Evaluating the effects of duloxetine on prophylaxis of oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: A randomized double-blind placebo controlled clinical trial.

BACKGROUND: Oxaliplatin is a key drug in treatment of gastrointestinal (GI) cancer. Peripheral neuropathy (PN) is a troublesome and dose-dependent adverse effect of oxaliplatin. It can occur in two distinct forms: acute and chronic. Its incidence is estimated about 65-98%, of which 22% of cases need to stop chemotherapy. In some cases, PN has a long-lasting effect on patient's quality of life (QOL). Therefore, this study was done to evaluate efficacy of duloxetine on prevention of oxaliplatin- induced peripheral neuropathy (OIPN) in patients with GI cancer. METHODOLOGY: In this randomized and double -blind clinical trial study conducted in a tertiary teaching hospital, eligible patients were divided into two groups. Treatment group received duloxetine the day before initiation of chemotherapy regimen at a dose of 30 mg/day for one week and then, the dose was titrated up to 60 mg/day until 12 weeks. For placebo group, one placebo capsule was prescribed daily for one week followed by 2 capsules daily until 12 weeks. In each of chemotherapy courses, PN was assessed using national cancer institute-common terminology criteria for adverse effects (NCI-CTCAE v4.03). Also, chemotherapy -related QOL at the baseline and 12 weeks was assessed by functional assessment of cancer treatment gynecologic oncology group - neurotoxicity (FACT/GOG-NTX). RESULTS: Forty patients were randomly assigned to treatment and placebo groups which were similar to each other in terms of chemotherapy regimen, type, and stage of cancer. Analysis of results obtained from the NCI-CTCAE (v4.03) showed that duloxetine could prevent worsening of paresthesia more than placebo (P = 0.025) and patients in duloxetine group experienced less peripheral sensory neuropathy (P = 0.001) than placebo group. Analysis of results obtained from the FACT/GOG-NTX demonstrated a significant worsening of tingling and discomfort in hands (P = 0.002, 0.001, respectively) and feet (P = 0.017, 0.019, respectively) in placebo group compared to duloxetine group. Also, patients experienced more cold temperature -induced pain in extremities (P = 0.001) in placebo group compared to duloxetine group. On the other hand, duloxetine could not improve QOL (P = 0.06) and had not significant effects on trouble feeling the shape of small objects in hand (P = 0.420) or trouble buttoning buttons (P = 0.086). The P-value < 0.05 was considered to be statistically significant.

Nasopharyngeal B-cell lymphoma with pan-hypopituitarism and oculomotor nerve palsy: a case report and review of the literature.

BACKGROUND: Primary nasopharyngeal lymphoma (NPL) is a very rare tumor of Waldeyer ring (WR) lymphoid tissue. It is challenging to differentiate lymphoma infiltration of pituitary from a pituitary adenoma, meningioma infiltration, and other sellar lesions to plan a suitable treatment strategy. We presented for the first time a unique case of NPL with an unusual presentation of oculomotor nerve palsy associated with pan-pituitary involvement in a diabetic patient. CASE PRESENTATION: A 64-year old diabetic woman with no previous history of malignancy presented with intermittent diplopia for about the last nine months. Severe headache, left eye ptosis and hypoglycemic episodes were added to her symptoms after a while. Further complaints include generalized weakness, loss of appetite, generalized musculoskeletal pain, and 6-7 kg weight loss within six months. Her family history was unremarkable. Physical examinations of eyes indicated left eye 3rd, 4th, and 6th nerve palsy. But, she was not anisocoric, and the pupillary reflexes were normal on both eyes. No lymphadenopathy, organomegaly and other abnormalities were found. Magnetic resonance imaging (MRI) showed a heterogeneous enhancement in the seller and suprasellar regions, enlargement of the stalk, parasellar dural enhancement and thickening of the sphenoid sinus without bone erosion. Also, both cavernous sinuses were infiltrated and both internal carotid arteries were encased by the neoplastic lesion. It suggested an infiltrative neoplastic lesion which compressed the cranial nerves. Pituitary hormone levels assessment indicated a pan-hypopituitarism. Following nasopharyngeal mucosal biopsy, the immunohistochemistry (IHC) findings revealed a low-grade non-Hodgkin's B-cell lymphoma. Systemic workup, including cerebrospinal fluid (CSF) studies, bone marrow aspiration, chest and abdominopelvic high-resolution computed tomography (HRCT) indicated no other involvement by the lymphoma. After chemotherapy courses, central adrenal insufficiency, partial central diabetes incipidious (CDI) and central hypothyroidism have been resolved. To our best knowledge, we found 17 cases of NPL with cranial nerve palsy, 1 case of NPL with pan-hypopituitarism and no NPL case with both cranial nerve palsy and pituitary dysfunction. CONCLUSIONS: The incidence of cranial neuropathy in patients with diabetes should not merely be attributed to diabetic neuropathy without further evaluation.

