The role of adjuvant treatment for early-stage uterine clear cell carcinomas.

BACKGROUND: Uterine clear cell carcinoma is a rare and aggressive subtype of endometrial carcinoma. Prospective clinical trials have not been feasible for this rare tumor, and data regarding the optimal adjuvant treatment regimen for early-stage uterine clear cell carcinomas is limited. Our study's objective was to determine if adjuvant chemotherapy or radiation therapy improves patients' outcomes in stage I and II uterine clear cell carcinoma. METHODS: Patients with stage I and II uterine clear cell carcinoma were identified at a single institution. All cases were reviewed by a gynecologic pathologist. Both pure and mixed non-serous uterine clear cell carcinomas were included. Primary outcomes were recurrence free survival and overall survival. RESULTS: A total of 71 patients were identified including 39 (55%) pure and 32 (45%) mixed clear cell carcinoma. Most patients were FIGO stage IA (77.5%). Most patients (n = 58, 82%) received adjuvant therapy, including 43 (61%) receiving chemotherapy, 50 (70%) receiving radiation therapy, and 35 (49%) receiving both. Recurrence free survival was not significantly different among patients receiving no or <6 cycles of chemotherapy versus patients receiving 6 cycles of chemotherapy (p = 0.39). However, median OS was significantly different among patients receiving no or <6 cycles of chemotherapy versus 6 cycles of chemotherapy (p = 0.004). On univariable analysis, 6 cycles of chemotherapy was significantly associated with improved OS (HR 0.1, 95% CI 0.01-0.07). Presence of LVSI, mutated p53, number of pelvic and para-aortic lymph nodes assessed, adjuvant chemotherapy (any number of cycles), and >2 medical co-morbidities were not significant predictors of OS on univariable analysis. On multivariable analysis, 6 cycles of adjuvant chemotherapy remained a significant predictor of improved OS (HR 0.1, 95% CI 0.01-0.8). CONCLUSIONS: In this study, administration of 6 cycles of chemotherapy appears to significantly improve OS. This finding suggests consideration of 6 cycles of adjuvant chemotherapy in patients with early-stage uterine clear cell carcinoma, however clinical trials are needed to confirm these findings.

IgG4-related hypophysitis: a retrospective cohort study.

PURPOSE: IgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for patients with histologically proven IgG4-related hypophysitis. METHODS: A prospectively maintained electronic database was searched over a 14-year period from 1 January 2007 to 31 December 2020 at a single academic centre to identify all patients with a histological diagnosis of IgG4-RH. A retrospective case note review from electronic health records was conducted for each case to extract data on their presentation, management and outcomes. RESULTS: A total of 8 patients (5 male) with a median age of 51 years were identified. The most common presenting symptoms were headache (4/8; 50%), fatigue (3/8; 37.5%) and visual impairment (2/8; 25%). Three patients were initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, ultimately all patients underwent transsphenoidal surgery. Post-operative changes included radiological reduction in pituitary mass in all patients that had imaging (7/7; 100%), improvement in vision (1/2; 50%), residual thick pituitary stalk (5/7; 71.4%), persistent anterior hypopituitarism (4/8; 50%) and panhypopopituitarism including diabetes insipidus (3/8; 37.5%). CONCLUSIONS: IgG4-RH is an increasingly recognised entity presenting with a variety of symptoms and signs. Clinical presentation is similar to other forms of hypophysitis. It is therefore important to consider IgG4-RH as a differential and to have a low threshold for pituitary biopsy, the diagnostic gold standard. The diagnosis of IgG4-RH will guide decisions for additional workup for IgG4-related disease, multi-disciplinary team involvement and follow-up.

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Cost-effectiveness analysis of tumor molecular classification in high-risk early-stage endometrial cancer.

