Locally advanced mid/low rectal cancer with synchronous resectable liver metastases: systematic review of the available strategies and outcome.

The management of patients with locally advanced mid/low rectal cancer with resectable liver metastases is complex because of the need to combine the optimal treatment of both tumors. This study aims to review the available treatment strategies and compare their outcome, focusing on radiotherapy (RT) and liver-first approach (LFA). A systematic review was performed in PubMed, Embase, and web sources including articles published between 2000 and 02/2023 and reporting mid-/long-term outcomes. Overall, twenty studies were included (n = 1837 patients). Three- and 5-year overall survival (OS) rates were 51-88% and 36-59%. Although several strategies were reported, most patients received RT (1448/1837, 79%; > 85% neoadjuvant). RT reduced the pelvic recurrence risk (5.8 vs. 13.5%, P = 0.005) but did not impact OS. Six studies analyzed LFA (n = 307 patients). LFA had a completion rate similar to the rectum-first approach (RFA, 81% vs. 79%) but the interval strategy-an LFA variant with liver surgery in the interval between radiotherapy and rectal surgery-had a better completion rate than standard LFA (liver surgery/radiotherapy/rectal surgery, 92% vs. 75%, P = 0.011) and RFA (79%, P = 0.048). Across all series, LFA achieved the best survival rates, and in one paper it led to a survival advantage in patients with multiple metastases. In conclusion, different strategies can be adopted, but RT should be included to decrease the pelvic recurrence risk. LFA should be considered, especially in patients with high hepatic tumor burden, and RT before liver surgery (interval strategy) could maximize its completion rate.

Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial.

BACKGROUND: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer. PATIENTS AND METHODS: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (α = 0.05, power = 0.80). The proposed treatment could be considered promising if ≥13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365). RESULTS: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation). CONCLUSION: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation.

Arterial endofibrosis in professional cyclists.

External Iliac Artery Endofibrosis (EIAE) is an uncommon disease usually affecting young, otherwise healthy, patients. It usually involves cyclists but cases have been reported in other groups of endurance athletes. The external iliac artery is the most affected anatomical site but other locations are described too. The precise pathophysiology and long-term evolution of the disease still remain unknown. The diagnosis may be challenging and delayed as the patients usually present symptoms only in extreme conditions and physical and instrumental examinations may be normal at rest. We present two cases of young professional cyclists who suffered of exercise-induced leg pain which led them to reduce running. Both patients were firstly treated with balloon angioplasty that rapidly failed to improve their symptoms. The successive open surgery with endofibrosectomy and autologous saphenous vein closure patch completely resolved physical limitations. EIAE is a rare disease that can induce arterial stenosis, thrombosis, dissection and secondary atheroma. After-exercise ankle-brachial index represents a useful diagnostic criterion. Careful observation of angio-CT may strengthen the suspect. Knowledge of the these features allows a better pre-operative assessment and an early effective treatment. Surgical revascularization remains the gold standard approach.

Why is it so difficult to develop a hepatitis C virus preventive vaccine?

With an estimated 3% of the world's population chronically infected, hepatitis C virus (HCV) represents a major health problem for which an efficient vaccination strategy would be highly desirable. Indeed, chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocarcinoma and liver failure worldwide and it is the most common indication for liver transplantation, accounting for 40-50% of liver transplants. Much progress has been made in the prevention of HCV transmission and in therapeutic intervention. However, even if a new wave of directly acting antivirals promise to overcome the problems of low efficacy and adverse effects observed for the current standard of care, which include interferon-α and ribavirin, an effective vaccine would be the only means to definitively eradicate infection and to diminish the burden of HCV-related diseases at affordable costs. Although there is strong evidence that the goal of a prophylactic vaccine could be achieved, there are huge development issues that have impeded reaching this goal and that still have to be addressed. In this article we address the question of whether an HCV vaccine is needed, whether it will eventually be feasible, and why it is so difficult to produce.

Endogastric capsule for E-cadherin gene (CDH1) promoter hypermethylation assessment in DNA from gastric juice of diffuse gastric cancer patients.

BACKGROUND: We investigated whether an endogastric capsule (EC) may be a valuable tool for collecting DNA from exfoliated cells from the gastric mucosa and for carrying out an analysis of promoter methylation status of the E-cadherin (CDH1) gene in poorly differentiated, diffuse gastric cancer (DGC). MATERIAL AND METHODS: Consecutive patients with a confirmed diagnosis of poorly differentiated DGC underwent collection of gastric juice by EC. Subjects without cancer and premalignant lesions were also accrued as controls. The samples of gastric juice were processed for DNA isolation and amplification. Then they were used for analysis of CDH1 promoter hypermethylation. RESULTS: The procedure successfully allowed the analysis of CDH1 promoter hypermethylation in 20 patients and 14 controls. This pilot study showed feasibility of the procedure and a significantly different CDH1 promoter hypermethylation status between DGC patients and controls was detected. CONCLUSIONS: The EC may represent an innovative and noninvasive tool for the analysis of a specific epigenetic change in DGC patients. Our findings deserve additional studies as this method may represent a cost-effective tool for early detection of sporadic as well as hereditary DGC in CDH1 germline mutations carriers.

Lymphatic, blood vessel and perineural invasion identifies early-stage high-risk radically resected gastric cancer patients.