Evaluation of the Expression of miRNAs, LncRNAs, and their Target Gene, Caspase 3 in Glioblastoma Multiform: A Case-Control Study.

Glioblastoma multiform (GBM) is an invasive cancer that causes high mortality in patients. Disruption of the apoptosis process is one of the main pathogenesis of the disease. Recently, LncRNAs and miRNAs have been shown to play an important role in the process of apoptosis. To follow the aim of study, 100 patients participated in the two groups of 50 individuals, including 50 GBM patients and 50 healthy individuals as the control group. Mononuclear cells were isolated from peripheral blood samples and RNA extraction was done. The expression changes of miR-17-5p, miR-20-5p, LINC01605, FAS-AS1, and Caspase 3 were examined using RT-PCR in both groups. Expression of LINC01605, miR-20-5p, and miR-17-5p increased in patients, while Caspase 3 and FAS-AS1 decreased; the difference was statistically significant between the two groups. In addition, it was found that these factors have the appropriate sensitivity and specificity as diagnostic markers. Finally, It is suggested to use the LINC01605, FAS-AS1, miR-20-5p, miR-17-5p, and Caspase 3 as apoptosis predictors in the GM patients.

RET/PTC rearrangement in papillary thyroid carcinoma arising in malignant struma ovarii with abdominal wall metastasis and cervical thyroid gland: a case report and review of the literature.

BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer. CASE PRESENTATION: We described a 47-year-old multigravida woman with bilateral adnexal and lower abdominal wall masses detected during the evaluation of abnormal uterine bleeding. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and surgical removal of abdominal wall mass. Then, the pathological evaluation revealed papillary thyroid carcinoma (PTC) within struma ovarii and metastatic PTC in the abdominal wall fibro adipose tissue. Further, cervical thyroid gland physical examination and ultrasound illustrated a nodule within the left lobe. Subsequently, a total thyroidectomy was performed, and a histological examination revealed PTC. Furthermore, all affected tissue, i.e., struma ovarii, abdominal wall metastasis, and cervical thyroid gland tested for BRAF and RAS mutations and RET/PTC 1 rearrangement. RET/PTC 1 rearrangement was identified among all three different sites. Finally, after six years of follow-up, the patient had no evidence of recurrence or distant metastasis. CONCLUSIONS: In light of these findings, malignant struma ovarii might yield a clue to cervical thyroid carcinoma, and the molecular analysis could provide valuable information for understanding the underlying mechanism, tumor clinicopathological behaviors, and prognosis.

Therapeutic response to ramucirumab + folfiri in patients with metastatic gastric cancer.

Background: Gastric tumors are important gastrointestinal malignancies, and the prediction of therapeutic responses and related factors are important to improve the prognosis. Hence the aim of this study was to determine the therapeutic response to ramucirumab + folfiri in patients with metastatic gastric cancer. Methods and Materials: In this prospective cohort, 13 consecutive patients with metastatic gastric cancer attending Taleghani Hospital that underwent ramucirumab + folfiri therapy were enrolled, and the therapeutic response among them was determined. Results: The results in this study demonstrated that initial therapeutic response was 92.3% and the Progression-free Survival (PFS) was 16.2 months (84.6%) (CI95%:13.2-19.3). The nine-month PFS was 69.2%. Total survival was 16.7 months (CI95%:13.5-19.9). Conclusion: Ultimately, according to the obtained results, it may be concluded that the therapeutic response to ramucirumab + folfiri in a patient with metastatic gastric cancer is good, and the use of this regimen is recommended.

177Lu-FAPI Therapy in a Patient With End-Stage Metastatic Pancreatic Adenocarcinoma.

ABSTRACT: A 52-year-old woman with metastatic pancreatic adenocarcinoma underwent imaging with 18F-FDG PET/CT and 68Ga-FAPI-46 PET/CT, which demonstrated malignancy recurrence in the surgical bed with multiple metastatic lesions, more extensive on 68Ga-FAPI-46 PET/CT. The patient was a candidate for therapy with 177Lu-FAPI-46 due to high uptake of lesions in 68Ga-FAPI-46 images and no other available therapeutic option. Posttreatment 177Lu-FAPI-46 scans showed rather rapid washout of the radiopharmaceutical from tumoral lesions. This case report suggests that, although 68Ga-FAPI-46 is a promising agent for tumor imaging, 177Lu-FAPI-46 may not be an optimal compound for theranostic applications.

