A NOTES approach for thoracic surgery: transgastric thoracoscopy via a diaphragmatic incision in a survival porcine model.

AIM: Recently the NOTES approach has been extended to mediastinum by a transesophageal access and to the thorax by a transvescical endoscopic approach. The aim of this study was to assess the feasibility and the safety of transgastric endoscopic approach to the thoracic cavity, with lung biopsy, in a survival porcine model. METHODS: The study was performed on four 20-30 kg female pigs (Sus scrofus domesticus). Following gastric wall incision, the muscular pars of the left diaphragmatic dome was incised along with the parietal pleura and the endoscope advanced into the thoracic cavity. In all animals, a thoracoscopy was performed as well as peripheral lung biopsy. At the end of the operation the endoscope was withdrawn from the thoracic cavity after pleural sac decompression and the diaphragmatic incision closed by endoscopic clips under maximal expansion of lungs. The gastric incision was finally closed by endoscopic clips. Chest-tube placement was not utilized. Animals were sacrificed by day 15 postoperatively. RESULTS: The gastroscope was easily introduced into the thoracic cavity that allowed to visualize the pleural cavity and to perform simple surgical procedures such as lung biopsies without complications. There were neither respiratory distress episodes nor surgical complications to report. No adverse event occurred during the survival period. The postmortem examination 15 days after surgery revealed a good closure of the diaphragmatic incision. At necropsy, the lung biopsies were completely healed. There were no signs of infection in both thoracic and peritoneal cavities. The length of follow-up and number of animals studied might have not been sufficient. CONCLUSION: This study demonstrates the feasibility of transgastric thoracoscopy in porcine model. Long-term follow-up of much larger series will be necessary for provision of more reliable answers if this approach should be adopted in the future and eventually translated for humans with advantages for patients.

[Analysis of a documental source of the Gynecological-Obstetric Institute of Milan. Year 1907]. / Analisi critica di una fonte documentaria dell'assistenza proveniente dall'Istituto Ostetrico-Ginecologico di Milano. Epoca di riferimento: 1907.

The look I have at those origins of the obstetric assistance that are historically accepted, both as documental and narrative sources or monumental and instrumental ones, it is for some way very similar to the curious glance, fascinated and respectful of an archaeologist who begins to look and study some vestiges emerged from deep in the past. He looks to these rests as if he looked at so many evidences of men's lives that have passed through the history and at facts that have characterized the evolution of our society during the last centuries as well. The aim of this work was an historical source of the contemporary assistance. The purpose is the critical analysis and the interpretation of this source itself. The instruments involved in this work are: the description of the source, its intrinsic and extrinsic examination and the interpretation compared to the midwifery considered in the historic context. The followed method is the ''historical method'' suggested by Federico Chabod. As the choose document is in some way a ''no name'', before I enter in this historiographical examination, I believe it is convenient to describe the place where such document was born and has attended to its aims.

Molecular mechanisms of blood vessel formation.

The formation of new blood vessels, angiogenesis, is a tightly regulated process. Extracellular angiogenic inducers stimulate the migration and proliferation of endothelial cells, while negative regulators counteract this effect. Changes in the relative balance of inducers and inhibitors activate the 'angiogenic switch', before stabilizer molecules activate the maturation of nascent blood vessels.

Natural orifices transluminal endoscopic surgery (NOTES): an overview of technical challenges and complications of transgastric procedures in anesthetized pigs.

AIM: Natural orifice transluminal endoscopic surgery (NOTES) is a new reality that is progressively gaining popularity in the scientific community. The aim of this study was to report the authors' experience with various peroral transgastric procedures performed on the porcine model. The technical difficulties and challenges that arose were also analyzed. METHODS: Ten anesthetized pigs, divided into an acute (3) and a survival group (7) underwent the following procedures using a double channel endoscope: peritoneoscopy (10), cholecystectomy (6),splenectomy (3), and gastrojejunostomy (3). RESULTS: All the procedures were completed successfully. There was one complication related to the gastric wall incision. In the survival experiment group all pigs (4) submitted to biliare procedures made an uncomplicated recovery after a follow-up period of 2 weeks. Gastrojejunostomies (3) were instead graved by one technical failure (anastomosis disruption at post-mortem examination) and one case of mortality (premature euthanasia for evidences of sepsis). Complete gastric cleansing was impossible to achieve and overinflation was a common problem. The creation of gastro-enteric anastomoses was technically difficult with the current available devices. CONCLUSION: Transgastric endoscopic surgery is technically feasible in a porcine model. A new instrumentation is needed and could strongly help to overcome the technical difficulties highlighted. More extensive animal studies are mandatory in order to evaluate the benefits and the limitations of this new technique.

