Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study.

BACKGROUND: The reverse treatment of patients with synchronous colorectal liver metastases (CRLM) is a sequential approach with systemic chemotherapy first, followed by liver resection, and finally, primary tumor resection. The aim of this study was to assess the feasibility, the radiological and pathological tumor response to neoadjuvant therapy, recurrence rates and long-term survival after reverse treatment in a cohort study. METHODS: Data from patients with CRLM who underwent a reverse treatment from August 2008 to October 2016 were extracted from our prospective hepato-biliary database and retrospectively analyzed for response rates and survival outcomes. Radiological tumor response was assessed by RECIST (Response Evaluation Criteria In Solid Tumor) criteria and pathological response according to TRG (Tumor Regression Grade). Disease-free and overall survival were estimated with Kaplan-Meier survival curves. RESULTS: There were 44 patients with 19 rectal and 25 colonic tumors. The reverse treatment was fully completed until primary tumor resection in 41 patients (93%). Radiological assessment after chemotherapy showed 61% of complete/partial response. Pathological tumor response was major or partial in 52% of patients (TRG 1-3). Median disease-free survival after primary tumor resection was 10 months (95% CI 5-15 months). Disease-free survival at 3 and 5 years was 25% and 25%, respectively. Median overall survival was 50 months (95% CI 42-58 months). Overall survival at 3 and 5 years was 59% and 39%, respectively. CONCLUSION: The reverse treatment approach was feasible with a high rate of patients with complete treatment sequence and offers promising long-term survival for selected patients with advanced simultaneous colorectal liver metastases.

Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement.

T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers.

Response of locally advanced rectal cancer (LARC) to radiochemotherapy: DW-MRI and multiparametric PET/CT in correlation with histopathology.

AIM: To prospectively evaluate histological significance and predictive value of changes in apparent diffusion coefficient (ADC) and 18F-FDG PET/CT parameters in locally advanced rectal cancer (LARC) after neoadjuvant radiochemotherapy (RCT). METHODS: Twenty-one patients with untreated LARC underwent pre-RCT and post-RCT 18F-FDG PET/CT and diffusion-weighted magnetic resonance imaging (DW-MRI), followed by surgery. For both datasets, two readers measured the tumor SUVmax, SUVmean, MTV, TLG, ADCmin, ADCmean, and respective differences (∆SUVmax, ∆SUVmean, ∆MTV, ∆TLG, ∆ADCmin, ∆ADCmean) for the whole tumor. Tumor regression grade according to Mandard (TRGm), percentage of residual tumor cells and fibrosis were estimated by two pathologists in consensus. Relationship between parameters was assessed on stepwise multivariate regression analysis and ROC curve analysis to evaluate their performance and predict the treatment response. RESULTS: Eighteen LARCs were analyzed. SUVmax and SUVmean decreased from 21.3 ±â€…8.9 to 9.3 ±â€…5.5 g/mL, (p = 0.0002) and 12.3 ±â€…5.1 to 5.4 ±â€…3.1 g/mL, (p = 0.0002), respectively, after RCT, whereas ADCmin and ADCmean increased from 396 ±â€…269 to 573 ±â€…313×10-6 mm2/s (p = 0.014) and 1159 ±â€…212 to 1355 ±â€…194×10-6 mm2/s (p = 0.0008), respectively. TRGm and percentage of residual tumor cells independently correlated with post-RCT SUVmean (ß = 0.73 and ß = 0.76, p < 0.001) and post-RCT SUVmax (ß = 0.72 and ß = 0.78, p < 0.001), whereas percentage of fibrosis independently correlated with ∆ADCmean (ß = 0.38, p = 0.008). Post-RCT, SUVmax and SUVmean performed well in predicting TRGm < 3 and residual tumor cells ≤ 20 %. ΔADCmean predicted fibrosis > 70 % well. CONCLUSION: Post-RCT SUVmean, SUVmax and ∆ADCmean are complementary parameters for respectively evaluating residual tumor burden and amount of fibrosis in LARC. However, only SUV independently correlated with TRGm.

Bacillus cereus bacteremia with central nervous system involvement: A neuropathological study.

