Patients with atherosclerotic peripheral arterial disease have a high risk of lung cancer: Systematic review and meta-analysis of literature.

PURPOSE: Lung cancer and atherosclerosis share common risk factors. Literature data suggest that the prevalence of lung malignancy in patients with peripheral arterial disease (PAD) is higher than in the general population. Our goal was to determine, through a systematic literature review, the prevalence of lung cancer in patients with PAD. METHODS: We consulted available publications in the Cochrane library, MEDLINE, PUBMED, EMBASE, and ClinicalTrials.gov. We included all articles, written in English or French, published between 1990 and 2020 reporting the prevalence of lung cancer in patients with PAD (atherosclerotic aortic aneurysm or peripheral occlusive diseases). Patients with coronary artery disease, cardiac valvulopathy or carotid stenosis were not included. We did not include case reports. We performed a critical analysis of each article. Data were collected from two independent readers. A fixed effect model meta-analysis allowed to estimate a summary prevalence rate. RESULTS: We identified 303 articles, and selected 19 articles according to selection criteria. A total of 16849 patients were included (mean age 68.3 years, 75.1% of males). Aortic aneurysms were found in 29% of patients and atherosclerotic occlusive disease in 66% of patients. Lung cancer was identified in 538 patients, representing a prevalence of 3%. DISCUSSION: Lung cancer is found in 3% of patients with atherosclerotic PAD. This prevalence is higher than that found in lung cancer screening programs performed in the general population of smokers and former smokers. These patients should be screened for lung cancer. Their selection may dramatically increase the benefit of lung cancer screening.

Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non-small-cell lung carcinoma.

BACKGROUND: Radiotherapy is a standard of care for locally advanced stage III N2 non-small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonstrated if immune cells are necessary to drive radiotherapy efficacy and predict patient's survival. PATIENTS AND METHODS: We retrospectively analysed tumour samples and clinical data from 113 patients, 89 resected (PORT) and 24 non-resected (DRC) N2-NSCLC treated with chemotherapy and radiotherapy (same radiotherapy department from 2002 to 2015). The immune environment was characterised with in situ multiplex staining (CD8, FoxP3, PD-L1 and cytokeratin) and correlated with clinical data and survival. RESULTS: High density of CD8+ T cells was associated with OS (p = 0.04, HR = 1.93 [0.99-3.78]) and DFS (p = 0.003, HR = 2.42 [1.31-4.47]) in the PORT. High density of CD8+/FoxP3+ double positive cells was associated with OS (p = 0.01, HR = 1.97 [1.11-3.48]) in the whole population, with OS (p = 0.05, HR = 1.92 [0.98-3.74]) and PFS (p = 0.03, HR = 1.83 [1.03-3.23]) in the PORT without reaching significance for the DRC. Intermediate PD-L1 expression in tumour cells (TPS = 1-49%) was associated with a higher survival in the PORT. CONCLUSIONS: Intra-tumoural CD8+ T cell and particularly CD8+/FoxP3+ double positive T cell densities predict survival in stage III N2-NSCLC suggesting the need for a pre-existing intra-tumour immunity to mediate the action of radiotherapy. Density of CD8+/FoxP3+ cells was the best predictor of patient's survival in multivariate analysis and could represent a biomarker of radiotherapy efficacy.

[Anal and vulvar hidradenoma papilliferum are similar: A study of 14 cases]. / Les hidradénomes papillifères de l'anus ressemblent à ceux de la vulve : étude de 14 cas.

