Posterior and Para-Aortic (D2plus) Lymphadenectomy after Neoadjuvant/Conversion Therapy for Locally Advanced/Oligometastatic Gastric Cancer.

Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13-106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13-18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival.

Preliminary Report on Computed Tomography Radiomics Features as Biomarkers to Immunotherapy Selection in Lung Adenocarcinoma Patients.

PURPOSE: To assess the efficacy of radiomics features obtained by computed tomography (CT) examination as biomarkers in order to select patients with lung adenocarcinoma who would benefit from immunotherapy. METHODS: Seventy-four patients (median age 63 years, range 42-86 years) with histologically confirmed lung cancer who underwent immunotherapy as first- or second-line therapy and who had baseline CT studies were enrolled in this approved retrospective study. As a control group, we selected 50 patients (median age 66 years, range 36-86 years) from 2005 to 2013 with histologically confirmed lung adenocarcinoma who underwent chemotherapy alone or in combination with targeted therapy. A total of 573 radiomic metrics were extracted: 14 features based on Hounsfield unit values specific for lung CT images; 66 first-order profile features based on intensity values; 43 second-order profile features based on lesion shape; 393 third-order profile features; and 57 features with higher-order profiles. Univariate and multivariate statistical analysis with pattern recognition approaches and the least absolute shrinkage and selection operator (LASSO) method were used to assess the capability of extracted radiomics features to predict overall survival (OS) and progression free survival (PFS) time. RESULTS: A total of 38 patients (median age 61; range 41-78 years) with confirmed lung adenocarcinoma and subjected to immunotherapy satisfied inclusion criteria, and 50 patients in a control group were included in the analysis The shift in the center of mass of the lesion due to image intensity was significant both to predict OS in patients subjected to immunotherapy and to predict PFS in patients subjected to immunotherapy and in patients in the control group. With univariate analysis, low diagnostic accuracy was reached to stratify patients based on OS and PFS time. Regarding multivariate analysis, considering the robust (two morphological features, three textural features and three higher-order statistical metrics) application of the LASSO approach and all patients, a support vector machine reached the best results for stratifying patients based on OS (area under curve (AUC) of 0.89 and accuracy of 81.6%). Alternatively, considering the robust predictors (six textural features and one higher-order statistical metric) and application of the LASSO approach including all patients, a decision tree reached the best results for stratifying patients based on PFS time (AUC of 0.96 and accuracy of 94.7%). CONCLUSIONS: Specific radiomic features could be used to select patients with lung adenocarcinoma who would benefit from immunotherapy because a subset of imaging radiomic features useful to predict OS or PFS time were different between the control group and the immunotherapy group.

Resectability of Pancreatic Cancer Is in the Eye of the Observer: A Multicenter, Blinded, Prospective Assessment of Interobserver Agreement on NCCN Resectability Status Criteria.

Objectives: To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. Background: The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Methods: Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss' k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed. Results: Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss' k range: 0.282-0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196-0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619-0.756). Neither reviewers' specialty nor hospital volume influenced the agreement. Conclusions: There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.

Current understanding of the role and regulation of miRNAs in Burkitt lymphoma.

Since its discovery in 1958, Burkitt lymphoma (BL) has been extensively studied and has become a model for tumorigenesis, but its pathogenesis has not been completely explained and understood yet. The aim of this review was to summarize the current knowledge about BL and, in particular, to discuss the role of miRNAs in its pathogenesis and their possible use as diagnostic and prognostic indicators. The impact of viral-encoded miRNAs is also discussed, with the Epstein-Barr infection being almost invariably detected in the endemic variant of this tumor.

Pancreatic trauma: The role of computed tomography for guiding therapeutic approach.

