Evaluation of acute, subacute, and subchronic toxicity of a hepatoprotective herbal formulation.

Background: The possible toxicity of natural products must be tested before being used in the market. The present work aimed to evaluate acute, subacute, and subchronic toxicity of an herbal formulation containing Anethum graveolens, Cynara scolymus, Citrus aurantium, Portulaca oleracea, and Silybum marianum. Material and methods: Acute toxicity (2000 mg/kg, single dose) and sub-acute toxicity (600 and 1200 mg/kg/day, 4 weeks) tests were performed on female and male rats according to OECD 423 and OECD 407 guidelines, respectively. In the subchronic study (12 weeks), the animals were divided into three groups (6 females and 6 males per group): control, low-dose group (food supplemented with 300 mg/kg of the herbal product), and high-dose group (600 mg/kg). Results: The herbal product at a single dose of 2000 mg/kg did not induce mortality for 14 days. In the sub-acute study, administration of the product for 28 days at 1200 mg/kg/day had no effect on survival, appetite (water and food consumption), body weight, serum biochemical parameters (BUN, creatinine, AST, ALT, ALP, bilirubin, albumin), histology of vital organs (liver, kidney, heart, brain), and hematological markers related to erythrocyte, platelet, and leukocyte. Similarly, in the subchronic study, the product did not induce mortality, change in histology of the vital organs, or alteration in hematological or biochemical parameters (except for an increase in ALP in female rats received 600 mg/kg). Conclusion: The formulated product shows no signs of toxicity in rats up to 2000 mg/kg, 1200 mg/kg, and 600 mg/kg in acute, subacute, and subchronic phases, respectively. It is suggested to monitor ALP levels in females in case of long-term use of the product.

Assessment of the Tumor-Stroma Ratio and Tumor-Infiltrating Lymphocytes in Colorectal Cancer: Inter-Observer Agreement Evaluation.

BACKGROUND: To implement the new marker in clinical practice, reliability assessment, validation, and standardization of utilization must be applied. This study evaluated the reliability of tumor-infiltrating lymphocytes (TILs) and tumor-stroma ratio (TSR) assessment through conventional microscopy by comparing observers' estimations. METHODS: Intratumoral and tumor-front stromal TILs, and TSR, were assessed by three pathologists using 86 CRC HE slides. TSR and TILs were categorized using one and four different proposed cutoff systems, respectively, and agreement was assessed using the intraclass coefficient (ICC) and Cohen's kappa statistics. Pairwise evaluation of agreement was performed using the Fleiss kappa statistic and the concordance rate and it was visualized by Bland-Altman plots. To investigate the association between biomarkers and patient data, Pearson's correlation analysis was applied. RESULTS: For the evaluation of intratumoral stromal TILs, ICC of 0.505 (95% CI: 0.35-0.64) was obtained, kappa values were in the range of 0.21 to 0.38, and concordance rates in the range of 0.61 to 0.72. For the evaluation of tumor-front TILs, ICC was 0.52 (95% CI: 0.32-0.67), the overall kappa value ranged from 0.24 to 0.30, and the concordance rate ranged from 0.66 to 0.72. For estimating the TSR, the ICC was 0.48 (95% CI: 0.35-0.60), the kappa value was 0.49 and the concordance rate was 0.76. We observed a significant correlation between tumor grade and the median of TSR (0.29 (95% CI: 0.032-0.51), p-value = 0.03). CONCLUSIONS: The agreement between pathologists in estimating these markers corresponds to poor-to-moderate agreement; implementing immune scores in daily practice requires more concentration in inter-observer agreements.

Multifocal Langerhans' Cell Histiocytosis in an Adult.

Introduction: Multifocal Langerhans' cell histocytosis is a rare condition that can affect multiple organs and manifest in various scenarios. While the condition is more commonly found in children, it can also occur in adults. Case Report: A 43-year-old female presented with refractory otorrhea and had a rubbery neck mass in the left mid-cervical area, as well as an itchy eczematoid lesion in the left parietal area. The otic lesion was eventually resected, and histopathologic examination confirmed the diagnosis of Langerhans histiocytosis. Conclusions: Although rare in adults, Langerhans histiocytosis should be considered as one of the differential diagnoses for ear canal polyps. If diagnosed, medical treatment should be pursued.

