Metabolic Carcinogenesis.

Several types of environmental, chemical and metabolic carcinogens exist both exogenously and endogenously. Humans are daily exposed to aforementioned carcinogens through various sources such as through water, air and food or through metabolic and inflammatory products. This chapter will summarize the links between exogenous and endogenous carcinogen exposure and their metabolism with the cancer pathogenesis and associated risks. This chapter will also cover the carcinogens acquired through lifestyle factors like tobacco use and occupational exposures to different chemicals like asbestos, arsenic, chloroform, vinyl chloride, etc. Moreover, environmental carcinogens such as radiation, sunlight, diet, smoke, etc. will also be discussed in this chapter. Furthermore, there are certain carcinogens that require bio-activation and various human enzymes that play a vital role in the metabolic carcinogenesis will also be recapitulated. Necessary preventive measures against carcinogenic exposure from the exogenous environment are significant to be taken into account to reduce the risks associated with the carcinogens.

Ultra-pH-sensitive nanoparticle of gambogenic acid for tumor targeting therapy via anti-vascular strategy plus immunotherapy.

Although the combination of anti-vascular strategy plus immunotherapy has emerged as the optimal first-line treatment of hepatocellular carcinoma, lack of tumor targeting leads to low antitumor efficacy and serious side effect. Here, we report an ultra-pH-sensitive nanoparticle of gambogenic acid (GNA) encapsulated by poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA) for tumor-targeting combined therapy of anti-vascular strategy plus immunotherapy. PEG-PAEMA-GNA nanoparticle was quite stable at pH 7.4 for 30 d. In contrast, it exerted size shrinkage, charge reversal and the release of GNA at pH 6.7 within 24 h. Moreover, PEG-PAEMA-GNA significantly enhanced the anti-vascular activity, membrane-disruptive capability and pro-apoptosis when pH changed from 7.4 to 6.7. Western blot analysis exhibits that PEG-PAEMA and its GNA nanoparticle facilitated the phosphorylation of STING protein. In vivo assays show that PEG-PAEMA-GNA not only displayed much higher tumor inhibition of 92 % than 37 % of free GNA, but also inhibited tumor vasculature, promoted the maturation of dendritic cells and recruited more cytotoxic t-lymphocytes for sufficient anti-vascular therapy and immunotherapy. All these results demonstrate that PEG-PAEMA-GNA displayed tumor-targeting combined treatment of anti-vascular therapy and immunotherapy. This study offers a simple and novel method for the combination of anti-vascular therapy and immunotherapy with high selectivity towards tumor.

Light-Driven Catalytic Activity of Green-Synthesized SnO2/WO3-x Hetero-nanostructures.

This work reports an environmentally friendly and economically feasible green synthesis of monometallic oxides (SnO2 and WO3) and their corresponding mixed metal oxide (SnO2/WO3-x) nanostructures from the aqueous Psidium guajava leaf extract for light-driven catalytic degradation of a major industrial contaminant, methylene blue (MB). P. guajava is a rich source of polyphenols that acts as a bio-reductant as well as a capping agent in the synthesis of nanostructures. The chemical composition and redox behavior of the green extract were investigated by liquid chromatography-mass spectrometry and cyclic voltammetry, respectively. Results acquired by X-ray diffraction and Fourier transform infrared spectroscopy confirm the successful formation of crystalline monometallic oxides (SnO2 and WO3) and bimetallic SnO2/WO3-x hetero-nanostructures capped with polyphenols. The structural and morphological aspects of the synthesized nanostructures were analyzed by transmission electron microscopy and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Photocatalytic activity of the synthesized monometallic and hetero-nanostructures was investigated for the degradation of MB dye under UV light irradiation. Results indicate a higher photocatalytic degradation efficiency for mixed metal oxide nanostructures (93.5%) as compared to pristine monometallic oxides SnO2 (35.7%) and WO3 (74.5%). The hetero-metal oxide nanostructures prove to be better photocatalysts with reusability up to 3 cycles without any loss in degradation efficiency or stability. The enhanced photocatalytic efficiency is attributed to a synergistic effect in the hetero-nanostructures, efficient charge transportation, extended light absorption, and increased adsorption of dye due to the enlarged specific surface area.

