Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign”

Most patients diagnosed with pancreatic cancer are classified as nonoperative candidates based on the contemporary guidelines of resectability. The advent of more potent control of systemic disease using neoadjuvant chemotherapy has enabled more aggressive operative interventions. In our multidisciplinary practice, patients with Stage III, locally advanced pancreatic cancer and superior mesenteric artery (SMA) encasement are now carefully triaged with high quality, preoperative imaging to determine if they can be considered candidates for operative resection with periadventitial dissection of the SMA. Patients displaying a “halo sign,” where the encased SMA remains fully patent and free from arterial invasion, are now candidates for SMA periadventitial dissection. This procedure involves the surgical stripping of the infiltrated neurolymphatic tissue off the SMA leaving behind a bare “skeletonized artery.” Alternatively, the “string sign” involving the SMA confers a more likely case of arterial invasion, where a complete oncologic resection cannot be achieved successfully. This method of patient selection in case of SMA involvement abandons the traditional metrics of circumferential degrees of the arterial encasement to guide surgical decisions. Our institutional approach has allowed us to meaningfully expand our operative methods of resection with the potential for improved longitudinal outcomes to pancreatic cancer patients who were deprived historically from the more effective and possibly curative treatment.     

Time for a More Holistic Approach to Peri-Pancreatoduodenectomy Care

Annals of Surgical Oncology -     

Digital image-analysis of nuclear morphometry, DNA-ploidy and AgNORs in breast-carcinoma cell imprints

A series (n = 322) of breast carcinomas was investigated from 1991 to 1993 using digital image analysis. Nuclear morphometry and DNA content, and AgNORs were evaluated on cell imprints from fresh tissue samples which were further stored frozen (-80-degrees-C). Data were correlated to morphological prognostic factors and immunocytochemical expression of cell markers assessed on frozen sections and evaluated by densitometry after image analysis processing. Nuclear morphometric parameters, DNA nuclear content and AgNORs were independent from the tumor size, histological grades, and the tumor content of immunodetectable pHER-2/neu, Cathepsin D, ER, PR, pS2, and p53. But, DNA index and hyperploidy degree correlated with the mitosis index (p < 0.01) and Ki67 immunostaining (p = 0.003, p < 0.0001) whereas the shape factor and nucleus large diameter correlated with the degree of cell anisocytosis (p < 0.01). Nuclear surface and large diameter were greater in ductal carcinomas (p = 0.028) and in comedocarcinomas (p < 0.001) than in lobular carcinomas. These results suggest that image analysis processing provides accurate data to refine histoprognostic grading and additional parameters to evaluate tumor proliferative activity.     

Immunotherapeutic targets in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.     

Gallbladder Findings after Cholecystectomy in Morbidly Obese Patients

Morbidly obese patients constitute a high risk group for the development of gallbladder disease. In our series 70 consecutive patients underwent vertical gastroplasty in an effort to manage morbid obesity. The mean age was 37 years (range 20-60), and the mean excess body weight was 92 kg (range 52-265). Six patients (8.5%) had undergone cholecystectomy before bariatric surgery because of symptomatic cholelithiasis. The remaining 64 patients underwent cholecystectomy at the time of vertical gastroplasty. Ninety-seven percent of the removed gallbladders had gross or histologic abnormalities, including cholelithiasis 18.5% (13 patients), and cholesterolosis 31% (22 patients). Histologically, chronic cholecystitis was present in all patients with cholelithiasis and cholesterolosis. Chronic cholecystitis alone was found in 27 patients (38.5%) and only two patients (3%) had normal findings. The mean excess body weight of the patients with cholesterolosis (96 kg) was not significantly greater than that of patients with cholelithiasis (89 kg) or chronic cholecystitis (88 kg). Our findings suggest that cholecystectomy should be performed in all morbidly obese patients concomitant with vertical gastroplasty.     

In-vivo and in-vitro evaluations for the effect of cyclophosphamide on the carcinogen metabolizing system of mouse-liver microsomes

The effect of the antineoplastic immunosuppressive alkylating agent cyclophosphamide (CPhA) on the modification of the carcinogen-metabolizing capacity was studied in vivo in mouse liver microsomes at different durations of treatment, from one to six consecutive days. The in vitro effect of increasing concentrations of the drug upon this enzyme system was also investigated. Following the administration of CPhA, a significant time-dependent decrease was observed in the activity of the low substrate level of the hepatic microsomal N-nitrosodimethylamine demethylase (NDMAdII). The high substrate level of the enzyme (NDMAdII) also exhibited a similar decrease which was not a subject for the treatment intervals where the greatest decrease (-60%; p<0.05) emerged at day 3 of the administration-point. The activity of the aryl hydrocarbon (benzo(alpha)pyrene) hydroxylase (AHH) revealed a significant increase at the single dose of CPhA, while at the repeated dose treatment (for 3 days) no alteration was noticed in the enzyme activity. This figure of expression in AHH was reversed to a significant inhibition at the 6 day-repeated dose, the time-point at which an almost identical effect was also observed in the hepatic content of cytochrome P450. The alterations in the metabolism of NDMA and benzo(alpha)pyrene which had been seen in the in vivo assays was further confirmed by the results of the in vitro experiment.