Neuroendocrine-Related Circulating Transcripts in Small-Cell Lung Cancers: Detection Methods and Future Perspectives.

No well-established prognostic or predictive molecular markers of small-cell lung cancer (SCLC) are currently available; therefore, all patients receive standard treatment. Adequate quantities and quality of tissue samples are frequently unavailable to perform a molecular analysis of SCLC, which appears more heterogeneous and dynamic than expected. The implementation of techniques to study circulating tumor cells could offer a suitable alternative to expand the knowledge of the molecular basis of a tumor. In this context, the advantage of SCLC circulating cells to express some specific markers to be explored in blood as circulating transcripts could offer a great opportunity in distinguishing and managing different SCLC phenotypes. Here, we present a summary of published data and new findings about the detection methods and potential application of a group of neuroendocrine related transcripts in the peripheral blood of SCLC patients. In the era of new treatments, easy and rapid detection of informative biomarkers in blood warrants further investigation, since it represents an important option to obtain essential information for disease monitoring and/or better treatment choices.

Effects of KEAP1 Silencing on the Regulation of NRF2 Activity in Neuroendocrine Lung Tumors.

BACKGROUND: The KEAP1/NRF2 pathway has been widely investigated in tumors since it was implicated in cancer cells survival and therapies resistance. In lung tumors the deregulation of this pathway is mainly related to point mutations of KEAP1 and NFE2L2 genes and KEAP1 promoter hypermethylation, but these two genes have been rarely investigated in low/intermediate grade neuroendocrine tumors of the lung. METHODS: The effects of KEAP1 silencing on NRF2 activity was investigated in H720 and H727 carcinoid cell lines and results were compared with those obtained by molecular profiling of KEAP1 and NFE2L2 in a collection of 47 lung carcinoids. The correlation between methylation and transcript levels was assessed by 5-aza-dC treatment. RESULTS: We demonstrated that in carcinoid cell lines, the KEAP1 silencing induces an upregulation of NRF2 and some of its targets and that there is a direct correlation between KEAP1 methylation and its mRNA levels. A KEAP1 hypermethylation and Loss of Heterozygosity at KEAP1 gene locus was also observed in nearly half of lung carcinoids. CONCLUSIONS: This is the first study that has described the effects of KEAP1 silencing on the regulation of NRF2 activity in lung carcinoids cells. The epigenetic deregulation of the KEAP1/NRF2 by a KEAP1 promoter hypermethylation system appears to be a frequent event in lung carcinoids.

Exogenous Lipoid Pneumonia due to Chronic Inhalation of Oily Product Used as a Lubricant of Tracheotomy Cannula.

Exogenous lipoid pneumonia (ELP) is caused by the inhalation of vaporized oily products. Long-term exposure can result in chronic disease, whereas acute form usually results from massive aspiration of fatty substances. It has an incidence of 1.0%-2.5%. In case of symptomatic patients, the clinical presentation mainly includes acute or chronic respiratory symptoms such as dyspnea, fever, cough and less frequently chest pain, hemoptysis, or weight loss. Radiological findings are often aspecific or misinterpreted, and ELP is sometimes misdiagnosed as a malignancy of the lungs. Patient history and radiological findings can lead to a suspicion of ELP, but histological microscopic findings of intra-alveolar lipid and lipid-laden macrophages are required to confirm the diagnosis The mainstay of treatment consists of avoiding ongoing exposure and providing supportive care as repeated whole-lung lavage, corticosteroids, and/or immunoglobulins. Surgery is reserved for cases of high suspicion of cancer or serious clinical impact (as recurrent infections). Prognosis is benign, even if it has been reported cases of progression to severe respiratory failure, cor pulmonale, superinfection, and association with lung cancer. Here, we describe a case of ELP due to chronic inhalation of oily product (Vaseline) used as a lubricant of tracheotomy cannula.

Left Supraclavicular Swelling: Sclerosing Perineurioma.

