Deep venous thrombosis and abortion: an unusual clinical manifestation of severe form of pectus excavatum.

Pectus excavatum is a chest wall malformation with a strong psychological and aesthetic impact. Rarely, pectus excavatum patients can show respiratory or cardiac symptoms occurring mainly during physical exertion. We report a case of a 34-year-old pregnant woman with a severe degree of pectus excavatum who developed serious cardiovascular disease resulting in spontaneous twin abortion at the twenty-first week of gestation. Cardiovascular disease was resolved after open surgical correction of pectus excavatum. This case shows how a tardive diagnosis and a delayed surgical approach for pectus excavatum can lead to severe consequences.

Colistin-based Treatment of Multidrug-resistant Gram-negative Bacterial Pulmonary Infections After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is a viable option for a select group of patients with end-stage lung disease. However, infections are a major complication after LT, accounting for significant morbidity and mortality. Several germs may be responsible; multidrug-resistant Gram-negative (MDR-GN) bacteria are emerging. Colistin is widely used in the treatment of these infections and is administered by inhalation and/or parenterally. At our institution, in patients with tracheostomy, colistin is administered by direct instillation in the airway during bronchoscopy. We reviewed a series of patients who underwent LT complicated by postoperative MDR-GN bacterial pulmonary infection. METHODS: From January 2015 to May 2017, 26 lung transplants were performed. In the postoperative course, 14 (54%) developed MDR-GN bacterial infection; respiratory specimen culture, blood tests, and chest X-ray were considered. Colistin was the only antibiotic usable. Thirteen patients received intravenous (IV) colistin; in the subgroup of patients with tracheostomy, colistin was instilled directly in the airway, and 6 patients received inhaled colistin. RESULTS: Seven patients needed tracheostomy. Pseudomonas aeruginosa was the predominant infection (86%), with Acinetobacter baumanii seen in 2 cases (14%). An early clinical-laboratory response was observed in 9 patients (64%). White blood cell count and C-reactive protein values improved (P = .02 and P = .001, respectively). A significant reduction in bacterial load was observed on microbiologic bronchoalveolar lavage specimens. CONCLUSION: Colistin instilled directly in the airway did not show side effects. The combination of IV and inhaled/instilled colistin could be a useful treatment option for MDR-GN infections after LT.

Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is only therapeutic option for patients affected by chronic respiratory failure. Chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the most important factor that influences post-transplantation quality of life. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP) seems to reduce the rate of lung function decline in transplant recipients with progressive BOS. METHODS: From 1991 until now, 239 LTs were performed at our center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were treated with ECP. At the beginning of the treatment, all patients showed a mean decline of forced expiratory volume in 1 second (FEV1) from baseline values of 45.8% ± 17.2%; 2 patients were in long-term oxygen therapy. RESULTS: Mean follow-up from November 2013 to June 2016 was 11.6 ± 7 months. Twelve patients (80%) showed lung function stabilization with an FEV1 range after treatment between -6% to +8% from the pre-treatment values. We did not report any adverse effects or increase of infections incidence. DISCUSSION: ECP seems to be an effective and well-tolerated therapeutic option for LT patients with BOS in terms of stabilization of lung function and increased survival.

Evaluation of Renal Function in Patients Undergoing Lung Transplantation.

BACKGROUND: Acute kidney injury and chronic kidney failure are serious complications after lung transplantation. Glomerular filtration rate (GFR) is the primary indicator of renal function. Several equations have been proposed to evaluate the estimated GFR (eGFR). We compared three different equations to determine which has the better correlation with the development of acute and chronic renal failure in lung recipients. METHODS: Twenty-two patients with a mean age of 54.4 ± 8.5 years underwent lung transplantation from 2010 to 2015. Thirteen (59%) had pulmonary fibrosis, 7 (32%) emphysema, 1 (4.5%) bronchiectasis, and 1 (4.5%) lymphangioleiomyomatosis. In all patients, eGFR was measured preoperatively using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Levey's Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. In 20 patients (90%) eGFR was calculated at 1, 3, and 6 months. RESULTS: According to CKD-EPI and MDRD, eight patients (36.3%) had preoperative reduction in eGFR, whereas 6 patients (27.2%) had preoperative reduction according to the CG (P = .04). The mean values were higher for the CG (103.2 vs. 102 vs. 94.4). Five patients (22.7%) developed perioperative acute renal failure requesting a dialysis treatment; four of these showed a preoperative eGFR to the highest CG (P = .05). At 1 and 6 months after lung transplantation, the CG, MDRD and CKD-EPI eGFR values were, respectively, 86.6, 84.1 and 76.6 mL/min/1.73m2 and 75.8, 72.7, and 72.3 mL/min/1.73m2. CKD-EPI eGFR values are more predictable than the other equations of AKI. CONCLUSIONS: Preoperative assessment of eGFR using the MDRD and CKD-EPI seems to correlate better than the CG to the prediction of acute renal failure, whereas for the chronic form the three equations seem equivalent.

