A new schedule of one week on/one week off temozolomide as second-line treatment of advanced neuroendocrine carcinomas (TENEC-TRIAL): a multicenter, open-label, single-arm, phase II trial.

BACKGROUND: There is no consensus on the second-line treatment of patients with progressive high-grade neuroendocrine neoplasms (NENs G3) and large-cell lung neuroendocrine carcinoma. These patients generally have poor performance status and low tolerance to combination therapy. In this trial, we aim to evaluate the efficacy and safety of temozolomide given every other week in patients with advanced platinum-pretreated NENs G3. PATIENTS AND METHODS: This trial is an open-label, non-randomized, phase II trial. Patients with platinum-pretreated metastatic neuroendocrine carcinoma were treated with 75 mg/m2/day of temozolomide for 7 days, followed by 7 days of no treatment (regimen one week on/one week off). The primary endpoint was the overall response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and tolerability. This study is registered with ClinicalTrials.gov, NCT04122911. RESULTS: From 2017 to 2020, 38 patients were enrolled. Among the patients with determined Ki67, 12 out of 36 (33.3%) had a Ki67 index <55% and the remaining 24 out of 36 (66.6%) had an index ≥55%. Overall response rate was 18% (7/38), including one complete response and six partial responses. The median PFS was 5.86 months [95% confidence interval (CI) 4.8 months-not applicable) and the median OS was 12.1 months (95% CI 5.6-20.4 months). The 1-year PFS rate was 37%. No statistically significant difference in median PFS [hazard ratio 1.3 (95% CI 0.6-2.8); P = 0.44] and median OS [hazard ratio 1.1 (95% CI 0.5-2.4); P = 0.77] was observed among patients with Ki67 <55% versus ≥55%. Only G1-G2 adverse events were registered, the most common being G1 nausea, diarrhea and abdominal pain. CONCLUSION: One week on/one week off temozolomide shows promising activity in patients with poorly differentiated NEN. The good safety profile confirmed the possibility of using this scheme in patients with poor performance status.

Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects.

Immune checkpoint inhibitors cause side effects ranging from autoimmune endocrine disorders to severe cardiotoxicity. Periodic Fasting mimicking diet (FMD) cycles are emerging as promising enhancers of a wide range of cancer therapies including immunotherapy. Here, either FMD cycles alone or in combination with anti-OX40/anti-PD-L1 are much more effective than immune checkpoint inhibitors alone in delaying melanoma growth in mice. FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3+ and CD8+ cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

QTL mapping of soybean oil content for marker-assisted selection in plant breeding program.

The present study was undertaken to detect and map the quantitative trait loci (QTL) related to soybean oil content. We used 244 progenies derived from a bi-parental cross of the Lineage 69 (from Universidade Estadual Paulista "Júlio de Mesquita Filho"/Faculdade de Ciências Agrárias e Veterinárias - Breeding Program) and Tucunaré cultivar. A total of 358 simple sequence repeat (SSR; microsatellite) markers were used to investigate the polymorphism between the parental lines, and for the polymorphic lines all the F2 individuals were tested. Evaluation of the oil content and phenotype was performed with the aid of a Tango equipment by near infra-red reflectance spectroscopy, using single F2 seeds and F2:3 progenies, in triplicate. The data were analyzed by QTL Cartographer program for 56 SSR polymorphic markers. Two oil-content related QTLs were detected on K and H linkage groups. The total phenotypic variation explained by QTLs ranged from 7.8 to 46.75% for oil content. New QTLs were identified for the oil content in addition to those previously identified in other studies. The results reported in this study show that regions different from those already known could be involved in the genetic control of soybean oil content.

A case of neonatal intrapericardial teratoma. Clinical and pathological findings.

AIM: It is of general agreement that complete surgical removal after birth of intrapericardial fetal teratomas is needed, because of the risk of severe cardiovascular and respiratory distress, related to the mass size, location and secondary pericardial effusion. Histological examination generally shows mature aspect of cells and tissues. METHODS: We present a case of grade II immature pericardial teratoma, diagnosed in utero and completely removed after birth. RESULTS: Even surgical removal was complete, histological aspects raised the need of long follow-up with serial alpha-fetoprotein determinations. CONCLUSION: A neonatal grade II immature pericardial teratoma was completely removed after birth. The follow-up of the patient, until 10 months of life, was good with no recurrence of the disease.