Acute gastrointestinal bleeding following aortic valve replacement in a patient with Heyde's sindrome. Case report.

A 58-year old man was admitted to the hospital because of melena. He had a 1-year history of mechanical aortic valve replacement and coronary stent placement because of myocardial infarction and he was taking warfarin and clopidogrel. Esophagogastroduodenoscopy and colonoscopy were negative for bleeding. Capsule endoscopy showed bleeding diffuse angiodysplasia of the small bowel. The patient was treated with octreotide 20 mg, at monthly interval. After 25 months there had been no recurrence of gastrointestinal bleeding. The case suggests that mechanical valve replacement may not prevent gastrointestinal bleeding in Heyde syndrome and that octreotide treatment should be considered in these cases.

Mean and long-term results of the surgical treatment of early gastric cancer.

AIM: Interest in the diagnosis and treatment of early gastric cancer (EGC) has been steadily increasing due to the high 5-year survival rate which can reach 85-100% after curative resection. The aim of this retrospective study was to analyze the clinical and histologic characteristics as well as the results of 45 patients undergoing surgical resection for EGC. METHODS: Between 1998 and 2004, 45 patients, 14 females and 31 males with a mean age of 60.2+/-15 years (range: 31-85) were recruited. Subtotal gastrectomy was performed in 28 (62.2%) patients and total gastrectomy in 17 (37.3%). D1 and D2 resections were performed in 36 and 9 patients, respectively. The carcinoma was limited to the mucosa in 26 (57.8%) patients and extended into the submucosa in 19 (42.2%). Lymph node invasion occurred in 4 (8.8%) patients. Mean follow-up was 36 months (range: 3-63). Survival was calculated using the Kaplan-Meier method. Multivariate analysis of clinic and histologic factors was performed to identify predictive factors for survival. RESULTS: The 5-year actuarial survival rate was 85% and there was no postoperative mortality. Statistical analysis did not demonstrate any significant statistical relationship between survival and parietal penetration (P = 0.67) or superficial extension (P = 0.38) of the tumor. Survival was clearly influenced (P < 0.001) by lymph node involvement. CONCLUSIONS: Prognosis of EGC is usually excellent but can be influenced by the presence of lymph node metastases.

Normalized performance and load data for the deepwind demonstrator in controlled conditions.

Performance and load normalized coefficients, deriving from an experimental campaign of measurements conducted at the large scale wind tunnel of the Politecnico di Milano (Italy), are presented with the aim of providing useful benchmark data for the validation of numerical codes. Rough data, derived from real scale measurements on a three-bladed Troposkien vertical-axis wind turbine, are manipulated in a convenient form to be easily compared with the typical outputs provided by simulation codes. The here proposed data complement and support the measurements already presented in "Wind Tunnel Testing of the DeepWind Demonstrator in Design and Tilted Operating Conditions" (Battisti et al., 2016) [1].

Carotid endarterectomy under local anesthesia in elderly: is it worthwhile?

Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded elder patients. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. A total of 262 carotid operations were performed under local anaesthesia between 1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of age. Twenty patients (26%) presented with asymptomatic critical stenosis. Transient ischemic symptoms were the reason for presentation in 35 patients (46%). Progressive stroke was documented in two patients (3%) and a stroke with persisting neurological deficit was demonstrated in 19 cases (25%). Coronary artery disease was present in 47 patients (38%) and arterial hypertension in 55 (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one thromboendarterectomies of the carotid bifurcation with direct closure were performed. Five patients had other types of reconstruction. Postoperative complications occurred in three patients. One had a transient neurological deficit and another a lethal stroke; the third patient died from myocardial infarction. The in-hospital mortality was 2.9%, which was not significantly higher than the results of the reconstructions in younger patients (1.5%). Surgery for carotid artery occlusive disease under local anaesthesia can be safely performed in selected patients of more than 75 yr of age.