The availability of different treatment options for radically resectable gastric cancer reopened the question of treatment selection and correct definition of high-risk categories. Lymphatic, blood vessel and perineural invasion (LBVI/PNI) seem to possess the necessary potential to provide useful information for the clinical management of this disease. Seven hundred and thirty-four patients with advanced gastric cancer who underwent curative gastrectomy were analysed according to the presence of LBVI/PNI. Patients were divided into two groups: group A for patients with LBVI/PNI (189 patients 26%) and group B for patients without LBVI/PNI (545 patients, 74%). The disease-free survival (DFS) for patients in group A was 32.1 months, whereas it was not reached for patients in group B (P=0.0001); the median overall survival was 45.5 months for patients in group A, whereas it was not reached for patients in group B (P=0.0001). At multivariate analysis, the presence of LBVI/PNI appeared an independent prognostic factor for DFS and OS. Our results were confirmed in subgroup analysis, separately considering stage I and early gastric cancer patients with and without LBVI/PNI. Taken together, our findings suggest the importance of LBVI/PNI in gastric cancer as it may provide additional information for identifying patients at high risk, who may be candidates for further medical treatment after or before surgery.

[Thymoma: diagnosis and surgical treatment]. / Timomi: diagnostica e terapia chirurgica.

Thymoma is the most common primary neoplasm of the tymus. The majority of thymomas are encapsulated masses and exhibit benign behavior. Less frequently they may be invasive, or rarely they may metastasize to distant sites. The usual clinical presentation is that of an anterior mediastinal mass found accidentally in an asymptomatic patient. Computed tomography and magnetic resonance may be helpful in the evaluation of adjacent structures. The histologic classification proposed by Muller-Hermelink is useful in predicting and defining the risk of invasiveness of thymomas showing a significant correlation between tumor cell type and stage. The treatment of choice is complete surgical excision; radiation therapy may be used adjunctively to surgery in the treatment of invasive tumors. The choice of surgical approach is conditioned by site and grading of thymoma. The prognosis of encapsulated thymoma is generally favorable; invasive tumors are associated with a worse prognosis but may respond to radical resection.

[Cystic lymphangioma: a case report of abdominal location]. / Linfangioma cistico: un caso a localizzazione addominale.

A case of cystic lymphangioma is reported, located on the mesentery of the jejunum in a fifty-seven year old patient. The lymphangioma is an extremely rare disease and it is often located in the neck and arm pit. An intra abdominal and mediastinal location takes place in just 5% of the examined cases. Pre operative exams are taken into account; computerized (Axial) tomography and echo tomography have made diagnosis possible. The surgical therapy is the preferred treatment; no therapeutic options exist. The radical extirpation of the mass becomes necessary to avoid relapses.

Fasting inhibits natriuretic peptides clearance receptor expression in rat adipose tissue.

OBJECTIVE AND DESIGN: The early phase of weight loss induced by fasting is associated with diuresis, natriuresis and reduction in blood pressure through unclear mechanisms. Atrial natriuretic peptide (ANP) is a cardiac hormone with potent natriuretic, diuretic and hypotensive effects mediated by 'biologically active' receptors (NPr-A). A second type of receptor mediates the clearance of ANP (the clearance receptor, NPr-C). Since NPr-C appears to be abundant in adipose tissue, we analysed NPr-C and NPr-A gene expression in white and brown adipose tissue (WAT and BAT) as well as in renal cortex of fasting rats. Plasma ANP, cyclic GMP and aldosterone were also measured. METHODS: Twelve male Wistar rats were deprived of food for about 50 h, and 12 other rats were fed ad libitum. Periepididymal WAT, interscapular BAT and left renal cortex were used for RNA extraction and northern blot analysis with rat NPr-C and NPr-A complementary DNA probes labelled with 32P-dCTP. Densitometric analysis of hybridization signals was corrected by beta actin expression before statistical analysis. Blood was drawn for ANP, cyclic GMP (cGMP) and aldosterone radioimmunoassays, which were also measured in a group of six rats deprived of food for 25 h. RESULTS: A dramatic decrease in NPr-C steady-state messenger RNA levels was observed both in WAT (about 3.6-fold, P < 0.001) and in BAT (about threefold, P < 0.01), but fasting did not affect the expression of NPr-A in adipose tissues. In the renal cortex NPr-C and NPr-A messenger RNA levels were unaffected by fasting. ANP and aldosterone levels were reduced after fasting whereas cyclic GMP was increased at 25 h, but the differences did not reach statistical significance. CONCLUSIONS: Fasting exerts a tissue-specific and gene-specific suppression of NPr-C gene expression in adipose tissue that appears to be accompanied by an increased biological activity of ANP. The natriuresis and diuresis and reduction of blood pressure induced by fasting might result from a reduced expression of NPr-C in adipose fat pads.

[Foreign bodies in the alimentary tract. Surgical treatment]. / I corpi estranei del canale alimentare. Trattamento chirurgico.

Gastro-intestinal foreign bodies are a by no means rare event in surgery and in the USA mortality is about 1500 people per annum. The surgical treatment of foreign bodies in the alimentary tract is reported here. Certain cases of voluntary ingestion in mental patients are reported, comparing personal experience with the data reported in the literature.

[Evaluation of the operative risk of gastric tumor surgery at an advanced age. Retrospective study]. / La valutazione del rischio operatorio nella chirurgia dei tumori gastrici in età avanzata. Studio retrospettivo.

A retrospective study was carried out in 41 over-70 year-olds who had been operated on for gastric cancer in 1984-86 at the General Surgery Division of Imola to see if age is an unfavourable prognostic factor in this situation. Age was not decisive in surgical results. Operative mortality is correlated with the degree of operative risk expressed on the basis of an analysis of the patient's biological state prior to the operation and of the specific and aspecific effects of surgery.

[Bronchogenic cysts of the mediastinum]. / Le cisti broncogene del mediastino.

The case of a bronchial cyst found on the mediastinal carina whose early symptoms resulted from compression of the airways is reported. The clinical, pathogenic and diagnostic aspects of these often congenital cystic malformations of the mediastinum are discussed.