Sulfonated PAM/PPy Cryogels with Lowered Evaporation Enthalpy for Highly Efficient Photothermal Water Evaporation.

Because of the increasing scarcity of water resources, the desalination of seawater by photothermal evaporation with harvested solar energy has gradually become a popular research topic. The interconnected macroporous cryogel prepared from polymerization and crosslinking below the freezing temperature of the reactant solution has an excellent performance in photothermal water evaporation after loading photothermal materials. In this study, polyacrylamide (PAM) cryogels were prepared by cryo-polymerization and sulfonated in an alkaline solution containing formaldehyde and Na2SO3. Importantly, the evaporation enthalpy of water in sulfonated PAM cryogel was reduced to 1187 J·g-1 due to the introduction of sulfonate groups into PAM, which was beneficial to increase the photothermal evaporation rate and efficiency. The sulfonated PAM cryogels loaded with polypyrrole and the umbrella-shaped melamine foam substrate were combined to form a photothermal evaporation device, and the evaporation rate was as high as 2.50 kg·m-2·h-1 under one-sun radiation. Meanwhile, the evaporation rate reached 2.09 kg·m-2·h-1 in the 14 wt% high-concentration saline solution, and no salt crystals appeared on the surface of the cryogel after 5 h of photothermal evaporation. Therefore, it was evidenced that the presence of sulfonate groups not only reduced the evaporation enthalpy of water but also prevented salting-out from blocking the water delivery channel during photothermal evaporation, with a sufficiently high evaporation rate, providing a reliable idea of matrix modification for the design of high-efficiency photothermal evaporation materials.

Membrane-disruptive homo-polymethacrylate with both hydrophobicity and pH-sensitive protonation for selective cancer therapy.

The membrane-disruptive strategy, which involves host defense peptides and their mimetics, is a revolutionary cancer treatment based on broad-spectrum anticancer activities. However, clinical application is limited by low selectivity towards tumors. In this context, we have established a highly selective anticancer polymer, i.e. poly(ethylene glycol)-poly(2-azepane ethyl methacrylate) (PEG-PAEMA), that can mediate the membrane-disruptive activity via a subtle pH change between physiological pH and tumor acidity for selective cancer treatment. Specifically, the resulting PEG-PAEMA can assemble into neutral nanoparticles and silence the membrane-disruptive activity at physiological pH and disassemble into cationic free-chains or smaller nanoparticles with potent membrane-disruptive activity after the protonation of the PAEMA block due to tumor acidity, resulting in high selectivity towards tumors. Dramatically, PEG-PAEMA exhibited a >200-fold amplification in hemolysis and <5% in IC50 against Hepa1-6, SKOV3 and CT-26 cells at pH 6.7 as compared to those at pH 7.4, thanks to the selective membrane-disruptive mechanism. Moreover, mid- and high-dose PEG-PAEMA demonstrated higher anticancer efficacy than an optimal clinical prescription (bevacizumab plus PD-1) and, significantly, had few side effects on major organs in the tumor-bearing mice model, agreeing with the highly selective membrane-disruptive activity in vivo. Collectively, this work showcases the latent anticancer pharmacological activity of the PAEMA block, and also brings new hope for selective cancer therapy.

Smart anti-vascular nanoagent induces positive feedback loop for self-augmented tumor accumulation.

