TTF-1/p63-positive poorly differentiated NSCLC: A histogenetic hypothesis from the basal reserve cell of the terminal respiratory unit

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast

The effect of body mass index on chest trauma severity and prognosis

AIM: Patients with thoracic trauma constitute one third of all the trauma cases, in west Sicily were recorded 941 thoracic trauma during the period between 2006 and 2009. Sicily is one of the Italian regions with the highest rate of obesity: some studies have demonstrated that obesity is an independent risk factor for mortality in high energy blunt traumas. MATERIAL OF STUDY: This study was conducted with trauma patients older than 20 years old who presented to our Department during the last five years. We only included thoracic injuries and politrauma with a thoracic involvement and a BMI > 25- Patients were divided into two groups: HET and LET patients. RESULTS: Thoracic trauma was more common in patients with a BMI > 25 than in normo-weight and clinic admission rate, length of hospital stay and ISS score increased in proportion with the increase of BMI. Both HET (high energy trauma) and LET (low energy trauma) revealed that overweight, obese and morbidly obese patients had greater admissions and length of hospital stay. DISCUSSION: The overweight and obese population has increased substantially over the last two decades and 61,5% of the Sicilian population is above normal weight. A large body mass with excess adiposity may contribute to HET injuries in several ways. Obesity has a number of comorbidities that reduce chances of recovery in overweight and obese patients experienced thoracic trauma both HET and LET. CONCLUSION: Obesity increases morbidity independently of injury severity in thoracic trauma patients. As BMI increased, length of hospital stay increased and prognosis deteriorates

Herpes Simplex Esophagitis in Immunocompetent Host: A Case Report

Introduction. Herpes simplex esophagitis is well recognized in immunosuppressed subjects, but it is infrequent in immunocompetent patients. We present a case of HSE in a 53-year-old healthy man. Materials and Methods. The patient was admitted with dysphagia, odynophagia, and retrosternal chest pain. An esophagogastroduodenoscopy revealed minute erosive area in distal esophagus and biopsies confirmed esophagitis and findings characteristic of Herpes Simplex Virus infection. Results. The patients was treated with high dose of protonpump inhibitor, sucralfate, and acyclovir, orally, with rapid resolution of symptoms. Discussion. HSV type I is the second most common cause of infectious esophagitis. The majority of symptomatic immunocompetent patients with HSE will present with an acute onset of esophagitis. Endoscopic biopsies from the ulcer edges should be obtained for both histopathology and viral culture. In immunocompetent host, HSE is generally a self-limited condition. Conclusions. HSE should be suspected in case of esophagitis without evident cause, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, careful history and assessment for an immune disorder such as HIV infection is crucial, to look for underlying immune deficiency

Epidemiology of Toxoplasma and CMV serology and of GBS colonization in pregnancy and neonatal outcome in a Sicilian population

Background: Aim of our study is to analyze the immunological status in pregnancy for two main TORCH agents, Toxoplasma and Cytomegalovirus (CMV), and the results of group B streptococcus (GBS) screening, assessing the risk for congenital infection in a population from Palermo, Italy. Methods: We retrospectively analyzed the medical records of all inborn live newborns who were born in our division during 2012, gathering information about the mother, the pregnancy and neonatal hospitalization at birth. Whenever data were available, we categorized the serologic status of the mothers for Toxoplasma and CMV. We also considered the results of rectal and vaginal swabs for GBS. We compared the results in Italian and immigrant mothers. The neonatal outcome was evaluated in all cases at risk. Results: Prevalence of anti-Toxo IgG antibodies was 17.97%, and was significantly higher in immigrant women (30% vs 16.4% in Italian women; p = 0.0008). Prevalence of anti-CMV IgG antibodies was 65.87%. Again, it was significantly higher in immigrant women (91.4% vs 62.5%, p = 3.31e-08). We compared those data with a previous study performed in our hospital in 2005-2006, and found that the prevalence of anti-Toxoplasma and anti-CMV antibodies in our population has remained stable, both in the immigrant and in the local population. Seroconversion rates and neonatal infections were rare: no seroconversions were observed for Toxoplasma, 4 seroconversions for CMV. One neonatal Toxoplasma infection and two neonatal CMV infections were documented. In some cases with dubious patterns or probable persistence of IgM, we performed additional tests and follow-up. Vaginal and rectal swabs were positive for GBS in 7.98% of cases, with no significant difference between the Italian and the immigrant population. No GBS neonatal sepsis was documented. Conclusions: The prevalence of Toxoplasma IgG antibodies in pregnant women was low in our population, if compared with European countries and with other parts of Italy, and is significantly higher in immigrant women. The prevalence of CMV IgG antibodies was intermediate if compared to other countries, and it was higher in immigrant women. GBS positivity was low, and comparable in Italian and immigrant mothers. Neonatal infection was rare for all these agents

Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response

Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA structure. In the future we intend to widen the TS structure analysis to the metastatic CRCs, because due to their higher genomic instability, they could present a TS variant form responsible of the fluoropyrimidines drug resistance and the worse prognosis

Utility of laser microdissection and pressure catapulting in the diagnosis of non small cell lung cancer: preliminary data.

