SARS-CoV-2 Igg seroprevalence in IBD patients treated with biologics: first vs. second pandemic wave in a prospective study.

OBJECTIVE: In a prospective study, SARS-CoV-2 IgG seroprevalence was assessed during the second pandemic wave (W2) in a cohort of Inflammatory Bowel Disease (IBD) patients using biologics. The secondary aim was to compare, in the same cohort, the frequency of seropositivity and of COVID-19 during the second vs. the first (W1) wave. PATIENTS AND METHODS: From November 2020 to March 2021, SARS-CoV-2 IgG seropositivity and the prevalence of COVID-19 were assessed in a cohort of IBD patients using biologics already studied at W1. INCLUSION CRITERIA: age ≥ 18 years; diagnosis of IBD; follow-up; written consent. EXCLUSION CRITERIA: SARS-CoV-2 vaccination. Risk factors for infection, compatible symptoms, history of infection or COVID-19, nasopharyngeal swab test were recorded. Data were expressed as median [range]. The χ2 test, Student's t-test, logistic regression analysis was used. RESULTS: IBD cohort at W1 and W2 included 85 patients: 45 CD (52.9%), 40 UC (47.1%). When comparing the same 85 patients at W2 vs. W1, a higher SARS-CoV-2 seroprevalence at W2 was at the limit of the statistical significance (9.4% vs. 2.3%; p=0.05). The prevalence of COVID-19 at W2 vs. W1 was 3.5% (3/85) vs. 0% (0/85) (p=0.08). Contacts with COVID-19 patients and symptoms compatible with COVID-19 were more frequent at W2 vs. W1 (18.8 % vs. 0%; p=0.0001; 34.1% vs. 15.3%; p=0.004). At W2, history of contacts and new onset diarrhea were more frequent in seropositive patients [4/8 (50%) vs. 12/77 (15.6%); p=0.01 and 4/8 (50%) vs. 2/77 (2.6%); p=0.0001]. At W2, the risk factors for seropositivity included cough, fever, new onset diarrhea, rhinitis, arthromyalgia, dysgeusia/anosmia at univariate (p<0.05), but not at multivariate analysis. History of contacts was the only risk factor for seropositivity at univariate (p=0.03), but not at multivariate analysis (p=0.1). CONCLUSIONS: During W2, characterized by a high viral spread, IBD and biologics appeared not to increase the prevalence of SARS-CoV-2 infection or COVID-19 disease. New onset diarrhea mimicking IBD relapse may be observed in patients with SARS-CoV-2 infection.

Low prevalence of SARS-CoV-2 infection in inflammatory bowel disease.

OBJECTIVE: Treatments used in Inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections and viral reactivation, however, it remains unclear whether IBD patients have increased risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The aim of the study was to examine the prevalence of SARS-CoV-2 IgG positivity in IBD patients followed at our referral center. The role of treatments for IBD and risk factors for infection were also evaluated. PATIENTS AND METHODS: In a prospective study, all IBD patients followed at our referral centre between May 27th and July 21st, 2020 and fulfilling the inclusion criteria were tested for SARS-CoV-2 IgG. Specific IgG antibodies were evaluated by a commercial ELISA kit and SARS-CoV-2 nasopharyngeal swab was performed in seropositive patients. RESULTS: Two-hundred and eighteen patients, 128 Crohn's disease (CD) and 90 Ulcerative colitis (UC) [age 44, (19-77) years; ongoing biologics in 115 (52.7%)] were enrolled. No patient had major SARS-CoV-2-related symptoms. SARS-CoV-2 IgG were detected in 3 out of 218 (1.37%) patients with IBD (2 CD and 1 UC), all on biologics (2.6%). In all of the 3 seropositive patients, the nasopharyngeal swab was negative. There was no relationship between SARS-CoV-2 seroprevalence and the demographic/clinical characteristics of IBD patients. In contrast, history of recent travel was more frequent in the SARS-CoV-2 seropositive patients (2/3; 66.6%) than in SARS-CoV-2 seronegative patients [7/215 (3.25%); p<0.0001]. CONCLUSIONS: The prevalence of SARS-CoV-2 IgG seropositivity in IBD patients appears to be comparable to the non-IBD population and not influenced by ongoing treatments. Risk factors for infection common to the general non-IBD population should be considered when managing patients with IBD.