Inhibition of autophagy, lysosome and VCP function impairs stress granule assembly.

Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of the protein quality control (PQC), were shown to regulate SG degradation. This is consistent with the idea that PQC may survey and/or assist SG dynamics. However, despite these observations, it is currently unknown whether the PQC actively participates in SG assembly. Here, we describe that inhibition of autophagy, lysosomes and VCP causes defective SG formation after induction. Silencing the VCP co-factors UFD1L and PLAA, which degrade defective ribosomal products (DRIPs) and 60S ribosomes, also impaired SG assembly. Intriguingly, DRIPs and 60S, which are released from disassembling polysomes and are normally excluded from SGs, were significantly retained within SGs in cells with impaired autophagy, lysosome or VCP function. Our results suggest that deregulated autophagy, lysosomal or VCP activities, which occur in several neurodegenerative (VCP-associated) diseases, may alter SG morphology and composition.

It could suddenly happen: delayed rupture of the trachea after total thyroidectomy. A case report.

INTRODUCTION: We report the case of a patient who presented with subcutaneous emphysema, dyspnea and cough 7 days after total thyroidectomy for cancer. In addition we review the Literature and discuss the therapeutic challenges as well as management options. CASE REPORT: A 17-year old female patient underwent a total thyroidectomy with right cervical lymph adenectomy for papillar cancer. Lung metastases are present. On postoperative day 7 she presented with face and neck swelling due to subcutaneous emphysema, dyspnea and persistent cough. The radiological evaluation revealed a tear on the right antero-lateral wall of the trachea. The patient underwent surgical exploration of the neck which confirmed the tracheal rupture and showed an important tracheal necrosis all around the tear. Due to the impossibility to make primary closure of the trachea or a tracheal resection, the tear was repaired with muscular flap interposition, (around the trachea as a scarf ), using the contralateral clavicular part of sternocleidomastoid muscle and prethyroid muscles bilaterally. The postoperative course was uneventful and the patient is alive 20 months after surgery and iodine induced adjuvant therapy. CONCLUSION: Delayed tracheal rupture should be suspected in all patients who present subcutaneous emphysema after thyroid surgery. The lesion should be promptly treated with primary closure or tracheal resection when possible. Muscular flap interposition could be a safe alternative option when the other procedures are contraindicated.

Efficacy and safety of fibrin sealant patch in the treatment of air leakage in thoracic surgery.

AIM: Air leakage represents a major problem in lung surgery. Absorbable fibrin sealant patch (AFSP), a collagen sponge coated with human fibrinogen and thrombin, can be used as an adjunct to primary stapling or suturing. This study compared the efficacy of AFSP with manual suturing after primary stapling. METHODS: This was a prospective, multicenter, randomized study. Patients undergoing lobectomy, bilobectomy, anatomical segmentectomy for lung cancer or wedge resection for pulmonary metastasis with air leakage grade 1 or 2 according to Macchiarini scale after stapler suture were randomized to receive AFSP or standard surgical treatment (ST). The primary endpoint was the reduction of intraoperative air leakage intensity. Duration of postoperative air leakage and number of days until removal of last chest drain were secondary endpoints. Safety was recorded for all patients. RESULTS: A total of 346 patients were enrolled in 14 centres, 179 of whom received AFSP and 167 ST. Intraoperative air leak intensity was reduced in 90.5% of AFSP patients and 82% of ST patients (P=0.03). A significant reduction in postoperative air leakage duration was observed in the AFSP group (P=0.0437). The median number of days until removal of last drainage was 6 (3-37) in the AFSP group and 7 (2-27) in the ST (P=0.38). Occurrence of adverse events was comparable in both groups. CONCLUSION: AFSP was more efficacious than standard ST as an adjunct to primary stapling in reducing intraoperative air leakage intensity and duration of postoperative air leakage in patients undergoing pulmonary surgery. AFSP was well tolerated.

