The pathology and treatment of pediatric obesity-related asthma

There is clear evidence that obesity and asthma are among today’s most prevalent, threatening, and burdensome childhood afflictions. Research strongly suggests that these two disorders, when occurring concurrently, are in fact, a distinct disease state. There exists two prominent asthma phenotypes, both of which are related in different degrees with obesity. These are early-onset, atopic and late-onset, non-atopic obesity-related asthma. The linkage between obesity and asthma is complex as both disorders cause a variety of metabolic and immunological changes that can affect different, yet interconnecting compartments and functions of the body. The main objective of this review is to summarize the principal findings that pathologically link obesity and asthma and the pharmacologic and non-pharmacologic therapies that are currently in use to combat this disorder

Association between hMLH1 hypermethylation and JC virus (JCV) infection in human colorectal cancer (CRC)

Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence

A shift from distal to proximal neoplasia in the colon: a decade of polyps and CRC in Italy

<p>Abstract</p> <p>Background</p> <p>In the last years a trend towards proximalization of colorectal carcinomas (CRC) has been reported. This study aims to evaluate the distribution of CRC and adenomatous polyps (ADP) to establish the presence of proximalization and to assess the potential predictors.</p> <p>Methods</p> <p>We retrieved histology reports of colonic specimens excised during colonoscopy, considering the exams performed between 1997 and 2006 at Cuneo Hospital, Italy. We compared the proportion of proximal lesions in the period 1997-2001 and in the period 2002-2006.</p> <p>Results</p> <p>Neoplastic lesions were detected in 3087 people. Proximal CRC moved from 25.9% (1997-2001) to 30.0% (2002-2006). Adjusting for sex and age, the difference was not significant (OR 1.23; 95% CI: 0,95-1,58). The proximal ADP proportion increased from 19.2% (1997-2001) to 26.0% (2002-2006) (OR: 1.43; 95% CI: 1.17-1.89). The corresponding figures for advanced proximal ADP were 6.6% and 9.5% (OR: 1.48; 95% CI: 1.02-2.17). Adjusting for gender, age, diagnostic period, symptoms and number of polyps the prevalence of proximal advanced ADP was increased among people ≥ 70 years compared to those aged 55-69 years (OR 1.49; 95% CI: 1.032.16). The main predictor of proximal advanced neoplasia was the number of polyps detected per exam (> 1 polyp versus 1 polyp: considering all ADP: OR 2.16; 95% CI: 1.59-2.93; considering advanced ADP OR 1.63; 95% CI: 1.08-2.46). Adjusting for these factors, the difference between the two periods was no longer significant.</p> <p>Conclusions</p> <p>CRC do not proximalize while a trend towards a proximal shift in adenomas was observed among people ≥ 70 years.</p

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability (P<0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients

Multiagent chemopreventive agent combinations

Cancer chemoprevention is a new discipline whose foundation rests upon epidemiologic evidence suggesting that dietary components such as beta-carotene, vitamin E, calcium and selenium may be inhibitors of carcinogenesis. Over the last decade, as molecular and biochemical mechanisms of the carcinogenesis process have been elucidated, the rationale of combining chemopreventive agents to target multiple pathways has strengthened. The process of identifying potential synergistic combinations of chemoprevention agents should be based upon a systematic process of preclinical development in vitro followed by testing in animal models of carcinogenesis. Surrogates of anticarcinogenesis effects might include biochemical, molecular and pathologic assessment of tissue from animal carcinogenesis models. If evidence of chemopreventive effect is found in animal models, systematic studies in humans are indicated. These studies should include a careful Phase I trial to describe optimal chemoprevention doses for all agents being tested in combination followed by Phase II trials to assess efficacy upon carcinogenesis biological and pathological surrogates. J. Cell. Biochem. Suppl. 34:121–124, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34899/1/19_ftp.pd

WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis

Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.Peer reviewe

The Novel Use of Rare Earth Magnets for the Extraction of Metallic Soft Tissue Foreign Bodies in Children