Hepatic follicular lymphoma in an old patient with Crohn's disease: a rare case and review of the literature.

OBJECTIVE: Crohn's Disease (CD) has been associated with non-Hodgkin lymphoma. Follicular Lymphoma (FL) limited to the liver is extremely rare, accounting for 1% to 4.4% of all Primary Hepatic Lymphoma (PHL). CASE PRESENTATION: In 2018, an 85-years old male patient with post-operative recurrence of ileal CD referred rare episodes of fever and mild diffuse abdominal pain. Since cholecystectomy in 2001, clinical history was characterized by recurrent episodes of cholangitis and common bile duct stones. In 2018, ultrasonography and MRI showed a solid focal hepatic lesion (FHL)(4.5 cm x 2.5 cm) in the IV hepatic segment. The radiographic aspect of the lesion was unusual. Initially, focal nodular hyperplasia was suspected. Clinical history of cholangitis and radiological findings subsequently suggested a diagnosis of Hepatic Abscess (HA). A progressive enlargement of the FHL (7.3 cm x 5.8 cm) despite antibiotic treatments, led to perform a liver biopsy. Histological and immunophenotypical analysis of the FHL (7.5 cm x 5.4 cm) enabled a final diagnosis of FL. The "in situ" hybridization for Epstein-Barr virus (EBER) was negative. No additional lesions related to FL were initially detected, thus suggesting a very rare case of PHL in an old patient with CD never treated with thiopurines. CONCLUSIONS: This case report highlights the need to consider a rare diagnosis of FL of the liver in patients showing a challenging focal hepatic lesion of unknown origin.

Contrast carotid ultrasound for the detection of unstable plaques with neoangiogenesis: a pilot study.

OBJECTIVES: To evaluate whether contrast ultrasonography can be used to distinguish asymptomatic from symptomatic carotid plaques and provide insight into underlying pathophysiological differences. DESIGN: Contrast carotid ultrasound was performed in both symptomatic and asymptomatic patients referred for carotid endarterectomy. MATERIALS AND METHODS: Of 77 consecutive patients referred for carotid artery evaluation, 64 underwent carotid endarterectomy for asymptomatic cerebrovascular disease and 9 underwent urgent surgery for acute neurological deficits with hemiparesis. The endarterectomy specimens were assessed immunohistologically. RESULTS: In all 9 patients undergoing urgent surgery, contrast ultrasonography showed the accumulation of diffuse microbubble contrast at the base of the carotid plaque. This pattern was observed only in 1/64 of the patients undergoing surgery for asymptomatic carotid disease. Immunohistologically staining of the endarterectomy specimens showed that the area of microbubble contrast at the base of the symptomatic plaques was associated with an increased number of small diameter (20-30 microm) microvessels staining for vascular endothelial growth factor (VEGF). CONCLUSIONS: Contrast carotid ultrasonography may allow the identification of microvessels with neoangiogenesis at the base of carotid plaques, and differentiate symptomatic from asymptomatic plaques.

Proctalgia in a patient with staples retained in the puborectalis muscle after STARR operation.

Stapled transanal rectal resection (STARR) is a novel surgical technique for the treatment of intussusception and rectocele causing obstructed defecation. In this procedure, a double full-thickness rectal resection is performed transanally using two circular staplers. We describe the case of a patient complaining of persistent pain, tenesmus and fecal urgency after STARR. The patient also had an external rectal prolapse requiring an Altemeier rectosigmoid resection; during this operation we found and removed several staples that had stuck to the puborectalis muscle during STARR. Some degree of muscle inflammation was found at histological analysis. The patient recovered fully after this reintervention. Among the complications reported after STARR, the present one had not previously been described. The retained staples might have caused proctalgia in this patient.

A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas.

Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.

Total mesorectal excision and low rectal anastomosis for the treatment of rectal cancer and prevention of pelvic recurrences.

