OBJECTIVE:To determine the prognostic significance of histologic type/subtype in a large series of patients with primary resected retroperitoneal sarcoma.
BACKGROUND:The histologic diversity and ...rarity of retroperitoneal sarcoma has hampered the ability to predict patient outcome.
METHODS:From a single-institution, prospective database, 675 patients treated surgically for primary, nonmetastatic retroperitoneal sarcoma during 1982 to 2010 were identified and histologic type/subtype was reviewed. Clinicopathologic variables were analyzed for association with disease-specific death (DSD), local recurrence (LR), and distant recurrence (DR).
RESULTS:Median follow-up for survivors was 7.5 years. The predominant histologies were well-differentiated liposarcoma, dedifferentiated liposarcoma, and leiomyosarcoma. Five-year cumulative incidence of DSD was 31%, and factors independently associated with DSD were R2 resection, resection of 3 or more contiguous organs, and histologic type. Five-year cumulative incidence for LR was 39% and for DR was 24%. R1 resection, age, tumor size, and histologic type were independently associated with LR; size, resection of 3 or more organs, and histologic type were independently associated with DR. Liposarcoma and leiomyosarcoma were associated with late recurrence and DSD (as long as 15 years from diagnosis). For solitary fibrous tumor, LR was uncommon (<10%), but early distant recurrence was common (36% at 5 years). Nomograms were developed to predict DSD, LR, and DR.
CONCLUSIONS:Histologic type/subtype is the most important independent predictor of DSD, LR, and DR in primary retroperitoneal sarcoma. Histology predicts the pattern and incidence of LR and DR and will aid in more accurate patient counseling and selection of patients for adjuvant therapy trials.
Tumors evade immune destruction by actively inducing immune tolerance through the recruitment of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg). We have previously described increased prevalence of ...these cells in pancreatic adenocarcinoma, but it remains unclear what mechanisms are involved in recruiting Tregs into the tumor microenvironment. Here, we postulated that chemokines might direct Treg homing to tumor. We show, in both human pancreatic adenocarcinoma and a murine pancreatic tumor model (Pan02), that tumor cells produce increased levels of ligands for the CCR5 chemokine receptor and, reciprocally, that CD4(+) Foxp3(+) Tregs, compared with CD4(+) Foxp3(-) effector T cells, preferentially express CCR5. When CCR5/CCL5 signaling is disrupted, either by reducing CCL5 production by tumor cells or by systemic administration of a CCR5 inhibitor (N,N-dimethyl-N-{{4-{2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl}amino}}benzyl-N,N-dimethyl-N- {{{4-{{{2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptan-8-ylcarbonyl}amino}}benzyl}}}tetrahydro-2H-pyran-4-aminiumchloride; TAK-779), Treg migration to tumors is reduced and tumors are smaller than in control mice. Thus, this study demonstrates the importance of Tregs in immune evasion by tumors, how blockade of Treg migration might inhibit tumor growth, and, specifically in pancreatic adenocarcinoma, the role of CCR5 in the homing of tumor-associated Tregs. Selective targeting of CCR5/CCL5 signaling may represent a novel immunomodulatory strategy for the treatment of cancer.
