Abstract Background The optimal treatment of small bowel adenocarcinoma is unknown. Methods The records of 491 patients with small bowel adenocarcinoma diagnosis between 1970 and 2005 were reviewed ...for patient and tumor characteristics, treatment effects, and survival. Results The median age at diagnosis was 62 years. The most common tumor locations were the duodenum (57%), jejunum (29%), and ileum (10%). The median overall survival was 20.1 months, with a 5-year overall survival of 26%. Greater age, male sex, higher stage and grade, residual disease after resection, and a lymph node ratio of 50% or greater predicted decreased overall survival in univariate analysis. Age and stage were predictive of survival in multivariate analysis. The overall survival with metastatic disease was poor. Adjuvant therapy was not associated with longer overall survival ( P = .44). Conclusions The prognosis of patients with small bowel adenocarcinoma is poor. Complete resection provides the only means of cure, and the role for adjuvant therapy remains uncertain.
Encouraging family forest owners to create early successional habitat is a high priority for wildlife conservation agencies in the northeastern USA, where most forest land is privately owned. Many ...studies have linked regional declines in wildlife populations to the loss of early successional habitat. The government provides financial incentives to create early successional habitat, but the number of family forest owners who actively manage their forests remains low. Several studies have analyzed participation of family forest owners in federal forestry programs, but no study to date has focused specifically on creation of wildlife habitat. The objective of our study was to analyze the experience of a group of wildlife-oriented family forest owners who were trained to create early successional habitat. This type of family forest owners represents a small portion of the total population of family forest owners, but we believe they can play an important role in creating wildlife habitat, so it is important to understand how outreach programs can best reach them. The respondents shared some characteristics but differed in terms of forest holdings, forestry experience and interest in earning forestry income. Despite their strong interest in wildlife, awareness about the importance of early successional habitat was low. Financial support from the federal government appeared to be important in motivating respondents to follow up after the training with activities on their own properties: 84% of respondents who had implemented activities received federal financial support and 47% would not have implemented the activities without financial assistance. In order to mobilize greater numbers of wildlife-oriented family forest owners to create early successional habitat we recommend focusing outreach efforts on increasing awareness about the importance of early successional habitat and the availability of technical and financial assistance.
In their comment, Desjarlais
claim that a small temperature drop occurs after isentropic compression of fluid deuterium through the first-order insulator-metal transition. We show that their ...calculations do not correspond to the experimental thermodynamic path, and that thermodynamic integrations with parameters from first-principles calculations produce results in agreement with our original estimate of the temperature drop.
BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO ...pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.
To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma.
We performed a retrospective ...review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT.
Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio RR = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001).
This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.
Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node ...dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + T
cell expansion associated with favorable pathologic responses (exploratory outcome).
Laser-driven shock compression experiments reveal the presence of a phase transition in MgSiO(3) over the pressure-temperature range 300-400 GPa and 10 000-16 000 K, with a positive Clapeyron slope ...and a volume change of ∼6.3 (±2.0) percent. The observations are most readily interpreted as an abrupt liquid-liquid transition in a silicate composition representative of terrestrial planetary mantles, implying potentially significant consequences for the thermal-chemical evolution of extrasolar planetary interiors. In addition, the present results extend the Hugoniot equation of state of MgSiO(3) single crystal and glass to 950 GPa.
By combining diamond-anvil-cell and laser-driven shock wave techniques, we produced dense He samples up to 1.5 g/cm(3) at temperatures reaching 60 kK. Optical measurements of reflectivity and ...temperature show that electronic conduction in He at these conditions is temperature-activated (semiconducting). A fit to the data suggests that the mobility gap closes with increasing density, and that hot dense He becomes metallic above approximately 1.9 g/cm(3). These data provide a benchmark to test models that describe He ionization at conditions found in astrophysical objects, such as cold white dwarf atmospheres.
Malignant melanoma is an aggressive, therapy-resistant malignancy of melanocytes. The incidence of melanoma has been steadily increasing worldwide, resulting in an increasing public health problem. ...Exposure to solar UV radiation, fair skin, dysplastic nevi syndrome, and a family history of melanoma are major risk factors for melanoma development. The interactions between genetic and environmental risk factors that promote melanomagenesis are currently the subject of ongoing research. Avoidance of UV radiation and surveillance of high-risk patients have the potential to reduce the population burden of melanoma. Biopsies of the primary tumor and sampling of draining lymph nodes are required for optimal diagnosis and staging. Several clinically relevant pathologic subtypes have been identified and need to be recognized. Therapy for early disease is predominantly surgical, with a minor benefit noted with the use of adjuvant therapy. Management of systemic melanoma is a challenge because of a paucity of active treatment modalities. In the first part of this 2-part review, we discuss epidemiology, risk factors, screening, prevention, and diagnosis of malignant melanoma. Part 2 (which will appear in the April 2007 issue) will review melanoma staging, prognosis, and treatment.
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