Discordance Between the Initial Diagnosis of Sarcomas and Subsequent Histopathological Revision and Molecular Analyses in a Sarcoma Reference Center in Brazil.

PURPOSE: To investigate the discordance in sarcoma diagnoses between nonspecialized institutions following revision by dedicated sarcoma pathologists at a reference center in Brazil and the relevance of molecular pathology in this context. METHODS: We conducted a retrospective analysis of sarcoma samples initially analyzed at outside laboratories and subsequently reviewed by two specialized pathologists between January 2014 and December 2020. After obtaining demographic and tumor characteristics, pathology results were matched and classified as complete discordance (CD; benign v malignant, sarcoma v other malignancies), partial concordance (similar diagnosis of connective tumor, but different grade/histological subtype/differentiation), and complete concordance (CC). The concordance for histology or grade, and the role of molecular assessments supporting the diagnosis were also independently determined. Statistical analyses were conducted through the kappa coefficient of agreement and adherence by χ2 test, χ2 test by Person, and Fisher exact test. RESULTS: In total, 197 cases were included, with samples obtained predominately from male patients (57.9%) and localized/primary tumors (86.8%). Following revision, the most frequent final diagnoses were undifferentiated pleomorphic sarcoma (17.8%), well-differentiated/dedifferentiated liposarcoma (8.6%), and leiomyosarcoma (7.6%). CD was found in 13.2%, partial discordance in 45.2%, and CC in 41.6% of reviews (P < .001). We found a concordance for histology or grade of 53.5% (P < .001) and 51.8% (P < .001), respectively. Molecular assessments, comprising next-generation sequencing panels (79.5%) and fluorescent in situ hybridization (20.5%), were performed in 44 (22.3%) cases, with findings classified as of diagnostic relevance in 31.8%. CONCLUSION: In nearly 60% of the cases, the initial sarcoma diagnosis was modified when revised by a reference center and dedicated pathologists, assisted by molecular pathology techniques. These results justify the assembly of referral networks in countries with limited health care resources.

Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management. METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up. RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient's comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards. CONCLUSION: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

Multivisceral resection for retroperitoneal liposarcoma-is it worth it? A 20-year single-center experience.

PURPOSE: Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. OBJECTIVE: Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. METHODS: A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. RESULTS: The overall survival rate at 5 years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5 years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). CONCLUSION: Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.

Trapeziectomy and Suture-Button Suspensionplasty for Basilar Thumb Arthritis: Is It Enough to Prevent First Ray Subsidence?

Introduction Trapeziectomy and suture-button suspensionplasty (SBS) are a novel option to treat end-stage trapeziometacarpal (TMC) osteoarthritis. Our purpose is to evaluate our outcomes with this technique and in this setting, with a minimum of 18 months of follow-up. Materials and Methods Twenty-eight patients were included, operated between 2016 and 2018. We recorded demographic data, preoperative Eaton stage, follow-up and operative times. The patients completed the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire and tip pinch, key pinch, and grip strength were measured. First metacarpal subsidence was calculated, and postoperative complications were documented. Results The average follow-up was 34 months. The mean QuickDASH was 32 at the final follow-up. The average strength results were 20 kg for grip, 3.6 kg for tip pinch, and 4.2 kg for key pinch. The rate of first ray subsidence was 10.7%. We encountered three complications: a hardware intolerance, a second metacarpal fracture, and a suture rupture. There was one reoperation to remove an implant. Conclusion Trapeziectomy and SBS functional results are similar to other techniques, with less subsidence of the first ray and allowing for early mobilization and fast recovery. This procedure is a safe and promising option in the treatment of TMC osteoarthritis, with good medium-term outcomes.

Is bilateral hallux valgus chevron osteotomy a safe procedure for ambulatory surgery?

