Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia. METHODS: A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms. RESULTS: Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival. CONCLUSIONS: The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.

C reactive protein to albumin ratio (CAR) as predictor of anastomotic leakage in colorectal surgery.

BACKGROUND: Anastomotic leakage (AL) is one of the most severe complications in colorectal surgery. Currently, no predictive biomarkers of AL are available. The aim of this study was to investigate the role of C reactive protein (CRP) to albumin ratio (CAR) as a predictor of AL in patients undergoing elective surgery for colorectal cancer. MATERIALS AND METHODS: Data on 1183 consecutive patients surgically treated for histologically proven colorectal cancer in the surgical units involved in the study were collected. Data included sex, age, BMI, ASA score, Charlson comorbidity index, localization, histology and stage of the disease, as well as blood tests including albumin and CRP at the 4th postoperative day. Differences in CAR between patients who developed AL and those who did not were analyzed, and the ability of CAR to predict AL was investigated with ROC analysis. RESULTS: CAR was significantly higher in patients with AL in comparison to those without, at the 4th postoperative day. In ROC analysis CAR showed a good ability in detecting AL (AUC 0.825, 95%CI: 0,786-0,859), greater than those of CRP and albumin alone. CAR also showed a high ability in detecting postoperative deaths (AUC 0.750, 95% CI 0,956-0,987). These findings were confirmed in multivariate analysis including the most relevant risk factors for AL. CONCLUSION: Our study evidenced that CAR, an inexpensive and widely available laboratory biomarker, adequately predicts AL and death in patients who underwent elective surgery for colorectal cancer.

Surgical treatment of hepatocellular carcinoma in the era of COVID-19 pandemic: A comprehensive review of current recommendations.

The new coronavirus disease 2019 (COVID-19) pandemic has resulted in a global health emergency that has also caused profound changes in the treatment of cancer. The management of hepatocellular carcinoma (HCC) across the world has been modified according to the scarcity of care resources that have been diverted mostly to face the surge of hospitalized COVID-19 patients. Oncological and hepatobiliary societies have drafted recommendations regarding the adaptation of guidelines for the management of HCC to the current healthcare situation. This review focuses on specific recommendations for the surgical treatment of HCC (i.e., hepatic resection and liver transplantation), which still represents the best chance of cure for patients with very early and early HCC. While surgery should be pursued for very selected patients in institutions where standards of care are maintained, alternative or bridging methods, mostly thermoablation and transarterial therapies, can be used until surgery can be performed. The prognosis of patients with HCC largely depends on both the characteristics of the tumour and the stage of underlying liver disease. Risk stratification plays a pivotal role in determining the most appropriate treatment for each case and needs to balance the chance of cure and the risk of COVID-19 infection during hospitalization. Current recommendations have been critically reviewed to provide a reference for best practices in the clinical setting, with adaptation based on pandemic trends and categorization according to COVID-19 prevalence.

The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a role in the formation of CSC. We investigated the role of hsa-miR-486-5p (miR-486-5p) in CRC, CSCs, and metastasis, in order to reach a better understanding of the biomolecular and epigenetic mechanisms mir-486-5p-related. The expression of miR-486-5p was investigated in three different matrices from CRC patients and controls and in CSCs obtained from the CRC cell lines HCT-116, HT-29, and T-84. In the human study, miR-486-5p was up-regulated in serum and stool of CRC patients in comparison with healthy controls but down-regulated in tumor tissue when compared with normal mucosa. miR-486-5p was also down-regulated in the sera of metastatic patients. In vitro, miR-486-5p was down-regulated in CSC models and it induced an inhibitory effect on stem factors and oncogenes in the main pathways of CSCs. Our results provide a step forward in understanding the role of mir-486-5p in CRC and CSC, and suggest that further studies are needed to investigate its diagnostic and prognostic power, possibly in combination with other biomarkers.

Blood cell count indexes as predictors of anastomotic leakage in elective colorectal surgery: a multicenter study on 1432 patients.

