Predicting Factors of Complete Pathological Response in Locally Advanced Rectal Cancer.

Background: Current treatment of choice for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (neo-CRT) followed by surgical resection and adjuvant chemotherapy. Some patients may experience complete pathological response (cPR) after the neoadjuvant treatment. However, the predicting factors are still debated. Methods: In this registry-based retrospective cohort study, 258 patients with locally advanced rectal cancer were included. Patients were categorized into two groups with or without cPR. Logistic regression analysis was recruited to investigate the odds ratio for all independent variables, and those with significant results were included in multivariate regression analysis. Results: Achievement of cPR was 21.3%. The odds ratio of cPR was significantly lower when the tumor distance from the anal verge was>10 centimeters (OR=0.24, P=0.040). Also, the odds of cPR with N1 involvement in comparison with N0 involvement decreased for 0.41 (P=0.043). It was also true for patients with N2 involvement in comparison with N0 involvement (OR=0.31, P=0.031). Higher odds ratio of cPR was observed in patients who underwent surgery in>12 weeks after neo-CRT (OR=2.9, P=0.022). Furthermore, the odds of cPR decreased for 0.9 with increasing in carcinoembryonic antigen (CEA) level (P=0.044). Conclusion: Patients with rectal cancer in clinical stage II or lower, without the involvement of the lymphatic system at diagnosis, and with tumors located in the lower parts of the rectum, with lower levels of CEA, and longer duration between neo-CRT and surgery were more likely to achieve cPR after neo-CRT. With the current knowledge, the "wait and watch policy" is still debated and needs to be defined more precisely by upcoming studies.

The first experience of sequential liver-kidney transplantation for the treatment of primary hyperoxaluria type-1 in Iran as a developing country.

Primary hyperoxaluria Type-1 (PH-1) is caused by a deficiency of alanine-glyoxylate aminotransferase manifesting as urolithiasis, nephrocalcinosis, and end-stage renal disease (ESRD). Among treatment options, best outcomes have been achieved by sequential liver-kidney transplantation (Seq-LKT). Herein, we report a patient with PH-1 and ESRD who underwent Seq-LKT in Iran. Criteria for diagnosis included a history of recurring calcium oxalate renal stones and elevated urine oxalate level combined with liver biopsy and absent enzymatic activity at the age of 13 years. Conservative treatment including pyridoxine, potassium citrate solution, high fluid intake, and hemodialysis was administered initially. Liver transplantation was performed at the age of 17 years from a deceased donor followed 4½ months later by a living-unrelated donor kidney transplantation. After two years of follow-up, the patient experienced no complications and had normal liver and renal function. This is the first successful experience of Seq-LKT in the treatment of PH-1 in Iran as a developing country with limited access to equipment and medications.

Clinical phenotype classification for selective immunoglobulin A deficiency.

Selective immunoglobulin A deficiency (SIgAD) is the most common predominantly antibody deficiency, with a wide range of presentations from asymptomatic to severe manifestations. Although many studies have investigated different aspects of SIgAD, no study has yet presented a comprehensive classification of this disease. Based on clinical manifestation of patients and various immune abnormalities associated with SIgAD, this group of patients could be classified into five different phenotypes including asymptomatic, minor infectious, allergic, autoimmune and severe phenotypes. This classification aids physicians in identifying patients and in choosing appropriate management and treatment as well as homogenized groups for molecular and genetic studies.

Seminal insulin-like growth factor-I may be involved in the pathophysiology of infertility among patients with clinical varicocele.

Varicocele, the most common cause of male infertility, is defined as abnormal dilation of the pampiniform plexus. Although different mechanisms have been proposed to explain the pathophysiology of infertility caused by varicocele, it is still open to debate. Previous studies have demonstrated the effect of insulin-like growth factor-I (IGF-I) on semen quality in animals and humans, but there are no studies on the probable role of seminal IGF-I in the pathophysiology of infertility among patients with clinical varicocele. We therefore aimed to examine the seminal IGF-I concentration in 49 patients with varicocele and primary infertility before and after varicocelectomy and compare the results with those of 50 healthy fertile men (in the control group). Mean seminal IGF-I level of patients before varicocelectomy (93.7 ± 67.2 ng/mL) was significantly different (P < 0.001) from that following varicocelectomy (58 ± 35.1 ng/mL) and from that of the controls (57.6 ± 22.1 ng/mL). However, mean seminal IGF-I levels of patients after varicocelectomy and the controls were not significantly different. Seminal IGF-I level was not correlated with grade and side of varicocele, and semen quality. We conclude that locally secreted IGF-I in the semen may be involved in the pathophysiology of infertility in patients with varicocele or semen.

Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients.

OBJECTIVES: Common variable immune deficiency (CVID) is the most frequent form of symptomatic primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and increased predisposition to autoimmunity and malignancies. The aim of this study was to reconsider important points of previously performed studies on Iranian CVID patients diagnosed and followed from 1984 to 2013. METHODS: Diagnosis was made using approved criteria including reductions of serum levels of immunoglobulins and exclusion of well-known single gene defects in individuals with an age >4 years and evidence of specific antibody deficiency. RESULTS: Detailed information on demographic data, survival rates, clinical phenotypes, immunologic and genetic data and treatment of 173 patients are provided. The early onset presentation (74.5%) and rate of consanguineous marriage (61.2%) were considerably higher in our cohort. Our study revealed clinically related correlations regarding consanguinity, the population of naïve CD4(+) T cells and switched-memory B cells, cytokine levels and special genetic factors (including HLA and AID genes). CONCLUSION: Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets.

Failure of isolated kidney transplantation in a pediatric patient with primary hyperoxaluria type 2.

PH type 2 is caused by decreased activity of GRHPR enzyme that eventually leads to ESRD and systemic oxalosis. Here, we describe an Iranian pediatric patient with PH2 and early ESRD development who received recommended treatment by undergoing isolated kidney transplantation. Diagnosis criteria included a history of reoccurring calcium oxalate renal stones and elevated oxalate levels combined with liver biopsy and decreased enzymatic activity at age five. ESRD prompted transplantation and was performed at age nine. On Day 12 post-op, his serum creatinine level increased. A graft biopsy showed calcium oxalate crystal deposits in renal tubes with no evidence of acute rejection, which resolved with intensive hydration and administration of a potassium citrate solution. Subsequent biopsies confirmed results found in first biopsy. Despite the immunosuppressive therapy, his serum creatinine level increased again after 11 months. Renal tubular obstruction then led to graft nephrectomy. Pathological analysis of tissue confirmed findings of past biopsies. This was a very rare case of early ESRD in PH2 resulting in a failed isolated kidney transplant. As the GRHPR enzyme is predominantly expressed in liver, we suggest a combined liver-kidney transplant may be beneficial in patients with PH2.