Antidiabetic potential and high synergistic antibacterial activity of silver nanoparticles synthesised with Musa Paradisiaca tepal extract.

This work investigates the Musa Paradisiaca plant and its tepal extracts. The research findings show that the tepal extracts of M. Paradisiaca contain high phytochemical activity. Hence we can conclude that these plants have a number of beneficial properties. Phytochemical analysis concludes that the plant is rich in flavonoids, phenolic compounds, tannins, terpenoids, and phytosterol. In the current work, silver nanoparticles (AgNPs) have revealed the antioxidant properties of M. Paradisiaca. The results show that the methanolic extracts of these tepals exhibit antioxidant potential and are also sources of natural antioxidant compounds, though comparatively, AgNPs have shown the best antioxidant activity. This work investigates the link between the ethnopharmacological statements and the bioactive constituents found in M. Paradisiaca toward all probable markers for cervical cancer via in vivo studies and molecular docking, to form a pharmacophore setting for the active target. However, most of the mechanisms of action of herbal medicines are not in total agreement, and the information collected from their traditional remedies over the years must not be neglected. Hence, it is sensible to investigate the options available in herbal medicine for cancer progression. Biosynthesised AgNPs are principally spherical and nanosized. It was also found that tepalmediated AgNPs exhibit excellent antimicrobial efficacy against tested human pathogens. This green method can be used as a better alternative source than the chemical fabrication of nanomaterials and the biosynthesised nanoparticles can be used in antibacterial medicines. The methanolictepal extract of M. Paradisiaca with AgNPs displayed proficient antidiabetic properties in the diabetes rat model and so could have a possible development for medical use in the future.

Usefulness of CT texture analysis in differentiating benign and malignant renal tumours.

AIM: To elucidate visually imperceptible differences between benign and malignant renal tumours using computed tomography texture analysis (CTTA) using filtration histogram based parameters. MATERIALS AND METHODS: A retrospective study was performed by texture analysis of pretreatment contrast-enhanced CT examinations in 354 histopathologically confirmed renal cell carcinomas (RCCs) and 147 benign renal tumours. A region-of-interest was drawn encompassing the largest cross-section of the tumour on venous phase axial CT. CTTA features of entropy, kurtosis, mean positive pixel density, and skewness at different spatial filters were calculated and compared in an attempt to differentiate benign lesions from malignancy. RESULTS: Entropy with fine spatial filter was significantly higher in RCC than benign renal tumours (p=0.022). Entropy with fine and medium filters was higher in RCC than lipid-poor angiomyolipoma (p=0.050 and 0.052, respectively). Entropy >5.62 had high specificity of 85.7%, but low sensitivity of 31.3%, respectively, for predicting RCC. CONCLUSIONS: Differences in entropy were helpful in differentiating RCC from lipid-poor angiomyolipoma, and chromophobe RCC from oncocytoma. This technique may be useful to differentiate lesions that appear equivocal on visual assessment or alter management in poor surgical candidates.

Antibacterial and anticancer potential of Brassica oleracea var acephala using biosynthesised copper nanoparticles.

INTRODUCTION: Brassica oleracea var acephala was studied for preliminary phytochemical screening. The results showed that the ethanolic crude extract of the leaf contain high phytochemical activity hence B.oleracea var acephala is rich in flavonoids, phenolic compounds, carbohydrates and phytosterols. MATERIALS AND METHODS: The ethanolic extract was used to synthesise copper nanoparticles. The copper nanoparticles were successfully synthesised from copper sulphate solution which was identified by the colour change from dark green colour of the extract. Thus the B.oleracea var acephala is a good source to synthesis copper nanoparticles. The synthesised copper nanoparticles were characterised using Scanning Electron Microscope (SEM) analysis. The SEM image displayed the high-density nanoparticles synthesised by leaf extracts and that the nanoparticles were crystals in shape. RESULTS: The copper nanoparticles (CNP) bind to the leaf extract. B.oleracea var acephala also has shown the antimicrobial and antioxidant activity. A comparative study was done between ethanolic its crude extract and nanoparticles. Both extracts exhibited zone of inhibition and better antioxidant potential but the CuNPs shows major zone of inhibition and showed more antioxidant activity. Anticancer activity of B.oleracea var acephala against Cervical HeLa cell line was confirmed using ethanolic crude extract and CNP. The results showed that HeLa cells proliferation was inhibited with increasing concentration of ethanolic crude extract and copper nanoparticles. From the results, it was seen that percentage viability of the cancer cells decreased with increased concentration of the samples whereas cytotoxicity against HeLa cell lines increased with the increased concentration of the samples. CONCLUSION: Thus B.oleracea var acephala possesses anticancer activity against HeLa cell lines.