How to achieve efficient drug accumulation in the tumor with low vascular density is a great challenge but the key to push the limit of anti-vascular therapeutic efficacy. Herein, we report a charge-reversible nanoparticles of gambogenic acid (CRNP-GNA) that would induce the positive feedback loop between increased tumor vascular permeability and improved drug accumulation. This positive feedback loop would remarkably improve tumor vascular permeability for efficient drug accumulation through few residue vessels. As compared to its charge-irreversible analogue in the latter injections, the accumulation in tumor and vascular permeability and retention indexes (VPRI) in CRNP-GNA group respectively boosted from nearly equal to 8.32 and 60 times, while its tumorous microvessel density decreased from nearly equal to only 7%. The self-augmented accumulation consequently amplified the antitumor efficacy via multiple pathways of anti-angiogenesis, vascular disruption and pro-apoptosis, where 5 out of 6 tumors in animal models were completely cured by CRNP-GNA. This work confirms that the underlying positive feedback loop for anti-vascular therapy could be induced by charge-reversible drug delivery nanosystem to achieve efficient and self-augmented drug accumulation even in the tumor with few vessels. It provides a novel strategy to conquer the dilemma between anti-vascular efficacy and drug accumulation.

An insight into recent developments of copper, silver and gold carbon dots: cancer diagnostics and treatment.

Cancer is one of the most fatal diseases globally, however, advancement in the field of nanoscience specifically novel nanomaterials with nano-targeting of cancer cell lines has revolutionized cancer diagnosis and therapy and has thus attracted the attention of researchers of related fields. Carbon Dots (CDs)-C-based nanomaterials-have emerged as highly favorable candidates for simultaneous bioimaging and therapy during cancer nano-theranostics due to their exclusive innate FL and theranostic characteristics exhibited in different preclinical results. Recently, different transition metal-doped CDs have enhanced the effectiveness of CDs manifold in biomedical applications with minimum toxicity. The use of group-11 (Cu, Ag and Au) with CDs in this direction have recently gained the attention of researchers because of their encouraging results. This review summarizes the current developments of group-11 (Cu, Ag and Au) CDs for early diagnosis and therapy of cancer including their nanocomposites, nanohybrids and heterostructures etc. All The manuscript highlights imaging applications (FL, photoacoustic, MRI etc.) and therapeutic applications (phototherapy, photodynamic, multimodal etc.) of Cu-, Ag- and Au-doped CDs reported as nanotheranostic agents for cancer treatment. Sources of CDs and metals alogwith applications to give a comparative analysis have been given in the tabulated form at the end of manuscript. Further, future prospects and challenges have also been discussed.

Simultaneous Cryogenic Radical and Oxidative Coupling Polymerizations to Polyaniline/Polyacrylamide Conductive Cryogels for Gas Sensing.

The macro-porous structure of polymer cryogels provides an appropriate channel for the adsorption and transport of substances, endowing its application in the field of electrochemical sensing. The combination mode of a polymer matrix and electro-active substance, particularly the distribution of an electro-active substance in the matrix, has an important effect on the overall performance of the sensor. In this work, through the simultaneous oxidation coupling polymerization of aniline (ANI) and radical polymerization of acrylamide (AAm) under cryogenic condition, conductive composite cryogels were prepared, aiming for the uniform distribution of PANI in the PAAm matrix. The possibility of simultaneous polymerizations was symmetrically investigated, and the obtained PANI/PAAm cryogels were characterized. Due to the acid-doping of PANI, the electrical conductivity of PANI/PAAm cryogels could be modulated with acidic and basic gases. Thus, the performance of the gas sensor was studied by making conductive PANI/PAAm cryogel sheets as resistive sensor electrodes. We found that the content of PANI, the sheet thickness and the dry/wet state of the cryogel influenced the response sensitivity and rate as well as the recovery properties. The response duration for HCl and NH3 gas was shorter than 70 and 120 s, respectively. The cyclic detection of HCl gas and the alternate detection of NH3/HCl were achieved. This gas sensor with advantages, including simple preparation, low cost and high sensitivity, would have great potential for the application to monitor the leakage of acidic and basic gases.

Rapid UV-radiation synthesis of polyacrylate cryogel oil-sorbents with adaptable structure and performance.