PURPOSE: Tumor molecular analyses in endometrial cancer (EC) includes 4 distinct subtypes: (1) POLE-mutated, (2) mismatch repair protein (MMR) deficient, (3) p53 mutant, and (4) no specific molecular profile. Recently, a sub-analysis of PORTEC-3 demonstrated notable differences in treatment response between molecular classification (MC) groups. Cost of testing is one barrier to widespread adoption of MC. Therefore, we sought to determine the cost-effectiveness of MC in patients with stage I and II high-risk EC. METHODS: A Markov decision model was developed to compare tumor molecular classification (TMC) vs. no testing (NT). A healthcare payor's perspective and 5-year time horizon were used. Base case data were abstracted from PORTEC-3 and the molecular sub-analysis. Cost and utility data were derived from public databases, peer-reviewed literature, and expert input. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Sensitivity analyses were performed to test model robustness. RESULTS: When compared to NT, TMC was cost effective with an ICER of $25,578 per QALY gained; incremental cost was $1780 and incremental effectiveness was 0.070 QALYs. In one-way sensitivity analyses, results were most sensitive to the cost of POLE testing, but TMC remained cost-effective over all parameter ranges. CONCLUSIONS: TMC in early-stage high-risk EC is cost-effective, and the model results were robust over a range of parameters. Given that MC can be used to guide adjuvant treatment decisions, these findings support adoption of TMC into routine practice.

Living Donor Liver Transplant for Budd-Chiari Syndrome Without Caval Replacement: A Single-Center Study.

OBJECTIVES: Adequate venous outflow is one of the most important factors responsible for optimal graft function in liver transplantation. Thrombosis of the inferior vena cava in cases of Budd-Chiari syndrome poses a major challenge to a transplant surgeon in establishing proper graft outflow. In deceased donor liver transplant, this problem can be dealt with relative ease as the liver graft includes donor inferior vena cava. However, this is not the case in living donor liver transplant. We present our findings of living donor liver transplant for Budd-Chiari syndrome and discuss techniques that have helped overcome this unique problem without the need for complete inferior vena cava replacement. MATERIALS AND METHODS: Our retrospective analysis included living donor liver transplant recipients from November 2006 to March 2020 at our center and selected patients who underwent this transplant for Budd-Chiari syndrome. We studied the extent and severity of inferior vena cava involvement in these cases. We developed a classification that not only helped to stratify patterns of venacaval disease but also helped to plan the surgical technique. The role of interventional radiology combined with surgery in management of extensive inferior vena cava stenosis was studied. RESULTS: Among 2952 cases of liver transplant in our unit from November 2006 to March 2020, 36 patients had Budd-Chiari syndrome; 21 had significant level of inferior vena cava thrombosis, which was managed with inferior vena cava thrombectomy with either patchplasty (n = 20) or segmental replacement (n = 1). None of our patients showed recurrence of primary disease during the median follow-up of 36 months (range, 8-158 mo). CONCLUSIONS: Establishment of adequate venous ouflow in thrombosed inferior vena cava is possible with proper planning of surgical technique and timely involvement of interventional radiology-guided interventions in patients with Budd-Chiari syndrome.

Living Donor Liver Transplant in Patients Aged 60 Years or Older: Experience from a Large Volume Centre in India.

BACKGROUND: With ageing population and higher prevalence of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in older patients, more and more living donor liver transplants (LDLTs) are being considered in this group of patients as eligibility for deceased donor liver transplant is restricted to those aged 65 years and younger. However, the short- and long-term outcomes of this group have not been reported from India, which does not have a robust national health scheme. The aim of this study was to provide guidelines for transplant in this group. METHODS: All patients aged 60 years and older (group 1) who underwent LDLT in our centre between January 2006 and December 2017 were studied. A propensity score-matched group in 1:2 ratio was created with comparable sex and Model for End-Stage Liver Disease score (group 2). The 2 groups were compared for duration of hospital stay, surgical complications, hospital mortality and 1-, 3- and 5-year survival. RESULTS: Group 1 consisted of 207 patients, and group 2 had 414 patients. The number of patients in group 1 gradually increased with time from 4 in 2006 to 33 in 2017 accounting for 15% of total cases. Group 1 had more patients with viral hepatitis, NASH and HCC, and they had a higher 30-day mortality due to cardiorespiratory complications. Although 1- and 3-year survival was similar, the 5-year survival was significantly lower in group 1. CONCLUSION: Five-year survival was lower in the elderly group due to cardiorespiratory complications and recurrence of HCC. Outcomes in the elderly group can be improved with better patient selection and preventing HCC recurrence.

Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? - A single-institution study.

OBJECTIVES: A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. METHODS: A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). RESULTS: In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. CONCLUSION: Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy.