INTRODUCTION: Several osteotomies of the first metatarsal have been described for treatment of hallux valgus but chevron osteotomy is one of the most common and well-established procedure for treating this deformity. Although there is a trend towards considering bilateral surgery there is lack of publications addressing bilateral treatment in ambulatory units. The aim of this study is to analyze results of bilateral and unilateral distal chevron osteotomies associated with lateral soft tissue release as ambulatory procedures. MATERIALS AND METHODS: A retrospective review was made about the patients treated at our ambulatory unit over a period of five years. Initially, general information as patient's satisfaction's rate and return to normal activity's time and evaluation of standardized follow-up charts and records made by the surgeon were recorded. Secondly, the hallux metatarsophalangeal interphalangeal scale developed by the American Orthopedic Foot & Ankle Society was used. RESULTS: A total of 194 patients with 230 feet operated were included in this study. We found 29 patients that didn't meet the inclusion criteria and were excluded. The unilateral group was composed by 139 feet and the bilateral group by 52 feet. The improvement between preoperative and discharge clinical and radiographic results was significant independently in both groups. A total of 14% of complications were found in our study, 19% in the unilateral group and 12% at the bilateral group. None of them required revision surgery. CONCLUSION: Bilateral distal chevron osteotomies, associated with lateral soft tissue release, are safe and effective ambulatory procedures. It was found a satisfactory deformity correction in moderate HV. Both patients that underwent unilateral and bilateral procedures had similar clinical and radiological outcomes with no increase in complications or return to normal activity time. With this study it was demonstrated that bilateral chevron osteotomies can be performed as ambulatory procedures.

Trapeziectomy with suture-button suspensionplasty versus ligament reconstruction and tendon interposition: a randomized controlled trial.

The purpose of the present study was to compare the results of patients operated with trapeziectomy and ligament reconstruction and tendon interposition (LRTI) using flexor carpi radialis tendon versus trapeziectomy followed by suspension of the first metacarpal to the second metacarpal using a Mini TightRope® suture button (suture button suspension: SBS). A single-center prospective randomized controlled trial was performed, comparing 37 patients with SBS and 39 with LRTI. All surgeries were performed by the same fellowship-trained hand surgeon. Patients were assessed by an independent observer at 40 months' follow-up. Pre- and postoperative strength, trapezial space ratio (TSR), range of motion, QuickDASH and visual analogue pain score were recorded. Both procedures improved functional parameters of pain, key strength, tip strength and grip strength while maintaining range of motion, without significant differences. In the SBS group, TSR decreased by 17%, compared to 28% in the LRTI group. The mean operative time was shorter in SBS (63 vs 91 minutes; p < 0.0001), as was immobilization time (2 vs 6 weeks; p < 0.0001), and patients resumed normal activity sooner (10 vs 12 week; p = 0.0138) and required less physical therapy (19.3 vs 13.1 weeks; p < 0.0001). We believe that our results are related to the hypothesis suggested by biomechanical studies that revealed better initial load bearing profile and maintenance of trapezial space following serial loading in cadaver models.

Percutaneous Scaphoid Fixation: Experience Value among Different Approaches.

Background Percutaneous scaphoid osteosynthesis is an attractive and increasingly popular option, as a treatment for acute scaphoid fractures in selected cases, and as an alternative to conservative treatment. The purpose of this study is to assess the radiographic positioning of the screw in percutaneous scaphoid fixation, taking into consideration the surgeons' experience, and the difference between volar and dorsal approaches. Methods We retrospectively assessed patients undergoing percutaneous scaphoid fixation from 2013 to 2019. Inclusion criteria are as follows: (1) scaphoid waist fractures (Herbert's B2), (2) a minimum of 18 years of age and a maximum of 55 years of age, (3) dominant hand, (4) manual work, (5) minimum follow-up time of 6 months, and (6) without associated lesions. Criteria for correct positioning are as follows: (1) on the axis or parallel to the scaphoid axis with a maximum deviation of 1.5 mm volar/dorsal, (2) without proximal/dorsal prominence, (3) correct scaphoid alignment/reduction, and (4) absence of threads in the fracture site. Radiographs were evaluated separately by a hand surgeon, a general orthopaedic surgeon, and an orthopaedic resident. Results With a total of 39 patients, a dorsal approach was performed in 10 patients and a palmar approach in 29 patients. We verified a very good interobserver reliability. The hand surgeon's team correctly positioned 15 (83.3%, 15/18), while the other team did 9 correctly (42.9%, 9/21). Comparing teams according to the approach used, the dorsal approach did not show a statistical difference, while the same was not true for the volar approach ( p < 0.05). Conclusion This points to a positive impact on the team's experience in the positioning of the screws, and therefore in the benefit of treatment by teams dedicated to the area, while daring to suggest that less-experienced surgeons should utilize the dorsal approach.