Venous thromboembolism in cancer and cancer immunotherapy.

Venous thromboembolism (VTE) is a clinical disease that includes deep vein thrombosis and pulmonary embolism. Amongst its underlying risk factors, cancer is of great importance. Stasis, endothelial injury, and hypercoagulability result in clot formation and VTE. Cancer can affect coagulability by favoring these three factors, resulting in VTE incidence. Immunotherapy is a novel therapeutic approach, targeting cancer by immune system enhancement. VTE is one of the most important adverse effects of immunotherapy, which complicates the administration of immunotherapy in cancer patients. The current review provides a brief overview of VTE epidemiology, pathophysiology, risk factors, biomarkers, the relationship of cancer and cancer immunotherapy to VTE incidence, and managing cancer-associated VTE.

Dietary acid load and the risk of cancer: a systematic review and dose-response meta-analysis of observational studies.

AIMS: Recent evidence suggests the link between adherence to an acidogenic diet and the risk of some types of cancers, such as colorectal and breast cancers. This systematic review and meta-analysis aimed to clarify the association between dietary acid load and cancer risk. DATA SEARCH AND SYNTHESIS: Online databases ( PubMed, Scopus, EMBASE, Scholar Google and ISI web of sciences ) were searched between January 1990 and May 2021. The risk ratio (RR) was extracted from eligible studies and random-effects meta-analysis was performed to calculate pooled RR of studies. Nine studies (three cohorts, six case-control) were included. Higher dietary acid load scores [including potential renal acid load (PRAL) and net endogenous acid production (NEAP)] were associated with the increased risk of cancer [RRPRAL, 1.77; 95% confidence interval (CI), 1.27-2.46; n = 8; RRNEAP, 1.58, 95% CI: 1.20-2.09, n = 7). Dose-response analysis suggested that a 20-score increase in dietary PRAL and NEAP was associated with 27 and 8% higher risk of cancer, respectively (RRPRAL, 1.27; 95% CI, 1.02-1.60; nonlinearity P = 0.12; RRNEAP, 1.08; 95% CI, 1.02-1.13, nonlinearity P = 0.06). A significant positive relationship between dietary PRAL and risk of cancer was only observed in the subgroup of women. Associations were significant in both men and women for dietary NEAP. Subgroup analyses based on cancer type were only possible for breast cancer. There was no significant association between dietary acid load (PRAL and NEAP) and breast cancer risk. CONCLUSION: Our analysis showed that high adherence to an acidogenic diet is associated with an increased risk of cancer. The protocol for this meta-analysis was registered in PROSPERO registration no. CRD42019146460.

Treatment of ampullary neuroendocrine tumor by Capecitabine (Xeloda®) and Temozolomide (Temodal®).

Neuroendocrine tumors of the gastrointestinal tract and pancreas include a range of rare and diverse neoplasms with unique tumor biology, natural history, and clinical management. Neuroendocrine tumors of the ampulla of Vater are extremely uncommon cancers that account for only about 0.3%-1% of all gastrointestinal neuroendocrine tumors. Approximately 139 cases have been reported to date. In this paper, we describe two patients with low to intermediate grades of ampullary neuroendocrine tumors that underwent multiple courses of chemotherapy with Capecitabine (Xeloda®) and Temozolomide (Temodal®). Our two patients had a dramatic response to this regimen. According to our study, it seems that ampullary neuroendocrine tumors have behavior like pancreatic neuroendocrine tumors which requires further studies in more patients.

Covid-19 and Thrombotic Thrombocytopenic Purpura: A Case Report.

Endothelial injury by toxins, drugs, immune complexes leads to activation of coagulation cascade and thrombosis, which result in platelet consumption and red blood cell injury. These thrombotic microangiopathies can potentially injure numerous organs and result in organ dysfunction. In this case, we present the fourth reported patient with thrombotic thrombocytopenic purpura associated with COVID-19.

COVID-19 associated thrombotic thrombocytopenic purpura (TTP) ; A case series and mini-review.