Macro-porous poly(lauryl acrylate) cryogel sheets as oil-sorbents were prepared through UV-radiation cryo-polymerizations in 1, 4-dioxane at low temperatures (-5, -2 and 0 °C) within 30 min. The influences of total monomer concentration, crosslinking monomer amount and polymerization temperature on the formation of cryogels were studied. The chemical structure and porous morphology were characterized through the techniques of Fourier transform infrared spectroscopy, thermal gravimetric analysis, contact angle measurement and scanning electron microscopy, confirming the features of high hydrophobicity, macro-porosity and good thermal stability. As well, the comparison between conventional gels prepared at room temperature and cryogels at lower temperatures was made, showing the higher rate of cryo-polymerization than conventional polymerization under the same UV-radiation condition. The swelling investigation was carried out with several organic solvents and oils. Enhanced performance of oil absorption was observed for those cryogels considering the absorption capacity and absorption rate. Variation of initiator amount and acrylate monomers could also modulate the absorption capacity. Those cryogel oil-sorbents exhibited wide adaptability, good reusability and high-temperature tolerance. Thus, this rapid and low-cost fabrication opens out a novel pathway to prepare efficient oil-sorbents used in waste water treatment.

Macroporous Oil-Sorbents with a High Absorption Capacity and High-Temperature Tolerance Prepared through Cryo-Polymerization.

The facile preparation and admirable performance of macro-porous poly(lauryl acrylate)-based oil-sorbents for organic solvents and oils are reported in this manuscript. Cryo-polymerizations of lauryl acrylate (LA) with ethylene glycol dimethacrylate (EGDMA) as the cross-linker were carried out at temperatures below the freezing point of the polymerization mixture. The polymerization medium and pore-forming agent was 1,4-dioxane. The influences of the total monomer concentration, EGDMA content and cryo-polymerization temperature on the structure of the obtained P(LA-co-EGDMA) cryogels were investigated with the techniques of Fourier transform infrared spectroscopy, scanning electron microscopy, contact angle measurement and thermo-gravimetric analysis. Through the modulation of the crosslinking density and porosity of these cryogels, the P(LA-co-EGDMA) oil-sorbents demonstrated a high absorption capacity for organic solvents and oils, recyclability and high-temperature tolerance. The absorption capacity reached 20-21 and 16-17 g/g for toluene and gasoline oil, respectively. Those fabricated sorbents survived high temperatures up to 150 °C without any change in absorption capacity as well as porosity. Considering the convenient synthesis process and absorption performance, the present work offers a remarkable opportunity to bring polymer cryogels to practical application in waste oil clean-up.

Cystoid macular oedema after phacoemulsification with and without type 2 diabetes mellitus; a hospital-based clinical prospective trial in Karachi.

OBJECTIVE: To know the outcomes of cystoid macular oedema after phacoemulsification in patients with and without type 2 diabetes mellitus using optical coherence tomography. METHODS: This non-concurrent, clinical, prospective study was carried out at Al-Ibrahim Eye Hospital, Karachi, from January to August 2015. After phacoemulsification with injectable posterior chamber intraocular lens implantation, eyes of patients were analysed. The patients were divided into diabetic and non-diabetic groups visual acuity, optical coherence tomography and dilated fundus examination were performed preoperatively (baseline) and post-operative 1st week and 6th week. SPSS 20 was used for data analysis. RESULTS: Of the 100 subjects, there were 50(50%) each in diabetic and non-diabetic group. Subsequently, 14(14%) patients were lost to follow-up, and 86 eyes of 86(86%) patients were analysed. Of them, 37(43%) were male and 49(57%) were female. The mean age of participants was 52.21±7.43 years (range: 38-62years). The non-diabetic group had 41(47.7%) patients and the diabetic group had 45(52.3%). There was no clinically significant cystoid macular oedema in either group. Central foveal thickness > 43.94 µm was observed in 1(2.5%) eye in the non-diabetic group and in none in the diabetic group at 1st post-operative week. At the 6th post-operative week, none of eyes in the non-diabetic group and 2(4.44%) eyes of the diabetic group showed macular oedema. There was no statistically significant difference in mean foveal volume between both groups at 1st week (p=0.896) and 6th week (p=0.230). CONCLUSIONS: Cystoid macular oedema after phacoemulsification was equally present in both diabetics and non-diabetics without any retinopathy.