A sclerosing perineurioma presents as a single asymptomatic papule or nodule located on the hands of adult patients; approximately 60 cases have been reported in medical literature since 1997. Histologically, it originates from the perineural cells of the peripheral nerves and presents epithelial membrane antigen (EMA) positivity and S100 protein negativity. Here, we present the case of a 58-year-old male admitted to our surgery unit complaining of left supraclavicular swelling of 1-cm in size, having no significant past medical history. A lymph node neck tumor was suspected, and the patient underwent surgery under local anesthesia in outpatient care. The intraoperative finding was a whitish mass, wooden-fibrous in consistency, strictly adhering to the skin and apparently fixed to the deep planes. Upon histological examination, a sclerosing perineurioma was diagnosed: neoplastic cells were immunoreactive for CD34, CD99, and EMA, and negative for S100 protein, smooth-muscle actin, pancytokeratin (AE1-AE3), CD31, neurofilaments, and beta-catenin. According to the benign biological tumor behavior, radical resection was considered an adequate treatment. Our case presents as peculiarity the unusual non-acral location (first reported as supraclavicular swelling) and the rare immunopositivity for CD34 and CD99.

Enhanced Recovery After Surgery: a patient centered process.

The Enhanced Recovery After Surgery (ERAS) is a model of care introduced in 1997 by a group of general surgeons from Northern Europe led by Henrik Kehlet. The core of this approach is to produce improvements in surgical patient outcomes, especially in the reduction of hospital stay, complications rate, early recovery and reduction of economic burdens. Simply elaborating and establishing a protocol is not enough and much more efforts and changes are needed to achieve the aim to offer a sustainable improvement in the overall quality of patient care, therefore, ERAS is not a single and rigid protocol but is a method, a "modus operandi", a new way of multidisciplinary teamwork with readiness to make changes as knowledge evolves, i.e., a revolution of medical-scientific thought: we have to move from the concept of "management of disease" to that of "health promotion".

Esophageal Achalasia: Predictive Value of Preoperative Resting Pressure of LES Correlated with Type of Fundoplication.

OBJECTIVE: The aim of the present study is to show the predictive value of the preoperative resting pressure of the lower esophageal sphincter (LES) correlated with the type of fundoplication (Nissen or Dor) after Heller myotomy in our series. MATERIALS AND METHODS: From January 1998 to June 2010, 88 patients affected by esophageal achalasia underwent surgery at our unit. However, our study focused on a sample of 36 patients, because many data were lost or was never recorded. Among these, 14 patients underwent laparoscopic Heller myotomy plus Nissen fundoplication (group N), whereas 22 patients underwent laparoscopic Heller myotomy plus Dor fundoplication (group D). Clinical evaluation was performed using a modified DeMeester symptom scoring system consisting of the assessment of three symptoms: dysphagia, regurgitation, and heartburn. To each symptom was assigned a score from 0 to 3, depending on its severity, and the reduction in the severity of each symptom after surgery was assessed. RESULTS: The surgical treatment is considered to be effective (p<0.0001). The preoperative resting pressures of LES were compared by Student's t-test, and it was found that patients who reported a greater improvement in the dysphagia symptom had a preoperative average pressure of LES that was significantly higher than that in other patients in both group N (p=0.03) and group D (p=0.01; p=0.003; p=0.001). The Dor treatment was shown to be more effective than the Nissen treatment (p<0.0001). CONCLUSION: The preoperative resting pressure of LES is a predictive factor of surgical success both before Dor fundoplication and before Nissen fundoplication, but its predictive power is influenced by the chosen type of fundoplication.

De Garengeot's Hernia: a Diagnostic Challenge.

Surgical literature defines the case of acute appendicitis in a sac of femoral hernia as de Garengeot's hernia. The diagnosis remains a very hard challenge for surgeon because the symptoms are aspecific and the most effective tools for preoperative evaluation (as abdominal computed tomography and abdominal ultrasound scan) can often be indeterminate or misinterpreted. We report the case of an 85-year-old white male admitted to our unit complaining of a 1-day history of vague abdominal pain, nausea, vomiting, and painful swelling in the right groin. Preoperatively, an incarcerated right femoral hernia was supposed and patient underwent surgery via oblique inguinal incision. The intraoperative finding was a de Garengeot's hernia and an appendectomy with hernia repair was performed. Patient had a regular course and was discharged on the second postoperative day.

The Post-Surgical Long-Term Behaviour of Lung Carcinoid Tumours.