[Early diagnosis of lung cancer: impact of autofluorescence bronchoscopy]. / Diagnostic précoce du cancer bronchique : apport de la bronchoscopie en autofluorescence.

INTRODUCTION: Less than 15% of all patients survive five years after a diagnosis of lung cancer. This poor prognosis is attributed to a lack of early detection. Among the methods of early diagnosis of bronchial cancer, autofluorescence bronchoscopy allows for the early identification of preinvasive bronchial lesions. The goal of this prospective study is to evaluate the contribution of the autofluorescence bronchoscopy, on a hospital site, over a period of one year. METHODS: All patients with an indication of autofluorescence bronchoscopy were included in the study. The following parameters were collected: age, sex, smoking status, FEV1, FVC, biopsy sites, histology, duration of examination. RESULTS: Two hundred and seventy-four patients were included. The average age was 63.8 years (+/-12), the smoking status was 35 packs/year (+/-19). A fluorescence abnormality was detected in 131 patients and 165 sites were biopsied. An histological abnormality was found in 76% of the samples, with 34 hyperplasia (28%), 56 squamous metaplasia (46%), three mild dysplasia (3%), two moderate dysplasia (2%), one severe dysplasia (1%), two carcinomas in situ (2%) and 21 invasive carcinomas (18%). CONCLUSION: Autofluorescence bronchoscopy is an effective examination for the detection of the preinvasive neoplasic lesions and may be proposed when lung cancer is suspected.

Isolation of stem/progenitor cells from normal lung tissue of adult humans.

OBJECTIVES: This study aimed to isolate and characterize stem/progenitor cells, starting from normal airway epithelia, obtained from human adults. MATERIALS AND METHODS: Cultures of multicellular spheroids were obtained from human lung tissue specimens after mechanical and enzymatic digestion. Tissue-specific markers were detected on their cells by immunohistochemical and immunofluorescent techniques. Ultrastructural morphology of the spheroids (termed as bronchospheres) was evaluated by electron microscopy, gene expression analysis was performed by reverse transcription-polymerase chain reaction, and gene down-regulation was analysed by an RNA interference technique. RESULTS: Bronchospheres were found to be composed of cells with high expression of stem cell regulatory genes, which was not or was only weakly detectable in original tissues. Morphological analysis showed that bronchospheres were composed of mixed phenotype cells with type II alveolar and Clara cell features, highlighting their airway resident cell origin. In addition to displaying specific pulmonary and epithelial commitment, bronchospheres showed mesenchymal features. Silencing of the Slug gene, known to play a pivotal role in epithelial-mesenchymal transition processes and which was highly expressed in bronchospheres but not in original tissue, led bronchospheres to gain a differentiated bronchial/alveolar phenotype and to lose the stemness gene expression pattern. CONCLUSIONS: Ours is the first study to describe ex vivo expansion of stem/progenitor cells resident in human lung epithelia, and our results suggest that the epithelial-mesenchymal transition process, still active in a subset of airway cells, may regulate transit of stem/progenitor cells towards epithelial differentiation.

Risk factors for lymph node metastases and their prognostic significance in early gastric cancer (EGC) for the Italian Research Group for Gastric Cancer (IRGGC).

BACKGROUND: Lymph node metastases are present in only about 15% of patients with early gastric cancer (EGC) and for this reason, the majority of these patients do not require lymphadenectomy. In Japan, EGC patients undergo less invasive treatment (endoscopic mucosal resection, wedge resection, laparoscopy). However, the indications for and results of these types of treatment are still uncertain. METHODS: In a multicentre retrospective study, we analysed the clinicopathological data referring to 584 early gastric cancer patients who underwent D2 gastrectomy. A comparison was made between patients with and without lymph node metastases in relation to numerous pre- and postoperative variables. Long-term survival and risk factors for lymph node metastases were analysed. The primary aim was to compare our results with those of Western and Japanese authors; we also evaluated the possibility of identifying a subset of patients at low risk of lymph node metastases who may be candidates for endoscopic treatment. RESULTS: The incidence of lymph node metastasis was 14.4%. Univariate and multivariate analyses showed that submucosal infiltration, diffuse histotype, tumour size and Kodama Pen A type were all related to the presence of lymph node metastases. Patients with types I, IIa and IIb mucosal tumours did not present lymph node metastases. Postoperative mortality was 2.2%. Five-year survival in relation to lymph node groups was 95% in N0 patients, 77% in N1 patients and 60% in N2 patients (p = 0.0001, Japanese N-stage). The number of positive lymph nodes also had a prognostic value. Patients with three or fewer positive lymph nodes presented a better 5-year prognosis (83%) than those with more than three positive lymph nodes (48%) (p = 0.0001). CONCLUSIONS: Our study confirms that lymph node involvement is an extremely important prognostic factor. For this reason, the therapeutic strategy of our surgical units is as follows: 1) D2 gastrectomy is the standard treatment even in early gastric cancer (EGC); 2) endoscopic mucosal resection (EMR) could be considered first in types I, IIa and IIb tumours that are diagnosed as limited to the mucosal layer.