HYPOTHESIS: Total mesorectal excision lowers the rate of pelvic recurrence and positively affects the survival after surgical treatment of rectal cancer. DESIGN: Case series. SETTING: Tertiary care university hospital. PATIENTS: Fifty-three consecutive patients were admitted with curative intent to surgery at the First Department of Surgery of the University of Rome "La Sapienza," Rome, Italy, with diagnoses of rectal carcinoma. The mean follow-up was 68.9 months; follow-up was complete for all patients who entered the trial. INTERVENTIONS: Low anterior resection and total mesorectal excision were performed in all cases, regardless of the location of the rectal cancer. A straight mechanical colorectal anastomosis was performed on a rectal stump, never exceeding 5 cm. No kind of adjuvant therapy was given. Mesorectum and open rectum were studied by serial transverse section at 5-mm intervals. A search for depth of penetration and distal intramural extension of the tumor was made. Lymph nodes were detected by clearing method, and nodal metastases (NM) and nonnodal metastases (NNM) were recorded as situated proximally, distally, or at the level of the tumor. RESULTS: There was no postoperative mortality. Clinical and radiologic leaks occurred in 2 and 4 patients, respectively. Mean disease-free survival was 65.9 months. Pelvic recurrence occurred in 5 patients (9%). Overall 5-year survival rate was 75%. Involvement of mesorectum by NM and NNM was detected in 27 and 24 cases, respectively. Both NM and NNM were found to be distal in 33% and 40% of cases, respectively. CONCLUSIONS: Microscopic spread to the distal mesorectum may exceed the intramural spread of rectal cancer. Failure to perform total mesorectal excision leaves a potentially residual disease in the distal mesorectum, thus predisposing the patient to pelvic recurrence.

A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells.

Renewed interest in cancer immunotherapy has been raised by the availability of a variety of tumor-associated antigens and animal models. We have recently described the presence of a new antigen, TLP, in sera and cancer tissue from lung and colorectal cancer patients. In order to develop an experimental model suitable for preclinical studies on cancer vaccines, we investigated the presence of TLP antigen in vitro, in the DHD-K12 cell line and in vivo, in metastases induced in syngeneic BDIX rats by DHD-K12 cell injection. TLP was not detected in any tissue of healthy rats nor in normal tissues of tumor-bearing rats. This is in agreement with our previous studies, in which we had demonstrated that TLP is expressed in human colorectal cancer and adenomas but not in normal colonic mucosa. Our results indicate TLP as a possible human tumor-specific antigen naturally expressed in DHD-K12 tumor syngeneic to immunocompetent BDIX rats.

Immunoreactive adrenomedullin in human fetoplacental tissues.

OBJECTIVE: Adrenomedullin is increased in maternal plasma in pregnancy and has been found in very high concentrations in amniotic fluid and umbilical plasma. To identify adrenomedullin-producing tissue in pregnancy we measured adrenomedullin concentration and distribution in fetoplacental tissues. STUDY DESIGN: By use of a specific radioimmunoassay we determined the concentrations of adrenomedullin and, by immunohistochemical studies, its localization and distribution in fetal membranes and placentas collected at elective cesarean section from 11 healthy pregnant women at term. RESULTS: The content of adrenomedullin in placentas (117.7 +/- 7.8 pg/mg wet tissue) and fetal membranes (168.7 +/- 2.3 pg/mg wet tissue) was similar to the adrenomedullin concentration in adrenal medulla (157.3 +/- 4.4 pg/mg wet tissue). Adrenomedullin staining appears to be greater in fetal membranes than in placentas and was localized in amnion and trophoblast cells. In term placentas positive staining was detected predominantly in extravillous trophoblast cells, although a few syncytiotrophoblast cells and endothelial cells of primary villi stained for adrenomedullin. CONCLUSION: This study provides evidence that is consistent with fetoplacental tissues as a site of synthesis or action of adrenomedullin during pregnancy.

Uterine diffuse adenomatoid tumor. Does it represent a different biological entity?