Arthroscopic Reduction-Association of the Scapholunate with an Absorbable Screw.

Background The treatment of chronic scapholunate instability is yet a controversial topic. Arthroscopic reduction-association scapholunate technique is a minimally invasive option in which a stable pseudoarthrosis at the scapholunate joint is obtained, allowing some degree of movement while maintaining the normal alignment of the wrist. The purpose of this study was to review the results of arthroscopic reduction-association scapholunate with an absorbable screw. Methods We retrospectively evaluated patients with dynamic or static, but reducible, chronic scapholunate instability who underwent arthroscopic reduction-association scapholunate between 2012 and 2015. An absorbable headless compression screw was used in the technique. Results A total of 33 patients (21 males, 12 females) were included. Average follow-up time was 17 months. At final follow-up, the average postoperative Disabilities of the Arm, Shoulder and Hand (DASH) score was 18 (range, 8-46). The average postoperative grip strength was 30 kg, 73% of the uninjured side. The average extension-palmar flexion arc was 112 degrees, 79% of the uninjured side. The scapholunate angle decreased from 70 degrees preoperatively to 52 degrees postoperatively. In the cases of static lesion, the scapholunate interval decreased from 4.1 mm preoperatively to 2.8 mm at final follow-up. One patient had a breakage of the screw at 4 months, four developed a complex regional pain syndrome, one had a prominence of the screw at the waist of the scaphoid, and four maintained symptoms of instability. From these 10 patients, 5 were submitted to revision surgery. Conclusion The arthroscopic reduction-association technique is capable of maintaining the reduction of the scapholunate joint and of improving symptoms, while preserving range-of-motion. The use of an absorbable screw is an option in this technique, and may diminish screw-related complications.

Leiomyosarcoma of the inferior vena cava: Survival rate following radical resection.

Leiomyosarcoma (LMS) of inferior vena cava (IVC) is a rare neoplasm affecting approximately 1/100,000 people. The prognosis is poor and potential curative intent occurs through challenging operations, such as vena cava resection, occasionally multivisceral when required, and vascular reconstruction. There are few retrospective series regarding this retroperitoneal neoplasm, and the aim of the present study was to discuss the experience at the São Paulo Cancer Institute and Clinics Hospital of University of São Paulo Medical School, São Paulo, Brazil. The current study is a retrospective review of 7 patients treated in the two tertiary hospitals between 2005 and 2013. Oncological and operative aspects were discussed, primarily regarding surgical aspects highlighting en bloc resection, vascular reconstruction, and the overall survival and recurrence rates. All the patients were treated with radical intent, 4 of whom underwent multivisceral resection, with the kidney being the most resected organ. The location of the IVC tumor was described using Kulaylat's description and the median tumor size was 10 cm. Vascular reconstruction was necessary in 4 patients. The overall survival rate at 3 and 5 years was 100, and 25%, respectively. The disease-free survival rate at 3 and 5 years was 57 and 20%, respectively. In conclusion, IVC LMS is a rare and severe retroperitoneal neoplasm, with multivisceral resections remaining a surgical challenge. The treatment requires numerous experienced surgeons and the impact of microscopic free margins remains unclear. Vascular reconstruction depends on several aspects regarding primarily the topography of the tumor.

Acute appendicitis, inflammatory appendiceal mass and the risk of a hidden malignant tumor: a systematic review of the literature.

