Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study.

BACKGROUND: Although several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. METHODS: From 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). RESULTS: Of 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2-152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. CONCLUSION: This study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. PATIENTS AND METHODS: Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. RESULTS: From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). CONCLUSIONS: Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.

Factors influencing survival after hepatectomy for metastases from gastric cancer.

PURPOSE: To investigate clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. METHODS: Retrospective multi-center chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors. RESULTS: One hundred and five patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting of the disease. In 89 cases a R0 resection was achieved, while in 16 a R+ hepatic resection was performed. Adjuvant chemotherapy was administered to 29 patients. Surgical mortality was 1% and morbidity 13.3%. Median disease-free survival was 10 months, median overall survival was 14.6 months. Overall 1, 3, and 5-year survival rates were 58.2%, 20.3%, and 13.1%, respectively. Survival was influenced independently by the factor T of the gastric primary (p < 0.001), by the curativity of surgical procedure (p = 0.001), by the timing of hepatic involvement (p < 0.001) and by adjuvant chemotherapy (p < 0.001). T4 gastric cancer, R+ resection, synchronous metastases, and abstention from adjuvant chemotherapy were associated with a worse prognosis; T4 gastric cancer and R+ resections displayed a cumulative effect (p < 0.001). CONCLUSIONS: Our data show that R0 resection must be pursued whenever possible. Furthermore, in the synchronous setting, the coexistence of T4 gastric primaries and R+ resections suggests prudence and probably abstention from hepatectomy. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results.

Lymphatic endothelial cells derived from metastatic and non-metastatic lymph nodes of human colorectal cancer reveal phenotypic differences in culture.

Colorectal cancer is one of the most frequent causes of death in Western countries. Most patients develop metastasis traveling through the lymphatic system, and regional lymph node metastasis is considered a marker for dissemination, increased stage, and worse prognosis. Despite rapid advances in tumor biology, the processes that underpin lymphatic invasion and lymph node metastasis remain poorly understood. The aim of this study was to establish an easy protocol for isolation of pure tumor lymphatic endothelial cells derived from lymph nodes to study differences compared with normal endothelial cells of uninvolved tissue from the same patients. Cells were isolated with very high purity via magnetic cell sorting and express the specific lymphatic markers Prox-1 and Lyve-1. They show differences in expression of adhesion molecules, chemokines, and growth factor secretion, and capability to form capillaries when seeded on basal membrane, thereby, revealing important differences between the two cell type. These cultures may provide a promising platform for the comparative analysis of both cell types at the molecular and biological level and to optimize treatment strategies.

Metachronous hepatic metastases from gastric carcinoma: a multicentric survey.

BACKGROUND: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. OBJECTIVE: To survey the clinical approach to the subset of patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. METHODS: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D >or= 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. RESULTS: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018) of the gastric primary and by the therapeutic approach to the metastases (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p<0.001). CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible.

Traumatic lesions of the diaphragm. Our experience in 33 cases and review of the literature.

We reviewed 33 consecutive patients with diaphragmatic injuries. Twenty-nine were admitted in emergency conditions after blunt (22 patients) or penetrating injury, presenting shock, dyspnoea, coma or acute abdomen in 21 cases; major associated lesions were found in 23 patients. Four patients presented acute complications of visceral herniation 2, 4, 84 and 216 months after the trauma. The diagnosis was preoperative in 23 cases, intraoperative in 9; in one case it was missed at laparotomy, becoming evident the day after. The sensibility of preoperative chest x-ray and CT was 86% and 100% in presence of visceral herniation, 14% and 0% in absence of visceral hernia. The diaphragmatic repair was always obtained by direct suture, following 20 haemostatic procedures (liver, spleen, mesenterium) and two bowel resections. The mortality rate was 24.4%; the morbidity rate was 48%. Traumatic lesions of the diaphragm are generally expression of particularly severe trauma whose outcome is mainly influenced by the associated lesions. They are also correlated to specific morbidity and mortality, so the surgical exploration is mandatory whenever this injury is suspected, considering that the preoperative diagnosis relies on visceral dislocation. Associated lesions influence the surgical strategy but a direct suture is usually effective in preventing specific complications.

[Results of elective open surgery for juxtarenal aortic aneurysms]. / I risultati del trattamento elettivo in open surgery degli aneurismi juxtarenali dell'aorta.

Review of the most significant surveys (data base: Pub Med on September 2003) of elective open surgery for Juxtarenal aneurysms and personal results of 106 cases (9.3% of AAA consecutively operated in the last 11 yrs.) are reported. Mortality and morbidity are discussed related to: technique of aortic cross-clamping; protective measures on splanchnic and renal perfusion; risks from previous CAD and chronic renal failure. Over all, the main predictive factor is the accuracy of the selected technique, without any difference among different approaches, and the same results of infrarenal aneurysms can be obtained.

Retrospective histologic comparison of Helicobacter pylori infection in gastric carcinoma, ulcerous disease and non-ulcerous dyspepsia.

Although a number of epidemiological, biological and clinical studies have been published, the effective role of Helicobacter pylori infection in gastric carcinogenesis remains unclear. In the present work we retrospectively compared Helicobacter infection rate, by means of histologic examination of gastric bioptic samples, in 70 patients affected by gastric carcinoma, 70 with ulcerous disease and 70 with non-ulcerous dyspepsia. The analysis was carried out by a single pathologist. The differences between the 3 groups were not statistically significant. From our present and previously reported data, the Helicobacter infection cannot be considered per se a significant risk factor for malignant gastric disease and further studies are needed to evaluate the role of Helicobacter infection in the development of some preneoplastic conditions such as chronic atrophic gastritis and intestinal metaplasia.

Combined surgical approach for carotid and coronary stenosis. Sixty-four patients and review of literature.

BACKGROUND: The proper role of combined carotid endarterectomy (CEA) and coronary bypass (CABG) is still controversial. We contribute to the discussion through the critical evaluation of 64 consecutive patients, whose data have been collected in a prospective way. METHODS: Between 1990 and 1999, 64 patients presenting a critical coronary disease (unemendable by PTA) associated with severe carotid stenosis (= or >70% if symptomatic, = or >80% if asymptomatic), underwent combined CEA-CABG. Cardiological symptoms were evident in 90.6% of cases. Thirty-five patients (54.7%) had a three-vessel coronaropathy, 18 (28.1%) a two-vessel disease and 11 (17.2%) severe stenosis of the common trunk; furthermore 7 patients (10.9%) had a low ejection fraction (<50%). A positive neurologic history was present in 22 (44%) patients. Thirty-four patients (55%) had a carotid stenosis >90%; a significant disease of the contralateral carotid axis was observed in 53% of cases: stenosis >50% in 30 patients and thrombosis in 4. CEA was performed with somato-sensorial evoked potential monitoring. RESULTS: The hospital mortality rate was 6.2% (4 patients). The cause of death was cardiac in 2 cases (1 early bypass thrombosis and 1 irreversible coronary spasm) and related to a multiorgan failure in 2. The neurologic morbidity rate was 0%. CONCLUSIONS: Our data highlight that in these high-risk patients the combined approach dramatically reduces the stroke risk although the mortality rate is still higher than that observed after CEA or CABG.