INTRODUCTION: Hidradenoma papilliferum (HP) is an adenomatous proliferation of mammary-like glands. These glands are located preferentially on the vaginal labia, the perineum and the anal skin. About ninety percent of HP occur on the vulva, with anal localization being much less common. AIM OF THE STUDY: To analyze the clinical and histological characteristics of anal HP and compare them to those seen on the vulva based on the literature. METHOD: A monocentric retrospective analysis (in the medical and surgical proctology department of the Saint-Joseph Hospital Group, Paris) of patients for whom a diagnosis of anal HP was made based on pathological analysis of a resected sample. RESULTS: A total of 14 female patients were included between 2012 and 2018. The mean age was 48.2 years (22-70). The tumor, single in all cases, was asymptomatic with very slow progression. It was located on the anal skin in all patients. It generally consisted of a round nodule measuring under 1cm that was barely prominent, translucent, depressible and mobile. In 15% of patients the tumor was ulcerated. Histologically, the tumor displayed the usual characteristics of HP. Only one relapse was seen, six years after resection. CONCLUSION: The clinical and histological aspects of anal HP are the same as those of the vulva, which are better documented, namely a small, rounded, pink, translucent or bluish, and mobile tumor, with a smooth surface, and more rarely ulceration or budding, and in most cases asymptomatic. All HP were diagnosed in women and were located at the anal margin. Histopathological examination of an excised sample confirms the diagnosis and rules out a malignant tumor. The frequency of anal HP may be underestimated.

[When to ask for a skin biopsy in a patient with leg ulcer? Retrospective study of 143 consecutive biopsies]. / Quand poser l'indication d'une biopsie cutanée chez un patient porteur d'ulcère de jambe ? Étude rétrospective sur 143 biopsies consécutives.

OBJECTIVE: A vascular cause is found in around 85% of leg ulcer patients, but non-vascular causes are also observed. Their diagnosis is based on a set of clinical arguments and skin biopsy with histological analysis. The aim of this study was to analyze the results of these biopsies and to find common criteria for ulcers whose skin biopsies had led to the diagnosis of a non-vascular ulcer. MATERIAL AND METHOD: A retrospective study was carried out on the analysis of 143 skin biopsies of leg ulcers. The reasons for the biopsy were mainly atypical clinical signs and/or the lack of improvement in care after 6 months, as advocated by the French health authorities. RESULTS: The skin biopsies led to a diagnosis of non-vascular ulcer in 4.9% of cases (7/143), including skin cancer (n=5, 3.5%), cutaneous leishmaniasis (n=1, 0.7%) and Pyoderma gangrenosum (n=1, 0.7%). The univariate statistical analysis revealed that an elevated rim and abnormal excessive granulation tissue were significantly more frequently found in these ulcers. All patients with a positive skin biopsy had associated vascular involvement. CONCLUSION: This study found a 5% rate of non-vascular causes of ulcers, mainly skin cancer. Elevated rims and abnormal excessive granulation tissue were the unusual features most commonly found in these ulcers. All patients whose skin biopsy revealed a non-vascular cause had associated vascular involvement. This information confirms the need to perform a skin biopsy, even in the presence of a vascular disease.

Central element in liver masses, helpful, or pitfall?

A central element was first described in focal nodular hyperplasia (FNH) as a so-called "central scar," and is normally associated with this entity. However, many other liver masses may present with a central element. Depending on its appearance, and the lesion itself, central elements can be essential, helpful, or confusing for diagnosis. Indeed, nodules that develop on liver vascular disorders, fibrolamellar hepatocellular carcinoma, large hemangioma, peripheral cholangiocarcinoma, or epithelioid hemangioenthelioma often present with a central element, thus increasing the level of diagnostic confidence when present. On the other hand, central elements are rare or atypical in liver metastases, hepatocellular adenoma, or hepatocellular carcinoma. In this setting, the presence of a central element can lead to a misdiagnosis. The description and details of the imaging features of these different central elements, especially on MRI, as well as a thorough evaluation of the entire lesion, can improve the diagnostic performance in these cases.

[Ankle and foot ulcerations in a diabetic patient revealing cutaneous leishmaniasis]. / Des ulcérations de cheville et du pied chez un diabétique révélant une leishmaniose cutanée.

