[Sex/gender differences in COVID-19 lethality: what the data say, and do not say]. / Differenze sesso/genere nella letalità COVID-19: cosa dicono e non dicono i dati.

BACKGROUND: scientific literature indicates that there are sex, and gender differences in the development, symptomatology and evolution of different diseases, in the response to drugs and in the therapeutic pathways. Even in the COVID-19 epidemic some sex/gender differences emerged. OBJECTIVES: to analyze COVID-19 epidemic data by gender and age in Italy, Germany, Spain, and Sweden, characterized by having implemented different pandemic containment policies, with the aim of observing any characteristics that can be interpreted with the lens of sex/gender differences. MATERIALS AND METHODS: we used confirmed cases and deaths associated with COVID-19 for Italy, Spain, Germany, and Sweden from respective national surveillance databases. Mortality data for Italy were also analysed. The period of investigation was March-May 2020. As indicators, we used the case fatality ratio adjusted for time delay and SMR for mortality. RESULTS: women are more vulnerable to COVID- 19 infection in the 30-60-year age group. Case fatality ratio is higher in men than women, with a ratio men/women equal to 1.7 in Italy, Spain, and Sweden and 1,4 in Germany. The ratio increases in the lower age groups. The analysis of the mortality data observed/expected in Italy in the same period with respect to 2015-2019 shows a comparable excess with SMR equal to 132 for men and 127 for women. CONCLUSIONS: COVID-19 affects both genders with some differences in the incidence, higher in women, and lethality, higher in men. These differences highlight the need to better understand the sex/gender and age interaction both for epidemiological surveillance and for a better gender-appropriateness of the ongoing prophylactic and therapeutic treatments. This would be possible if all health indicators (symptoms, past illnesses, primary and hospital-level health care, hospitalization, etc.) were provided by age and gender. Analysis of the causes of death could help to better understand the increase in mortality for both genders, in particular for women, for whom a lower lethality for COVID-19 appears from data.

Computed tomographic evaluation of mesentery: diagnostic value in acute mesenteric ischemia.

OBJECTIVE: To evaluate the computed tomographic appearances of mesentery in acute mesenteric ischemia (AMI) to recognize characteristic features and their prognostic values. METHODS: Computed tomographic examinations of 34 patients with a confirmed diagnosis of AMI were retrospectively reviewed to evaluate the number of mesenteric vessels, diameter of the superior mesenteric artery and superior mesenteric vein, mesenteric fat stranding, mesenteric vessel pneumatosis and ascites. RESULTS: Overall, at least one of these mesenteric signs was present in all but 1 patient. In all AMI of arterial occlusive type and in 68% of nonocclusive mesenteric ischemia, the number of arterial vessels was reduced (P = 0.067). Mesenteric vessel pneumatosis and reduced number of venous vessels were significantly associated with higher mortality (P = 0.027 and P = 0.042, respectively). Reperfusion signs were associated with a reduced mortality (28.7% vs 65.5%). CONCLUSION: Considering its characteristic features and its possible prognostic value, the evaluation of mesentery will supply additional information in the interpretation of computed tomography in AMI.

Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin.

PURPOSE: The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy. METHODS: Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m(2) i.v. only on day 1, with leucovorin 100 mg/m(2) i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion. RESULTS: The percentage of patients presenting with grade >/=2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade >/=2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001). CONCLUSIONS: This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.

Folinic acid, 5-fluorouracil and etoposide after curative resection for gastric cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the survival benefit of adjuvant chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) in gastric cancer patients undergoing previous surgery with a curative intent. METHODOLOGY: The clinical outcome of 49 patients with resected gastric cancer treated with adjuvant chemotherapy was compared with that of 85 surgically treated historical controls who did not receive any adjuvant treatment. The chemotherapy regimen consisted of six cycles of daily 1-hour intravenous infusions of folinic acid 100 mg/m2 and 5-FU 400 mg/ m2, and a 2-hour infusion of etoposide 100 mg/m2, for three days every 28 days. RESULTS: The 5-year relapse-free survival was 32% in the adjuvant arm and 27% in the control arm (p = 0.6). At the last follow-up, there were 32 deaths in the adjuvant arm and 60 in the control arm. The median duration of survival was respectively 23 and 19 months, and the 5-year survival rates were 34% and 29% (p = 0.4). The chemotherapy was well tolerated. CONCLUSIONS: Our data suggest that ELF adjuvant treatment is a safe and well tolerable combination chemotherapy in patients with resected gastric cancer, but it does not seem to improve prognosis in comparison with historical controls.

Adjuvant epirubicin with or without Ifosfamide for adult soft-tissue sarcoma.