AIM: To evaluate the role of computed tomography (CT) for diagnosing traumatic injuries of the pancreas and guiding the therapeutic approach. METHODS: CT exams of 6740 patients admitted to our Emergency Department between May 2005 and January 2013 for abdominal trauma were retrospectively evaluated. Patients were identified through a search of our electronic archive system by using such terms as "pancreatic injury", "pancreatic contusion", "pancreatic laceration", "peri-pancreatic fluid", "pancreatic active bleeding". All CT examinations were performed before and after the intravenous injection of contrast material using a 16-slice multidetector row computed tomography scanner. The data sets were retrospectively analyzed by two radiologists in consensus searching for specific signs of pancreatic injury (parenchymal fracture and laceration, focal or diffuse pancreatic enlargement/edema, pancreatic hematoma, active bleeding, fluid between splenic vein and pancreas) and non-specific signs (inflammatory changes in peri-pancreatic fat and mesentery, fluid surrounding the superior mesenteric artery, thickening of the left anterior renal fascia, pancreatic ductal dilatation, acute pseudocyst formation/peri-pancreatic fluid collection, fluid in the anterior and posterior pararenal spaces, fluid in transverse mesocolon and lesser sac, hemorrhage into peri-pancreatic fat, mesocolon and mesentery, extraperitoneal fluid, intra-peritoneal fluid). RESULTS: One hundred and thirty-six/Six thousand seven hundred and forty (2%) patients showed CT signs of pancreatic trauma. Eight/one hundred and thirty-six (6%) patients underwent surgical treatment and the pancreatic injures were confirmed in all cases. Only in 6/8 patients treated with surgical approach, pancreatic duct damage was suggested in the radiological reports and surgically confirmed in all cases. In 128/136 (94%) patients who underwent non-operative treatment CT images showed pancreatic edema in 97 patients, hematoma in 31 patients, fluid between splenic vein and pancreas in 113 patients. Non-specific CT signs of pancreatic injuries were represented by peri-pancreatic fat stranding and mesentery fluid in 89% of cases, thickening of the left anterior renal fascia in 65%, pancreatic ductal dilatation in 18%, acute pseudocyst/peri-pancreatic fluid collection in 57%, fluid in the pararenal spaces in 45%, fluid in transverse mesocolon and lesser sac in 29%, hemorrhage into peri-pancreatic fat, mesocolon and mesentery in 66%, extraperitoneal fluid in 66%, intra-peritoneal fluid in 41% cases. CONCLUSION: CT represents an accurate tool for diagnosing pancreatic trauma, provides useful information to plan therapeutic approach with a detection rate of 75% for recognizing ductal lesions.

The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: adipophilin.

BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05). CONCLUSIONS: Our preliminary results suggest that lipid metabolism is altered in BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be specifically recognized by a monoclonal antibody against adipophilin, which may therefore be a useful marker for Burkitt lymphoma because of its peculiar expression pattern. Moreover this peptide might represent an interesting candidate for interventional strategies.

EBV Reactivation and Chromosomal Polysomies: Euphorbia tirucalli as a Possible Cofactor in Endemic Burkitt Lymphoma.

Burkitt lymphoma is endemic in the Equatorial Belt of Africa, its molecular hallmark is an activated, MYC gene mostly due to a chromosomal translocation. Especially in its endemic clinical variant, Burkitt lymphoma is associated with the oncogenic Epstein-Barr virus (EBV), and holoendemic malaria acts as an amplifier. Environmental factors may also cooperate in Burkitt lymphomagenesis in the endemic regions, such as plants used as traditional herbal remedies. Euphorbia tirucalli, a plant known to possess EBV-activating substances, has a similar geographical distribution to endemic Burkitt's Lymphoma and is used as a hedge, herbal remedy and toy in the Lymphoma BeltI. In this study we aimed at determining if exposure to Euphorbia tirucalli could contribute to lymphomagenesis, and at which extent. Lymphoblastoid and cord blood-derived cell lines were treated with plant extracts, and the expression of EBV-coded proteins was checked, to assess EBV reactivation. The occurrence of chromosomal translocations was then investigated by FISH. Our preliminary results suggest that E. tirucalli is able to reactivate EBV and determine chromosomal alterations, which leads to c-MYC altered expression. The existence of genomic alterations might determine the accumulation of further genetic alteration, which could eventually lead to a transformed phenotype.

Traditional and new prognosticators in breast cancer: Nottingham index, Mib-1 and estrogen receptor signaling remain the best predictors of relapse and survival in a series of 289 cases.