Adenomatoid tumor represents a type of mesothelioma apparently confined to the genital tract and characterized by its benign behavior. Its morphological aspects are well known and, until now, it has been described as a nodular mass except for a case diffusely infiltrating the entire myometrium in an immunosuppressed patient. We report a case of benign mesothelial tumor characterized by histological, immunophenotypical and ultrastructural features of an otherwise typical adenomatoid tumor but diffusely growing below uterine serosal surface into the myometrium without discernible borders. The existence of a diffuse type of adenomatoid tumor might reflect a different nature of this neoplasm leading to the hypothesis that this variant of benign mesothelioma represents a distinct biological entity.

Intraoperative diagnosis of nervous system lesions.

OBJECTIVE: To determine the accuracy of comparative cytologic and frozen section intraoperative diagnosis in neuropathology and the relevance of diagnostic accuracy during both craniotomic and stereotactic biopsies and to provide further data on rare and/or diagnostically controversial lesions. STUDY DESIGN: Both cytologic and frozen section preparations were employed in the intraoperative diagnosis of 85 consecutive central and peripheral nervous system lesions obtained from classical surgery (70 samples, 4 of which were intramedullary) and stereotactic biopsies (15 samples). RESULTS: Combining cytologic and frozen section details allowed a fair diagnosis in 81 cases (95.29%), confirmed on paraffin sections. In the remaining cases intraoperative misdiagnosis was due to technical-staining defects (1 case); absence of tumor differentiation, resolved only by ultrastructural examination (2 cases); and marked tumor heterogeneity, resolved by wide tissue sampling and immunohistochemistry (1 case). CONCLUSION: Besides providing a general description of cytologic and frozen section criteria useful in intraoperative diagnostic neuropathology and adding further details about some problematic and/or rare entities, our work confirmed: (1) the usefulness of comparative cytologic and frozen section examination in the intraoperative diagnosis of central nervous system lesions, (2) the relevance of the accuracy of intraoperative diagnosis during both craniotomy and stereotaxis, including intramedullary samples; and (3) the importance of fair "conduct" in intraoperative neuropathology, always comparatively considering morphologic and clinicoradiologic data.

Immunohistochemical localization of nitric oxide synthase in human fetal membranes.

SUBJECT: It has been demonstrated that L-arginine-nitric oxide (NO) system is present in the myometrium during pregnancy where it can regulate uterine contractility. MATERIAL AND METHOD: We have studied by immunohistochemistry the localization of constitutive endothelial nitric oxide synthase (ecNOS) and brain nitric oxide synthase (bNOS) in human fetal membranes in term non laboring women. RESULTS: The amniotic epithelium and the trophoblast of chorion layer stained intensively for bNOS, while for ecNOS the immunoreactivity was weak and restricted to trophoblast cells. CONCLUSION: These findings are suggestive for NO production by the fetal membranes in term pregnancy.

Value of cytology as an adjunctive intraoperative diagnostic method. An audit of 2,250 consecutive cases.

OBJECTIVE: To evaluate the role of intraoperative cytology (IC) in the improvement of diagnostic accuracy obtained by frozen section (FS) alone. STUDY DESIGN: Comparison of 2,250 intraoperative cytologies performed along with frozen sections, with the final diagnoses achieved on paraffin sections. RESULTS: In 18 cases the diagnoses were deferred until the paraffin sections at the time of intraoperative consultation. The diagnostic accuracy in distinguishing benign from malignant lesions by combined intraoperative cytology and frozen section was 99.2%. The accuracy rate is significantly higher than that reported in large series based on frozen section preparations alone. Sensitivity and specificity were, respectively, 98.2% and 100%. The diagnostic accuracy of each technique alone was 94.9% for FS (sensitivity 89.9%, specificity 97.9%) and 96% for IC (sensitivity 94.9%, and specificity 96.8%). Although specific diagnoses were more frequently formulated on the bases of frozen section examination, FSs were not diagnostic in 113 case in which cytology allowed a specific diagnosis. CONCLUSION: Our results emphasize the increasingly important diagnostic role of intraoperative cytology as an adjunct to frozen section. The approach does have limitations.