[Surgical treatment of adrenal metastases. Personal experience]. / Trattamento chirurgico delle metastasi surrenaliche. Esperienza personale.

The adrenal glands are often the site of metastases. However, there is much discussion as to the benefits of surgical resection. Personal experience of surgical treatment in 4 patients, one of whom died postoperatively after bilateral adrenalectomy for metachronous metastases, is reported. Surgery achieved pain relief in all patients, average survival was 30 months and 1 patient is still alive after 68 months. The present study shows that surgery is advisable in patients who present the following characteristics: 1) the primary tumor has been resected or is radically resectable, 2) there is no evidence of other metastatic lesions, 3) the adrenal metastasis is unilateral and complete resection is possible, 4) the patient's general physical condition is good.

Response of glutamine metabolism to exogenous glutamine in humans.

To determine whether exogenous glutamine affects whole body glutamine metabolism, preliminary experiments were performed to verify that L-[1-13C]-, L-[U-14C]-, and L-[3,4-3H]glutamine given simultaneously by vein provided similar estimates of glutamine appearance rates [Ra; 355 +/- 24, 373 +/- 19, and 393 +/- 24 (SE) mumol.kg-1.h-1, respectively, P = NS] in six healthy men; glutamine oxidation accounted for 32 +/- 3 and 51 +/- 5% (P < 0.01) of glutamine Ra when it was measured using L-[U-14C]- and L-[1-13C]glutamine, respectively. Five subjects received two 5-h intravenous infusions of L-[3,4-3H]glutamine and a simultaneous nasogastric infusion of L-[1-13C]glutamine on 2 separate days in the postabsorptive state, along with saline on 1 day and natural L-glutamine (856 +/- 45 mumol.kg-1.h-1) on another day in a randomized order. Splanchnic glutamine extraction (determined from [13C]glutamine appearance into systemic blood) reached 74 +/- 4 and 53 +/- 5% during the enteral infusion of tracer alone and in combination with a large load of glutamine, respectively. Glutamine infusion was associated with increased plasma glutamine concentration (from 630 +/- 50 to 1,297 +/- 75 microM), Ra (from 258 +/- 20 to 589 +/- 45 mumol.kg-1.h-1), and oxidation (from 179 +/- 20 to 477 +/- 47 mumol.kg-1.h-1, all P < 0.01), no change in glutamine release from proteolysis, and a decline in glutamine de novo synthesis (from 156 +/- 15 to 93 +/- 13 mumol.kg-1.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and pharmacological properties of thieno[2',3':4,5]pyrimido [2,1-b][1,3,4]thiadiazine derivatives.

A new series of 2-substituted-7,8-dimethyl-3H,9H-thieno[2',3':4,5]pyrimido[2,1- b][1,3,4]thiadiazin-9-ones 5a-d and 6a,b was synthesized through the hydrazinium(1+) salt of 3-amino-2,3-dihydro-5,6-dimethyl-2-thioxo- thieno[2,3-d]pyrimidin-4(1H)-one, 2. These derivatives and two analogs 10a,b were tested for their analgesic and antiinflammatory properties. The pharmacological results are discussed in comparison with those of related compounds previously tested.

Early gastric cancer: prognostic factors in 223 patients.

A retrospective study of 223 patients treated for early gastric cancer (EGC) is reported, representing 21.2 per cent of the 1051 patients with gastric cancer treated over the same period. Two main types of surgical procedure were used: subtotal resection of the stomach for EGC of the two lower thirds and total gastrectomy for lesions of the upper third. A lymphadenectomy of groups 1 and 2, according to the procedure of the Japanese Research Society for Gastric Cancer (R2 resection), was performed in all patients. The mean duration of follow-up was 7.5 years. Univariate analysis showed a significant difference in survival rates only between patients with and without involved nodes (log rank = 6.05, P = 0.0139). Other prognostic factors were not identified. A bivariate analysis was performed to evaluate the joint effect of node status and the Kodama classification: survival rates for patients with EGC of the penetrating (Pen) A type and node positive falls to around 57 per cent within 6 years. This group of patients has a tumour that should probably be considered as a 'non-early' lesion. To improve the survival of patients with a Pen A, node positive lesion, adjuvant chemotherapy may be appropriate.

