposure to operating room smoke in personnel who have had long-term exposure to surgical smoke is also needed.

Ductal carcinoma in situ: size and resection volume predict margin status.

OBJECTIVES: There is strong evidence that breast conservation surgery (BCS) with negative margins for ductal carcinoma in situ (DCIS) is associated with low rates of recurrence. Our goal was to identify factors associated with positive margins in BCS for DCIS. METHODS: A retrospective database review identified 823 patients diagnosed with DCIS. The current analysis included 546 of those patients treated with BCS from 2000 to 2006 with complete data regarding tumor and lumpectomy dimensions. Variables analyzed included tumor size, lumpectomy volume, estrogen and progesterone receptor status, histologic subtype, grade, and age at diagnosis. χ analysis and t tests were used to identify factors that may predict positive margins. A multivariate regression model was developed to determine independent variables predictive of positive margin status. RESULTS: A total of 33% of specimens had positive margins. Lumpectomy volume, tumor size, nuclear grade (low vs. high), and number of slides positive for DCIS were all significant for positive margin status by bivariate analysis. On multivariate analysis, tumor size (P < 0.001; odds ratio, 2.37; 95% confidence interval, 1.712, 3.296) and resection volume (P = 0.0006; odds ratio, 0.48; 95% confidence interval, 0.318, 0.729) remained significantly associated with positive margin status. Age at diagnosis, histologic subtype, tumor grade, and estrogen and progesterone status all were not associated with margin status. CONCLUSIONS: Positive margins after BCS for DCIS are associated with larger lesions and a smaller volume of resection. With 33% of patients having positive margins, these data suggest that a more aggressive initial resection may avoid positive margins and thus lower the risk of recurrence or the need for additional surgery.

Cytotoxicity of Pseudomonas secreted exotoxins requires OxyR expression.

BACKGROUND: Nosocomial infections often lead to sepsis and multisystem organ failure in critically injured patients, including burn and trauma patients. A better understanding of the bacterial response to the host immune system is essential to develop better antimicrobials against pathogens. Pseudomonas aeruginosa combats host-initiated oxidant stress through expression of the transactivating factor, OxyR. Here we have tested the premise that OxyR regulates Pseudomonal cytotoxicity through secreted exotoxin production. MATERIALS AND METHODS: Wild-type P. aeruginosa (PAO1) and a deletion mutant lacking the oxyR gene (Delta oxyR) were grown for 18 h in Luria broth and the supernatant containing the secreted products was removed using centrifugation. Secreted proteins were isolated using ammonium sulfate precipitation. ER-MP20(+) myeloid progenitor cells were harvested from the bone marrow of C57Blk/6J mice. These cells were differentiated into dendritic cells and macrophages. Various concentrations (0-20 microg/100 microL) of the bacterial proteins were added to the medium and cells were allowed to differentiate for 7 days. Cellular viability was then assayed using a proliferation assay. These studies were repeated on two other macrophage cell lines, human U937 and murine P388D1. RESULTS: At a protein concentration of 5 microg/100 microL PAO1 supernatant protein, cellular proliferation was significantly reduced to 4.2 +/- 2.8% compared to untreated controls, while the DeltaoxyR supernatant protein remained at 103.3 +/- 4.0% of untreated controls (P < 0.05). Similar significant results were seen in the U937-, P388D1-, and ER-MP20(+)-derived macrophage cells. CONCLUSIONS: Taken together, our data indicate that OxyR regulates the secretion of potent cytotoxic factors by P. aeruginosa.

New perspectives for a new century: implications of pathogen responses for the future of antimicrobial therapy.

Although the discovery of new classes of antibiotics has lagged behind in the last three decades, the incidence of life-threatening nosocomial infections that are resistant to multiple antibacterial agents has increased steadily. Recent advances in bacterial pathogenicity through the identification of a number of virulence factors and the bacterial genetics behind it have opened the way to a clearer understanding of the pathogen-host relationship. Bacteria communicate with each other through specific signaling chemicals to act as a community rather than individual cells to achieve a critical density or a "quorum." Establishment of quorum is the initiating signal for turning on a variety of virulence factors essential for the pathogenicity and dissemination of pathogens through the host. Pathogenic bacteria use a variety of biochemical mediators, collectively called "virulence factors," to invade and attack host tissues and to avoid detection and elimination by the host immune system. Delineating the specific responses the host immune system elicits in response to specific virulence factors and quorum-sensing molecules is essential to the development of new diagnostic methods for early detection of an infection and the prognosis to a given antibacterial therapy. Identification of inhibitors of virulence factors will represent new antimicrobial therapeutic modalities, and this can be used synergistically with current antibiotic therapy because they act through independent prokaryotic pathways to inhibit bacterial growth and survival.