PURPOSE: Human papillomavirus (HPV) is implicated as a causative factor in vulvar squamous cell carcinoma (VSCC). This study evaluates if p16-positivity, a surrogate for HPV, predicts for better response rates to chemoradiation therapy and survival. MATERIALS AND METHODS: We conducted a retrospective chart review of women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000 to 2016 for VSCC. p16 stain-positivity was defined as diffuse strong "block" immunoreactivity within invasive tumor. RESULTS: Seventy-three women with median follow-up of 13.4 months were analyzed. Thirty-three (45.2%) had p16+ tumors. Median age was 73 years (range: 37-89); with p16+ tumors, the median age was 60 years vs 73 years for women with p16- tumors (p < 0.001). The distribution of tumor size and stage by p16-status were similar. The complete clinical response (cCR) rate for p16+ tumors was 63.6% vs 35.0% for p16- tumors (p = 0.014). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 53.8% vs 31.4% for p16+ vs p16-, respectively (p = 0.067). The combined complete response (cCR orpCR [CCR]) rate was 63.6% for p16+ and 30.0% for p16- (p = 0.004). Two-year vulvar control (VC) for women with p16+ tumors was 75.5% vs. 49.5% for p16- (p = 0.008). In women with p16+ tumors who achieved CCR, 2-year VC was 92.3% vs 52.1% for CIR (p = 0.009). For p16- tumors, 2-year VC was 67.3% vs 41.1% for CCR and CIR (p = 0.072). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p = 0.013). OS was not statistically different between p16+ cohorts, but was improved for p16- patients with CR vs CIR, 72.9% vs 18.8% (p = 0.026). CONCLUSIONS: p16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes.

Pixelated spatial gene expression analysis from tissue.

Here, we present a technique that performs on-chip picoliter real-time reverse transcriptase loop mediated isothermal amplification (RT-LAMP) reactions on a histological tissue section without any analyte purification while preserving the native spatial location of the nucleic acid molecules. We demonstrate this method by amplifying TOP2A messenger RNA (mRNA) in a prostate cancer xenograft with 100 µm spatial resolution and by visualizing the variation in threshold time of amplification across the tissue. The on-chip reaction was validated by mRNA fluorescence in situ hybridization (mFISH) from cells in the tissue section. The entire process, from tissue loading on microchip to results from RT-LAMP can be carried out in less than 2 h. We anticipate that this technique, with its ease of use, fast turnaround, and quantitative molecular outputs, would become an invaluable tissue analysis tool for researchers and clinicians in the biomedical arena.

Functional interaction of histone deacetylase 5 (HDAC5) and lysine-specific demethylase 1 (LSD1) promotes breast cancer progression.

We have previously demonstrated that crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) facilitates breast cancer proliferation. However, the underlying mechanisms are largely unknown. Here, we report that expression of HDAC5 and LSD1 proteins were positively correlated in human breast cancer cell lines and tissue specimens of primary breast tumors. Protein expression of HDAC5 and LSD1 was significantly increased in primary breast cancer specimens in comparison with matched-normal adjacent tissues. Using HDAC5 deletion mutants and co-immunoprecipitation studies, we showed that HDAC5 physically interacted with the LSD1 complex through its domain containing nuclear localization sequence and phosphorylation sites. Although the in vitro acetylation assays revealed that HDAC5 decreased LSD1 protein acetylation, small interfering RNA (siRNA)-mediated HDAC5 knockdown did not alter the acetylation level of LSD1 in MDA-MB-231 cells. Overexpression of HDAC5 stabilized LSD1 protein and decreased the nuclear level of H3K4me1/me2 in MDA-MB-231 cells, whereas loss of HDAC5 by siRNA diminished LSD1 protein stability and demethylation activity. We further demonstrated that HDAC5 promoted the protein stability of USP28, a bona fide deubiquitinase of LSD1. Overexpression of USP28 largely reversed HDAC5-KD-induced LSD1 protein degradation, suggesting a role of HDAC5 as a positive regulator of LSD1 through upregulation of USP28 protein. Depletion of HDAC5 by shRNA hindered cellular proliferation, induced G1 cell cycle arrest, and attenuated migration and colony formation of breast cancer cells. A rescue study showed that increased growth of MDA-MB-231 cells by HDAC5 overexpression was reversed by concurrent LSD1 depletion, indicating that tumor-promoting activity of HDAC5 is an LSD1 dependent function. Moreover, overexpression of HDAC5 accelerated cellular proliferation and promoted acridine mutagen ICR191-induced transformation of MCF10A cells. Taken together, these results suggest that HDAC5 is critical in regulating LSD1 protein stability through post-translational modification, and the HDAC5-LSD1 axis has an important role in promoting breast cancer development and progression.