Fatal granulomatous amoebic encephalitis caused by Acanthamoeba in a newly diagnosed patient with systemic lupus erythematosus.

Granulomatous amoebic encephalitis (GAE) caused by certain species belonging to the genus Acanthamoeba, Balamuthia, or Naegleria presents as a subacute or chronic illness. Amoebic encephalitis caused by Acanthamoeba is seen more often in immunosuppressed individuals. Thus, it may often be associated with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), organ transplantation, administration of steroids and systemic lupus erythematosus (SLE). The clinical progression is rapid, most often leading on to mortality of the patients. The diagnosis in most of these patients is established on postmortem examination. We describe a case of fatal granulomatous amoebic encephalitis in a patient recently diagnosed to be having SLE, who was receiving corticosteroids, cyclophosphamide, methotrexate, and hydroxychloroquine. The patient presented in an altered sensorium and expired after being hospitalized for 6 days. Postmortem examination of the brain showed extensive areas of necrosis and neutrophilic infiltrate with trophozoites and cysts of Acanthamoeba.

Pediatric meningiomas an aggressive subset: a clinicopathological and immunohistochemical study.

BACKGROUND: Meningiomas are uncommon neoplasms in the pediatric age group and differ in various aspects from their adult counterparts. They account for 0.4-4.6% of all primary brain tumors. AIMS: To retrospectively analyze the clinicopathological and immunohistochemical features of pediatric meningiomas. MATERIALS AND METHODS: Meningiomas in patients under 18 years of age diagnosed between January 2001 to December 2011 were analyzed retrospectively. The hematoxylin and eosin stained sections and Ki 67 labelling index (LI) were reviewed for all the cases Results: The pediatric meningiomas accounted for 1.52% of total meningiomas (15/983). The mean age at presentation was 12 years with male to female ratio of 1.5:1. The presenting symptoms were headache, seizures, and motor deficits. The histology included 9 cases (60%) of atypical meningioma (WHO grade II) followed by 4 cases (26.67%) of WHO grade-I and 2 cases (13.33%) of anaplastic meningioma (WHO grade III). Five cases had a recurrence. Ki67 LI ranged from 0.5% to 1.5% in grade I, 0.5% to 15% in grade II and 13% to 24% in grade III meningiomas. CONCLUSION: Meningiomas are rare in children and show a male preponderance. There was a higher incidence of atypical and anaplastic meningiomas in pediatric population.

Assessment of expression of epidermal growth factor receptor and p53 in meningiomas.

BACKGROUND: Meningiomas represent about 30% of primary adult central nervous system tumors. Though slow growing, they recur, causing significant morbidity and mortality. OBJECTIVE: The objective of the following study is to grade meningiomas according to World Health Organization (WHO) 2007 criteria and to correlate the grade with degree of expression of epidermal growth factor receptor (EGFR) and p53. MATERIALS AND METHODS: Meningiomas diagnosed in the year 2010 in the Department of Pathology of our institute, were included in the study. Clinical and radiological findings were noted from medical records. The histopathology slides were reviewed and the tumors were graded according to WHO 2007 criteria. Tissue microarrays (TMA) were prepared and immunohistochemical analysis with epithelial membrane antigen, Vimentin, Ki67, EGFR and p53 was performed on the TMA slides. RESULTS: A total of 79 meningiomas diagnosed during the study period included 30 male and 49 female patients with an age range of 10-75 years. There was a female preponderance with M:F ratio of 1:1.63. EGFR was found to be higher in grade I (82.93%) compared with grade II (35.71%) and grade III tumors (20%) with an overall positivity of 60.81%. Mean p53 indices were higher in grade III (50%) compared with grade II (39.29%) and grade I tumors (38.46%) with an overall positivity of 39.44%. Ki67 labeling index (LI) was significantly high in grade III (16.4%) compared with grade II (6.46%) and grade I tumors (3.13%). CONCLUSION: EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).

ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines.

BACKGROUND: The human ATP-dependent SWItch/sucrose nonfermentable (SWI/SNF) complex functions as a primary chromatin remodeler during ontogeny, as well as in adult life. Several components of the complex have been suggested to function as important regulators of tumorigenesis in various cancers. In the current study, we have characterised a possible tumour suppressor role for the largest subunit of the complex, namely the AT-rich interaction domain 1B (ARID1B). METHODS: We performed Azacytidine and Trichostatin A treatments, followed by bisulphite sequencing to determine the possible DNA methylation-induced transcription repression of the gene in pancreatic cancer (PaCa) cell lines. Functional characterisation of effect of ARID1B ectopic expression in MiaPaCa2 PaCa cell line, which harboured ARID1B homozygous deletion, was carried out. Finally, we evaluated ARID1B protein expression in pancreatic tumour samples using immunohistochemistry on a tissue microarray. RESULTS: ARID1B was transcriptionally repressed due to promoter hypermethylation, and ectopic expression severely compromised the ability of MiaPaCa2 cells to form colonies in liquid culture and soft agar. In addition, ARID1B exhibited significantly reduced/loss of expression in PaCa tissue, especially in samples from advanced-stage tumours, when compared with normal pancreas. CONCLUSION: The results therefore suggest a possible tumour-suppressor function for ARID1B in PaCa, thus adding to the growing list of SWI/SNF components with a similar function. Given the urgent need to design efficient targeted therapies for PaCa, our study assumes significance.

Incidence of malignancies in biopsy-proven inflammatory myopathy.

BACKGROUND: Inflammatory myopathy (IM) as a manifestation of paraneoplastic syndrome has been well-documented. However, the prevalence of malignancies reported varies across the studies. There are very few studies reported from Asia, only one from India. AIM: The aim of this analysis was to study the prevalence of malignancy in biopsy-proven cases of IM in India and to study the difference between malignant and non-malignant groups. MATERIALS AND METHODS: The study was a retrospective review of case records of patients with a biopsy-proven IM attending Tertiary Care University Hospital. RESULTS: Of the total 86 patients with biopsy-proven IM, 22 patients were polymyositis, 63 patients had dermatomyositis (DM) and one was with an inclusion body myositis, not included for further analysis. Associated malignancy was diagnosed in 6 (7%) patients, and five of them were females. Diagnosis of associated malignancy was identified at the time of diagnosis of IM in four (66.7%) patients. All the six patients with an associated malignancy had DM. Only one patient died within 1 year of diagnosis. Creatinine kinase was much lower in patients with malignancy associated IM than in patients with no malignancy (P < 0.0001). CONCLUSION: The prevalence of malignancy was very low in our cohort as compared to the studies from other countries. Breast cancer was the most common malignancy associated with DM. The type of associated malignancy was quite variable.

Making sense of postoperative CT imaging following laparoscopic partial nephrectomy.

The increasing popularity of laparoscopic partial nephrectomy (LPN) necessitates radiologists to become familiar with the operative techniques as well as normal and abnormal postoperative findings. Due to the varying presentation of abnormal changes following LPN and their similarities with other disease entities, radiologists should be cognizant of common pitfalls to avoid inadvertent misdiagnosis. A few common pitfalls discussed in this paper are the identification of laparoscopic port placement issues, recognizing a myriad of post-surgical materials, differentiating haemostatic materials from postoperative abscess and infection, non-absorbable suture material mimicking rim calcifications, as well as hints for differentiating exuberant granulation tissue from tumour recurrence.