INTRODUCTION: Thrombotic microangiopathies are a group of disorders that are mainly related to endothelial dysfunction. This category of endothelial dysfunction results of several imbalances between platelets, endothelium and immune system, also cytokine production. AIM OF THIS STUDY: To report cases with thrombotic thrombocytopenic purpura (TTP) and COVID-19 and review COVID-19 endothelial dysfunction literature. METHODS: Primary laboratory data, peripheral blood smear, ADAMTS13 antigen activity level, and antibody ordered for each of these four patients. Treatments for COVID-19 administered for all patients. Traditional treatments for TTP also were administered. RESULTS: There were numerous schistocytes (more than 5%) in peripheral blood smears for each patient. ADAMTS13 antigen activity level was below 10%, and ADAMTS13 antibody was elevated for each patient. COVID-19 PCR was positive for all patients, and CT-Scans were indicative of the involvement of COVID-19. CONCLUSION: In this case series, we reported four COVID-19 patients who presented with signs and symptoms of anemia and thrombocytopenia, resulting in thrombotic thrombocytopenic purpura.

Adding Oral Pioglitazone to Standard Induction Chemotherapy of Acute Myeloid Leukemia: A Randomized Clinical Trial.

BACKGROUND: The hypothesis of an effect by thiazolidinedione on leukemia cells was proposed 2 decades ago, but there is little clinical evidence regarding its efficacy. We evaluated the safety and efficacy of adding pioglitazone to standard induction chemotherapy in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: In this randomized clinical trial, newly diagnosed AML patients were randomized to 1 of 2 groups. Patients in both groups received cytarabine (100 mg/m2 per day for 7 days) and daunorubicin (60 mg/m2 per day for 3 days). Patients in the pioglitazone group additionally received oral pioglitazone (45 mg per day). The 2 groups were compared according to remission rate, laboratory findings, and adverse events during treatment. RESULTS: Forty patients were evaluated, 20 patients in each group. The complete remission rate was 20% more in the pioglitazone group compared to the control group (P = .202). Complications due to pioglitazone discontinuation were observed in 2 cases. The mean serum alanine aminotransferase in the fourth treatment week was significantly more in pioglitazone group compared to the control group (65.5 vs. 33.6 mg/dL, P = .039). The mean serum creatinine in all treatment phases was significantly higher in the pioglitazone group compared to the control group (P < .05). There were no significant differences between the 2 groups regarding other laboratory findings (P > .05). CONCLUSION: Adding pioglitazone to cytarabine and daunorubicin increased the remission rate in AML patients compared to control subjects. Although this difference in remission rate between the 2 groups was not statistically significant, it could be important in the clinical setting. Pioglitazone may provide benefits as an adjuvant therapy for AML patients without causing serious adverse events.

Cytarabine and Doxorubicin-Induced Palmoplantar Erythrodysesthesia Syndrome: The Possible Role of Voriconazole Interaction.

Palmoplantar Erythrodysesthesia Syndrome (PPES) caused by chemotherapeutic agents is rarely life threatening and requires a reduction in dose or discontinuation of chemotherapy. The use of cytarabine and doxorubicin in the treatment of acute myeloid leukemia (AML) along with voriconazole can potentially alter the metabolism of the drugs and cause some interactions. In this study, we presented a case of AML who received cytarabine and doxorubicin as a chemotherapy regimen and voriconazole as a prophylactic anti-fungal. In this combination, voriconazole probably inhibits the P-glycoprotein pump, which leads to an increase in the cytarabine concentration. The emphasis of this report is the awareness of clinicians and pharmacotherapists about these interactions.

Cronkhite-Canada Syndrome Associated with Metastatic Colon Cancer.

Cronkhite-Canada syndrome is characterized by gastrointestinal and ectodermal manifestations. In this paper, we describe a 64-year-old Iranian male, presenting with Cronkhite-Canada syndrome with metastatic colon cancer. The patient was suffering from hair loss, which occurred on the scalp at first and then, during 5 months, extended to the whole body. After that, his sense of taste was impaired, and 2 months later, gastrointestinal symptoms gradually started, with weight loss of 20 kg over 2 months with an initial weight of 100 kg. Finally, he was admitted to our center 10 months after the onset of symptoms. On skin examination, generalized hair loss and hyperpigmentation and dysmorphic nail changes were observed. Multiple polyps within the colon and sigmoid were observed on colonoscopy. According to biopsies, a serrated adenoma and an invasive adenocarcinoma were reported in the ascending colon and sigmoid, respectively. Other polyps were pseudopolyps, and their characteristics were not significant. Computed tomography of the lungs and abdomen showed multiple adenopathies. On biopsy, metastatic adenocarcinoma was reported. The patient underwent chemotherapy with FOLFIRI and ERBITUX. Finally, after 5 courses of chemotherapy, his regimen was changed to FOLFOX and Avastin because of evidence of progression on computed tomography. The etiology of Cronkhite-Canada syndrome is currently unknown, and the optimal therapy has not been reported so far. This syndrome has many complications; the major of them is malignancy, and the prognosis is poor with a mortality rate of 50%. Therefore, annual monitoring is necessary in these patients.