Laparoscopic resection of solitary gastric schwannoma.

We report a case of successful laparoscopic resection of a solitary schwannoma of the gastric fundus performed on emergency. The patient was a 52-year-old man who presented with an upper gastrointestinal hemorrhage. At admission, the endoscopy and hydro-CT scan showed a submucosal tumor, 2.5 cm in maximum diameter, with an area of central ulceration arising from the anterior wall of the gastric fundus. A wedge laparoscopic resection of the gastric wall was performed under endoscopic guidance. The defect in the anterior wall was repaired in part by linear stapler and in part using a continuous suture. The postoperative recovery was uneventful and the patient was discharged on the 4th postoperative day. Laparoscopic approach represents a safe and efficient approach for the treatment of benign tumors of the stomach, also on emergency basis.

Langerhans cell histiocytosis of vulva and cervix in a 19-year-old woman.

Langerhans cell histiocytosis of the female genital tract is a rare disease. A clinical diagnosis is impossible to establish because no typical lesions are found. Immunohistochemistry of bioptic samples is the easier technique to obtain the correct diagnosis. We present a case of a 19-year-old woman with Langerhans cell histiocytosis of mandible and maxilla with subsequent cervical and vulvar histiocytosis.

Modifications of interphasic NORs as a diagnostic parameter of atypical lesions of the female breast.

Seventy-five breast samples including normal tissue, hyperplastic, metaplastic, atypical and neoplastic lesions were employed for the determination of interphasic Nucleolar Organizer Regions (NORs) modifications and Proliferating Cell Nuclear Antigen (PCNA) immunoreactivity. Interphase NORs were quantitatively and qualitatively modified in atypical lesions and breast carcinomas, whereas only modifications in the Ag-NORs count were found in benign samples. Our results investigated the nature of interphase NORs in the hope of finding a use for their evaluation in the diagnosis and biological clarification of breast epithelial atypia.

Benign fibrous mesothelioma: report of a case.

A case of fibrous benign mesothelioma is reported, together with some considerations on the diagnosis and the treatment of this rare tumour. Preoperative diagnosis is often impossible and so surgery is of great value both for treatment and diagnosis.

Immunohistochemical localization of endothelin-1 in placenta and fetal membranes in term and preterm human pregnancy.

PROBLEM: The aim of the study was to determine the ET-1 localization on human placenta and fetal membranes and to compare its distribution between term and preterm pregnancies in laboring and non-laboring tissues. METHODS: Tissues obtained from nine term elective cesarean section, eight spontaneous vaginal term delivery, and 13 preterm delivery from both cesarean section (N = 6) and vaginal delivery (N = 7) were studied by immunohistochemistry. RESULTS: Immunoreactive ET-1 (IR-ET-1) was detected in villous and nonvillous trophoblast in all groups, although laboring tissues showed strong staining in the syncytiotrophoblast of the villi. ET-1 immunostaining of endothelial cells was observed in all placental villous vessels with a considerable variability within groups. In the fetal membranes, intensive immunopositive staining was observed in the chorionic trophoblast following vaginal deliveries in term and preterm tissues. CONCLUSIONS: This is the first study to report the localization of IR-ET-1 in human fetal membranes and placenta, and suggests that amnion and trophoblast represents a source of ET-1 production or, alternatively, a site for ET-1 binding.

[Blue nevus of the endocervix]. / Nevo blu dell'endocervice.

We report a case of blue nevus of the uterine cervix discovered in a cone removed for other reasons. The lesion can be interpreted as a visceral analogue of the cutaneous blue nevus. Histological and Immunohistological studies suggest the melanocytic nature of the lesion.

Rhabdomyosarcoma of the urinary bladder in an elderly patient.

A pleomorphic rhabdomyosarcoma arising in the left side of the trigone of the urinary bladder in a 68 year old woman is reported. The prognosis for survival was very poor, owing to the tumor's extremely aggressive clinical course. After resection, the tumor recurred locally. General and local conditions did not allow any adjuvant treatment. The patient died of disease four months later.