INTRODUCTION: Acute appendicitis is significantly common. Despite the increased use of computed tomography, the number of perforated cases has been stable in the past three decades. Between 2% and 6% of patients with acute appendicitis present appendiceal mass, often described as inflammatory phlegmon or abscess. Malignant tumors are confirmed by pathological analysis in 0.9-1.4% of all appendectomies performed to treat acute appendicitis. However, recent series demonstrate an elevated incidence of malignancies, ranging from 5.9 to 12%, in patients with inflammatory appendiceal mass. METHODS: The analysis was based on a systematic review of the literature. The articles were searched in PubMed for the period from 1987 to 2016. Articles presenting the incidence of the hidden malignancy among patients with appendiceal inflammatory mass were selected. Variables as age, interval appendectomy rate, the incidence of neoplasm, time to surgery, minimally invasive assessment, histology, right colectomy rate and morbidity were analyzed. RESULTS: A total of 13.244 patients were described as presenting acute appendicitis. Appendiceal tumor is present in approximately 1% of the appendectomies, while the rate of neoplasm varies from 10 to 29% in patients presenting appendiceal inflammatory mass. Interval appendectomies, despite been the minority of the procedures, disregard the higher morbidity associated with right sided colectomies. The review of literature also describes oncologic, histologic and clinical aspects of patients presenting appendiceal neoplasm, describing the most frequent histologic subtypes of this illness. CONCLUSION: Hidden appendiceal neoplasm in acute appendicitis are rare, fortunately. However, its incidence is much higher in patients presenting appendiceal inflammatory mass. Hence, interval appendectomy should be considered in this subgroup of patients.

Pancreaticoduodenectomy in patients with type 1 Neurofibromatosis: Report of two cases and literature review.

INTRODUCTION: Type 1 Neurofibromatosis (NF1) is one of the most common autosomal dominantly inherited multisystem disorders. It is associated with an increased risk of developing neurologic and gastrointestinal (GI) malignant neoplasms. The incidence of GI involvement is reported in 10-25% of patients. Less than 5% of NF1 patients with GI neoplasms manifest symptoms. The presence of synchronic gastrointestinal stromal and neuroendocrine tumors is rare in these patients. PRESENTATION OF CASES: The first case is a 37 year-old male patient with a history of abdominal pain for a few months. Imaging study showed a periampullary mass and a solid lesion at the third duodenal portion. He was submitted to a pancreatoduodenectomy and histological anaylisis showed two low-grade neuroendocrine tumors and a gastrointestinal stromal tumor. The second case is a 47 year-old female patient with a routine computed tomography scan showing a duodenal and a jejunal lesion. Duodenopancreatectomy was performed and histological analysis showed a neuroendocrine adenocarcinoma of the duodenum and two jejunal lesions compatible with GI tumors. DISCUSSION: GI symptoms such as jaundice, pain and bleeding in NF1 patients should prompt urgent admission Occasionally, associated gastrointestinal tumors may be incidentally found in asymptomatic NF1 patients. The presence of a periampullary or duodenal neoplasia such as neuroendocrine tumors should be evaluated. CONCLUSION: Although rare, the synchronic presentation of gastrointestinal tumors in patients with NF1 should be ruled out since it can lead to higher morbidity and mortality rates. Single-stage surgical management is feasable and yields satisfactory results.

Safety in selective surgical exploration in penetrating neck trauma.

BACKGROUND: Selective management of penetrating neck injuries has been considered the standard of care with minimal risks to patient safety. In a previous non-randomized prospective study conducted at our center, selective management proved to be safe and reduced unnecessary exploratory cervicotomies. In the present study, the role of clinical examination and selective diagnostic tests were assessed by reviewing demographic and clinical data. A comparison of results between two groups (mandatory surgical exploration versus selective surgical exploration) was made to check the safety of selective management in terms of the rates of morbidity and mortality. METHODS: A retrospective analysis at the Emergency Department of the Hospital das Clínicas of the University of Sao Paulo was performed by a chart review of our trauma registry, identifying 161 penetrating neck trauma victims. RESULTS: Of the 161 patients, 81.6 % were stabbed and 18.4 % had gunshot injuries. Stratifying the wound entry points by neck zones, we observed that zone I was penetrated in 32.8 %, zone II in 44.1 % and zone III in 23.1 % of all the cases. Thirty one patients (19.2 %) had immediate surgical exploration, which had a mean length of stay of 6 days, a complication rate of 12.9 % and a mortality rate of 9.4 %. Of the 130 who underwent selective surgical exploration 34 (26.1 %) required operative procedures after careful physical examination and diagnostic testing based on clinical indications. The mean length of stay for the selective surgical exploration group was 2 days with a complication rate of 17.6 % with no mortality, and virtually all of them were related to associated injuries in distant body segment. No statistical significance was found comparing mortality and complication rates between the two groups. Selective approach avoided 59 % of unnecessary exploratory cervicotomies. CONCLUSION: Careful evaluation of asymptomatic and stable patients with minor signs of injury can safely avoid unnecessary neck explorations with low rates of morbidity. This should be the standard management of such patients.

