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.

[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.

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.

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.

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.

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.

Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers.

Ethane exhalation was measured in 42 control subjects, 52 patients with various non-alcoholic liver diseases, and 89 alcohol abusers who had been admitted to hospital for alcohol withdrawal and assessment of liver disease (six with normal liver tests, 10 with steatosis with or without fibrosis, six with alcoholic hepatitis, 29 with cirrhosis, 34 with both cirrhosis and alcoholic hepatitis, and four with both cirrhosis and a hepatocellular carcinoma). Ethane exhalation was similar in control subjects and in patients with non-alcoholic liver diseases, but was five times higher in alcohol abusers. Ethane exhalation in alcohol abusers was significantly, but very weakly, correlated with the daily ethanol intake before hospital admission, and the histological score for steatosis, but not with the inflammation or alcoholic hepatitis scores. Ethane exhalation was inversely correlated with the duration of abstinence before the test. In nine alcoholic patients, the exhalation of ethane was measured repeatedly, and showed slow improvement during abstinence. Ethane exhalation was significantly but weakly correlated with the Pugh's score in patients with alcoholic cirrhosis. It is concluded that the mean ethane exhalation is increased in alcohol abusers. One of the possible mechanisms may be the presence of oxidizable fat in the liver. The weak correlation with the Pugh's score is consistent with the contribution of many other factors in the progression to severe liver disease.

Mucin immunohistochemistry of the columnar epithelium of the oesophagus (Barrett's oesophagus).

Columnar cell lined lower oesophagus (CELLO), often considered to be a precancerous lesion, is characterized by a glandular mucosa with a predominance of sulphomucins in the specialized epithelium. This histochemical abnormality can be correlated with abnormal differentiation which may also be studied by anti-mucus antibodies (anti-M1, anti-M3, anti-SIMA, anti-LIMA). The purpose of this prospective study is to define the mucin profile in a large population of CELLO by immunohistochemistry and to compare it with the results of histochemistry. Biopsies of 79 patients with reflux oesophagitis were included. Thirty-eight had CELLO and 41 had a histologically normal cardia. Six surgical specimens of oesophageal adenocarcinomas were also included. The histochemical methods confirmed the preponderance (57.9%) of type III intestinal metaplasia (IM) found in 57.9% of cases. The immunohistochemical methods showed a similar antigenic profile of type II and III IM with positivity of anti-SIMA and anti-M3 antibodies in the goblet cells, and positivity of anti-LIMA antibodies in both the goblet and intermediate cells of the specialized epithelium. The mucus secreting cells of the oesophageal adenocarcinomas had the same immunohistochemical profile. These results are similar to those of Filipe et al. in type II and III IM surrounding gastric adenocarcinomas. Immunohistochemical methods allow us to subdivide type II and type III IM into 2 subgroups according to the positivity or negativity of the anti-LIMA antibodies in the intermediate cells. Among the 41 normal cardias in patients with reflux oesophagitis, 10 contain sulphomucin secreting cells positive with anti-LIMA antibodies. We suggest that this anti-LIMA positivity may be a step preceding type III IM in specialized epithelium.

[Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. / Traitement de l'hépatite alcoolique par la silymarine. Une étude comparative en double insu chez 116 malades.

A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.

[Obstructive jaundice caused by granulomatous stenosis of the extrahepatic bile ducts in sarcoidosis]. / Ictère obstructif par sténose granulomateuse des voies biliaires extra-hépatiques au cours d'une sarcoïdose.

A 37-year-old black West Indian woman with sarcoidosis developed obstructive jaundice due to stenosis involving the entire length of the common hepatic bile duct associated with stenosis of the cystic duct. Neither gallstones nor extrahepatic biliary tract lymph node involvement were found. Stenosis was ascribed to biliary involvement of sarcoidosis because of the presence of noncaseating granulomas in the cystic duct and the gallbladder neck. There was no hepatic involvement. Cholecystectomy and left hepaticojejunostomy were performed. Postoperative recovery was unremarkable. Jaundice disappeared and liver tests returned to normal values. This case report underlines the importance of verifying the patency of the extrahepatic biliary tract before severe cholestasis can be ascribed to intrahepatic involvement of sarcoidosis.