INTRODUCTION: Metallic foreign bodies (mFB) are common following penetrating injuries in children. The mFB commonly occur in the head and neck region and extremity soft tissues. Removal may be indicated due to morbidity related to pain or migration. Extraction can be challenging to localize, often requiring wide exposure, and may be difficult to achieve in cosmetically sensitive areas. Different technological adjuncts have been used to facilitate foreign body removal including fluoroscopy, ultrasound, and more recently in adults, surgical magnets. The most powerful commercially available magnets are rare earth magnets comprised of neodymium iron and boron (Ndy). With the goal of reducing radiation exposure and the morbidity of mFB removal with associated soft tissue injury in children, a strategy was introduced utilizing Ndy to optimize extraction with minimal soft tissue surgical dissection. MATERIALS AND METHODS: Two children with extremity mFB treated with Ndy between January 2021 and July 2021 were analyzed. We utilized commercially available ring type neodymium-iron-boron magnets with dimensions of 1 3/8-inch outer diameter x 1/8-inch inner diameter and 1/16 inch thick with a power of 13 200 gauss that were processed for use according to our hospital protocols. Our main clinical indication was for the detection and retrieval of small ferromagnetic foreign bodies embedded in superficial extremity soft tissues. RESULTS: In the operating room under general anesthesia, the mFB were localized utilizing fluoroscopy. A 1.0 cm skin incision was made into the subdermal soft tissues overlying the area of the mFB. No surgical tissue dissection was performed. The mFB could not be visualized in the soft tissue. Using fluoroscopy to localize the mFB, the Ndy was then placed into the wound in close proximity to the mFB. The mFB were immediately magnetized to the Ndy and the mFB were extracted from the soft tissues without any further surgical dissection. Two simple interrupted nylon sutures were placed to close the incision. The total operative time was 2 and 2.5 minutes respectively. The children recovered uneventfully and are without complication. CONCLUSIONS: The use of Ndy to remove extremity soft tissue mFB in children appears to be feasible, safe, and efficient. Use of the Ndy allowed extraction via a small incision, optimizing the aesthetic result and avoiding the need for cross-sectional imaging, extensive surgical dissection, tissue reconstruction and prolonged operative time or x-ray exposure. The development of magnets of increasing energy density may be indicated to further optimize metallic soft tissue foreign body extraction in children in a minimally invasive manner

A novel low cost minimally invasive surgical system allows for the translation of modern pediatric surgical technology to low- and middle-income nations

BACKGROUND: There is a critical need for pediatric surgical humanitarian care. The role of minimally invasive surgery (MIS) in these environments with its reduction in pain and wound care, operative time, length of hospitalization, and morbidity is logical. However, the costs, logistics and feasibility of MIS in Low- and Middle-Income Countries (LMIC) can be challenging. Our goal was to develop a new low cost rapidly deployable minimally invasive surgical system (RDMIS) for use during remote pediatric general surgical (GPS) missions in LMIC. METHODS: RDMIS system components consist of a universal serial bus (USB) interfaced laparoscopic camera, portable computer and a battery powered wireless portable laparoscopic light source. The surgeon transports the RDMIS in a single standard carry-on luggage. Utilizing prepositioning logistics from prior World Pediatric GPS missions, a standard MIS tower system (sMIS) was maintained on site. RESULTS: The RDMIS was utilized to carry out procedural components of laparoscopic appendicostomy and laparoscopic cholecystectomy. Both sMIS and RDMIS were interchanged during the cases to allow for subjective comparison of surgical exposure and visualization. The RDMIS system allowed for safe and effective visualization and dissection of surgical structures. All children recovered uneventfully and were discharged the following day and have had no complications. The RDMIS system costs were significantly less than those of sMIS. CONCLUSIONS: RDMIS appears to be a safe, inexpensive option that will allow for the translation of modern MIS technology during GPS in remote locations. Further studies validating the RDMIS are indicated, however, the lower costs, ease of transport and potential benefit to children in the LMIC may be significant