Bacillus cereus is a widely-distributed, gram-positive or variable, rod-shaped bacterium frequently considered a contaminant in clinical specimens. It is recognized as a potential pathogen inducing self-limiting emetic or diarrheal food poisoning or localized infection in immunocompetent patients. True B. cereus bacteremia is uncommon and mainly observed in fragile patients, notably in immunocompromised individuals. We report clinical, radiological, and pathological findings of a 64-year-old patient with a history of acute myeloid leukemia who initially presented a fever while neutropenic after the induction of a second cycle of chemotherapy. He developed B. cereus bacteremia with invasive infection and a fatal outcome. The clinical and radiological data of this case are compared to a previously-published series of 21 patients from our institution with B. cereus bacteremia. This study highlights the clinical challenge to diagnose B. cereus and the importance of the delay between the detection of B. cereus and the initiation of an effective targeted antibiotic therapy. This case presented an aggressive evolution with multiple necrotic and hemorrhagic foci in the brain. Upon histological examination, B. cereus virulence was notably reflected by the dissection of blood vessel walls by the bacilli and luminal occlusion, a pattern that has not been yet reported.
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Papillary thyroid carcinoma with nodular fasciitis-like stroma and ß-catenin mutations should be renamed papillary thyroid carcinoma with desmoid-type fibromatosis.

Various histological variants of papillary thyroid carcinoma have been reported, some with clinical implications, some with peculiar, sometimes misleading morphologies. One of these rare and poorly characterized variants is papillary thyroid carcinoma with nodular fasciitis-like stroma, of which fewer than 30 cases have been documented, mostly as isolated reports. It is a dual tumor comprising a malignant epithelial proliferation that harbors typical features of conventional papillary thyroid carcinoma, admixed with a prominent mesenchymal proliferation resembling nodular fasciitis or fibromatosis. Thus, the terms papillary thyroid carcinoma with nodular fasciitis-like stroma and papillary thyroid carcinoma with fibromatosis-like stroma are used interchangeably; however, the former term suggests a self-limited and regressing disease, whereas the latter one suggests a recurrent and potentially aggressive one. Better genetic and ultrastructural characterization could lead to more appropriate terminology and management. We performed detailed clinicopathological and molecular analyses of two cases of PTC with prominent mesenchymal proliferation that developed in the thyroid gland of two male patients aged 34 and 48. In both cases, the epithelial component harbored a heterozygous somatic activating BRAF mutation (p.V600E). Also, in both cases, the mesenchymal component showed typical aberrant nuclear and cytoplasmic immunoreactivity for ß-catenin and harbored a heterozygous somatic activating mutation in the corresponding CTNNB1 gene (p.S45P). This mutation has never been reported in thyroid stroma; in other tissues, it is typical of desmoid-type fibromatosis rather than nodular fasciitis-like stroma. We therefore propose that in cases of papillary thyroid carcinoma with a prominent mesenchymal component, mutations in CTNNB1 should be sought; when they are present, the term 'papillary thyroid carcinoma with desmoid-type fibromatosis' should be used. As the mesenchymal component of these tumors is not expected to concentrate radioactive iodine, special considerations apply to clinical evaluation and follow-up, which should be brought to the attention of the treating specialist.

Very long-lasting remission of refractory T-large granular lymphocytes leukemia and myeloma by lenalidomide treatment.

BACKGROUND: Large granular lymphocyte leukemias (LGLLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating from either mature T cells (CD3+) or natural killer (NK) cells (CD3-). Both T-cell and NK-cell LGL leukemia can manifest as indolent or aggressive neoplasia. These rare lymphoproliferative disorders are often associated with autoimmune diseases and impaired hematopoiesis. Symptomatic patients are treated with immunosuppressive drugs. The co-association of T-LGLL with clonal B-cell disorders is reported in more than 10% of patients. CASE PRESENTATION: We describe the case of a 57-yr-old white male patient with no history of autoimmune disorders, with refractory T-LGLL and myeloma who was treated with bortezomib and subsequently with lenalidomide. After 30 months of on-going lenalidomide therapy, the patient is in partial remission from myeloma and in continuous complete hematological remission from T-LGLL. CONCLUSIONS: As far as we know, this is the first report of a patient with refractory T-LGLL treated with bortezomib and lenalidomide. As refractory T-LGLL is a challenging condition, we think that lenalidomide and bortezomib deserve further investigation.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions.

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding that, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.