Here, we report a retrospective evaluation of long-term behaviour of lung carcinoids after surgery. A total of 23 patients (17 with typical pulmonary carcinoids and 6 with atypical pulmonary carcinoids) were enrolled in our hospital from April 1994 to July 2009. All patients underwent intervention at the Unit of Surgery and then were followed at the Unit of Oncology. The standard protocol for patient monitoring consisted of follow-up at 3 months after surgery, 6 months after first control and annually for 5 years. The follow-up evaluations consisted in blood tests, imaging of chest and abdomen, bone scintigraphy, and brain computed tomography. In case of disease recurrence, patients underwent chemotherapy (etoposide, carboplatin) and radiotherapy. All patients were followed for a mean of follow-up period of 100 months, ranging between 20 and 203 months. In the group of typical carcinoid, the observed recurrence rate at 5 years was zero, at 10 years was 5.8 %, whereas the observed mortality rate at 5 and 10 years was zero. In the group of atypical carcinoid, both the recurrence rate and the mortality rate at 5 and 10 years were 16.6 %. A statistical significant difference (p = 0.002) in the recurrence rate between stage I and stage II was observed. The overall prognosis of pulmonary carcinoids was favourable, and the typical carcinoids presented a better prognosis than the atypical ones. The stage at time of diagnosis could be considered as a predictive prognostic factor.

Nipple-areola-complex sparing mastectomy: five years of experience in a single centre.

This study aimed at assessing the outcomes of nipple-areola-complex-sparing mastectomy (NSM) of breast cancer in a single-centre and single-surgeon series after 5 years of experience. From June 2007 to January 2012, 58 female patients with breast cancer were admitted for NSM at our unit and 55 of these underwent NSM. All patients underwent a preoperative clinical and instrumental evaluation. The clinical evaluation consisted of physical examination by taking measurements of the prosthesis and through anamnesis. The instrumental evaluation used were mammography, chest X-ray, abdominal and breast ultrasound, blood test and, if necessary, magnetic resonance imaging. Specific inclusion criteria have been met in recruiting patients: clinically negative axillas, tumours < 3 cm in any of the quadrants, tumours more than 1 cm away from the NAC. The patients underwent a surgical and oncological follow-up. The surgical follow-up consisted in treating wounds, managing drainages and tissue expanders and then planning the replacement surgeries. The oncological follow-up consisted of periodical medical (such as blood tests including cancer markers) and radiological evaluations (such as mammography, chest X-ray, abdominal and transvaginal ultrasound scan and/or thorax-abdomen computed tomography) to assess the disease progression, and, if necessary the patients underwent chemotherapy or hormonal therapy. Out of 58 recruited patients undergoing NSM, only 3 patients (5.1 %) had an occult tumour in the NAC at intraoperative extemporaneous histological examination and required the NAC removal. The other 55 patients (94.9 %) did not have neoplastic involvement of NAC and at an average follow-up period of 21.7 months (range 3-55 months) only 4 (7.2 %) had disease progression. Nipple-Sparing Mastectomy is a highly specialized and oncologically sure procedure to be performed only in reference centres on selected patients.

Fibrosing mediastinitis as a cause of right claudication.

Fibrosing mediastinitis is a rare benign disorder caused by proliferation of acellular collagen and dense paucicellular fibrous tissue within the mediastinum. Its precise cause, pathogenesis and links to infectious (such as histoplasmosis or tuberculosis) and non-infectious (such as sclerosing cholangitis) diseases remain speculative. Affected patients present signs and symptoms related to obstruction of mediastinal hollow organs, such as large vessels, esophagus and airways. The present study reports the first case described in medical literature of medullar compression by a mediastinal mass penetrated into the spinal canal through neural foramens and causing claudication.

Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer.