This randomized study compared the efficacy of epirubicin-based adjuvant chemotherapy on the disease-free interval (DFI) and overall survival of patients with high-risk soft-tissue sarcomas. After curative surgery, 43 of the 88 enrolled patients were assigned to surgery with or without radiotherapy and 45 to surgery plus chemotherapy (26 epirubicin, 19 epirubicin + ifosfamide) with or without radiotherapy. The trial closed prematurely because of poor patient accrual. There was a statistical significant difference in the 5-year disease-free survival of the patients receiving adjuvant chemotherapy with or without radiotherapy (69%) and that of those treated with surgery with or without radiotherapy (44%) ( p= 0.01). The 5-year survival of the patients treated with adjuvant chemotherapy with or without radiotherapy was 72% as against 47% of those treated with surgery with or without radiotherapy ( p= 0.06). The power of the study was 0.65 for both the DFI and overall survival. The results of the study suggest a possible advantage of epirubicin-based adjuvant chemotherapy in patients with soft-tissue sarcoma at high risk of relapse.

MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria.

Lynch syndrome (LS) is a tumor predisposing condition caused by constitutional defects in genes coding for components of the mismatch repair (MMR) apparatus. While hypermethylation of the promoter of the MMR gene MLH1 occurs in about 15% of colorectal cancer samples, it has also been observed as a constitutional alteration, in the absence of DNA sequence mutations, in a small number of LS patients. In order to obtain further insights on the phenotypic characteristics of MLH1 epimutation carriers, we investigated the somatic and constitutional MLH1 methylation status of 14 unrelated subjects with a suspicion of LS who were negative for MMR gene constitutional mutations and whose tumors did not express the MLH1 protein. A novel case of constitutional MLH1 epimutation was identified. This patient was affected with multiple primary tumors, including breast cancer, diagnosed starting from the age of 55 y. Investigation of her offspring by allele specific expression revealed that the epimutation was not stable across generations. We also found MLH1 hypermethylation in cancer samples from 4 additional patients who did not have evidence of constitutional defects. These patients had some characteristics of LS, namely early age at onset and/or positive family history, raising the possibility of genetic influences in the establishment of somatic MLH1 methylation.

The role of surgical lung biopsy in the management of interstitial lung disease: experience from a single institution in the UK.

OBJECTIVES: Interstitial lung disease (ILD) includes a wide spectrum of pulmonary pathologies. The role of surgical lung biopsy (SLB) in the diagnosis of ILD is still controversial. The purpose of this study was to ascertain whether SLB is worthwhile in the management of ILD. METHODS: One hundred and three patients underwent SLB for ILD from April 2008 to March 2010 at a single institution. Outcomes included patient demographics, preoperative investigations, preoperative diagnosis and treatment, surgical approach, number and site of biopsies, complications, length of postoperative stay and postoperative pathological diagnosis and treatment. RESULTS: Fifty-one (49.6%) patients were male and 52 (50.4%) were female. The median age was 58 (range 26-78). Major complications were seen in 7 patients (6.8%). Five patients (4.9%) died within 30 days following surgery. Definitive pathological diagnosis (DPD) was reached in 72 (69.9%) patients, whereas no DPD was achieved in 31 (30.1%). Within the group of patients who received DPD, this differed from the clinical diagnosis in 53 patients (51.5%), and was concordant in 19 (18.4%). The DPD was helpful in guiding the management of 47 patients (45.6%), who had a change in their treatment following the procedure. The median hospital stay was 4 days (range 2-42 days). CONCLUSIONS: SLB is a well-recognized procedure. Although it provides a diagnosis for the majority of patients, in our series SLB was inconclusive in a considerable number of cases and did not lead to a therapeutic change for more than half of all patients. Furthermore, SLB is not without risk and can be associated with a prolonged hospital stay. We believe that SLB should be performed in a select group of patients with ILD after discussion by a multidisciplinary panel.

Magnetic resonance imaging: is there a role in clinical management for acute ischemic colitis?

AIM: To validate the utility of magnetic resonance imaging (MRI) for the clinical management of acute ischemic colitis (IC). METHODS: This is a magnetic resonance (MR) prospective evaluation of 7 patients who were proved to have acute IC on the basis of clinical, endoscopic and computed tomography (CT) findings and who were imaged in our institution between February 2011 and July 2012. The mean age of the patients was 72.28 years. Abdominal CTs were obtained using a 64-detector row configuration for all patients with un-enhanced and contrast-enhanced scans, in the late arterial phase (start delay 45-50 s) and in the portal venous phase (start delay 70-80 s). The MR examinations were performed using a 1.5T superconducting magnet, using Fast Imaging Employing Steady State Acquisition and T2-weighted fast-recovery fast-spin echo sequences in axial and coronal plane. CT and MRI examinations were analysed for the presence of colonic abnormalities and associated findings. RESULTS: Segmental involvement was seen in 6 patients (85.71%), with a mean length of involvement of 412 mm (range 145.5-1000 mm). Wall thickness varied between 6 mm and 17.5 mm (mean 10.52 mm) upon CT examinations and from 5 to 15 mm (mean 8.8 mm) upon MR examinations. The MRI appearance of the colonic wall varied over the time: Type I appearance with a 3 layer sandwich sign was seen in 5 out of 12 examinations (41.66%), patients underwent MR within a mean of 36 h (ranging from 1 to 54 h) after the CT examination. Type II and III appearance with a 2 layer sign, was seen in 4 examinations (33.33%), patients underwent MR within a mean of 420.5 h (ranging from 121 to 720 h) after the CT examination. In the remaining three MRI examinations, performed within a mean of 410 h (ranging from 99.5 to 720 h) the colonic wall appeared normal. CONCLUSION: MRI, only using precontrast images, may be used as a substitute for invasive procedures in diagnosis and follow-up of acute IC.