IMPORTANCE: Specialist palliative care benefits patients undergoing medical treatment of cancer; however, data are lacking on whether patients undergoing surgery for cancer similarly benefit from ...specialist palliative care. OBJECTIVE: To determine the effect of a specialist palliative care intervention on patients undergoing surgery for cure or durable control of cancer. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center randomized clinical trial conducted from March 1, 2018, to October 28, 2021. Patients scheduled for specified intra-abdominal cancer operations were recruited from an academic urban referral center in the Southeastern US. INTERVENTION: Preoperative consultation with palliative care specialists and postoperative inpatient and outpatient palliative care follow-up for 90 days. MAIN OUTCOMES AND MEASURES: The prespecified primary end point was physical and functional quality of life (QoL) at postoperative day (POD) 90, measured by the Functional Assessment of Cancer Therapy–General (FACT-G) Trial Outcome Index (TOI), which is scored on a range of 0 to 56 with higher scores representing higher physical and functional QoL. Prespecified secondary end points included overall QoL at POD 90 measured by FACT-G, days alive at home until POD 90, and 1-year overall survival. Multivariable proportional odds logistic regression and Cox proportional hazards regression models were used to test the hypothesis that the intervention improved each of these end points relative to usual care in an intention-to-treat analysis. RESULTS: A total of 235 eligible patients (median IQR age, 65.0 56.8-71.1 years; 141 male 60.0%) were randomly assigned to the intervention or usual care group in a 1:1 ratio. Specialist palliative care was received by 114 patients (97%) in the intervention group and 1 patient (1%) in the usual care group. Adjusted median scores on the FACT-G TOI measure of physical and functional QoL did not differ between groups (intervention score, 46.77; 95% CI, 44.18-49.04; usual care score, 46.23; 95% CI, 43.08-48.14; P = .46). Intervention vs usual care group odds ratio (OR) was 1.17 (95% CI, 0.77-1.80). Palliative care did not improve overall QoL measured by the FACT-G score (intervention vs usual care OR, 1.09; 95% CI, 0.75-1.58), days alive at home (OR, 0.87; 95% CI, 0.69-1.11), or 1-year overall survival (hazard ratio, 0.97; 95% CI, 0.50-1.88). CONCLUSIONS AND RELEVANCE: This randomized clinical trial showed no evidence that early specialist palliative care improves the QoL of patients undergoing nonpalliative cancer operations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03436290
Background
Metastatic disease is the leading cause of mortality in colorectal cancer. Resection of colorectal liver metastases, when possible, is associated with improved long-term survival and the ...possibility of cure. However, nationwide studies suggest that liver resection is under-utilized in the treatment of colorectal liver metastases. This study was undertaken to understand attitudes and practice patterns among medical oncologists in the Deep South.
Methods
A survey of medical oncologists in the states of Alabama, Mississippi, and the Florida panhandle was performed. Respondents were queried regarding perceptions of resectability and attitudes towards surgical referral.
Results
We received 63 responses (32% response rate). Fifty percent of respondents reported no liver surgeons in their practice area. Commonly perceived contraindications to liver resection included extrahepatic metastatic disease (72%), presence of > 4 metastases (72%), bilobar metastases (61%), and metastases > 5 cm (46%). Bilobar metastatic disease was perceived as a contraindication more frequently by non-academic medical oncologists (70% vs. 33%,
p
= 0.03).
Conclusions
Wide variations exist in perceptions of resectability and referral patterns for colorectal liver metastases among surveyed medical oncologists. There is a need for wider dissemination of resectability criteria and more liver surgeon involvement in the management of patients with colorectal liver metastases.
Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising ...from ADM, the associated transcriptional changes, and markers of disease progression.
Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq). Developmental trajectories were generated. Data were compared with gastric metaplasia, KrasG12D-induced neoplasia, and human pancreatitis. Results were confirmed by immunostaining and electron microscopy. KrasG12D was expressed in injury-induced ADM using several inducible Cre drivers. Surgical specimens of chronic pancreatitis from 15 patients were evaluated by immunostaining.
scRNA-seq of ADM revealed emergence of a mucin/ductal population resembling gastric pyloric metaplasia. Lineage trajectories suggest that some pyloric metaplasia cells can generate tuft and enteroendocrine cells (EECs). Comparison with KrasG12D-induced ADM identifies populations associated with disease progression. Activation of KrasG12D expression in HNF1B+ or POU2F3+ ADM populations leads to neoplastic transformation and formation of MUC5AC+ gastric-pit-like cells. Human pancreatitis samples also harbor pyloric metaplasia with a similar transcriptional phenotype.
Under conditions of chronic injury, acinar cells undergo a pyloric-type metaplasia to mucinous progenitor-like populations, which seed disparate tuft cell and EEC lineages. ADM-derived EEC subtypes are diverse. KrasG12D expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations and offers an alternative origin for tumorigenesis. This program is conserved in human pancreatitis, providing insight into early events in pancreas diseases.