The KEAP1/Nrf2 pathway is a master regulator of several redox-sensitive genes implicated in resistance of tumor cells against chemotherapeutic drugs. Recent data suggest that epigenetic mechanisms may play a pivotal role in the regulation of KEAP1 expression. We performed a comprehensive genetic and epigenetic analysis of the KEAP1 gene in 47 non-small cell lung cancer tissues and normal specimens. Promoter methylation analysis was performed using a quantitative methylation specific PCR assay in real time. Methylation at the KEAP1 promoter region was detected in 22 out of the 47 NSCLCs (47%) and in none of the normal tissues analyzed. Somatic mutations were detected in 7 out of the 47 tumors (15%) and loss of heterozygosity (LOH) in 10 out of the 47 (21%) of the cases. Overall, we found at least one molecular alteration in 57% of the cases. Approximately one third of the tumors had two alterations and this feature was associated with higher risk of disease progression in univariate COX regression analysis (HR = 3.62; 95% CI 1.24-10.65, p = 0.02). This result was confirmed by Kaplan-Meier analysis, which demonstrated an association between worst outcome and KEAP1 double alterations (p = 0.01, Log rank test). Our results further suggest that deregulation of the NRF2/KEAP1 system could play a pivotal role in the cancerogenesis of NSCLC. In addition identifying patients with KEAP1 genetic and epigenetic abnormalities may contribute to disease progression prediction and response to therapy in lung cancer patients.

Giant esophageal lipoma.

A case of a giant esophageal pedunculated lipoma diagnosed in a 67-year-old male patient with recent onset of dysphagia is reported. Following the initial endoscopic and radiologic evaluation, the diagnosis was suspected by endo-ultrasonography and confirmed by histopathology. The treatment consisted of an esophagotomy with submucosal resection, through a left sided cervical incision. The review of the literature confirmed the rarity of this neoplasm, and the difficulty of a correct preoperative diagnosis, since a possible progression to squamous carcinoma has been demonstrated.

Hyperthermia in the treatment of post-actinic osteosarcomas: our anecdotal experience.

Irradiation-induced sarcomas are a late sequelae of irradiation therapy. Most sarcomas have been reported to occur after exposure to a radiation dose of 55 Gys and above, with a dose ranging from 16 Gys to 112 Gys. These tumours are very aggressive and an early detection is needed for a timely intervention. Surgery is only effective treatment for local control instead chemotherapy is a valuable tool for systemic control of disease. Irradiation therapy use is controversial because of its side effects on a site previously irradiated. Irradiation therapy combined with hyperthermia is a new treatment that overcomes these problems without limiting the effect of radiation therapy. It may become a tool for local control of the unresectable tumours or an adjuvant treatment of the surgery. In this report we present a rare case of irradiation-induced recurrent osteosarcoma involving the chest wall that was treated with surgical resection followed by radiation therapy combined with hyperthermia as an adjuvant treatment of the surgery.

Fundoplication after heller myotomy: a retrospective comparison between nissen and dor.

OBJECTIVE: A retrospective comparison between Nissen and Dor fundoplication after laparoscopic Heller myotomy for achalasia. MATERIALS AND METHODS: From 1998 to 2004 a first group of 48 patients underwent Heller myotomy and Nissen fundoplication for idiopathic achalasia (H+N group). From 2004 to 2010 a second group of 40 patients underwent Heller myotomy followed by Dor fundoplication (H+D group). Some patients received a previous endoscopic treatment with pneumatic dilatation or endoscopic injection of botulinum toxin that provided them only a temporary clinical benefit. Changes in clinical and instrumental examinations from before to after surgery were evaluated in all patients. Clinical evaluation was carried out using a modified DeMeester symptom score system. RESULTS: Dor fundoplication treatment reduced both dysphagia and regurgitation severity scores significantly more than Nissen fundoplication (p<0.0001). Indeed, the incidence of dysphagia was significantly higher in patients treated with floppy-Nissen than in those treated with Dor fundoplication: by defining dysphagia as a DeMeester score equal to 3 (arbitrary cut-off), at the end of follow-up dysphagia occurred in 17.65% and 0% (p=0.037) of patients belonging to the H+N and H+D groups, respectively. CONCLUSION: Heller myotomy followed by Dor fundoplication is a safe and valuable treatment. The procedure showed a lower incidence of postoperative dysphagia versus Nissen fundoplication and a negligible incidence of postoperative GERD in a long-term postoperative follow-up.

Ectopic hepatic tissue misdiagnosed as a tumor of lung.