Transanal resection of rectal lipoma mimicking rectal prolapse: description of a case and review of the literature.

Submucosal lipomas of the large bowel are uncommon. Occasionally, they occur in the rectum and may cause aspecific symptoms; presentation with rectal prolapse is very unusual and may lead to a misdiagnosis of simple mucosal prolapse. The paper describes an additional case of a prolapsing rectal mass that led to diagnosis and surgical treatment of a rectal lipoma under local anesthesia.

Outcome of surgical treatment of colorectal cancer in the elderly.

The aim of this study is to compare the clinical features and the perioperative and long-term outcomes after primary surgery for colorectal cancer (CRC) in the elderly population with those observed in younger patients. All the patients over the age of 55 who underwent primary surgery for CRC in our clinic from 1988 to 2008 were included in this study and divided into two age groups: 55-75 and >75 years considering the age of diagnosis. 914 consecutive patients were enrolled in the study (352 > 75 years). In the elderly group, tumors were predominantly right sided, and the overall number of comorbidities was statistical more frequent. Elderly patients underwent emergency surgery more than the control group (p = 0.0008). There were no significant differences between the two groups in terms of curative and palliative resections. The overall operative mortality rate was 5.9% in the study group compared with 2.1% in the control study (p = 0.0033). The overall 3-year, 5-year and 10-year survival rates were, respectively, 37, 16.2 and 5.1% in the study group, when compared with 52.3, 35.1 and 24.7% in the control group (p = 0.022, p = 0.0001 and p = 0.0001, respectively). More patients were lost during the follow-up in the elderly group (p = 0.0003) and more deaths unrelated to cancer were found in the study group compared with the control group (p = 0.0005). The cancer specific mortality was similar between the two groups. In conclusion, elderly patients that underwent major colorectal resection have an acceptable perioperative morbidity, mortality and survival rate when compared with younger patients. Age alone should not be considered a reason to deny surgery to these patients.

Diffuse cutaneous metastases as the only sign of extranodal tumor spread in a patient with adenocarcinoma of the colon.

Cutaneous metastases from large bowel cancer are uncommon and are usually associated with organ involvement. Localization of lesions to the skin is mainly attributed to vascular and anatomical relationship, since most of them are seen in the abdominal wall or in a surgical scar. We report a 73-year-old woman in whom metastatic nodules from a poorly differentiated adenocarcinoma of the right colon developed throughout the skin (buttock, trunk, chest wall, arms, and neck) and remained the only sign of extranodal tumor spread until patient's death, seven months later. This unusual behaviour suggests that localization of neoplastic cells to the skin may be a site-specific process, determined by adhesion molecules and/or by growth factors found at that site.

Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the Multidisciplinary Oncology Group on Gastrointestinal Tumors.

The aim of this study was to investigate the safety profile of continuous oral capecitabine at fixed dose in patients older than 75 years, having metastatic colorectal and gastric cancer. Capecitabine was administered at a fixed dose of 2000 mg daily without interruptions. Thirty-four patients were considered evaluable for toxicity and efficacy. The median age was 81 years (range 76-85). The median duration of treatment was 113 days (range 24-238 days). No grade 4 toxicity was observed. One patient had grade 3 nausea and vomiting, and one had grade 3 diarrhea. Partial responses were observed in six patients with colorectal cancer, and in one patient with gastric cancer. This study suggests that continuous oral capecitabine at a fixed daily dose of 2000 mg is well tolerated, and that it allows for the simplification and ease of dosing in elderly patients with metastatic colorectal and gastric cancer.

FOLFOX-4 stop and go and capecitabine maintenance chemotherapy in the treatment of metastatic colorectal cancer.

OBJECTIVE: Patients with metastatic colorectal cancer (MCC) usually receive FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of progressive disease, with an increase in the incidence of neurotoxicity which is correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated with a low incidence of severe neurotoxicity in the treatment of MCC patients. METHODS: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m(2) day 1, leucovorin 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) and 22 h 600 mg/m(2) days 1 and 2, every 2 weeks). Patients who achieved objective response (OR) or stable disease (SD) then received oral capecitabine 2,500 mg/m(2) days 1-14 every 3 weeks; L-HOP was reintroduced as soon as progression occurred. RESULTS: Twenty-eight of the 29 patients who achieved OR or SD then received capecitabine. FOLFOX-4 was reintroduced in 18 patients (56.2%). The median response duration (RD) was 9.2 months and median progression-free survival (PFS) was 8.6 months. Twenty-eight patients (87.5%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.1%). CONCLUSIONS: FOLFOX-4 stop and go and capecitabine maintenance chemotherapy was associated with a very low incidence of grade 3 neurotoxicity. Although the number of patients enrolled was far too low for a definite conclusion, RD and PFS were comparable to those usually reported in the treatment of MCC patients.