BackgroundImmune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. With the exception of a few candidate biomarkers, the prognostic role of soluble immune ...checkpoint-related proteins in clear cell renal cell cancer (ccRCC) patients is largely uninvestigated.MethodsWe profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay. Gene expression in tumors from a subset of participating patients (n = 47) and another 533 primary ccRCC from TCGA were analyzed to elucidate potential mechanisms. Our primary endpoint is overall survival; secondary endpoint is recurrence-free survival. Multivariate Cox proportional hazard model, unconditional logistic regression model, and Kaplan-Meier analysis were applied in the study.ResultssTIM3 and sLAG3 were significantly associated with advanced (stage III) disease (P < 0.05). sPD-L2 was the strongest predictor of recurrence (HR 2.51, 95%CI 1.46–4.34, P = 9.33E-04), whereas high sBTLA and sTIM3 was associated with decreased survival (HR 6.02, 95%CI 2.0–18.1, P = 1.39E-03 and HR 3.12, 95%CI 1.44–6.75, P = 3.94E-03, respectively). Risk scores based on sTIM3 and sBTLA indicated that the soluble immune checkpoint-related proteins jointly predicted recurrence and death risks of ccRCC (P = 0.01 and 4.44E-04, respectively). Moreover, sLAG3 and sCD28 were found negatively correlated with cytolytic activity of T cells in tumors (rho = −0.31 and − 0.33, respectively).ConclusionsOur study provides evidence that soluble immune checkpoint-related proteins may associate with advanced disease, recurrence and survival in ccRCC patients, which highlights the prognostic values of soluble immune checkpoint-related proteins. Future independent validation in prospective studies is warranted.
BACKGROUND:The authors prospectively evaluated the efficacy of lymphovenous bypass in patients with lymphedema secondary to cancer treatment.
METHODS:The authors prospectively enrolled 100 ...consecutive patients with extremity lymphedema secondary to cancer treatment. Sixty-five patients underwent lymphovenous bypass with indocyanine green fluorescent lymphangiography. Evaluation included qualitative assessment and quantitative volumetric analysis before and 3, 6, and 12 months after bypass.
RESULTS:Lymphovenous bypass was performed in 89 upper extremities and 11 lower extremities. For upper extremity lymphedemas, the mean preoperative volume differential was 32 percent. Symptom improvement was reported by 96 percent of patients and quantitative improvement was noted by 74 percent. The overall mean volume differential reduction was 33 percent at 3 months, 36 percent at 6 months, and 42 percent at 12 months after surgery. The mean volume differential reductions at 3, 6, and 12 months after lymphovenous bypass in patients with stage 1 or 2 lymphedema (58, 52, and 61 percent, respectively) were significantly larger than those in the patients with stage 3 or 4 lymphedema (12, 16, and 17 percent, respectively). Eleven bypasses were performed in seven patients with lower extremity lymphedema, with a mean preoperative volume differential of 38 percent. Only four (57 percent) of these patients reported symptom improvement; postoperative volume measurements were available for only two of these four.
CONCLUSIONS:Lymphovenous bypass can be effective in reducing lymphedema severity, particularly in patients with early-stage upper extremity lymphedema. Indocyanine green lymphangiography accurately identified functional lymphatic vessels and may have a role in objectively assessing lymphedema severity and patient selection.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.
OBJECTIVE:A comprehensive literature review of VLNT with updates and comparisons on current application, techniques, results, studies and possible future implications.
BACKGROUND:Lymphedema is a ...debilitating condition that often results secondary to treatment of cancer. Unfortunately there is no cure. However, microsurgical procedures such as VLNT has gained popularity as there have been increasing reports that VLNT may help alleviate the severity of lymphedema.
METHODS:A review of literature was conducted over major medical indices (PubMed-MEDLINE, Factiva, Scopus, Sciencedirect, EMBASE). Search terms were focused on vascularized, lymph node transfer (also autologous, lymph node transplant) to cover both human and animal studies. Each study was verified for the nature of the procedure; a free microsurgical flap containing lymph nodes for the purpose of relieving lymphedema.
RESULTS:There are human and animal studies that individually report clear benefits, but because of methodological shortcomings comparative studies with uniform patient selection and monitoring are lacking.
CONCLUSIONS:Although the results with the use of VLNT for treatment of lymphedema have been largely positive, further exploration into standardized protocols for diagnosis, treatment optimization, and patient outcomes assessment is needed.
There is accumulating anecdotal evidence that anosmia and dysgeusia are associated with the COVID-19 pandemic. To investigate their relationship to SARS-CoV2 infection, the American Academy of ...Otolaryngology-Head and Neck Surgery developed the COVID-19 Anosmia Reporting Tool for Clinicians for the basis of this pilot study. This tool allows health care providers to confidentially submit cases of anosmia and dysgeusia related to COVID-19. We analyzed the first 237 entries, which revealed that anosmia was noted in 73% of patients prior to COVID-19 diagnosis and was the initial symptom in 26.6%. Some improvement was noted in 27% of patients, with a mean time to improvement of 7.2 days in this group (85% of this group improved within 10 days). Our findings suggest that anomia can be a presenting symptom of COVID-19, consistent with other emerging international reports. Anosmia may be critical in timely identification of individuals infected with SARS-CoV2 who may be unwittingly transmitting the virus.
