Brief Report: Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion

Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers.     

Money and trust among strangers

What makes money essential for the functioning of modern society? Through an experiment, we present evidence for the existence of a relevant behavioral dimension in addition to the standard theoretical arguments. Subjects faced repeated opportunities to help an anonymous counterpart who changed over time. Cooperation required trusting that help given to a stranger today would be returned by a stranger in the future. Cooperation levels declined when going from small to large groups of strangers, even if monitoring and payoffs from cooperation were invariant to group size. We then introduced intrinsically worthless tokens. Tokens endogenously became money: subjects took to reward help with a token and to demand a token in exchange for help. Subjects trusted that strangers would return help for a token. Cooperation levels remained stable as the groups grew larger. In all conditions, full cooperation was possible through a social norm of decentralized enforcement, without using tokens. This turned out to be especially demanding in large groups. Lack of trust among strangers thus made money behaviorally essential. To explain these results, we developed an evolutionary model. When behavior in society is heterogeneous, cooperation collapses without tokens. In contrast, the use of tokens makes cooperation evolutionarily stable.     

Bronchial carcinoid tumors: clinical and radiological correlation

PURPOSE: To evaluate the incidence of bronchial carcinoid tumor (BCT) in population affected by various lung tumors, retrospectively reviewed between 1986-2001, and to emphasize the radiographic patterns if they are characteristic. MATERIALS AND METHODS: In the above mentioned period, chest x-ray and CT were performed in 1110 patients, both male and female, affected by lung neoplasms. RESULTS: 20 patients were affected by BCT (16 males, and 13 females), aged between 26 and 75 years (mean age 57.5), with histopathologic diagnosis of typical (9 cases, 31%) and atypical (20 cases, 69%) bronchial carcinoid tumors. Localized right lung lesion were as follows: 7 cases in superior, 9 in middle and 4 in inferior lobes; in the left lung, 5 cases in superior, and 4 in inferior lobes. Size of the lesions was as average 2.4 cm in diameter (with a range of 0.5-12 cm). On x-ray and CT images, BCT appeared as a well marginated nodule, of which 9 were peripheral and 20 central. DISCUSSION AND CONCLUSION: BCT are classified as neuroendocrine carcinomas,and are divided in typical and atypical forms, with variable grade of malignancy. Central neoplasms are symptomatic due to bronchial obstruction (i.e., pneumonia, atelectasis, bronchiectasis, emphysema and/or lung abscess); if airway obstruction is partial, then cough, wheezing and recurrent pulmonary infections occur. Peripheral tumors are generally asymptomatic and they are discovered occasionally, when chest x-ray is made for other reasons. Radiographic features are similar in typical and atypical BCT. In central tumors a rounded well circumscribed hilar mass is noted, with lobulated or bumpy margins. Central cavitation is not referred to. Peripheral BCT appear as a solitary nodule, inferioer then 3 cm in size, marginated, surrounded by normal pulmonary tissue. Signs and symptoms of BCT are evasive and vague. No current clinical or laboratory procedures are useful in confirming the diagnosis; particularly, no imaging modalities are able to differentiate between BCT and other pulmonary tumors. For this reason, a clinical radiologic endoscopic and histopathologic approach is necessary. CT is more sensiticve then conventional radiography, especially in detecting small lesions, calcification and enlarged lymph nodes. MRI may be useful in those patients, who cannot tolerate IV contrast media. Scintigraphy may be employed in discovering relapses and long standing metastases.     

Endorectal coil MRI in local staging of rectal cancer

PURPOSE: The choice of the therapeutic strategies in patients affected with rectal cancer is strictly dependent by the tumor stage. So, in order to obtain an improvement in preoperative staging accuracy, new imaging modalities are now under investigation. The aim of this work is the evaluation of endorectal-coil MRI in the local staging of rectal cancer. MATERIAL AND METHODS: Fourty-three patients affected with histologically proven rectal cancer, have been evaluated by an high-field strength magnet (1.5 T). In 14/43 patients neoadjuvant pre-operative chemotherapy had been previously performed. In all cases axial SE T1w and FSE T2w sequences and coronal or sagittal FSE T2w sequences, with and without fat suppression, were performed. Basing upon the TNM staging system and the previously reported MRI signs the local extent of the tumor was evaluated, focusing about the rectal wall infiltration and the perirectal lymph nodes involvement. All the patients underwent surgery and a comparative evaluation of MRI and pathological staging was done. RESULTS: At MRI the tumor was detected in 38/43 patients. In evaluating wall infiltration the MRI results agreed with pathological results in 89% of patients and showed 92% accuracy in T1-T2 stage and 94% in T3. In evaluating perirectal lymph nodes metastases MRI showed 69% accuracy, 82% sensitivity and 55%specificity. DISCUSSION AND CONCLUSIONS: The poor accuracy of CT and body-coil MRI in evaluating wall involvement in patients with rectal cancer is mainly related to their inability to demonstrate the single layers of the rectal wall. So transrectal ultrasound is now the first choice modalitiy in local staging of rectal cancer. However transrectal ultrasound showed low sensitivity in detecting perirectal lymph nodes metastases and low accuracy in evaluating the patients previously undergone to neoadjuvant chemotherapy or radiotherapy. On the other hand the improvement of MRI sequences and the availability of the endorectal coils allowed to visualize the single layers of the rectal wall so making the endorectal-coil MRI a reliable imaging technique to stage rectal cancer. The results of our work demonstrate a good diagnostic accuracy of endorectal-coil MRI in local staging of rectal cancer, in particular the degree of rectal wall infiltration was well demonstrated, while the perirectal lymph nodes metastases were demonstrated with less accuracy. The long examination time, the costs and the movement-related artefacts are the main limits of MRI. In particular the movement-related artifacts sometime do not allow the visualization of the wall layers so lowering the diagnostic accuracy in demonstrating the tumor wall infiltration. In conclusion, even though endorectal coil MRI proved to be a reliable imaging technique in local staging of rectal cancer, at present we are not able to state what may be its real role in diagnostic evaluation of the patients with rectal cancer, in particular if compared to endorectal ultrasound. Further, comparative studies, based upon larger patients series are probably needed to draw a definitive conclusion.     