Analysis of squash smear cytology of ependymomas.

BACKGROUND: Ependymomas constitute 8-10 and 1-3% of central nervous system tumors in children and adults, respectively. Though intraoperative squash smear cytology is well documented, grading is rarely described. OBJECTIVES: (1) To assess cytomorphology and grade ependymomas in squash smears. (2) To compare utility of hematoxylin and eosin (H&E) and toluidine blue (TB) staining. STUDY DESIGN: Ependymomas diagnosed from 2004 to 2010 were retrieved from pathology records. Intraoperative squash smears stained with TB and H&E were studied. RESULTS: Histological sections of 29 ependymomas were graded according to WHO 2007 classification. There were 3 myxopapillary (grade I), 13 grade II, and 13 grade III (anaplastic) ependymomas. Perivascular pseudorosettes were seen in 23 smears, and 11 showed rosettes. Less cohesive cells at the periphery of fragments with unipolar cytoplasmic processes were seen in all smears. The background was fibrillary in all except in myxopapillary ependymoma. Metachromatic material was seen in myxopapillary ependymoma around vessels and in globi. The nucleus was round with stippled chromatin and 1-2 small nucleoli could be seen. All smears of grade III ependymomas showed pleomorphism, mitoses, microvascular proliferation and necrosis. CONCLUSION: Ependymomas can be diagnosed and graded reliably by squash smear. Myxoid stroma was better appreciated by TB staining. TB and H&E complement each other in squash smears for cytomorphology.

Rabies viral encephalitis: clinical determinants in diagnosis with special reference to paralytic form.

BACKGROUND: Rabies is an important public health problem in developing countries such as India where an alarmingly high incidence of the infection is reported every year despite the availability of highly effective, potent and safe vaccines. In clinical practice, diagnosis of the furious (encephalitic) form of rabies poses little difficulty. In contrast, the paralytic form poses a diagnostic dilemma, to distinguish it from Guillain-Barré syndrome. The problem is further compounded in the absence of a history of dog bite, clinical features resembling a psychiatric syndrome. METHOD: The present study analysed the spectrum of neurological manifestations in 47 cases of rabies encephalitis (34 paralytic, six encephalitic, and seven psychiatric manifestations) from two hospitals in south India, confirmed at post-mortem by demonstration of a viral antigen in the brain. A history of dog bite was elicited in 33 patients and fox bite in one. Twenty-two patients received postexposure prophylaxis. The incubation period ranged from 7 days to 4 years. Clinical features were analysed, looking for any clinical pointers that provide clues to a diagnosis of paralytic rabies. RESULTS AND DISCUSSION: Fever, distal paresthaesias, fasciculation, alteration in sensorium, rapid progression of symptoms and pleocytosis in cerebrospinal fluid should alert the neurologist to consider rabies encephalomyelitis. Detection of the viral antigen in the corneal smear and a skin biopsy from the nape of the neck had limited usefulness in the ante-mortem diagnosis. Although a few clinical signs may help indicate rabies encephalomyelitis antemortem, confirmation requires neuropathological/neurovirological assistance. The preponderance of atypical/paralytic cases in this series suggests that neurologists and psychiatrists need to have a high index of clinical suspicion, particularly in the absence of a history of dog bite.

Optic chiasmatic-hypothalamic gliomas: is tissue diagnosis essential?

