A case of pathologic complete response after neoadjuvant triplet chemotherapy for locally advanced colon cancer with mismatch repair enzyme proficiency

Patients with potentially resectable colon cancer and expected to have negative margins should undergo resection rather than neoadjuvant chemotherapy. Recent studies have suggested that neoadjuvant immunotherapy may be an option for tumors with mismatch repair enzyme deficiency (dMMR), but standard treatment for locally advanced colon cancer with mismatch repair enzyme proficiency (pMMR) is still unclear. A 37-year-old male patient was diagnosed with clinical stage IIIC (T4b N1a M0) transverse colon cancer. Mismatch repair proteins were proficient. After 3 cycles of oxaliplatin (85 mg/m2, day 1), irinotecan (150 mg/m2, IV, day 1), leucovorin (200 mg/m2, IV, day 1), and 5-fluorouracil (3000 mg/m2, 46 hours of continuous infusion initiating from day 1), there was a remarkable reduction in the tumoral mass on the abdominal computed tomography. A right hemicolectomy was performed. A pathologic complete response was obtained. Although there is no consensus on which patients are suitable for neoadjuvant therapy in pMMR locally advanced colon cancer, triplet chemotherapy may be a reasonable option in selected patients

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Tumor budding in laryngeal carcinoma

Background: Tumor budding was defined as a single cancer cell or a cluster of fewer than five cancer cells in the stroma of the invasive tumor margin. It has been suggested as a prognostic factor in various cancers, such as esophageal, lung, colorectal, and endometrial. There are only a few studies about the prognostic signifi cance of tumor budding in laryngeal carcinomas. Materials and Methods: A total of 81 patients with laryngeal carcinoma diagnosed between 2011 and 2016 and treated by partial or total laryngectomy were evaluated. Clinicopathologic parameters were correlated with the presence and grade of tumor budding. Results: The study was consisted of 77 (95.1%) male and 4 (4.9%) female patients. The mean age of the patients was 60.2 years (min: 42 and max: 78). Median follow-up time was 25 months (min: 7 and max: 54) (SD ±11.5). Histopathologic diagnosis was squamous cell carcinoma (SCC) in all patients. Of the 62 cases showing budding, 2 (3.2%) were stage 1, 12 (19.4%) stage 2, 16 (25.8%) stage 3, and 32 (51.6%) were stage 4. Fifteen cases with budding (24.2%) showed lymphovascular invasion (LVI). None of the nonbudding cases had LVI and perineural invasion (PNI). Statistical analysis revealed that LVI and PNI were signifi cantly associated with budding (P = 0.017 and P = 0.012). Among the tumors showing budding, 37% had lymph node metastasis (LNM). In nonbudding cases 15% had LNM. There was a statistically significant correlation between LNM and budding (P = 0.017). None of the parameters correlated with grade of tumor budding statistically. Conclusion: The results of this study suggest that tumor budding might be used as a prognostic factor in laryngeal SCCs

Genetic variants in nuclear-encoded mitochondrial proteins are associated with oxidative stress in obsessive compulsive disorders

Obsessive compulsive disorder is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The mutations or polymorphic variants in mitochondrial DNA-encoded genes or nuclear genes result in oxidative stress, which has recently been associated with various psychiatric disorders. In order to understand the association of mitochondrial disorders with oxidative stress in obsessive compulsive disorder, we examined genetic variants of manganese superoxide dismutase and uncouple-2 antioxidant genes and malondialdehyde and glutathione, markers of oxidative stress. The study sample comprised 104 patients with OCD and 110 healthy controls. For manganese superoxide dismutase, the frequencies of CT (Ala/Val) genotype (p < 0.01) in patients were significantly lower than those of controls. In contrast, CC (Ala/Ala) genotype was significantly more frequent in patients than controls (p < 0.05). For uncouple-2 I/D, the frequencies of ID genotype (p < 0.01) and I allele (p < 0.05) were lower in patients as compared with controls. In contrast, DD genotype was more prevalent in patients than controls (p < 0.01). While whole blood glutathione was significantly diminished (p < 0.0001), serum malondialdehyde was significantly elevated in patients compared with controls (p < 0.0001). Malondialdehyde levels were significantly elevated in subjects with DD genotype of UCP-2 I/D (p < 0.05) and CC genotype of manganese superoxide dismutase (p < 0.05) as compared with II or ID and TT or CT genotype, respectively. Malondialdehyde levels in patients carrying CC (p < 0.05) or CT (p < 0.05) genotype were significantly higher than those of carrying TT genotype. In conclusion, CC genotype of manganese superoxide dismutase or DD genotype of UCP-2 might result in mitochondrial disorders by increasing oxidative stress in obsessive compulsive disorders. (C) 2011 Elsevier Ltd. All rights reserved

Prognostic significance of tumor budding in muscle invasive urothelial carcinomas of the bladder

WOS: 000474443200007PubMed ID: 30183610Objective: The aim of this study was to evaluate the prognostic significance of tumor budding in muscle invasive urothelial carcinoma of bladder (MIBC). Material and methods: A total of 60 patients who underwent radical cystectomy and cystoprostatectomy for MIBC were included in the study. The correlations between tumor budding, and tumor necrosis, lymphovascular invasion (LVI), perineural invasion (PNI) and histopathological data with distant metastasis were evaluated. The correlation between progression free (PFS) and overall survival (OS) rates and the presence, and grade of tumor budding was investigated. Results: A statistically significant correlation was not seen between tumor budding, necrosis, LVI, and PNI. There was a strong correlation between distant organ metastasis, and presence of tumor necrosis. There was no statistically significant correlation between PFS, OS and tumor budding. A statistically significant relationship was observed between OS and tumor stage, lymph node metastasis, and distant organ metastasis. Conclusion: In our study, statistically significant effect of tumor budding on survival rates in MIBCs was not observed. Also, no significant correlation was observed between tumor budding and tumor necrosis, LVI, and PNI