BACKGROUND: The aim of this study was to evaluate a series of blood count inflammation indexes in predicting anastomotic leakage (AL) in elective colorectal surgery. METHODS: Demographic, pathologic, and clinical data of 1432 consecutive patients submitted to colorectal surgery in eight surgical centers were retrospectively evaluated. The neutrophil to lymphocyte (NLR), derived neutrophil to lymphocyte (dNLR), lymphocyte to monocyte (LMR), and platelet to lymphocyte (PLR) ratios were calculated before surgery and on the 1st and 4th postoperative days, in patients with or without AL. RESULTS: There were 106 patients with AL (65 males, mean age 67.4 years). The NLR, dNLR, and PLR were significantly higher in patients with AL in comparison to those without, on both the 1st and 4th postoperative days, but significance was greater on the 4th postoperative day. An NLR cutoff value of 7.1 on this day showed the best area under the curve (AUC 0.744; 95% CI 0.719-0.768) in predicting AL. CONCLUSIONS: Among the blood cell indexes of inflammation evaluated, NLR on the 4th postoperative day showed the best ability to predict AL. NLR is a low cost, easy to perform, and widely available index, which might be potentially used in clinical practice as a predictor of AL in patients undergoing elective colorectal surgery.

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients.

Colorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH+ and CD44+/CD326+ colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients' samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted.

Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.

OBJECTIVE: Deciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available. DATA SOURCE: English-language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database. STUDY SELECTION: The search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma." RESULTS: Forty-four cases included in 16 articles, published in the period under investigation, were analyzed in detail. CONCLUSIONS: The mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X-ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme.

Surgical management of primary and recurrent carcinoma showing thymous-like elements (CASTLE).

INTRODUCTION: Carcinoma showing thymous-like elements (CASTLE) is a rare tumor with only a few cases described in the scientific literature. The aim of the present review is to analyze the data available on the therapeutic options employed in CASTLE tumors and to outline the best surgical management to adopt. MATERIALS AND METHODS: English-language articles published from 1985 through November 2016, and related to CASTLE cases were retrieved using the Pubmed database and specific key-words. RESULTS: Eighty seven cases included in 23 papers, published in the period under investigation, were analyzed in detail. The mean age of the patients was 50.2 years and the male to female ratio 1:1.2. There were performed 31 (35.6%) lobectomies, 29 (33.3%) total thyroidectomies, 15 (17.2%) subtotal thyroidectomies, 4 (4.6%) excisions, 3 (3.4%) partial thyroidectomies, 1 (1.1%) hemithyroidectomy, and 8 (9.2%) additional procedures including tracheal, pharyngeal, and esophageal resections. Lymph node dissection and radiotherapy were associated in 59 (67.8%) and 44 (50.6%) cases respectively. Among the patients with available data 62 (75.6%) were free of disease, 16 (19.5%) were alive with disease, 3 (3.7%) died for the disease, and 1 (1.2%) died for cerebrovascular complications at the time of follow-up. Globally 20 (24.4%) cases of local or distant recurrence were reported. Surgery and radiotherapy, alone or in combination were the treatments most frequently used for recurrences. CONCLUSIONS: CASTLE is a rare tumor which generally respond well to complete surgical resection and adjuvant radiotherapy. These treatments can be further employed for the recurrences, which occur in 24.4% of the cases, along with specific chemotherapy regimens and palliative procedures. KEY WORDS: Cancer, CASTLE, Excision, Lobectomy, Thymous-like elements, Thyroidectomy.

MicroRNA Expression Analysis of Centenarians and Rheumatoid Arthritis Patients Reveals a Common Expression Pattern.

Micro-RNA (miRNA) are a family of small non-coding ribonucleic acids that inhibits post-transcriptionally the expression of their target messenger RNA (mRNA). We are interested in studying the involvement of miRNA in longevity and autoimmune diseases. In this study we compared the different expression of seven microRNAs between human plasma healthy controls, plasma samples of centenarians and samples from patients with rheumatoid arthritis. We used the Life Technologies' protocol to quantify seven miRNAs from 62 plasma samples: 20 healthy human controls, 14 centenarians, 28 patients with rheumatoid arthritis. TaqMan MicroRNA assays were used to analyze the expression profiles of miR-125b-5p, miR-425-5p, miR-200b5p, miR-200c-3p, miR-579-3p, miR-212-3p, miR-21-5p and miR-126-3p. The relative expression of mature miRNAs was analyzed using software REST. Our results show that miR-425-5p, miR-21 and miR-212 significantly decreased in centenarians and in patients with rheumatoid arthritis compared with controls. Furthermore in this work we highlight a connection between corticosteroid treatment and miRNAs expression.

Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients.