[Respiratory function tests as a predictive indicator of postoperative course in patients undergoing pneumonectomy because of neoplasms]. / Le prove di funzionalità respiratoria come indice predittivo del decorso postoperatorio nei pazienti pneumonectomizzati per neoplasia.

Postoperative morbidity and mortality were correlated with the preoperative results of three widely used pulmonary function tests (FVC, FEV1, FEV1/FVC) in 100 consecutive patients who underwent pneumonectomy for lung carcinoma. Factor analyzed following operation included thirty-day mortality, incidence of cardiovascular and respiratory complications, number of individuals requiring prolonged mechanical ventilation. Nineteen patients had a forced vital capacity (FVC) of 70% or less of the normal value, seven had a one-second forced expiratory volume (FEV1) of 1.5 liters or less, and thirty-three had a FEV1 of less than 2 liters. Fourteen patients had a FEV1/FVC ratio of 65% or less. There were no differences in morbidity or mortality between these patients and those presenting higher test scores. As a general rule, decisions regarding operability and extent of resection cannot be made solely on the basis of the three spirometry tests reviewed.

Determination of glutamine and alpha-ketoglutarate concentration and specific activity in plasma using high-performance liquid chromatography.

A method is described for measuring glutamine (GLN) and alpha-ketoglutarate (KG) concentration and specific activity (SA) using high-performance liquid chromatography (HPLC). Plasma GLN and KG are separated on miniature ion-exchange columns. KG is derivatized with O-phenylene diamine, the derivative is extracted in ethyl acetate, dried, and dissolved in pH 7 phosphate buffer. The isolated GLN is enzymatically converted to KG and analysed as such. Derivatized samples are stable for weeks at -20 degrees C. Samples are injected onto a reversed-phase HPLC column. Absolute standards are injected to determine the nmol content of unknown samples. alpha-Ketoadipate and [3H]-glutamine are used as internal standards to quantitate KG and GLN concentrations, respectively. Collection of the entire peak of interest permits determination of the radioactivity in the GLN and KG peaks; this together with the determination of the nanomoles injected permits the calculation of the SA. Typical precision is 3.5 and 4.6% for GLN and KG concentrations and 5.3 and 3.3% for GLN and KG SA, respectively. Analysis time is ca. 7 min. Using this method, the turnover rate of GLN carbon was determined during a 5-h infusion of L-[U-14C]glutamine in a human subject.

Adenomyoma of the stomach. Report of a case and review of the literature.

A case of adenomyoma of the prepyloric antrum and a review of the previous reported in the literature are presented. The tumor is composed of cysts and glandular structures lined by cuboidal-to-columnar epithelium surrounded by hypertrophic smooth muscle bundles. Furthermore, glands resembling Brunner's and/or heterotopic pancreatic tissue are present in some patients. The endoscopic characteristics of the lesion are discussed, as well as the diagnostic and therapeutic approaches.

Omeprazole in H2 receptor antagonist-resistant reflux esophagitis.

We conducted a retrospective review of 25 patients with severe reflux esophagitis treated with omeprazole because of failure of H2 receptor antagonists to heal their esophagitis. Prior to beginning omeprazole (40 mg/day), all patients were on H2 antagonists for at least 9 months and still had endoscopic evidence of longitudinal (grade II) or circumferential (grade III) distal esophageal ulceration. Omeprazole therapy brought about complete endoscopic healing in 24 of 25 patients (96%). Twenty-three of 24 healed patients were then restarted on H2 antagonists as maintenance therapy. Repeat endoscopy was performed if symptoms recurred. Fourteen of 24 patients (58%) had recurrence of endoscopic esophagitis documented between 26 and 300 days from the time of starting maintenance therapy. Two of these 14 patients opted for antireflux surgery, whereas the remaining 12 were once again given omeprazole, which again resulted in symptom resolution in all patients. These data suggest that most patients with H2 receptor antagonist-resistant ulcerative esophagitis cannot be successfully maintained on H2 antagonists even after the ulcers have been healed with omeprazole. Further studies are required to determine the role of omeprazole compared to other treatments in the long-term maintenance therapy of these patients.