INTRODUCTION: Cutaneous leishmaniasis is a parasitic disease that typically manifests as a typical crusted ulcer called the oriental sore. Its localization on the lower limbs can be mistaken for a leg ulcer. CASE REPORT: An 81-year-old male, native of Algeria, with type 2 diabetes, arterial hypertension and arteriopathy developed a chronic ulceration of the right ankle and foot compatible with the diagnosis of infectious diabetic foot. Non-improvement with antibiotics, local treatment and rest, and the absence of any hemodynamic arteriopathy led to skin biopsies. Polymerase chain reaction performed on biopsy samples for parasitological investigations yielded the diagnosis of cutaneous leishmaniasis due to Leishmania major. Complete healing was obtained with topical care alone, the patient having declined an etiological treatment. DISCUSSION: Cutaneous leishmaniasis is one of the rare infectious etiologies of chronic leg ulcers. Several therapeutic options, including abstention, can be proposed.

Imaging of intestinal involvement in endometriosis.

Deep gastrointestinal involvement in endometriosis is characterised by fibrous, retractile thickening of the intestinal wall. The most common location is the upper rectum, in contiguity with a lesion of the torus uterinus. As part of a preoperative assessment, it is essential to establish an accurate and exhaustive map of intestinal lesions so that the surgeon can plan his actions. Transvaginal sonography and MRI correctly analyse pelvic and rectal involvement. Given the frequency of multiple intestinal sites, particularly sigmoid and associated ileo-caecal lesions, water enema CT should be performed. The role of rectal endoscopic sonography is debated.

[Extemporaneous examination in lung pathology: the pathologist's view]. / L'examen extemporané en pathologie thoracique. Le point de vue du pathologiste.

Extemporaneous examination of a thoracopulmonary lesion has an unquestionable interest when pre-surgical diagnostic workup has not allowed determining its exact nature. This examination, the sole objective of which is to guide the surgical approach, is especially important in lung pathology, due to the limited non-surgical access to thoracic lesions and the morbidity and mortality of repeated surgery. Its yield as a decision-making procedure is of utmost importance in many clinical situations, and a close collaboration between thoracic surgeons and pathologists is required to ensure its quality, in a context of mutual confidence that requires time and experience. After a presentation of the indications and practical modalities of extemporaneous examination, we will underline its limitations and insist on difficult situations for the pathologist and inadequate indications.

Genetic influences on the end-stage effector phase of arthritis.

K/BxN T cell receptor transgenic mice are a model of inflammatory arthritis, most similar to rheumatoid arthritis, that is critically dependent on both T and B lymphocytes. Transfer of serum, or just immunoglobulins, from arthritic K/BxN animals into healthy recipients provokes arthritis efficiently, rapidly, and with high penetrance. We have explored the genetic heterogeneity in the response to serum transfer, thereby focussing on the end-stage effector phase of arthritis, leap-frogging the initiating events. Inbred mouse strains showed clear variability in their responses. A few were entirely refractory to disease induction, and those which did develop disease exhibited a range of severities. F1 analyses suggested that in most cases susceptibility was controlled in a polygenic additive fashion. One responder/nonresponder pair (C57Bl/6 x NOD) was studied in detail via a genome scan of F2 mice; supplementary information was provided by the examination of knock-out and congenic strains. Two genomic regions that are major, additive determinants of the rapidity and severity of K/BxN serum-transferred arthritis were highlighted. Concerning the first region, on proximal chromosome (chr)2, candidate assignment to the complement gene C5 was confirmed by both strain segregation analysis and functional data. Concerning the second, on distal chr1, coinciding with the Sle1 locus implicated in susceptibility to lupus-like autoimmune disease, a contribution by the fcgr2 candidate gene was excluded. Two other regions, on chr12 and chr18 may also contribute to susceptibility to serum-transferred arthritis, albeit to a more limited degree. The contributions of these loci are additive, but gene dosage effects at the C5 locus are such that it largely dominates. The clarity of these results argues that our focus on the terminal effector phase of arthritis in the K/BxN model will bear fruit.

Cigarette smoking and hepatic lesions in patients with chronic hepatitis C.