The ectopic or accessory liver lobe is an uncommon congenital anatomic abnormality. It is considered to be the outcome of an abnormal development of liver tissue during embryologic period. In some cases, it may be secondary to a trauma or a surgical operation. Literature reports only anecdotal cases; there are not series. The most common localization is the abdominal cavity, but very rarely it can also be found in the thoracic cavity. In most cases, preoperative correct diagnosis is very difficult because it is unlikely to consider this rare condition in course of differential diagnosis. Most cases are misdiagnosed, and patients undergo surgical intervention with suspect of lung lesion. Some times the intrathoracic accessory lobe is an intraoperative incidental finding. In this report, we present the case of a young female patient who underwent surgical treatment for a suspect pulmonary lesion that at histological examination resulted to be an intrathoracic accessory hepatic lobe.

Estudo preliminar sobre a hidroquímica da bacia de Jací-Paraná (RO)

This study present the hydrochemical parameters of the streams of the Jaci-Paraná area. The samples were colected during October/84 to November/85, including dry an wet seasons. The parameters presented are pH, specific conductance, humic material, oxygen consumed, sulfate, calcium, manesium, sodium, potassium, chloride, iron, Kjeldahl nitrogen, silica. These waters are very poor in dissolved solids concentrations.

O Projeto Estudo de uma Bacia Experimental em Jaci-Paraná (RO), tem como um dos seus objetivos o estudo hidroquímico do rio e igarapés da área. Neste trabalho são apresentados os resultados dos parâmetros físico-químicos pH, condutibilidade elétrica, material húmico, consumo orgânico, sulfato, cálcio e magnésio (alcalinos terrosos), sódio e potássio (alcalino), cloretos, ferrom, nitrogêncio de Kjeldahl e sílica. analisados durante os anos outubro/84 á novembro/85, compreendendo os períodos chuvoso e seco. As amostras de água foram coletadas no rio Jaci-Paraná, no igarapé Tamanduá (drena e bacia) e no igarapé Bejarana (Fig. 1).

Interpretação hidrogeoquímica das águas subterrâneas da ilha de Marajó

Information obtained in a research survey carried oat by IDESP was used to investigate, groundwater hydrogeochemistry on Marajó island. The samples were collected in both dug and drilled wells. The results of physico-chemistry analyses indicated a wide range of concentrations in the water quality parameters which reflects the hydrogeologic complexity on the area. The largest total dissolved solids concentrations ocuured in the central and northern part of the area while the lowest levels were found in the south, southeast and northwest. The waters were predominantly of the sodium-chloride type followed by the mixed-chloride and mixed-bicarbonate types. The Schöeller semi-logarithmic diagram was used to identify waters with similar chemical characteristics. The variation in groundwater composition along the subsurficial flow path indicated a dissolution phenomenon with the dissolved ions increasing from the active groundwater flushing zone to the zone of very sluggish flow. This resulted in a variable mixture of fresh and brackish groundwater. The reduction of sulfate by oxidation of organic matter,the base exchange and adsorption are phenomena that exert an important control on the water chemistry.

As pesquisas desenvolvidas pelo IDESP na Ilha de Marajó possibilitaram estudos de hidrogeoquímica das águas subterrâneas. As amostras foram coletadas em poços escavados e em poços tubulares. Os resultados das análises físico-químicas evidenciaram significativas variações nas concentrações dos parâmetros de qualidade de água, refletindo a complexidade hidrogeológica da área. As maiores concentrações de sólidos totais dissolvidos ocorrem na parte central e norte da área, sendo pequena na parte sul, sudeste e noroeste. As águas são predominantemente do tipo sódio-cloretada, seguidas pelos tipos mista-cloretada e mista-bicarbonatada. A utilização de diagramas semi-logarítimicos de Schoeller possibilitou o agrupamento das águas subterrâneas com características químicas similares. A evolução da composição das águas subterrâneas evidencia o aumento da concentração dos íons dissolvidos das zonas de fluxo ativo em áreas de recarga para as zonas de fluxo muito lento. Misturas de águas doces com águas salobras conatas ocorrem em proporções variadas. A redução de sulfatos pela matéria orgânica e a troca de bases e adsorção são fenômenos que atuam na concentração dos íons dissolvidos.