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Single-cell RNA sequencing of lineage-traced acinar cells in metaplasia identifies a gastric pyloric-like transition and the formation of tuft and enteroendocrine cells. These populations are susceptible KrasG12D-induced transformation.
Rates of melanoma have dramatically increased among adolescents and young adults in recent years, particularly among young women. Exposure to ultraviolet radiation from intentional tanning practices ...is likely a major contributor to this epidemic. Southern and coastal regions have higher melanoma mortality rates among non-Hispanic whites in other parts of the U.S., yet little is known about tanning practices of adolescents and young adults in these regions. This study determines the prevalence and methods of intentional tanning utilized by an undergraduate population located on the United States' Gulf Coast.
Undergraduate students enrolled at a university on the Gulf Coast completed an online survey from March-April 2016, self-reporting their engagement, knowledge, and attitudes regarding outdoor tanning (OT), indoor tanning (IT) and spray tanning (ST). Univariate and multivariate analyses were performed to identify factors associated with tanning behaviors.
2668 undergraduates completed the survey. Of these, 64.9% reported OT tanning, 50.7% reported ever IT, and 21.2% reported ever ST.
In the largest study to date of intentional tanning behaviors of adolescents and young adults from coastal regions, we found high rates of intentional tanning behaviors. There was also significant engagement in spray tanning by this population, not previously reported for adolescents and young adults in a sample of this size. We also identified a high association between different tanning methods, indicating this population engages in multiple tanning behaviors, a phenomenon whose health consequences are not yet known.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The management and outcomes for patients with metastatic melanoma have been revolutionized by immunotherapy. This case report highlights the role of surgery as an adjuvant to systemic therapies when ...there is oligoprogressive disease. We describe a 74-year-old man with metastatic melanoma who initially had a complete radiographic response after dual agent immunotherapy but subsequently developed a large metastasis in the retroperitoneum. After multidisciplinary discussion, he underwent margin negative resection that required en bloc segmental resection of the infra-renal inferior vena cava. To our knowledge, this is the first reported resection of a melanoma metastasis in this location.
The active ingredient in sunless tanning products (STPs) is a simple sugar, dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed within the viable layers of skin and not ...fully contained within the stratum corneum. Additionally, spray tanning and other aerosolized application methods have increased the risk of internal exposure through mucous membranes and inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by‐product of fructose metabolism, and an excess of DHA in cells can induce advanced glycation end (AGE) products and oxidative stress. Therefore, exogenous and endogenous exposures to DHA may be harmful to cells, and it has already been demonstrated that exogenous exposure to DHA is cytotoxic in immortalized keratinocytes. Still, little is known about the exogenous DHA exposure effects on other skin components. In this study, we explore the effects of exogenous DHA exposure in a human melanoma cell line, A375P. Melanoma cells were sensitive to DHA and displayed a transient burst of reactive oxygen species within an hour of exposure. Cell cycle arrest at G2/M was observed within 24 h of exposure, and apoptosis, monitored by the cleavage of PARP‐1 and Caspase‐3, was detected within 72 h of exposure to DHA. Together, these demonstrate that exogenous exposure to DHA has cytotoxic effects in our selected cell model and indicates the need to further investigate the exogenous exposure effects of DHA in other relevant exposure models.
We present a case report wherein a 55-year-old female presented to our clinic with chronic nausea, vomiting, and dehydration in the setting of a complex past surgical history, including laparoscopic ...incisional hernia repair in 2007 with intraperitoneal TiMeshTM. She then developed chronic nausea and vomiting and was hospitalized numerous times for dehydration. Due to her ongoing symptoms, she was taken to the operating room for exploration. A large, firm, mobile mass was identified within a loop of small bowel and was found to be a large bezoar firmly attached to a piece of intraluminal mesh. She progressed well postoperatively and, on outpatient follow-up, her pre-operative abdominal symptoms had completely resolved. To our knowledge, this is the first reported case of gallstone-like bezoar formation around an intraluminal hernia mesh causing small bowel obstruction and chronic abdominal pain.
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