Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis: a pilot study.

BACKGROUND: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. METHODS: A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. RESULTS: We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. CONCLUSION: These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

18F-FDG PET/CT for response assessment in Hodgkin lymphoma undergoing immunotherapy with checkpoint inhibitors.

Our aim was to evaluate Hodgkin Lymphoma (HL) response to checkpoint inhibitors with 18F-FDG PET/CT. Forty three refractory or relapsed HL patients were investigated before immunotherapy, 8 weeks and 17 weeks after administration of either nivolumab or pembrolizumab. The median follow-up was 19 months. Best clinical response was complete response (CR) in 26 patients, partial response (PR) in 5 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 4 patients. At the early assessment, Deauville Score (DS) resulted significantly different in responder group compared to nonresponders. SUVmax was significantly lower in responders, while there was no relevant modification in the tumor burden. At interim evaluation, DS well differentiated responder group. A significant decrease in glucose metabolism and tumor burden parameters was observed in responder patients, who presented with a longer progression-free survival then nonresponders. 18F-FDG PET/CT provides a reliable indication of treatment response under checkpoints inhibitors, even at an early assessment.

Open partial nephrectomy: ancient art or currently available technique?

Renal cell carcinoma (RCC) accounts for 3 % of adult solid tumors, with the highest incidence between 50 and 70 years of age. Nephron-sparing surgery was initially reserved to patients with small renal masses detected in anatomically or functionally solitary kidney or in the presence of multiple bilateral tumors or hereditary forms of RCC, which posed a high risk of developing a tumor in the contralateral kidney. Nowadays, partial nephrectomy (PN) has grown up to an established approach for the treatment of small renal masses. In patients with T1a-staged RCCs, PN has proven to be associated with better survival, long-term renal function preservation with lower dialysis need or renal transplantation. Currently, most of the kidney masses are incidentally detected, up to 40 %, with smaller size due to the widespread use of imaging modalities such as ultrasound, computed tomography and magnetic resonance. Here we review the role of open PN in the management of small renal masses particularly focusing on indications, oncological outcomes and comparison with laparoscopic and robotic PN. Recent studies demonstrate that PN confers better survival, oncologic equivalence and lower risk of severe chronic kidney disease compared to radical nephrectomy becoming then the gold-standard surgical technique, even if increasingly challenged by laparoscopic and/or robot-assisted partial nephrectomy which in the hands of experts seems to achieve comparable outcome results albeit with slightly higher complication rate.

Computer-assisted and fractal-based morphometric assessment of microvascularity in histological specimens of gliomas.

Fractal analysis is widely applied to investigate the vascular system in physiological as well as pathological states. We propose and examine a computer-aided and fractal-based image analysis technique to quantify the microvascularity in histological specimens of WHO grade II and III gliomas. A computer-aided and fractal-based analysis was used to describe the microvessels and to quantify their geometrical complexity in histological specimens collected from 17 patients. The statistical analysis showed that the fractal-based indexes are the most discriminant parameters to describe the microvessels. The computer-aided quantitative analysis also showed that grade III gliomas are generally more vascularized than grade II gliomas. The fractal parameters are reliable quantitative indicators of the neoplastic microvasculature, making them potential surrogate biomarkers. The qualitative evaluation currently performed by the neuropathologist can be combined with the computer-assisted quantitative analysis of the microvascularity to improve the diagnosis and optimize the treatment of patients with brain cancer.

Angioarchitectural heterogeneity in human glioblastoma multiforme: a fractal-based histopathological assessment.

There is currently no standard technique to objectively quantify the microvascularization of brain tumors. Fractal analysis has been proposed as a useful descriptor of tumor microvascularity. Standardization of the fractal analysis methodology could offer a new tool for this type of characterization. In this study, we applied fractal analysis to the characterization of the different angioarchitectures found in specimens of glioblastoma multiforme (GBM), the most common and most malignant type of human brain tumor. A retrospective series of 114 primary GBM specimens was carried out. To quantify neoplastic microvascularity, the level of two-dimensional geometrical complexity of the microvascular patterns was assessed using the box-counting algorithm, which estimates the microvascular fractal dimension (mvFD). mvFD makes information on the non-Euclidean space filled by vessels embedded in the tumor microenvironment available because it depends on vessel number, shape, magnitude and distribution pattern. A mean mvFD value of 1.44 ± 0.17 (range: 1.06-1.87) was found. The coefficient of variation was 44%. The high geometric variability, found objectively, in these samples reflects the angioarchitectural heterogeneity underlying GBM. The present study shows that angioarchitectural subtypes can be identified by mvFD, making this parameter a potential tool for quantifying different neoplastic microvascular patterns.

Biological treatment for liver tumor and new potential biomarkers.

The search for effective and efficacious therapy for liver tumor was started many years ago and is still ongoing. Despite all of the surgical advances, much work needs to be done to improve understanding of the biology of the tumor and its treatment. The rules of hepatic surgery are changing because of two recent major trends: (1) technical simplification, and (2) the endeavor to treat an increasing number of patients. T lymphocytes are potent cellular effectors of the immune system and possess a memory that responds to rechallenge by the same antigen. Being more specific and less toxic than chemotherapy, tumor infusion could be an ideal adjuvant therapy for patients with primary and secondary liver malignancies. Moreover, tumor cell vaccines have demonstrated efficacy in terms of minimal residual disease and are being investigated, but the requirement for an adequate supple of autologos tumor may limit the general applicability of these approaches. Various studies have demonstrated the aberrant expression of germ-cell proteins called cancer-testis (CT) antigens in liver neoplastic cells. Their selective normal-tissue expression makes them ideal antigens for immune targeting of malignant disease. Specific expression of CT antigens also suggests their application as tumor markers to detect circulating hepatocellular carcinoma (HCC) cells, as an adjuvant diagnostic tool, and as indicators for recurrence and prognosis. Biological therapy is now generating more clinical trials. More studies need to be performed and further experiments need to be done, although currently this seems a valid pathway for the treatment of liver cancer. Cytoreduction treatment of liver tumor and the vaccine might be the future of the treatment of primary and secondary liver tumor.