Oxaliplatin, 5Fluorouracil and Leucovorin (FOLFOX4) as First Line Chemotherapy in Elderly Patients with Advanced Gastric Cancer.

BACKGROUND: Gastric cancer is considered the fourth most common cancer and second most common cause of cancerrelated mortalities worldwide. Gastric cancer develops more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen has shown a notable activity against gastric cancer. AIM: To evaluate the responses and complications of FOLFOX4 regimen as first line chemotherapy in elderly patients with advanced gastric cancer. MATERIALS AND METHODS: From October 2014 to November 2015, a total of 21 patients with metastatic or local AGC (advanced gastric cancer) were analyzed. All patients were administered a FOLFOX4 regimen consisting of a 2h infusion of oxaliplatin 85 mg/m2 (day 1), continuous infusion of 1000mg/ m2 5Fu in 24h., and leucovorin 200 mg/m2 in 2h infusion as a firstline chemotherapy. RESULTS: A total of 18 patients were assessable for efficacy and toxicity. One of 18 patients achieved a complete response, and 12 had partial responses, giving an overall response rate of 72.6%. Three (16%) patients demonstrated stable disease and 2 (12%) progression. The median progression free survival was 7.3 months, and the median overall survival was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCICTC were seen. CONCLUSIONS: The FOLFOX4 regimen used in our study was both active and acceptable for AGC in elderly patients as neoadjuvant and main therapy.

Renal Lymphangiectasia: A Curious Cause of Pleural Effusion.

Renal lymphangiectasia is a disorder of the lymphatic system of the kidneys, which can be congenital or acquired. Although the exact etiology remains unknown, an obstructive process resulting from several causes, including infection, inflammation or malignant infiltration, has been suggested to be responsible for the acquired form. This disorder may be associated with several pathologies. We report a case of a 24-year-old man with renal lymphangiectasia presenting with polycythemia, ascites and pleural effusion associated with hepatitis C virus (HCV) infection in an intravenous (IV) drug user. Our case is the first in the literature that shows an association between HCV infection and IV drug use.

Efficacy of taxotere, thalidomide, and prednisolone in patients with hormone-resistant metastatic prostate cancer.

PURPOSE: To evaluate the efficacy and safety of combination treatment with thalidomide and taxotere in patients with hormone-resistant prostate cancer. MATERIALS AND METHODS: This clinical trial was performed on 16 patients with hormone-resistant prostate cancer. RESULTS: Mean age of the participants was 72.7 ± 5.39 years (range, 65 to 85 years). In 94% of patients who received the drug combination, prostate-specific antigen level decreased more than 50%. The mean time to progression was 15 months and mean survival time was 23 months. This combination therapy had some adverse events. CONCLUSION: Addition of anti-angiogenic agents, such as thalidomide, can improve therapeutic outcome in this group of patients.

Role of endoscopic ultrasound in evaluation of pancreatic neuroendocrine tumors--report of 22 cases from a tertiary center in Iran.

BACKGROUND: The pancreatic neuroendocrine tumor (pNET) is relatively rare and generally felt to follow an indolent course. EUS has an important role in detection of pNET. This is a review of clinical and radiological presentation and pathologic reports of 22 patients with pNET. PATIENTS AND METHODS: In this study we analyzed clinical and radiological presentations and pathologic reports of all relevant cases who were referred to Taleghani hospital for 3 years since 2008. RESULTS: A total of 22 patients 28-74 years old (mean=49) were enrolled between 2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16 (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases but EUS was capable of detecting the lesions in these patients, cysts being found in 4 (19%) patients. CONCLUSION: EUS is a highly sensitive procedure for the localization of functional pNETs and especially insulinomas. Nonfunctional tumors were detected in more advanced and late stages and cystic lesions were more common in this group.

A patient with chronic hepatitis C and a pancreatic mass in endoscopic ultrasound.

We report a rare case of pancreas tumor (lymphoma) in a patient with a history of chronic hepatitis C virus (HCV) infection without treatment, with a high viral load (20,199,805 IU/ml). He presented with abdominal pain, jaundice, weight loss and sweating. Computed tomography showed a hypodense mass located in the head of the pancreas, and immunohistochemistry of a specimen obtained by endoscopic ultrasound-guided fine needle aspiration revealed non-Hodgkin's lymphoma of the pancreas, B cell type. An association of HCV infection with pancreatic lymphoma has only been reported rarely in the literature and its clinical significance is uncertain.