Lymphedema is a common and debilitating condition. Management options for lymphedema are limited and controversial. The purpose of this prospective study was to provide a preliminary analysis of ...lymphaticovenular bypass for the treatment of upper limb lymphedema in breast cancer patients.
Twenty patients with upper extremity lymphedema secondary to treatment of breast cancer underwent lymphaticovenular bypass using a "supermicrosurgical" approach. The mean age of the patients was 54 years, 16 patients had received preoperative radiation therapy, and all patients had received axillary lymph node dissection. The mean duration of lymphedema was 4.8 years, and the mean volume differential of the lymphedematous arm compared with the unaffected arm was 34 percent. Evaluation included qualitative assessment and quantitative volumetric analysis before surgery and at 1 month, 3 months, 6 months, and 1 year after the procedure.
The mean number of bypasses performed per patient was 3.5 (range, two to five), and the size of bypasses ranged from 0.3 to 0.8 mm. The mean operative time was 3.3 hours (range, 2 to 5 hours). Hospital stay was less than 24 hours for all patients. The mean follow-up time was 18 months. Nineteen patients (95 percent) reported symptom improvement following surgery, and 13 patients had quantitative improvement. The mean volume differential reduction was 29 percent at 1 month, 36 percent at 3 months, 39 percent at 6 months, and 35 percent at 1 year. No patients experienced postoperative complications or lymphedema exacerbation.
Lymphaticovenular bypass may effectively reduce the severity of lymphedema in breast cancer patients. Long-term analysis is needed.
Molecular subtypes of pancreatic cancer Collisson, Eric A; Bailey, Peter; Chang, David K ...
Nature reviews. Gastroenterology & hepatology,
04/2019, Letnik:
16, Številka:
4
Journal Article
Recenzirano
Cancers that appear morphologically similar often have dramatically different clinical features, respond variably to therapy and have a range of outcomes. Compelling evidence now demonstrates that ...differences in the molecular pathology of otherwise indistinguishable cancers substantially impact the clinical characteristics of the disease. Molecular subtypes now guide preclinical and clinical therapeutic development and treatment in many cancer types. The ability to predict optimal therapeutic strategies ahead of treatment improves overall patient outcomes, minimizing treatment-related morbidity and cost. Although clinical decision making based on histopathological criteria underpinned by robust data is well established in many cancer types, subtypes of pancreatic cancer do not currently inform treatment decisions. However, accumulating molecular data are defining subgroups in pancreatic cancer with distinct biology and potential subtype-specific therapeutic vulnerabilities, providing the opportunity to define a de novo clinically applicable molecular taxonomy. This Review summarizes current knowledge concerning the molecular subtyping of pancreatic cancer and explores future strategies for using a molecular taxonomy to guide therapeutic development and ultimately routine therapy with the overall goal of improving outcomes for this disease.
OBJECTIVE:The aim of this study was to examine the long-term impact of physiologic surgical options, including vascularized lymph node transplant (VLNT) and lymphovenous bypass (LVB), on patients ...with secondary lymphedema of the upper or lower extremity (UEL/LEL).
SUMMARY BACKGROUND DATA:VLNT and LVB have become increasingly popular in the treatment of lymphedema. However, there is a paucity of long-term data on patient outcomes after use of these techniques to treat lymphedema.
METHODS:An analysis of prospectively collected data on all patients who underwent physiologic surgical treatment of secondary lymphedema over a 5.5-year period was performed. Patient demographics, surgical details, subjective reported improvements, Lymphedema Life Impact Scale (LLIS) scores, and postoperative limb volume calculations were analyzed.
RESULTS:274 patients with secondary lymphedema (197 upper, 77 lower) were included in the study. More than 87% of UEL patients and 60% of LEL patients had reduction in excess limb volume postoperatively. At 3 months postoperatively, patients with UEL had a 31.1% reduction in volume difference between limbs, 33.9% at 6 months, 25.7% at 12 months, 47.4% at 24 months and 47.7% at 4 years. The reduction in limb volume difference followed a similar pattern but was overall lower for LEL patients. Greater than 86% of UEL and 75% of LEL patients also had improvement in LLIS scores post-operatively. 59 complications occurred (12.9%); flap survival was >99%.
CONCLUSION:Patients with secondary UEL/LEL who undergo VLNT/LVB demonstrate improved functional status and reduced affected limb volumes postoperatively. Patients with UEL appear to have a more substantial reduction in limb volume differential compared to LEL patients.
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