Molecular profiling of pediatric and young adult colorectal cancer reveals a distinct genomic landscapes and potential therapeutic avenues.

Colorectal cancer (CRC) is a global health concern, and the incidence of early onset (EO) CRC, has an upward trend. This study delves into the genomic landscape of EO-CRC, specifically focusing on pediatric (PED) and young adult (YA) patients, comparing them with adult (AD) CRC. In this retrospective monocentric investigation, we performed targeted next-generation sequencing to compare the mutational profile of 38 EO-CRCs patients (eight PED and 30 YA) to those of a 'control group' consisting of 56 AD-CRCs. Our findings reveal distinct molecular profiles in EO-CRC, notably in the WNT and PI3K-AKT pathways. In pediatrics, we observed a significantly higher frequency of RNF43 mutations, whereas APC mutations were more prevalent in adult cases. These observations suggest age-related differences in the activation of the WNT pathway. Pathway and copy number variation analysis reveal that AD-CRC and YA-CRC have more similarities than the pediatric patients. PED shows a peculiar profile with CDK6 amplification and the enrichment of lysine degradation pathway. These findings may open doors for personalized therapies, such as PI3K-AKT pathway inhibitors or CDK6 inhibitors for pediatric patients. Additionally, the distinct molecular signatures of EO-CRC underscore the need for age-specific treatment strategies and precision medicine. This study emphasizes the importance of comprehensive molecular investigations in EO-CRCs, which can potentially improve diagnostic accuracy, prognosis, and therapeutic decisions for these patients. Collaboration between the pediatric and adult oncology community is fundamental to improve oncological outcomes for this rare and challenging pediatric tumor.

Superior rectal artery preservation to reduce anastomotic leak rates in familial adenomatous polyposis patients treated with total colectomy and ileorectal anastomosis.

BACKGROUND: Total colectomy with ileorectal anastomosis (TC/IRA) is one of the prophylactic surgical options in patients with familial adenomatous polyposis (FAP). This study investigated the effectiveness of superior rectal artery (SRA) preservation during TC/IRA in reducing anastomotic leakage (AL). METHODS: This retrospective study was based on prospectively collected data (01/2000 - 12/2022) at the National Cancer Institute, Milan, Italy. FAP patients undergoing TC/IRA were enrolled. A 1:1  propensity score matching (PSM) was performed. Associations between SRA preservation and complications were investigated using univariate and multivariate analysis. RESULTS: The study population included 211 patients undergoing TC/IRA (Sex: 106 Male, 105 Female; Age: median 30 yrs, IQR: 20-48 yrs), 82 with SRA preservation (SRA group) and 129 without SRA preservation (controls). After PSM, 75 patients were considered for each group. SRA preservation was associated with fewer complications (OR 0.331, 95% CI 0.116; 0.942) in univariate logistic regression analysis. AL events were significantly fewer in the SRA group than in the control group (0 vs 12, p = 0.028). The SRA group had fewer overall surgical complication and pelvic sepsis rates (p = 0.020 and p = 0.028, respectively). Median operative time was significantly longer in the SRA group (340 min vs 240 min, p<0.001), and median hospital stay was significantly shorter (6 vs 7 days, p=0.017). Twenty-seven patients in the SRA group experienced intraoperative anastomotic bleeding, which was controlled endoscopically. Superimposable results were obtained analyzing the whole patient cohort. CONCLUSIONS: SRA preservation can be considered an advantage in this patient population, despite adding a further technical step during surgery and thereby prolonging the operative time. Intraoperative endoscopic checking of possible anastomotic bleeding sites is recommended.

Thrombolytic therapy for delayed occlusion of knitted Dacron bypass grafts in the axillofemoral, femoropopliteal and femorotibial positions.

Selective intra-arterial streptokinase therapy successfully reopened ten axillofemoral and lower extremity Dacron bypass grafts that had undergone delayed closure from two to 47 months after implantation. In four, completion arteriograms revealed no runoff obstruction acquired since implantation; additional runoff obstruction had developed in the remaining six. All of the grafts without obstruction have remained open from two to 11 months. Three of the six grafts with obstruction have remained open from two and one-half to four months after specific surgical correction of the obstructive lesion. We conclude that intra-arterial streptokinase therapy is an effective means to reopen knitted Dacron grafts that have undergone delayed closure in the axillofemoral and above-knee femoropopliteal positions.

Radiologic and histologic differentiation of neuromuscular disorders of the gastrointestinal tract: visceral myopathies, visceral neuropathies, and progressive systemic sclerosis.

Forty patients with neuromuscular disorders of the gastrointestinal tract were evaluated histologically and radiologically. Eighteen patients with progressive systemic sclerosis had predominant circular muscle thinning and fibrosis. Visceral myopathy (11 patients) was characterized by vacuolar degeneration of the smooth muscle cells with thinning and fibrosis typically affecting the longitudinal layers. Visceral neuropathy (five patients) had degeneration of myenteric plexus neurons with various patients having intranuclear inclusions, Schwann cell proliferation, or inflammatory cell infiltration. Radiologically, these syndromes had diffuse abnormalities of gastrointestinal motor function manifested by small and large intestinal dilatation, esophageal hypomotility (progressive systemic sclerosis and visceral myopathy), or disordered hypercontractility (visceral neuropathy). Marked duodenal enlargement typified visceral myopathy, and although all types may have dilated small intestine, only progressive systemic sclerosis has packing of valvulae. Colonic sacculations were found in progressive systemic sclerosis, lack of haustrations and increased colonic caliber in visceral myopathy, and hypercontractility in visceral neuropathy. Complete barium contrast examination will assist in differentiation of true obstruction from pseudoobstruction, will define the diffuse nature of the syndrome, and will help establish an accurate diagnosis by identifying features specific for these entities.

Acute myocardial ischemia detected in vivo by computed tomography.

Normal and acutely ischemic myocardium was imaged by dynamic computed transmission tomography (CT) in dogs during injection of contrast material. The rotary fan-beam CT scanner used could obtain 16 sequential, ungated, 3.0-second scans at 13-20-second intervals. Time-attenuation curves of myocardial enhancement, which were constructed from serial CT images of normally functioning anterior and lateral left ventricular myocardium, demonstrated mean +/- SEM baseline values: 37 +/- 3.3 and 32 +/- 4.0 CT#s; mean +/- SEM peak enhancement: 72 +/- 4.1 and 73 +/- 3.9 CT#s; and decay in enhancement having mean +/- SD time constants: 3.12 +/- 0.27 and 3.17 +/- 0.22 minutes. Regions of acutely ischemic myocardium demonstrated lower but not significantly different baseline values (mean +/- SEM = 25 +/- 4.3 CT#s) from normal (mean +/- sEM = 37 +/- 3.3 CT#s), without a peak and decay in enhancement. The authors conclude that regions of experimentally-produced acute ischemia are readily detected in vivo by dynamic CT imaging as absent or markedly reduced myocardial contrast enhancement.