Prognostic significance of micropapillary pattern in lung adenocarcinoma and expression of apoptosis-related markers: caspase-3, bcl-2, and p53

Demirag, Funda/0000-0003-4790-8369WOS: 000294073500002PubMed: 21851414Cakir E, Yilmaz A, Demirag F, Oguztuzun S, Sahin S, Yazici UE, Aydin M. Prognostic significance of micropapillary pattern in lung adenocarcinoma and expression of apoptosis-related markers: caspase-3, bcl-2, and p53. APMIS 2011; 119: 574-80. We evaluated the clinicopathological characteristics and prognostic significance of lung adenocarcinoma with micropapillary pattern (MPP) and analyzed the expression of apoptosis-related markers: caspase-3, bcl-2, and p53. A series of 166 lung adenocarcinoma that had been surgically resected between 2004 and 2009 were reviewed. Histopathologic patterns, presence of tumor necrosis, mitosis, lymphovascular and perineural invasion, the status of pleura, and tumor differentiation were examined. Of the 166 patients; 71 were stage I, 35 stage II, 51 stage III, and nine stage IV. Histologically they were divided into two groups: MPP-positive (n = 55) and MPP-negative (n = 111). The following items were significantly more frequent in the MPP positive group: female gender (p = 0.03), lymph node metastasis (p = 0.031), and pleural invasion (p = 0.045). Age, smoking status, tumor stage, lymphatic invasion, perineural invasion, mitotic count, and survival rates had no statistically significant difference between groups (p > 0.05). In MPP positive tumors, visceral pleural invasion was identified significantly more frequent than in MPP negative tumors, at stage I. Tumors with MPP showed elevated expressions of caspase-3 (94.5%), p53 (60%), and bcl-2 (54.5%). In MPP positive group, the expression of these three markers had no statistically significant impact on survival. In whole population, bcl-2 expression was correlated with a better outcome. We conclude that MPP is associated with poor prognostic factors both in early and late stages in lung adenocarcinoma. Bcl-2 provides prognostic information independent from the MPP

Angiotensin-converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first-degree relatives

Background Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including schizophrenia (SZ) and bipolar disorders (BDs). As SZ and BD have some susceptibility genes in common and since unaffected first-degree relatives of these patients carry a high likelihood of these susceptibility genes, we aimed to elucidate the role of angiotensin-converting enzyme (ACE) genetic variants in patients with SZ, BD and their first-degree relatives

Intraoperative squash cytology and histology of giant cell ependymoma: A diagnostic dilemma

Giant cell ependymomas (GCE) are extremely rare tumors, with 24 cases described in the literature. Squash cytology is a rapid, reliable, simple technique for intraoperative consultation in neurosurgical practice. We describe a rare case of GCE arising at level of L4-L5 in a 66-year-old woman and discuss the cytologic/histologic features. Intraoperative smears were highly cellular with a prominent fibrillary background and exhibited papillary structures and sheets composed of highly atypical and bizarre cells. Some of the cells showed nuclear pseudoinclusions and rarely formed pseudorosette-like arrays. Intraoperative diagnosis was high grade glial tumor. On paraffin sections, besides extensive polymorphism, there were no microvascular proliferation, necrosis, and mitosis and the final diagnosis was WHO grade II GCE. GCE may be a diagnostic challenge on intraoperative smears, frozen, and paraffin sections. It must be kept in mind in the differential diagnosis of giant cell exhibiting benign and malignant tumors of brain

Clinical Impact Of Visceral Pleural, Lymphovascular And Perineural Invasion In Completely Resected Non-Small Cell Lung Cancer

Objectives: This study is conducted to show the relationship between visceral pleural, lymphovascular, and perineural invasion, and other clinicopathologic characteristics and their significance as prognostic factors. Methods: The clinicopathologic characteristics of 289 patients who underwent a potentially curative surgical resection between 2000 and 2009 in our clinic were reviewed retrospectively. The prognostic factors were then evaluated by univariate and multivariate analysis. The patients who were given neoadjuvant-adjuvant chemotherapy and/or radiotherapy and who died due to postoperative mortality were excluded. Data from 188 patients were analyzed. Results: Out of the 188 patients (108 diagnosed as adenocarcinoma and 80 squamous cell carcinoma), 66 patients had lymphovascular invasion, 53 patients had perineural invasion, and 92 patients had visceral pleural invasion. Visceral pleural invasion was related with T factor, tumor histology, dimension, stage, and differentiation. Lymphovascular invasion was related with N status and stage. Perineural invasion was observed more frequently in tumors with moderate/poor differentiation. Visceral pleural and lymphovascular invasion were found to be poor prognostic factors but we could not show statistically meaningful effect of perineural invasion on survival. Conclusion: The presence of visceral pleural or lymphovascular invasion can show higher risk of mortality whereas perineural invasion has no effect on prognosis. (C) 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.WoSScopu

Paraoxonase-1 55/192 genotypes in schizophrenic patients and their relatives in Turkish population

Background Oxidative stress and free radical-induced toxicity have been implicated in the pathophysiology of schizophrenia. In this study, we examined paraoxonase (PON1)-55/192 polymorphisms and PON1 activity in patients with schizophrenia, first-degree relatives of schizophrenic patients, and healthy controls