Intrathecal Bupivacaine Monotherapy with a Retrograde Catheter for the Management of Complex Regional Pain Syndrome of the Lower Extremity.

UNLABELLED: Complex regional pain syndrome (CRPS) presents a therapeutic challenge due to its many presentations and multifaceted pathophysiology. There is no approved treatment algorithm and clinical interventions are often applied empirically. In cases of CRPS where symptoms are localized to an extremity, a targeted treatment is indicated. We describe the use of intrathecal bupivacaine monotherapy, delivered through a retrograde catheter, in the treatment of CRPS affecting the lower extremity. The patient, a 57-year-old woman with a history of failed foot surgery, was seen in our office after 2 years of ineffective treatments with local blocks and neurolytic procedures. We advanced therapy to moderately invasive procedures with an emphasis on neuromodulation. A combined central and peripheral stimulation technique that initially provided 75% pain relief, failed to provide lasting analgesia. We proceeded with an intrathecal pump implant. Based on the results of dorsal root ganglion (DRG) mapping, L5-S1 was identified as the optimal target for therapy and a retrograde catheter was placed at this level. Various intrathecal medications were tested individually. An intrathecal morphine trial was ineffective (visual analog scale [VAS] 7), while intrathecal clonidine provided excellent pain relief (VAS 0) that was limited by severe side effects. Bupivacaine provided 100% analgesia with tolerable side effects (lower extremity weakness and minor bladder incontinence) and was selected for intrathecal infusion. After 14 months, bupivacaine treatment continued to control pain exacerbations. We conclude that CRPS patients benefit from early identification of the predominant underlying symptoms and a targeted treatment with moderately invasive techniques when less invasive techniques fail. KEY WORDS: Intrathecal bupivacaine, bupivacaine monotherapy, retrograde catheter, complex regional pain syndrome (CRPS), dual stimulation, dosal root ganglion (DRG) testing.

The role of repetition and reinforcement in school-based oral health education-a cluster randomized controlled trial.

BACKGROUND: Repetition and reinforcement have been shown to play a crucial role in the sustainability of the effect of Oral Health Education (OHE) programs. However, its relevance to school-based OHE imparted by different personnel is not depicted by the existing dental literature. The present study was undertaken to determine the effectiveness of the repeated and reinforced OHE (RR-OHE) compared to one-time OHE intervention and to assess its role in school-based OHE imparted by dentist, teachers and peers. METHODS: The study was a cluster randomized controlled trial that involved 935 adolescents aged 10-11 years. Twenty four boys' and girls' schools selected at random in two towns of Karachi, Pakistan were randomly assigned to three groups to receive OHE by dentist (DL), teachers (TL) and peer-leaders (PL). The groups received a single OHE session and were evaluated post-intervention and 6 months after. The three groups were then exposed to OHE for 6 months followed by 1 year of no OHE activity. Two further evaluations at 6-month and 12-month intervals were conducted. The data were collected by a self-administered questionnaire preceded by a structured interview and followed by oral examination of participants. RESULTS: The adolescents' oral health knowledge (OHK) in the DL and PL groups increased significantly by a single OHE session compared to their baseline knowledge (p < 0.05) and the increase was sustained over 6 months. Although one-time OHE resulted in a significant improvement in adolescents' oral health behavior (OHB) related to the prevention of gingivitis in the two groups (p < 0.05), no significant change was observed in their behavior towards prevention of oral cancer. One-time teacher-led OHE was ineffective in improving adolescents' OHK and OHB. The oral hygiene status (OHS) of the participants in all three groups did not change statistically after one-time OHE. The OHK, OHB and OHS indices increased significantly 6 months after RR-OHE than the initial scores (p < 0.001) irrespective of OHE strategy. Although the OHK scores of the DL and PL groups decreased significantly at 12-month evaluation of RR-OHE (p < 0.05), the said score of the TL group; and OHB and OHS scores of all three groups remained statistically unchanged during this period. CONCLUSIONS: The repetition and reinforcement play a key role in school-based OHE irrespective of educators. The trained teachers and peers can play a complementary role in RR-OHE.