Can we respect the principles of oncologic resection in an emergency surgery to treat colon cancer?

Patients with colorectal cancer admitted to the emergency room are generally at more advanced stage of the disease and are usually submitted to a resection with curative intent in a smaller scale. In such scenario, one of the aspects to be considered is whether the principles of oncologic resection are observed when those patients diagnosed with colon cancer are treated with surgery. We selected 87 patients with adenocarcinoma of colon and/or upper rectum submitted to an emergency surgical resection. The major variables reviewed retrospectively were: the extent of resection performed, the number of dissected regional lymph nodes and the overall survival rate. Intestinal obstruction was observed in 67 patients (77%) while perforation was found in 20 patients (23%). Seven (8%) specimens had circumferential compromised margins, all found in patients with T4 tumors combine with poor clinical status. The number of dissected regional lymph nodes was greater than, or equal to, 12 in 71% of patients. While the average days of stay in the ICU was 5.7 days, the median was 3 days. The morbidity and peri-operative mortality stood at 33.6% and 20%, respectively. The outcome of an emergency surgery of colorectal cancer observed in this study was similar to those found in the literature. The principles of oncologic resection were respected when considering and analyzing the extent of the resection, the surgical margins and the number of dissected lymph nodes.

Popliteal lymph node dissection for metastases of cutaneous malignant melanoma.

Popliteal lymph node dissection is performed when grossly metastatic nodal disease is encountered in the popliteal fossa or after microscopic metastasis is found in interval sentinel nodes during clinical staging of cutaneous malignant melanoma. Initially, an S-shaped incision is made to gain access to the popliteal fossa. A careful en bloc removal of fat tissue and lymph nodes is made to preserve and avoid the injury of peroneal and tibial nerves as well as popliteal vessels, following the previous recommendations. This rare surgical procedure was successfully employed in a patient with cutaneous malignant melanoma and nodal metastases at the popliteal fossa. The technique described by Karakousis was reproduced in a step-by-step fashion to allow anatomical identification of the neurovascular structures and radical resection with no post-operative morbidity and prompt recovery. Popliteal lymph node dissection is a rarely performed operative procedure. Following a lymphoscintigraphic examination of the popliteal nodal station, surgeons can be asked to explore the popliteal fossa. Detailed familiarity of the operative procedure is necessary, however, to avoid complications.

Transition from cyclosporine-induced renal dysfunction to nephrotoxicity in an in vivo rat model.

Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical decisions. This study aimed to clarify these issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day) treatments (3 and 9 weeks, respectively). Renal function was assessed on serum and urine; kidney tissue was used for histopathological characterization and gene and/or protein expression of markers of proliferation, fibrosis and inflammation. In the short-term, creatinine and blood urea nitrogen (BUN) levels increased and clearances decreased, accompanied by glomerular filtration rate (GFR) reduction, but without kidney lesions; at that stage, CsA exposure induced proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF-ß1), factor nuclear kappa B (NF-κß) and Tumor Protein P53 (TP53) kidney mRNA up-regulation. In the long-term treatment, renal dysfunction data was accompanied by glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up-regulation of the mammalian target of rapamycin (mTOR) and the antigen identified by monoclonal antibody Ki-67 (Mki67), accompanied by mTOR protein overexpression. Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by modification of molecular mechanisms and biomarkers, being mTOR one of the key players for kidney lesion evolution, thus suggesting, by mean of molecular evidences, that early CsA replacement by mTOR inhibitors is indeed the better therapeutic choice to prevent chronic allograft nephropathy.

Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals.

This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1ß, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1ß and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.