The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-1) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right (L/R) asymmetry. In zebrafish, there is strong genetic evidence that oep functions as an obligatory co-factor for the correct signaling of a transforming growth factor-beta (TGFbeta)-related gene, nodal, during gastrulation and during L/R asymmetry development. Expression of Cr-1 and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-1 expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of Cr-1 in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-1-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta-catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-2. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of beta-casein and whey acidic protein. In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

Carboplatin and alpha-2b interferon intraperitoneal combination as first-line treatment of minimal residual ovarian cancer. A pilot study.

21 untreated ovarian cancer patients with stage III and minimal tumour size, were given weekly intraperitoneal (i.p.) carboplatin (150 mg/m2) and alpha-2b interferon (IFN) (30 million U/m2) for a total of 12 courses, from June 1989 to February 1993. To date, a total of 248 courses have been administered. Toxicity was seldom severe, although fever (179 courses), fatigue (141 courses) and other IFN-related side-effects were very frequent. No patient refused to continue treatment, but in 5 patients IFN dose had to be reduced, and in 1 it was discontinued. The IFN mean delivered dose intensity was 19.8 million U/m2 week. Grade 3-4 myelotoxicity occurred in 7 patients (39 courses), but no deaths related to treatment occurred. The actual mean dose intensity of carboplatin was 121.5 mg/m2 week. To date, 20 patients have completed treatment and are evaluable for response. Of 11 patients with tumour size < or = 5 mm, 10 (91%) achieved a pathological complete response (pCR) as did 4/9 (44%) of those with tumour > 5 mm at entry, for a 70% (95% confidence interval 50-90) overall pCR rate. At a median follow-up of 21 months (range 4-46), only one death occurred. The probability of being alive at almost 4 years was 91% in the entire group (100% in those with tumour size less than 5 mm). Only 1 of 14 patients who achieved a pCR relapsed. This i.p. combination seems a feasible approach to previously untreated ovarian cancer patients with minimal tumour burden. IFN dosage should be reduced to improve tolerance. In view of the very high pCR rate achieved in the group of patients with smaller tumours, a randomised trial is warranted to compare this approach to standard treatment in these patients.

Preoperative chemoimmunotherapy with Carboplatin, epidoxorubicin, 5-Fluorouracil and alpha-2b interferon in locally advanced inoperable gastric-cancer.

Twenty-six patients with locally advanced, inoperable gastric cancer were treated with carboplatin, epidoxorubicin, 5-fluorouracil (FEP) plus alpha 2b interferon. Total gastrectomy was performed in patients achieving clinical complete or partial response. The overall response rate after neoadjuvant chemotherapy was 67%. In 13/15 patients undergoing surgery no residual tumor was evident after resection. After a median follow-up of 14 months, 4/13 disease-free patients have relapsed. The median survival time is 13 months for all patients, and 19 months for disease-free patients; in four patients survival time exceeds twenty-four months. Our multimodality program is effective in locally advanced gastric cancer and warrants further evaluation.

Expression of amphiregulin, cripto-1, and heregulin-alpha in human breast-cancer cells.

Cripto-1 (CR-1), amphiregulin (AR), and heregulin alpha (HRGalpha) are three recently discovered epidermal growth factor (EGF)-related peptides. The expression of these proteins was determined in MCF-7, ZR-75-1, T-47D, SK-BR-3, MDA-MB-231, MDA-MB-468, and Hs-578T human breast cancer cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blotting, and immunocytochemistry (ICC). The expression of CR-1 mRNA was detected by RT-PCR in all of the breast cancer cell lines. AR mRNA was detected by Northern blot analysis in MCF-7, ZR-75-1, T-47D, MDA-MB-231, and MDA-MB-468 cells while HRGalpha mRNA was expressed in only MDA-MB-231 and Hs-578T cells. All estrogen receptor-positive cell lines were found to express AR mRNA, and estrogen was able to induce AR mRNA expression in estrogen-depleted MCF-7 cells. CR-1 and AR proteins could be immunocytochemically detected in the breast cancer cell lines that were expressing CR-1 and AR mRNA using monospecific rabbit polyclonal antibodies. The anti-CR-1 antibody was also used to examine 26 human primary breast carcinomas by ICC for CR-1 expression. Seventy-five percent of the carcinomas were found to express the CR-1 protein while the adjacent non-involved breast epithelium was negative. These data demonstrate that CR-1, AR, and HRGalpha are coexpressed in human breast cancer cells and suggest that these three EGF-related peptides might perform a role in the autocrine growth regulation of human breast carcinoma cells.