Pathology Reports: Discrepancy Patterns of Second Opinions in a Referral Cancer Center.

OBJECTIVE: To evaluate the diagnostic mismatch (discrepancy) of pathology reports in consulted specimens referred for second opinion. MATERIALS AND METHODS: This cross-sectional study was conducted at a major cancer center, Omid Hospital. In this study, 350 primary pathology reports and 350 reviewed pathology reports were extracted from the archives of Omid Hospital from 2011 to 2020 and assessed in terms of the extent of discrepancy, by two pathologists and one oncologist. The required data for each sample were entered into a checklist and then statistically analyzed. Cases with the same diagnosis on both reports were assigned to the matched group and the rest were assigned to the minor or major mismatch (discrepancy) group. Minor mismatches included changes in diagnosis that did not lead to changes in treatment (may lead to changes in prognosis or provide additional information to the oncologist) and major mismatches included changes in diagnosis leading to changes in treatment or remedies. RESULTS: Two hundred seven cases (59.1%) out of three hundred fifty cases had concordant results between the diagnosis of the first pathologist and the reviewing pathologist. In one hundred forty-three cases (40.9%) mismatch (discrepancy) was observed, including eighty- two cases (23.4%) with minor mismatches (discrepancy) and sixty-one cases (17.4%) with major mismatches (discrepancy). In the major mismatch group, fifteen cases (4.3%) changed from malignant to benign, eighteen cases (5.1%) changed from benign to malignant, two cases (0.6%) changed from one stage to another stage of Disease and twenty-six cases (7.4%) had changes in the type of malignancy. In this study, it was found that there was no significant relationship between anatomical areas of sampling and diagnostic mismatch (p = 0.254). The study also found that the rate of diagnostic mismatch in specimens obtained by resection or excisional biopsy was greater than that of small biopsies (eighty cases (22.8%) and sixty-two cases (17.7%, respectively)). There was no significant relationship in this regard (p = 0.077). CONCLUSION: Compared to most similar studies, the present study reported the highest discrepancy between the diagnosis of the first pathologist and the reviewing pathologist (40.9%).

Remission of Prurigo Pigmentosa after Breaking Ketogenic Diet and Resuming Regular Diet.

Prurigo pigmentosa (PP) is a rare skin disorder presenting as erythematous urticarial papules on the chest and leaving reticulated pigmentation. Although the etiology of PP is unknown, conditions associated with ketosis such as diabetes mellitus, ketogenic diet (KD), and anorexia nervosa are implicated. Herein, we report a 21-year-old woman who developed PP after adhering to a KD and responded to resuming a regular diet.

Middle Ear Primary Oncocytic Schneiderian Papilloma: A Case Report.

Introduction: Chronic otitis media is a significant health problem, but middle ear and mastoid neoplasms, either benign or malignant, are extremely rare. Case Report: Here is a report from a 51-year-old female who presented persistent otorrhea with an aural polyp. The patient was operated on with the probable diagnosis of cholesteatoma. During surgery, a fragile mass was discovered, and histopathologic examination reported the diagnosis of a primary oncocytic Schneiderian papilloma. Microscopically it has pseudostratified epithelium of columnar cell epithelium with eosinophilic granular cytoplasm and hyperchromatic nuclei. The treatment of choice for Schneiderian papillomas is complete surgical removal. Conclusions: Although very rare, oncocytic Schneiderian papilloma should be considered a differential diagnosis of ear neoplasms such as auditory canal polyps.

Polyomavirus Associated Nephropathy: Frequency and Graft Survival Analysis in Northeast of Iran.