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a broad spectrum of clinical presentations and incompletely understood pathogenesis. This autoimmune disease is characterized by alterations in both the innate and adaptive immune system that lead to the loss of immunologic tolerance. In autoimmune diseases particularly in SLE, early diagnosis, flare or remission phases can be difficult to identify. Proteomics can help to find new therapeutic targets and it also could help to better understand the cellular mechanisms. The aim of this study was to observe the variations in plasma and Peripheral Blood Mononuclear Cells (PBMCs) proteome in order to increase our knowledge about pathogenesis and to find possible diagnostic markers and/or therapeutic targets for improving diagnosis and treatment. The comparative proteomic analyses showed that several proteins were differentially expressed in the PBMCs from SLE patients. Among these, PRDX2 may be used as candidate biomarker or target protein for further investigations. In plasma, we showed that plasma clusterin levels increased in SLE patients compared to healthy controls, but this increase is not statistically significant. These proteomic results provide suggestions for understanding the molecular mechanisms of SLE, as well as the physiological changes correlated with SLE disease.

Breast Nodular Fasciitis: A Comprehensive Review.

BACKGROUND: This article describes the demographic, clinical, pathological and prognostic features of breast nodular fasciitis through a comprehensive review of the cases reported in modern literature. MATERIAL AND METHODS: English-language articles published from January 1970 to October 2015 and related to breast nodular fasciitis were non-systematically retrieved using the PubMed database. Titles, abstracts and references were evaluated in order to include the most relevant studies. The demographic characteristics of the patients and the signs and symptoms of the disease were reviewed, as well as the results of the radiological and diagnostic procedures employed and of the treatments adopted. RESULTS: 26 papers reporting on 28 cases were enrolled; however, manuscripts published before 1990 were excluded because of old methodologies, technologies and clinical approaches. Thus, 22 cases included in 20 papers were analyzed in detail. CONCLUSION: The rarity and the unspecific clinical and radiological characteristics of breast nodular fasciitis make the differential diagnosis and management challenging. Knowledge of the clinical, pathological and prognostic aspects of this condition is crucial for breast care specialists in order to improve their diagnostic and therapeutic interventions.

Impact of transthoracic endoscopic sympathectomy on plantar hyperhidrosis.

INTRODUCTION: The aim of this study is to evaluate the impact of transthoracic endoscopic sympathectomy on plantar hyperhidrosis in patients operated on for upper limb hyperhidrosis. MATERIALS AND METHODS: From 2003 to 2011, 41 consecutive patients underwent videothoracoscopic T3-T4 sympathicotomy or T3-T4 ganglion block at our Unit for upper limb hyperhidrosis. Twenty-one (51%) were affected by palmar hyperhidrosis and 20 (49%) by palmar and axillary hyperhidrosis combined. The patients affected by the plantar form were 26 (63%). Clinical follow-up was performed at 3, 6 and 12 months after surgery. Phone interviews and/or clinical assessment were made after a variable period of time (range 6 months to 8 years) to asses long term results. RESULTS: Plantar hyperhidrosis improved in 14 patients, which represents the 54% of the sufferers and the 34% of all patients. It was partially regressed in 11 patients (79%) and resolved in 3 cases (21%). There were not significant differences between patients treated with sympathicotomy and those treated with ganglion block. CONCLUSIONS: Transthoracic endoscopic sympathectomy performed through T3-T4 sympathicotomy or ganglion block improves plantar hyperhidrosis in approximately 54% of the affected patients, with a partial and complete resolution rate of 79% and 21% respectively.

Is sternotomy always necessary for the treatment of mediastinal ectopic thyroid goiter?

UNLABELLED: Ectopic thyroid goiter accounts approximately for 1% of all substernal goiters and for 10-15% of all mediastinal masses. Sternotomy is generally accepted as the most adequate approach for the removal of ectopic thyroid goiters of the anterior mediastinum. We report two cases of mediastinal ectopic goiter removal through a cervical incision, without sternotomy. The technique is based on a careful and gentle traction of the mass by means of traction stitches and simultaneously on a blunt digital dissection, in order to exteriorize the lesion in the neck, as much as necessary to ligate its vascular pedicle before completing the removal. When performed with caution and precision, this approach can avoid sternotomy in selected patients with ectopic thyroid goiter. KEY WORDS: Ectopic thyroid, Sternotomy, Thyroidectomy.

Molecular analysis of appendiceal mucinous cystadenoma and rectal adenocarcinoma in a patient with urothelial carcinoma: a case report.