An unusual case of a patient who lost his native kidneys and renal allograft from cholesterol crystal emboli.

Cholesterol crystal emboli (CCE) syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature.

Antibody-mediated rejection: importance of lactate dehydrogenase and neutrophilia in early diagnosis.

We report the importance of elevated serum lactate dehydrogenase (LDH) and neutrophilia (NT) in two renal transplant recipients who developed renal impairment in the early post-operative period. One of our recipients developed oliguria and increased serum creatinine with unexplained elevation of LDH and NT. The biopsy was C4d positive with platelet and fibrin thrombi in the glomerular capillaries and arterioles and interpreted as acute vasculitis or thrombotic form of antibody-mediated rejection (VAMR) with positive donor-specific antibodies (DSA). Despite intensive treatment, this graft was lost. When another patient developed a similar picture, prompt immunoadsorption was started without waiting for a confirmatory biopsy or DSA, and both were later reported as positive. Improvement in renal function was associated with decreasing levels of LDH and NT. Neither of these was elevated in cases of acute cellular rejection (ACR) or antibody mediated rejection (AMR) with isolated tubular injury (TAMR). It may therefore be reasonable to assume that LDH and NT are potential diagnostic and prognostic markers of VAMR.

Malignant sarcoma of the pelvic bones: treatment outcomes and prognostic factors vary by histopathology.

BACKGROUND: Treatment of malignant sarcomas of the pelvis poses a challenge for local disease control and oncologic outcome. Many reports have described the dismal outcomes. Most studies are retrospective series coming out of single centers, thus biased toward patient selection and are of limited statistical power. METHODS: The authors used the Surveillance, Epidemiology, and End Results database to analyze 1185 pelvic sarcoma cases from 1987 to 2006. Kaplan-Meier and Cox regression were used to analyze the significance of prognostic factors. The analysis was repeated for different histopathological subtypes to determine specific prognostic factors in each case. RESULTS: Incidence of pelvic sarcoma in 2006 was 89 per 100,000 persons; it has significantly increased since 1973 (P < .05). The overall 5-year survival for all the patients with pelvic sarcoma was 47%, with osteosarcoma having the worst 5-year survival at 19% and patients with chordoma having the best 5-year survival at 60%. Independent prognostic factors included age, stage, grade, size of primary lesion, histopathology, and treatment-related factors. Comparing the patients only with high-grade lesions, patients with Ewing sarcoma have the best prognosis. CONCLUSIONS: This is an analysis of patients with pelvic sarcomas derived from a population-based registry. Survival and prognostics vary with histopathological diagnoses. Although surgical resection was associated with superior outcomes for osteosarcoma and chondrosarcoma, there was no significant difference in outcomes of patients with Ewing sarcoma treated with surgery and/or radiotherapy.

Bedside lung mechanics predict survival in hypoplastic lung disease.

Newer bedside pulmonary mechanics using conventional ventilators allow for CONTINUOUS serial determinations of tidal volume (V(T)). We sought to determine whether the degree of pulmonary hypoplasia could be measured using bedside pulmonary graphics and whether survival could be predicted in potential extracorporeal membrane oxygenation (ECMO) candidates. Data on all neonates considered for or treated with ECMO at our center between April 2000 and March 2005 were collected. The "maximal bedside V(T)" was measured daily at the peak pressure where "beaking" began with a peak end expiratory pressure of 4 cm H(2)O. Twenty-two patients were reviewed: eight ECMO plus fourteen similar patients in whom the threshold for ECMO intervention was not achieved. Independent of need for ECMO, any patient with V(T) of < 3 mL/kg or < 0.2 mL/cm length died ( N = 4). All other measures of lung capacity or blood gas assessments were less valuable than V(T) in predicting survival. We conclude that bedside V(T) can be easily measured and that values < 3 mL/kg or < 0.2 mL/cm length demarcate severe lung hypoplasia, which in our patient population was incompatible with survival. We speculate that bedside V(T) may assist in evaluating the utility of ECMO.