BACKGROUND: Optic chiasmatic-hypothalamic gliomas are sellar-suprasellar lesions with variable radiological features. The advocated treatment is mainly primary radiotherapy without a histological diagnosis. However, in developing countries, like India infective granulomas (tuberculomas) in the suprasellar region radiologically can mimic optic chiasmatic-hypothalamic gliomas. Hence primary radiotherapy without histological confirmation may have deleterious consequences. AIM: The aim of the paper was to analyze the sensitivity and specificity of magnetic resonance imaging (MRI) in these lesions and to analyze the feasibility of primary radiotherapy. PATIENTS AND METHODS: The magnetic resonance imaging (MRI) characteristics of 24 patients with either histologically proven optic chiasmatic "pilocytic astrocytoma" or radiologically suspected optic chiasmatic-hypothalamic gliomas were analyzed. They were grouped into three groups on the basis of radiological features and treated with a suspected diagnosis. The final diagnosis was correlated with preoperative diagnosis, and the feasibility of managing these lesions without a histopathological confirmation is discussed. RESULTS: The three radiological groups were: Group-1 solid tumors with or without microcysts in 9 patients (histology: 8 pilocystic astrocytomas and 1 tuberculoma); Group-2 mixed tumors with solid and cystic components in 9 patients (histology: 7 pilocytic astrocytomas and 2 craniopharyngiomas); Group-3 ring enhancing lesions in 6 patients (all the 6 patients initially received antituberculous treatment, in 3 patients the lesion resolved and in the remaining 3 patients the lesion was subjected to biopsy as it did not resolve, the biopsy was suggestive of pilocytic astrocytoma). Thus, MRI was shown to have a sensitivity of 83.33% and a specificity of 50% for diagnosing optic chiasmatic-hypothalamic gliomas. CONCLUSIONS: Various lesions like craniopharyngiomas, tuberculomas can mimic optic chiasmatic-hypothalamic gliomas radiologically, and it is not possible to diagnose them with certainty on the basis of radiological findings alone. Biopsy and tissue diagnosis should always be sought before instituting radiotherapy or chemotherapy for optic chiasmatic-hypothalamic gliomas.

Removal of fluoride from aqueous solution using protonated chitosan beads.

In the present study, chitosan in its more usable bead form has been chemically modified by simple protonation and employed as a most promising defluoridating medium. Protonated chitosan beads (PCB) showed a maximum defluoridation capacity (DC) of 1664mgF-/kg whereas raw chitosan beads (CB) possess only 52mgF-/kg. Sorption process was found to be independent of pH and altered in the presence of other co-existing anions. The sorbents were characterized using FTIR and SEM with EDAX analysis. The fluoride sorption on PCB follows both Freundlich and Langmuir isotherms. Thermodynamic parameters, viz., DeltaG degrees , DeltaH degrees DeltaS degrees and Ea indicate that the nature of fluoride sorption is spontaneous and endothermic. The sorption process follows pseudo-second-order and intraparticle diffusion kinetic models. 0.1M HCl was identified as the best eluent. The suitability of PCB has been tested with field samples collected from a nearby fluoride-endemic area.

Uptake of fluoride by nano-hydroxyapatite/chitosan, a bioinorganic composite.

A bioinorganic composite namely nano-hydroxyapatite/chitosan (n-HApC) composite which could be employed for technology development was prepared and studied for its defluoridation efficiency. It has been observed that there was a slight enhancement in the defluoridation capacity (DC) of n-HApC composite (1560mgF(-)/kg) than nano-hydroxyapatite (n-HAp) which has a DC of 1296mgF(-)/kg. The sorbents were characterized with XRD and TEM studies. The fluoride sorption was explained with Freundlich and Langmuir isotherms. Thermodynamic parameters such as DeltaG degrees , DeltaH degrees , DeltaS degrees and Ea were calculated in order to understand the nature of sorption. The sorption process was found to be controlled by pseudo-second-order and pore diffusion models. Field studies were carried out with the fluoride containing water sample collected from a fluoride-endemic area in order to test the suitability of the sorbents at field conditions.

Enhanced fluoride sorption by mechanochemically activated kaolinites.