A possible hepatotoxicity of cigarette smoke has been recently suggested by epidemiological and experimental studies. Our aim was to study the possible relationships between smoking and liver fibrosis and activity in patients with chronic hepatitis C. A cross-sectional study was performed in a group of 310 patients with chronic hepatitis C consecutively hospitalized for their first liver biopsy. The relationships between age, gender, alcohol consumption, route of contamination, tobacco consumption, and Knodell fibrosis and activity scores were examined in univariate, age-adjusted, and multivariate analyses. One hundred and seventy-six patients (57%) were current smokers. Smokers were younger (P <.001), more often of male gender (P =.001), more often alcohol consumers (P =.001), and more often had a history of intravenous drug use (P =.0001) than never smokers. Smoking was related to increased fibrosis and activity scores in age-adjusted (P =.009 and P =.005, respectively) and multivariate analyses (P =.03 and P =.04, respectively). Smoking increases the severity of hepatic lesions in patients with chronic hepatitis C.

From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins.

Rheumatoid arthritis is a common and debilitating autoimmune disease whose cause and mechanism remain a mystery. We recently described a T cell receptor transgenic mouse model that spontaneously develops a disease with most of the clinical, histological, and immunological features of rheumatoid arthritis in humans. Disease development in K/BxN mice is initiated by systemic T cell self-reactivity; it requires T cells, as expected, but B cells are also needed, more surprisingly. Here, we have identified the role of B cells as the secretion of arthritogenic immunoglobulins. We suggest that a similar scenario may unfold in some other arthritis models and in human patients, beginning with pervasive T cell autoreactivity and ending in immunoglobulin-provoked joint destruction.

Changes in liver fibrosis at the end of alpha interferon therapy and 6 to 18 months later in patients with chronic hepatitis C: quantitative assessment by a morphometric method.

BACKGROUND/AIMS: The aims of the study were to determine, in patients with chronic hepatitis C treated with alpha interferon: (i) changes in the morphometric evaluation of liver fibrosis at the end of treatment and 6, 12 and 18 months after treatment; (ii) the predictive value of histologic lesions for the response to treatment, in particular the predictive value of morphometric evaluation of liver fibrosis. METHODS: Seventy patients with chronic hepatitis C who participated in two trials of recombinant interferon alpha 2b treatment were studied. Liver specimens were obtained before and at the end of treatment and 6, 12 or 18 months later. Histologic lesions were assessed according to the Knodell system. Quantitative study of total fibrosis and of Disse space collagen was done by the computerized automated morphometric method. RESULTS: A significant decrease in morphometric Disse space collagen was observed at the end of treatment and 6 months later. This decrease was also observed, although it was not significant, 12 and 18 months after treatment. There was no relationship between this decrease and the biochemical and virological responses or the dose of interferon. The pretreatment Knodell activity score, but not the morphometric evaluation of fibrosis, was a significant predictor of sustained response. CONCLUSION: A decrease in Disse space collagen, as assessed by the sensitive morphometric method, was observed at the end of and 6 months after treatment. This observation is consistent with an anti-fibrogenetic effect of alpha interferon. Mild or moderate histologic activity was associated with a sustained response to therapy.

Predictors of sustained response to alpha interferon therapy in chronic hepatitis C.

BACKGROUND/AIMS: The aim of this study was to determine the predictors for sustained response to alpha interferon therapy in a large population of patients with chronic hepatitis C, using multivariate analysis. METHODS: Two hundred and ninety-six patients were included in four controlled trials of alpha interferon. Pretreatment serum HCV RNA levels were assessed by the branched DNA version 2.0 assay and HCV genotypes by the reverse hybridization assay (LiPA). RESULTS: Sustained responses were observed in 37%, 14% and 6% of the patients with low, medium and high pretreatment serum HCV RNA levels, respectively (p<10(-4)). Sustained responses were observed in 5%, 4%, 32% and 27% of the patients with genotype 1a, 1b, 2a and 3a, respectively (p<10(-4)). The multivariate analysis showed that a non-transfusional source of HCV infection, low serum HCV RNA levels and HCV genotypes non-1 (2a or 3a) were independent factors associated with sustained response to interferon therapy. CONCLUSION: Virological factors (low pretreatment serum HCV RNA level and HCV genotype non-1a and non-1b), when adjusted in a large population of patients, using improved technology, are the main independent predictors of sustained response to alpha interferon therapy.

Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C.

The role of alcohol intake in the occurrence of severe liver disease in chronic hepatitis C virus (HCV) carriers is still debated. A cross-sectional study has been conducted in 233 chronic hepatitis C virus carriers. Weekly self-reported alcohol consumption (SRAC) was evaluated, serum HCV RNA levels were measured by a branched DNA technique (Quantiplex 2.0) and HCV genotypes were determined. A liver biopsy was performed simultaneously and liver lesions were graded with the Knodell histological activity index. Data were examined by uni- and multivariate analyses. Alcohol consumption was relatively low (< 140 g/per week in 193/233 patients [80%]). We found a highly significant correlation between SRAC and serum HCV RNA levels (r = .26, P = .001). Fibrosis was significantly correlated with age and alcohol consumption. These results suggest that in HCV carriers, alcohol consumption, even with low alcohol intake, increases viremia and hepatic fibrosis. Chronic HCV carriers should be advised to avoid regular alcohol intake.

Organ-specific disease provoked by systemic autoimmunity.

Rheumatoid arthritis (RA) is a chronic joint disease characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone destruction. Its etiology and pathogenesis are poorly understood. We describe a spontaneous mouse model of this syndrome, generated fortuitously by crossing a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint disease highly reminiscent of RA in man. The trigger for the murine disorder is chance recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells. Thus, a joint-specific disease need not arise from response to a joint-specific antigen but can be precipitated by a breakdown in general mechanisms of self-tolerance resulting in systemic self-reactivity. We suggest that human RA develops by an analogous mechanism.

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C.

BACKGROUND & AIMS: In patients with chronic hepatitis C treated with interferon alfa, sustained normalization of alanine aminotransferase was observed in about 20%, and no predictive factor of response could be clearly identified. The aims of this study were to assess the efficacy of an escalating dose of interferon and to determine the predictive factors of response. METHODS: Seventy-five patients were randomly assigned to two groups. Twenty-five patients received a dosage of 3 million units of recombinant interferon alfa-2b three times weekly for 24 weeks, and 50 patients received a dose that was increased to 5 million units at 8 weeks in nonresponders and to 10 million units 8 weeks later in persistent nonresponders. Multivariate analysis was performed to determine the features associated with response. RESULTS: A sustained response was observed in 17% of the patients with constant dosage and in 19% of patients with an escalating dosage. Low pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype were found to be independent predictive factors of sustained response. CONCLUSIONS: In patients with chronic hepatitis C, an escalating dosage of interferon did not improve the overall rate of response. Low pretreatment serum hepatitis C virus RNA levels and genotype other than 1b were the only predictive factors of sustained response.

Long-term histologic and viral changes in patients with chronic hepatitis C who responded to alpha interferon.

We assessed the long-term outcome in 24 patients with chronic hepatitis C who responded to alpha interferon. All patients were followed up for 12 months, and 16 patients were followed up 41 +/- 9 months. During the follow-up period, 18 of the 24 patients (75%) relapsed (serum ALT levels increased again); 16 had an early relapse within the 6 months and two had a late relapse 21 and 36 months after therapy; one cirrhotic patient with relapse died. Serum HCV RNA remained detectable in the two patients before the late relapse and in three of the six patients with sustained biochemical response. Histologic assessment 13 to 31 months after therapy showed a decrease in activity in most patients, even in some of those with relapse, but the decrease in portal inflammation was more marked (p < 0.05) in patients with sustained biochemical response. Liver HCV RNA was not detectable in the two sustained responders who were negative for serum HCV RNA. Despite biochemical remission induced by interferon therapy, HCV replication persists in many patients with a potential risk of late relapse. In contrast, some patients have no long-term detectable HCV RNA, suggesting clearance of HCV. Long-term histologic improvement of portal inflammation in most patients confirms the beneficial effect of interferon.