INTRODUCTION: In this report, we present the case of a patient affected by appendiceal cystadenoma, a colorectal adenocarcinoma, and a concomitant bladder carcinoma, as well as the results of the molecular study of the most relevant mutational pathways involved in these tumors. CASE PRESENTATION: A 68-year-old Italian man was admitted to our unit complaining of macrohematuria, rectorrhagia, and rectal tenesmus for about 2 months. A colonoscopy showed the presence of a rectal lesion at 11cm from the anal margin; multiple biopsies were performed and a diagnosis of moderately differentiated adenocarcinoma was made. Abdominal ultrasonography and total body computed tomography performed subsequently to stage the rectal cancer showed the presence of two round nodules, interpreted as swollen lymph nodes of neoplastic origin, at the anterior aspect of the iliopsoas muscle and a budding lesion affecting the bladder. The patient underwent transurethral biopsy of the lesion in the right retrotrigonal region; the diagnosis was grade II urothelial carcinoma. The patient underwent an open anterior rectal resection with loco-regional lymphadenectomy. An enlarged appendix and a voluminous whitish soft-tissue lesion requiring an appendicectomy were detected perioperatively. Transurethral resection of the bladder lesion was also performed. The histological examination revealed that the nodular lesions in the appendix were due to a cystadenoma. For mutation analysis, genomic deoxyribonucleic acid was isolated from tumor tissue samples; for PIK3CA mutations, screening revealed that all three samples analyzed carried mutations in exon 9. CONCLUSIONS: Appendiceal mucoceles are rare but require adequate surgical treatment, given their malignant potential and the possibility of causing peritoneal pseudomyxoma. It is essential to make a correct preoperative evaluation based on a colonoscopy rather than ultrasound and computed tomography to exclude synchronous neoplasias often associated with mucoceles and to plan the optimum surgical strategy. The association between appendiceal mucoceles and other neoplasias is relatively frequent, especially with colorectal cancer. Oncogenic activation in the PIK3CA-depending pathway may contribute substantially to the pathogenesis of the different solid tumors in the same patient.

Epidemiology of thyroid cancer in an area of epidemic thyroid goiter.

The aim of this study was to analyze and describe the epidemiological characteristics and trends of thyroid cancer in the province of Sassari (Sardinia, Italy), an area with epidemic thyroid goiter, in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. An increasing trend in the incidence of thyroid cancer in the province of Sassari was evidenced. This trend seems to follow the general worldwide trend and does not seem to be related to the high incidence of thyroid goiter in the area. The frequencies of the different histological subtypes were similar to those reported in numerous national and international reports. Women are affected earlier than men and, therefore, suffer greater professional, economic, and social impacts. Overall mortality is low and a relative 5-year survival is excellent, especially in comparison to other malignancies.

Preneoplastic and neoplastic gallbladder lesions occasionally discovered after elective videocholecystectomy for benign disease. A single centre experience and literature review.

INTRODUCTION: In this study we retrospectively reviewed data on 311 consecutive elective cholecystectomies, performed for benign disease (cholelithiasis, cholecystitis) in our institution in the last six years, in order to determine the frequency of unexpected gallbladder pre-neoplastic and neoplastic lesions and analyse their clinical, diagnostic and therapeutic features. MATERIALS AND METHODS: Three hundred eleven consecutive patients underwent elective cholecystectomy for benign gallbladder disease in our Institution from January 2005 to March 2011. Clinical records and histo-pathological reports were reviewed in order to detect occult gallbladder pre-neoplastic and neoplastic lesions and describe the clinical, diagnostic and therapeutic findings. Eight patients were excluded for lacking of important clinical data. RESULTS: Out of 303 patients examined, 26 (8.6%) were found to be affected by a concomitant pre-neoplastic or neoplastic lesion. Ten (3.3%) were found to have a benign lesion, 13 (4.3%) a dysplasia of the gallbladder epithelium and 3 (1%) a gallbladder adenocarcinoma. DISCUSSION: Dysplasia was found in 4,3% of cases and surgery represents the interruption of an eventual malignant evolution. Adenomiomatosis and adenomas represent the most frequent benign occult lesions discovered; surgery is the definitive cure for such lesions. Occult gallbladder adenocarcinoma was detected in 1% of cases in absence of any preoperative clinical or radiological suspect. Cholecystectomy is curative in stage T1a disease, while a re-resection is necessary for more invasive non metastatic disease.

Impact of age on the quality of lymphadenectomy for colorectal cancer.

The aim of this study was to evaluate the impact of patient age on the number of lymph nodes dissected during surgery for colorectal cancer. Clinical and histopathological data of 231 consecutive patients who underwent elective surgery for colorectal cancer were reviewed retrospectively. Patients were divided into those aged ≤70 years and >70 years. Our findings suggest that patient's age influences the number of lymph nodes detected in surgical specimens; this number was lower in patients aged >70 years and decreased with further aging.