Histopathological and immunohistochemical findings on tissue microarrays, overall survival (OS), disease-free survival (DFS) and incidence of relapses (R) were recorded and statistically analyzed in 289 breast cancers. A higher R and a shorter DFS were significantly related to larger tumors, lymph node invasion, higher tumor grade, absence of estrogen receptors (ER), triple negative tumors, and presence of lymphovascular invasion (LVI). Longer OS was observed to be significantly associated with smaller tumor size (T), lymph node negativity, lower tumor grade, absence of LVI, lower Mib-1 expression and with the presence of ER. At multivariate analysis, only T for DFS and lymph node status and triple negativity either for DFS or OS had independent prognostic value. In the 194 lymph node-negative women DFS and OS were inversely related to tumor grade, absence of ER, Mib-1 expression in more than 15% of neoplastic cells and, only for DFS, presence of LVI. In the 95 lymph node-positive the number of involved nodes was the most discriminating parameter either for DFS or OS; T, Her-2 status and presence of LVI were significantly related to DFS. ER negativity was related to higher grade, progesterone receptors (PR) negativity, Her-2 negativity, hence to triple negativity, to basal-like type, Mib-1expression over 15% of neoplastic cells. Her-2 positivity was related to higher grade, ER positivity and PR positivity. Basal-like type was not an independent prognosticator, while triple negative type has a significant relation to shorter OS. The Nottingham prognostic index accurately identifies prognostic groupings and Mib-1 expression and ER signaling are the key biological predictors even in single cases.

Primary osteosarcoma of the kidney with retroperitoneal hemorrhage. Case report and review of the literature.

Primary osteosarcoma of the kidney is a very rare neoplasm with a very poor prognosis and unclear histogenesis. Only 20 cases have been reported in the literature. It has a strong tendency to recur locally and spread to distant sites. We present the clinical case of a 79-year-old man affected by a primary osteosarcoma of the kidney presenting with substantial retroperitoneal tumor hemorrhage. Laparotomy revealed a massive retroperitoneal hematoma due to a bleeding large stony renal mass with multiple bizarre calcifications. The diagnosis of primary renal osteosarcoma was made on the basis of hematoxylin-eosin staining and confirmed by electron microscopy. Hematoma drainage and radical nephrectomy were performed. To our knowledge this is the first case of bleeding renal osteosarcoma reported in the literature. The most important clinical findings, the pathogenesis and the treatment modalities of this rare neoplasm are discussed.

Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours.

Beclin 1 is is an autophagy gene, the role of which as a tumour suppressor has recently been recognized in a few studies. We examined the expression of Beclin 1 protein in 212 primary human brain tumours, including 97 high-grade glial tumours, 29 low-grade glial tumours, 4 grade III meningiomas, 19 grade II meningiomas, 52 grade I meningiomas, and 11 medulloblastomas. In 94 cases, including 56 glial tumours, 35 meningiomas, and 3 medulloblastomas we also assessed Beclin 1 mRNA expression by real-time RT-PCR. In most high-grade astrocytic, ependymal neoplasms and atypical meningiomas we found a decrease of cytoplasmic protein expression that was, instead, high in the majority of low-grade tumours and in medulloblastomas. The expression level of Beclin 1 mRNA was significantly lower in glioblastomas than in grade II (p=0.04) and grade I (p=0.01) astrocytomas; in grade III than in grade I astrocytomas (p=0.01); in grade II than in grade I meningiomas (p=0.03); and in all glial tumours when compared to all meningiomas (p<0.0001). Cytoplasmic expression is thought to be linked to the functional protein. Our observations are in line with studies that demonstrated decreased expression of Beclin 1 in human breast, ovarian, prostate and ovarian cancer and furtherly support its involvement also in brain tumours, which had previously been demonstrated in a few experimental studies, both in spontaneous and in therapy-induced autophagy. Furthermore, our study suggests possible differences of Beclin 1 involvement and its role among the different histotypes of brain neoplasms. Further studies are needed to highlight Beclin 1 function in tumour suppression and/or in tumour survival through autophagy and other related programmed cell death processes in brain tumours.