Treatment of morbid obesity and gastroesophageal reflux with hiatal hernia by Lap-Band.

BACKGROUND: Esophageal reflux is common in obese patients. Hiatal hernia is considered a potential contraindication to placement of a Lap-Band. METHODS: Esophageal investigation in patients who were candidates for a Lap-Band included clinical evaluation of symptoms (scoring system), endoscopic and radiologic evaluation, 24-h pH test, and stationary manometry. Patients with gastroesophageal reflux (GER) with or without hiatal hernia underwent the Lap-Band procedure. RESULTS: GER was diagnosed in 12/40 morbidly obese patients, 11 of whom received a standard Lap-Band (3 patients were radiologically diagnosed with transient hiatal hernia). One patient with a large hiatal hernia underwent closure of the diaphragmatic esophageal hiatus, and the Lap-Band was positioned similarly to an Angelchik prosthesis. All but 1 patient who was lost at follow-up were symptom-free (range 1-24 months). CONCLUSION: GER with or without hiatal hernia is not a contraindication for obese patients undergoing a Lap-Band procedure. It accomplishes by a single operation satisfactory treatment of these two disturbing diseases.

Follow-up of Lap-Band complications.

BACKGROUND: Proximal gastric pouch dilation (PGPD) and band dislocation (BD) are the most frequent complications of laparoscopic adjustable silicone gastric banding (LASGB). METHODS: Conservative treatment of PGPD and BD was attempted in all patients by deflation of the band. In the case of failure, laparoscopic exploration was performed. RESULTS: From January 1996 to July 1998, 8 of 40 patients who underwent LASGB experienced PGPD (n = 7) or BD (n = 1). Debanding was performed in 3 patients with PGPD, while in 4 the pouch dilation was successfully treated with deflation of the band. Two patients (PGPD and BD) were treated with band repositioning. Weight loss was not influenced in patients treated conservatively, compared with patients who did not experience complications. CONCLUSIONS: PGPD and BD are not always responsible for band failure in LASGB. Conservative treatment can be successful, and repositioning of the band is feasible in selected cases.

Conversion of Lap-Band to gastric bypass for dilated gastric pouch.

An 18-year-old female who had undergone a laparoscopic adjustable gastic banding developed several episodes of gastric pouch dilatation (GPD), treated conservatively. The last GPD (31 months after Lap-Band placement) involved the lesser curvature of the stomach and was refractory to medical treatment. Conversion to an open gastric bypass was performed. Gastric bypass is an option in the case of Lap-Band failure.

Neoadjuvant chemotherapy in locally advanced gastric-cancer - preliminary-results of a phase-ii trial with a modified famtx combination.

Twenty-two patients with locally advanced inoperable gastric cancer received neoadjuvant chemotherapy with a modified 5-fluorouracil, doxorubicin, methotrexate (FAMTX) regimen. The patients who achieved at least a stable disease were considered eligible for surgery with curative intent, which was performed in 19 cases. 16 patients (all responsive to neoadjuvant chemotherapy) were rendered disease-free by the combined approach. No treatment-related deaths occurred; grade III leukopenia was observed in only 3 cases. The preliminary results of this study indicate the feasibility of our treatment approach; randomized trials are awaited to properly evaluate the role of neoadjuvant chemotherapy in locally advanced gastric cancer.

Intraperitoneal adjuvant immunochemotherapy in operable gastric cancer with serosal involvement.

Since the peritoneal cavity is the most common site of initial recurrence in patients after surgery for gastric cancer, an intraperitoneal (IP) adjuvant treatment was tested in patients with resected gastric cancer with serosal involvement. Between March 1986 and September 1991, 44 consecutive patients with resected T3/T4-N0/N+ gastric cancer were given an IP combination, including cisplatin or carboplatin, etoposide, and alpha interferon-2b. The overall survival of these patients was compared with that observed in 47 historical controls (admitted to the same institutions from 1983 to 1986) with similar prognostic characteristics, who had not received adjuvant treatment after surgery. No major complication relating to the IP route was observed. Mild to moderate abdominal pain occurred in nine patients. Grade 3-4 myelotoxicity occurred in 14 patients. Interferon had to be reduced in five patients and suspended in one because of severe fatigue. Emesis occurred in 23/28 patients given cisplatin and 9/16 given carboplatin. At the time of this analysis (September 1992) median follow-up was 42 months (range 12-78) in the group receiving IP treatment, and 97 months (range 74-128) in the historical controls. There had been 20 deaths among treated patients compared with 36 in the control group. The 5-year estimated survival rate was significantly better in the patients who received IP adjuvant treatment (44% +/- 9 versus 23% +/- 6; P = 0.016). Using the Cox proportional hazard model with a backward procedure to correct for the influence of prognostic pretreatment variables, IP treatment again afforded a significant advantage in terms of survival (P = 0.04). Adjuvant IP immunochemotherapy appears to improve prognosis compared with historical controls in patients having operable gastric cancer with serosal infiltration.