BACKGROUND & OBJECTIVE: Polyomavirus-associated nephropathy (PVAN), mainly caused by the BK virus, is one of the most important infectious complications of kidney transplantation. The leading histopathologic characteristics of PVAN is viral cytopathic effects, such as nucleomegaly with smudged or clumped chromatin and intranuclear ground-glass inclusion, mostly in tubular epithelial cells. Moreover, tubular necrosis, tubulitis, interstitial inflammation, atrophy, and fibrosis have been noted. Positive immunohistochemistry (IHC) staining for SV-40 highlights the infected epithelial cells of renal tubules. METHODS: A total of 85 core needle biopsies of transplanted kidneys were evaluated histologically and were stained for SV-40 using the IHC method. In addition, a follow-up of graft failure was performed. RESULTS: Our findings revealed that the frequency of polyomavirus infection in kidney transplant patients in the Northeast of Iran is 4.7%. There was no significant correlation between PVAN and graft rejection. Although a higher rate of graft loss was observed in PVAN patients, in comparison with non-PVAN patients (25% vs. 14.8%), the difference was not statistically significant. Moreover, patients with immunohistochemically confirmed PVAN and those with histopathologic features of viral-like cytopathic effects had significantly lower graft survival in the follow-up period (42.5 vs. 196.8 months and 109.4 vs. 205.7 months, respectively). CONCLUSION: The frequency of polyomavirus infection in kidney transplant patients in the Northeast of Iran is 4.7%. There was no significant correlation between PVAN and graft rejection. Furthermore, we observed that polyomavirus infection accelerates the course of graft loss.

Mucoepidermoid Carcinoma Superimposed on a Warthin's Tumor: A Case Report and Review of the Literature.

INTRODUCTION: Warthin's tumor (WT) is the second most common neoplasm of the parotid gland and consists of two components, including lymphoid stroma and glandular epithelium. The malignant transformation of this tumor occurs most often in the lymphoid component; however, the carcinomatous transformation of the epithelial component is rare. CASE REPORT: We present a patient who had a mass in the right mandibular angle two years before referral. A cystic mass was reported on sonography, and the patient underwent superficial parotidectomy with a pre-operative impression of lymphangiomatouse-like lesions. In the microscopic view, the sections revealed salivary gland neoplastic lesion with the diagnosis of WT. On the periphery of the neoplasm, another neoplastic lesion was observed along with infiltrative borders and diagnosis of mucoepidermoid carcinoma. CONCLUSION: The WT is one of the most common tumors of the salivary glands. Malignancy transformation of the WT is a rare event. However, due to the importance of the treatment type, the surgeon should consider this issue in cystic lesions suspected of WT.

Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma.

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and ß-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/ß-catenin pathway and therefore prolongs the survival of rats with HCC.

Effects of Rhus coriaria L. hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of Rhus coriaria L. (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.

Arteriovenous malformations of the colon: A report of two cases and review of the literature.

BACKGROUND: Arteriovenous malformations are one of the most common vascular disorders of the colon. Vascular disorders present as painless, high-volume rectal bleeding. CASE PRESENTATION: This study elucidates two rare cases of vascular disorders that are diagnosed as angiodysplasia of the left colon and cavernous hemangioma of the colon and rectum. The chief complaint in two patients was rectorrhagia. The patients who were diagnosed of ulcerative colitis were treated with sulfadiazine and prednisone. Due to continuous bleeding, the patients were referred to the surgery department for operation. The patients underwent total proctocolectomy. CONCLUSION: We discuss the faults in the diagnosis and management of vascular disorders of the intestine.

Prevalence of chronic kidney disease and its risk factors in Gonabad, Iran.

INTRODUCTION: Chronic kidney disease (CKD) is an important health problem in Iran, with an increasing prevalence rate. Knowledge about the prevalence and risk factors of this disease in different health jurisdictions can help in planning to control this condition. MATERIALS AND METHODS: In this cross-sectional study, 1285 individuals aged between 20 and 60 years old were recruited. Participants were selected from the general population residing in Gonabad, Iran, via simple random sampling in 2012. Demographic data were collected. Urine and blood test were performed, and the glomerular filtration rate was estimated based on the simplified Modification of Diet in Renal Disease equation. RESULTS: Sixty-five participants (5.1%) had CKD (5.1% men and 5% women; P = .90). The mean age was significantly higher in the CKD group (P = .001). Hypertension and diabetes mellitus were significantly more prevalent among the participants with CKD than those without CKD (P < .001 for both). Proteinuria was significantly associated with CKD, whereas a history of urinary tract infection, a history of nephrolithiasis, smoking, serum uric acid level, lipid profile, and blood glucose level were not. CONCLUSIONS: Chronic kidney disease has a high prevalence rate in this part of Iran. We suggest further studies in other parts of our country for the better estimation of the prevalence of CKD in Iran and for better planning to prevent and treat this condition.