Adjuvante simultane Radiochemotherapie nach operiertem Uteruszervixkarzinom in der High-Risk-Situation Ergebnisse einer Pilotuntersuchung

BACKGROUND: The most important factors for prognosis of cervical cancers are age and histological criteria such as the tumor size, the involvement of lymph nodes, lympho-vascular space involvement as well as microvessel involvement and poor tumor differentiation (grading 3). Here we present the results of concomitant chemo-radiation at high-risk situation of patients with cervical cancer after surgery. PATIENTS AND METHODS: The study comprised 34 patients with median age of 40 years (26-63 years) after Wertheim surgical technique for cervical cancer at the FIGO Stages IB (n = 19) and IIB (n = 15). All patients were treated between November 1995 and June 1999 by a schedule of concomitant chemoradiation. The indication for this treatment was given by the positive histological proof of lymph node metastasis, microvessel or lympho-vascular space involvement as well as a G3 grading. The chemo-therapy was given in week 1 and 5 (day 1-5 and day 29-33). The dosage of cisplatin was 20 mg/m2/d on every day and 5-FU was given as a 120-h infusion with 600 mg/m2/d. The external beam radiotherapy was applied to the pelvis with 1.8 Gy per fraction up to 50.4-54 Gy. In two patients the paraaortal region was irradiated too because of the involvement of these lymph nodes. RESULTS: The median observation time was 48 months (3-68 months). 30 patients are alive (88%) in complete response. Four patients died. The mean survival was 61 +/- 3 months. We have seen only slight acute toxicities of grade 1 and 2. Three patients suffered from a grade 3 diarrhea and three patients developed a grade 3 leukopenia. In seven patients we found a secondary lymphedema as a late toxicity. CONCLUSION: The concomitant chemoradiation containing cisplatin in high-risk situation for cervical cancer after surgery improves the outcome and survival in these patients.     

A simplified technique for the en bloc procurement of abdominal organs that is suitable for pancreas and small-bowel transplantation

BACKGROUND: Graft shortage makes multiorgan procurement mandatory. We describe the results of a simplified method for the en bloc procurement of multiple organs, which permits isolated transplantation of all abdominal grafts, including the pancreas and the small bowel, to different recipients. METHODS: Three hundred forty-three multiorgan procurements were done with a simplified en bloc technique. RESULTS: None of the 1374 grafts that were procured sustained injuries that potentially precluded transplantation. Seventy-two grafts that were procured from 18 donors (5%) who were diagnosed with a neoplasm were discarded. Overall, 339 grafts that were procured from 325 donors were discarded because of specific contraindications, and 963 grafts (74%) were transplanted. Ninety-seven pancreata were transplanted. In 3 instances the pancreas and the small bowel were procured simultaneously and transplanted to different recipients. A total of 287 liver grafts were also transplanted at 13 different institutions. In 42 instances, the liver was not allocated to our center. Forty liver teams (95%) from 11 different institutions agreed to procure their grafts according to the simplified en bloc technique. Our team performed 18 procurements, and a surgeon from the liver transplantation team, who was assisted by one of the members of our team, performed 22 procurements. In all, 576 kidneys were transplanted, either alone or simultaneously, with other abdominal grafts at 15 different institutions. CONCLUSIONS: This procurement method has high yields, allows pancreas and small-bowel procurement, and can be learned readily.     

Endoscopic treatment of colorectal polyps in a digestive endoscopy outpatient department

The aim of this report was to evaluate the effectiveness of the endoscopic treatment of colonic polyps to allow secondary prophylaxis in order to prevent the onset of cancer arising from adenomas. From October 2002 to January 2004 we performed 487 colonoscopies on a patient group with the following indications: screening prior to kidney transplant; screening for colorectal cancer (patients positive at faecal occult blood testing); follow-up of patients who had undergone colonic resections for colorectal cancer; patients with other diseases. Colorectal polyps were diagnosed in 15 males and 15 females, with a mean age of 63 years. All the neoplasms were resected during colonoscopy and specimens sent for histological study. The histological examinations yielded the following results: 4 hyperplastic polyps; 9 tubular adenomas (6 with mild, 2 with mild-to-moderate, and 1 with severe dysplasia); 8 tubulo-villous adenomas (3 with mild, 1 with mild-to-moderate, and 4 with moderate dysplasia); 4 villous adenomas (3 with mild and 1 with severe dysplasia); 1 adenocarcinoma; 1 inflammatory polyp; in 3 cases we were unable to retrieve the polyps after polypectomy. Colonoscopic detection of a neoplasm allows us to remove it and send to the pathology laboratory for definitive histological diagnosis. Moreover, snare polypectomy can be a radical treatment for dysplastic polyps without stromal axis and basal membrane infiltration. We therefore conclude that colonoscopy allows not only early diagnosis of colonic neoplasms, but also radical curative treatment in the early stages.