The early effects of intravenous L-propionyl carnitine on ulcerative trophic lesions of the lower limbs in arteriopathic patients: a controlled randomized study.

Large numbers of patients with severe peripheral arteriopathic disorders (Stage IV) present a characteristic clinical history of pain and ulcerative trophic lesions requiring either major or minor amputation. Recent studies have shown that L-propionyl-carnitine (LPC) can possibly moderate the tissue damage induced by ischaemia in peripheral arteriopathic disorders. In the present study 12 patients with severe obstructive chronic arteriopathy were treated either with 2 g of LPC (plus heparin and buflomedil) by slow infusion b.i.d, or by placebo plus heparin and buflomedil. In the LPC-treated patients, one lesion was completely healed (17%); two showed a > 50% decrease in the surface of the ulcerative lesion (34%) and three a reduction in such surface < 50% (50%). Control patients showed a reduction < 50% of the ulcerative lesions in two cases (34%), unaltered limits of the ulcer margin in three cases (50%) and worsening of such a lesion in one case. In addition, the LPC-treated patients showed a progressive reduction in the evening pain symptom as monitored by the fewer requested doses of the analgesic compound ketoprofen (77 vs 125 requests for administration in treated and control patients, respectively). The long-term effect of LPC treatment evaluated after three months showed that in treated patients only one minor (digital) amputation was performed, whereas in the control group two patients underwent minor (digital and foot) and one major (above knee) amputations. In conclusion, the results of the present preliminary study suggest that LPC administration can improve the healing of ulcerative lesions, can reduce the need for analgesic medication and can lessen the incidence of amputation.

[Solitary gastric plasmacytoma. Case report and review of the literature]. / Plasmocitoma solitario gastrico. Caso clinico e revisione della letteratura.

The authors report a case of extramedullary gastric plasmacytoma followed from the clinical onset of the disease until the death of the patient. The literature on this topic was reviewed. The male patient underwent total gastrectomy with left splenopancreatectomy when he was 40 years old; after surgery followed by adjuvant chemotherapy and radiotherapy, the plasmacytoma relapsed; the patient died 4 years after the first operation. Gastric plasmocytoma is a rare pathological entity; different postsurgical therapeutical approaches are derived from the inclusion of this gastric neoplasm in the lymphomas or in the extramedullary plasmacytomas. The authors emphasize a better response of the disease to adjuvant chemotherapy than to radiotherapy after surgery. it suggests the necessity of a separation of gastric plasmacytomas from the other gastric lymphomas.

Biliary leaks after laparoscopic cholecystectomy. Results of the endoscopic treatment.

BACKGROUND: Significant postoperative bile leaks occur in approximately 0.8 to 1.1% of patients. The goal of endoscopic therapy is to eliminate the transpapillary pressure gradient, thereby permitting preferential transpapillary bile flow rather than extravasation at the site of leak. METHODS. Sixty-four patients were retrospectively evaluated. Endoscopic treatment comprised endoscopic sphincterotomy followed by insertion of a naso-biliary drainage or a stent. Retained stones were extracted by standard procedures. RESULTS: The cystic duct remnant was the site of bile extravasation in 50 cases, ducts of Luschka were the source in 4 cases, common bile duct in 6 cases and common hepatic duct in 4 cases. Retained bile duct stones were detected in 21 cases and papillary stenosis in 4 cases. Endoscopic therapy involved sphincterotomy in 25 cases with stones extraction in 21 cases followed by nasobiliary drain insertion, and placement of stent in the remainder. Bile leaks resolved in 96.9% of patients, on average 3 days in cases of associated stones or papillary stenosis, and 6.5 days in the remainder. Two cases of mild pancreatitis were evidenced from endoscopic treatment. CONCLUSIONS: Endoscopic management is the treatment of choice for postcholecystectomy bile leaks.