Kaolinite clay obtained from the mines was processed and studied for its fluoride sorption capacity. The surface area of the clay mineral was increased from 15.11 m(2)/g (raw) to 32.43 m(2)/g (activated) by mechanochemical activation. Batch adsorption studies were conducted to optimize various equilibrating conditions like the effect of contact time, dosage, pH for both raw and micronized kaolinites (RK and MK). The effect of other interfering anions on the defluoridation capacity (DC) of the sorbents was studied. Sorption of fluoride by the sorbents was observed over a wide pH range of 3-11. The studies revealed there is an enhanced fluoride sorption on MK. FTIR and XRD were used for the characterization of the sorbent. The surface morphology of the clay material was observed using SEM. The adsorption of fluoride was studied at three different temperatures, viz., 303, 313 and 323 K. The sorption data obtained at optimized conditions were subjected to Freundlich and Langmuir isotherms. Sorption intensity (1/n) (0.770-0.810) has been evaluated using Freundlich isotherm, whereas the values of sorption capacity Q(0) (0.609, 0.714 and 0.782 mg/g) and binding energy b (0.158, 0.145 and 0.133 L/mg) at three different temperatures have been estimated using Langmuir isotherm. Adsorption process was found to be controlled by both Freundlich and Langmuir isotherms. Thermodynamic studies revealed that the sorption of fluoride on MK is endothermic and a spontaneous process. The kinetic studies indicate that the sorption of fluoride on MK follows pseudo-first-order and intraparticle diffusion models.

Defluoridation chemistry of synthetic hydroxyapatite at nano scale: equilibrium and kinetic studies.

This study describes the advantages of nano-hydroxyapatite (n-HAp), a cost effective sorbent for fluoride removal. n-HAp possesses a maximum defluoridation capacity [DC] of 1845 mg F(-)/kg which is comparable with that of activated alumina, a defluoridation agent commonly used in the indigenous defluoridation technology. A new mechanism of fluoride removal by n-HAp was proposed in which it is established that this material removes fluoride by both ion-exchange and adsorption process. The n-HAp and fluoride-sorbed n-HAp were characterized using XRD, FTIR and TEM studies. The fluoride sorption was reasonably explained with Langmuir, Freundlich and Redlich-Peterson isotherms. Thermodynamic parameters such as DeltaG degrees , DeltaH degrees , DeltaS degrees and Ea were calculated in order to understand the nature of sorption process. The sorption process was found to be controlled by pseudo-second-order and pore diffusion models. Field studies were carried out with the fluoride containing water sample collected from a nearby fluoride endemic area in order to test the suitability of n-HAp material as a defluoridating agent at field condition.

Major histocompatibility complex class I expression can be used as a diagnostic tool to differentiate idiopathic inflammatory myopathies from dystrophies.

AIM: Utility of major histocompatibility complex (MHC) Class I antigen immunostaining was studied to differentiate idiopathic inflammatory myopathies from dystrophies. MATERIALS AND METHODS: Forty muscle biopsies including seven dermatomyositis (DM), six polymyositis (PM), two sporadic inclusion body myositis (sIBM), 20 dystrophies (one Duchenne, three Becker's, four alpha, one gamma sarcoglycanopathy, nine limb girdle, one myotonic and one fascioscapulohumeral muscular dystrophy) and five controls were stained with antibody for MHC Class I antigen (Novocastra clone W6/32 HL 1:100 dilution). RESULTS: Polymyositis and sIBM showed MHC class I antigen positivity along sarcolemma of single and small groups of muscle fibers. The regenerating fibers in the perifascicular area in DM showed intense cytoplasmic positivity of MHC class I antigen. Muscle fibers in all dystrophies except regenerating fibers and control normal muscle were negative for MHC. Capillaries and lymphocytes were positive controls. There were no false positives in the study. CONCLUSION: MHC Class I immunostaining can be used as a complementary diagnostic tool for the diagnosis of idiopathic inflammatory myopathies.

Lipid storage myopathies with unusual clinical manifestations.

We describe the clinical presentation, course and pathologic findings found in three adult patients with lipid storage myopathy. Excessive lipid storage was found in Type 1 fibers of muscle. Clinical improvement on oral levo-carnitine therapy suggests the possibility of carnitine deficiency as the most likely etiology in two of the patients and one had mitochondrial myopathy confirmed on genetic analysis.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.