Role of FNA cytology in the management of carcinoma breast.

OBJECTIVE: To evaluate the utility and role of fine needle aspiration cytology (FNAC) in essential surgical management of carcinoma breast. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: PNS Shifa, Karachi, Combined Military Hospital (CMH), Pannu Aqil and PNS Rahat from August 1998 to August 2003 [05 years]. PATIENTS AND METHODS: The study included one hundred cases of carcinoma of breast-97 females and 3 males, confirmed on histopathological examination and surgically treated at PNS Shifa, CMH Pano Aqil and PNS Rahat. FNA cytology was the primary tool of investigation in all. The benefit of the procedure was evaluated considering the ease of the procedure, cost, safety, reliability as screening procedure and its effect on sparing the patients from excision or incision biopsy and thus additional anesthesia. RESULTS: Sensitivity of the procedure was 78%, specificity 100%, predictve value 100% and overall diagnostic accuracy 72%. Out of 78 cases, diagnosed as positive for malignancy on FNAC and later confirmed by histopathological examination, 58 underwent frozen section examination followed by definitive surgery (modified radical mastectomy). Remaining 20 cases underwent additional core biopsy. Out of these, 12 cases underwent definitive surgery without frozen section and 8 patients underwent frozen section examination followed by definitive surgery. A single case required general anesthesia (GA) while the patients undergoing core biopsy required a local anesthesia (LA) as well. Cases remaining undiagnosed by FNA-cytology (22 cases) required either an excision biopsy (17 cases) or incision biopsy (5 cases) under GA followed by definitive surgery, thus requiring general anesthesia twice during the management. CONCLUSION: FNA-cytology can positively affect the surgical management of carcinoma breast. It can be utilized to select the patients for frozen section examination and can thus spare the patients from additional procedure of excision or incision biopsy under separate anesthesia. It may be adopted as a routine procedure in surgical outpatient.

Mid-term to long-term followup of two-stage reimplantation for infected total knee arthroplasty.

Between January 1989 and December 1994, 94 patients (96 knees) had a two-stage reimplantation for treatment of an infected total knee arthroplasty. All patients were treated with an interval antibiotic-loaded static cement spacer and had antibiotic-loaded bone cement for prosthesis fixation at the time of reimplantation. The purpose of this study was to assess the long-term risk of reinfection and the mechanical durability of these reimplantation arthroplasties. Patients were followed up for a median of 7.2 years (range, 2.5-13.2 years). At final followup, 15 knees (16%) had required reoperation. Nine knees (9%) had component removal for reinfection and six knees (6%) were revised for aseptic loosening. The median time to reoperation for reinfection was 1 year (range, 0.1-9.8 years). The risk of recurrent infection was not correlated with the type of organism, patient demographics, or method of prosthesis fixation at reimplantation. The survivorship free of implant removal for any reason was 90% (confidence intervals, 83.9-96.4%) at 5 years and 77.3% (confidence intervals, 65.5-89.6%) at 10 years. The survivorship free of implant removal for reinfection was 93.5% (confidence intervals, 88.5-98.7%) at 5 years and 85% (confidence intervals, 73.8-96.3%) at 10 years. Survival free of revision for mechanical failure (aseptic loosening or radiographic loosening) was 96.2% (confidence intervals, 92-100%) at 5 years and 91% (confidence intervals, 80.8-98.3%) at 10 years. These results suggest that the high likelihood of early success after two-stage reimplantation of an infected TKA is well maintained throughout long-term followup, with a modest rate of late recurrent infection or mechanical implant failure.