Neutrophil gelatinase-associated lipocalin: a novel biomarker for the early diagnosis of acute kidney injury in the emergency department.

Acute kidney injury (AKI) is a common medical problem among critical patients. In current clinical practice, AKI is diagnosed by measuring serum creatinine concentration, which is an unreliable and delayed marker of the deterioration of kidney function. Its rise occurs when a significant amount of renal function has been lost. Many are the factors able to modify physiological levels, such as age, gender, ethnicity, dietary protein intake, muscle mass or metabolism, hydration status and drugs. Definitely, creatinine, as well as blood urea nitrogen (BUN) or urine markers of kidney injury (fractional excretion of sodium, urinary concentrating ability, casts), do not directly reflect cell injury, but rather the delayed functional consequences of the damage. Due to the lack of sensitive and specific biomarkers, the identification of early stages of AKI has been impossible but, recently, neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a novel biomarker of AKI from several etiologies, such as cardiac surgery, contrast nephropathy, kidney transplantation and sepsis. This protein, produced in a number of human tissues and particularly in the distal nephron, has siderophore-chelating property and acts as an iron-trasporting shuttle. NGAL increases in both serum and urine 48 hours before the rise of creatinine, and shows a strong correlation with change in creatinine concentrations. An early diagnosis of AKI allows the early institution of therapeutic measures for the protection of renal function and improves the prognosis. This possibility is particularly important in the Emergency Department for the treatment of critical patients with potential nefrotoxic therapies. Use of NGAL as early marker of AKI in the Emergency Department is discussed.

[Mono-symptomatic hematuria: first symptom of metastatic pulmonary carcinoma]. / Ematuria monosintomatica: primo sintomo di carcinoma polmonare metastatico.

The occurrence of secondary bladder neoplasms is very uncommon, especially when the bladder is the only site of metastasis. The Authors report on one case of bladder metastasis from primary small cell carcinoma of the lung.

[Cystic nephroma: report of two cases and review of literature]. / Nefroma cistico: nostra esperienza su due casi e revisione della letteratura.

Cystic nephroma is an uncommon lesion, whose etiology and pathogenesis is still debated: some Authors designate it as being of neoplastic origin, other ones of dysplastic or hamartomous origin. Also epidemiology makes difficult its pathogenetic interpretation, as being especially affected children under age of fourth year and adults within the 5th and 6th decade. The Authors report two cases of cystic nephroma examined in two female patients 30 and 74 aged. The most interesting matters are: 1) Possibility of a pre-operative diagnosis of founded suspicion, based on pathologic criteria, codified in literature (unilateral and multilocular cyst which doesn't communicate with the renal collecting system, separated by delicate septae without mature renal tissue) and on respective ultrasonographic, CT and angiographic patterns; 2) Possibility of programming a surgical-conservative strategy; 3) Knowledge about possibility of foci association of adeno-carcinoma or nephroblastoma in the lesion, that, nevertheless, if not widespread, it should not modified neither therapeutical proceeding nor prognosis, generally favourable.

[Inverted papilloma associated with transitional cell carcinoma in the upper urinary tract: report of one case and review of the literature]. / Associazione di papilloma invertito e carcinoma uroteliale nell'alta via escretrice: presentazione di un caso e revisione della letteratura.

Inverted papilloma of the pelvis and the ureter is a rather uncommon (only 40 cases in the relevant literature) benign epithelial tumor, occasionally harboring foci of malignancy. Since it does not metastasize, a conservative treatment is advisable, but a strict follow up is always required. The Authors report a case of inverted papilloma of the ureter near which an area of transitional carcinoma was discovered.

[Extrinsic ureteral endometriosis: description of a case]. / Endometriosi ureterale estrinseca: descrizione di un caso.

After a brief review about pathogenetic hypothesis of the endometriosis of the ureter, the Authors describe a case occurred to their observation. Diagnostic problems and choice in treatment (especially partial ureterectomy, end-to-end ureteral anastomosis and omentoplasty) are discussed.