Background: There are controversies about the adequacy of tumor tissue sample on which the sequencing of molecular diagnosis could be performed to achieve the targeted-therapy on lung cancer. The aim of this study is to demonstrate the role of the Laser Microdissection Pressure Catapulting (LMPC) technique to obtain adequate tumor tissue sample for the molecular analysis of gene mutations in the target therapy of lung cancer. Findings: From a consecutive series of 24 patients with a diagnosis of locally-advanced or metastatic Non Small Cell Lung Cancer (NSCLC), we performed 29 diagnostic procedures using the system of LMPC, to obtain an homogeneous samples where it was possible to run the sequencing of the 4 most frequently mutated exons of Epidermal Growth Factor Receptor (EGFR) (exon 18, 19, 20, 21). Results: There were 14 males (58.3%) and 10 females (41.7%), with a mean age of 61 years old. Twenty one patients were affected by adenocarcinomas, 2 by squamous cell carcinomas and 1 by large cell carcinoma. We were able to obtain the sequencing on 26 out 29 samples (89,6%) for EGFR mutation. EGFR mutation rate in our population was 7,7%. In 5 samples, we found a polymorphism in exon 20 and one of them carried a mutation on exon 18 as well. In another sample we found the deletion of exon 19. On the other 20 samples we did not find any mutation. Conclusions: Our preliminary data suggest that the LMPC technique permits to obtain the tumor cells sample more homogeneous facilitating the application of biological molecular analysis for EGFR-gene mutation in a larger number of patients with NSCLC

Porcine model for gluteal artery perforator flap: Anatomy and technique

Although flap anatomy is well studied on cadavers and microsurgical techniques are well practiced on rats, still there are few training models for learning the techniques of perforator flap harvesting. The cadaver has no bloodstream, so accuracy of dissection cannot be evaluated and flap viability cannot be verified. Training on humans carries a high risk of flap damage. A living model for perforator flap harvest is needed to learn the technique before starting with its clinical application

Porcine model for deep superior epigastric artery perforator flap harvesting: Anatomy and technique

BACKGROUND Microsurgical training on rats before starting with clinical practice is a well-established routine. Animal model training is less widespread for perforator flaps, although these flaps represent a technical challenge. Unlike other flaps, they require specific technical skills that need to be adequately trained on a living model 1 : a cadaver is not enough because no bleeding, vessel damage, or vasospasm can be simulated. 2 The purpose of this study was to assess the suitability of the porcine abdomen as a training model for the deep inferior epigastric artery perforator (DIEAP) flap, commonly used in human breast reconstruction. METHODS A female swine (Sus scrofa domesticus, ssp; weight 25kg) was used. The procedure was performed with the pig under general anesthesia and in the supine position. A deep superior epigastric artery perforator (DSEAP) flap was harvested on the left side of the abdomen, including the 3 cranial nipples and stopping in the midline to spare the contralateral flap for another dissection (as in bilateral breast reconstructions in humans; Fig. 1). All steps of a DIEAP harvest were simulated: superficial vein harvest, suprafascial perforator dissection, intramuscular perforator harvest with preservation of the nerves, and flap isolation. Observation of capillary refill was used to confirm flap viability at the end of the dissection. The procedure was recorded by means of a GoPro camera and simultaneously with a head mounted (4 7 magnification) Loupecam system. Photographs were taken using 2 cameras during surgery at relevant time points. RESULTS At the end of the dissection, the flap was viable. The subcutaneous adipose tissue of the pig is less represented than in human and pigs have an additional muscular layer, the panniculus carnosus, which is the analogue of the human Scarpa's fascia. The rectus fascia is thinner. The perforators are lined in 2 rows: 1 lateral and 1 medial, as in the DIEAP, and the intercostal nerves cross the vessels, as happens in humans. The porcine rectus abdominis muscle is thinner than the human one, but vessels' branching faithfully reproduces the human model. 1 We identified 5 perforating vessels of more than 1mm in diameter (2 lateral and 3 medial). We isolated a lateral perforator first and a medial one last: the latter was eventually used to nourish the flap (Fig. 2). CONCLUSIONS The DSEAP flap allows one to closely reproduce all the steps of DIEAP flap harvesting and also to carry out the intramuscular dissection of 2 perforators for each side (up to 4 for each animal), confirming the adequacy of this pig model for microsurgical training. The deep superior epigastric artery is dominant in pigs. 3 Despite this anatomical difference, the DSEAP allows one to reproduce the main steps of DIEAP flap harvesting, providing an excellent training model. Moreover, the presence of double perforating rows allows simulating the dissection twice on each side

3D CT scan for perioperative identification of anatomical variations of lungs

Aim: The aim of this study is to investigate anatomical lung variations and vascular patterns using volumetric 3D computed tomography (CT) representations. Methods & results: We considered 24 major thoracic surgery performed in our ward. In these, we discovered some interesting anatomical variations of the main pulmonary fissures. These findings were not visible on the plain x-ray or during routine examination of a preoperative CT scan. After re-examination of 3D CT scan reconstruction the anatomical variations were detected. Discussion: General thoracic surgeons must familiarize themselves with anatomical variations in lungs. 3D images may aid the general thoracic surgeon in performing safer surgeries. Conclusion: 3D CT scan should be performed before surgery if possible

Wider implications of video-assisted thoracic surgery versus open approach for lung metastasectomy

Lung metastasectomy is considered a safe and potentially curative procedure despite there is not a strong evidence that metastasectomy prolongs long-term survival in patients with lung metastases. Moreover, the debate is open regarding the best approach for lung metastasectomy, video-assisted thoracic surgery versus open approach. A systematic review of literature to clarify what is the best approach to prolong survival in patients with lung metastases was performed. Our study confirms that overall survival is equivalent for video-assisted thoracic surgery and thoracotomy, therefore the ‘gold standard’ surgical treatment for lung metastases remains a point of debate. The choice of the surgical approach still depends more on the single center or surgeon practice than on strong scientific evidence. A prospective randomized trial could clarify the question