A report of a rare gastric cancer case: leptomeningeal carcinomatosis.

Leptomeningeal carcinomatosis (LMC) from gastrointestinal cancer would be rare. A 56-years old man with complaint of dyspepsia and histopathologic examination of the biopsy specimens has shown: adenocarcinoma. At the end of adjuvant chemo radiation therapy, the patient has affected by headache and mild confusion. In cerebrospinal fluid (CSF) cytology, a plenty of malignant cells have seen and unfortunately after a short time for about 4 days after ICU admission, the patient has died. This could be due to heavy burden of disease in central nervous system.

Primary Small Cell Carcinoma of the Esophagus (PSCEC) Associated with Paraneoplastic Sweating Syndrome: A Case Report and Literature Review.

INTRODUCTION: Primary small cell carcinoma of the esophagus (PSCEC) associated with paraneoplastic sweating syndrome is a rare disease characterized with rapid growth rate, metastasis at the time of diagnosis, and poor prognosis. The lung is the most common site for small cell carcinoma but this malignancy includes 0.1% to 1% of all gastrointestinal and 0.8% to 2.7% of esophageal malignancies. So far more than 200 cases of PSCEC have been reported in literature. CASE REPORT: The patient is a 54-year-old female from the Golestan province who presented with dysphagia, 19 kg-weight loss (from 105 kgs to 86 kgs), and excessive sweating. She was admitted in the thoracic surgery ward, at Ghaem Hospital, in the Mashhad University of Medical Sciences, with a pathological diagnosis of small cell carcinoma. She underwent transhiatal total esophagectomy. Excessive sweating was eradicated after surgery and she was discharged after 13 days without any complication. She received chemotherapy and at her 5-year follow up, she showed no recurrence or metastasis. CONCLUSION: PSCEC usually requires chemotherapy with or without surgery. A favorable outcome, with total resection of the lesion combined with chemotherapy, was obtained. However, due to the rarity of the disease there is no definitive choice of treatment.

Calretinin Immunohistochemistery: An Aid in the Diagnosis of Hirschsprung's Disease.

OBJECTIVES: Definite diagnosis of Hirschsprung's disease (HD) is based on histopathological study, but there are limitations associated with standard histology and histochemistry in this regard. The aim of this study was to investigate calretinin immunostaining patterns in both ganglionic and aganglionic HD intestinal specimens and to compare them with control specimens. MATERIALS AND METHODS: Specimens included 30 patients with histopathologic diagnosis of HD and 20 patients that underwent colectomy for other reasons (as control group). Eighty paraffin wax blocks of full thickness intestinal specimens (30 blocks of ganglionic segments, 30 blocks of aganglionic segments and 20 blocks of control group) were studied. Calretinin immunoreactivity and pattern of staining for ganglion cells (nuclear and cytoplasmic) and also nerve fibers in different layers of bowel were evaluated in IHC stained slides. RESULTS: There were positive immunostaining of nerve fibers in the lamina propria, submucosa and muscularis propria in control and patient group. There were also nuclear and cytoplasmic staining of ganglion cells in submucosa and muscularis propria in all specimens of both control group (100%) and ganglionic segments (100%). Calretinin immunoexpression of nerve fibers in muscularis propria of the aganglionic segments was negative in all but two cases (6.7%). This method had sensitivity of 93.3% and specificity of 100% for diagnosis of HD in full thickness specimens of intestinal wall. The positive predictive value was 100% and negative predictive value was 93.8%. CONCLUSION: Calretinin immunohistochemistry can be used on suction rectal biopsies as a reliable and adjunctive method to diagnose HD.