Vibrational spectroscopy and imaging for concurrent cellular trafficking of co-localized doxorubicin and deuterated phospholipid vesicles.

Simultaneous tracking of nanoparticles and encapsulated payload is of great importance and visualizing their activity is arduous. Here we use vibrational spectroscopy to study the in vitro tracking of co-localized lipid nanoparticles and encapsulated drug employing a model system derived from doxorubicin-encapsulated deuterated phospholipid (dodecyl phosphocholine-d38) single tailed phospholipid vesicles.

Role of mometasone furoate aqueous nasal spray for management of adenoidal hypertrophy in children.

OBJECTIVES: To study the role of mometasone furoate aqueous nasal spray for the management of adenoidal hypertrophy in children with more than 50 per cent obstruction, and to assess its impact on change in quality of life. METHODS: A prospective, randomised, double-blind, interventional placebo-controlled study was conducted. A total of 100 children aged 2-12 years completed treatment and follow up. The symptoms and degree of obstruction were evaluated by nasopharyngoscopy conducted pre-treatment and 24 weeks post-treatment. Subjects received mometasone furoate nasal spray at a daily dose of 200 µg for 8 weeks, followed by a dose of 200 µg on alternate days for 16 weeks. RESULTS were compared with those of a matched control group who were given saline nasal spray. RESULTS: With mometasone treatment, there was an 89.8 per cent reduction in clinical symptom score, and the degree of obstruction dropped from 87 to 72 per cent (p < 0.0001). A statistically significant change in quality of life scores was seen in patients treated with the mometasone nasal spray (score change of 37.47) as compared with those given saline nasal spray (score change of 11.25) (p = 0.0001). CONCLUSION: Mometasone nasal spray appears to be effective in treating children with obstructive adenoids.

Bannayan-Riley-Ruvalcaba syndrome: MRI neuroimaging features in a series of 7 patients.

SUMMARY: Bannayan-Riley-Ruvalcaba syndrome is a congenital disorder characterized by macrocephaly, intestinal polyposis, lipomas, and pigmented macules of the penis. There is limited published radiologic literature on the syndrome. The purpose of this study was to review the brain MR imaging findings in Bannayan-Riley-Ruvalcaba syndrome as well as to compare and contrast the findings with other brain disorders that also have brain cysts and white matter lesions. All brain MR imaging studies were reviewed in patients with a diagnosis of Bannayan-Riley-Ruvalcaba syndrome from our hospital. All 7 patients were evaluated with brain MR imaging. MR imaging results showed white matter cysts in the parietal lobe (7/7), frontal lobe (3/7), and temporal lobe (1/7). These were predominantly surrounded by white matter T2 hyperintensities associated with macrocephaly. Cystic lesions on MR imaging in Bannayan-Riley-Ruvalcaba syndrome are prevalent, and knowledge of this differential diagnosis can allow the radiologist to suggest a diagnosis of this condition in a child with macrocephaly.

Profilin-1 downregulation has contrasting effects on early vs late steps of breast cancer metastasis.

Profilin1 (Pfn1), a ubiquitously expressed actin-binding protein, has an indispensable role in migration and proliferation of normal cells. Seemingly contrary to its essential cellular functions, Pfn1's expression is downregulated in breast cancer, the significance of which is unclear. In this study, expression profiling of Pfn1 in human breast cancer specimens correlates lower Pfn1 expression levels with propensity to metastasize. Xenograft experiments further establish a causal relationship between loss of Pfn1 expression and increased dissemination of breast cancer cells (BCCs) from the primary mammary tumor. BCCs exhibit a hyperinvasive phenotype (marked by matrix metalloproteinase-9 upregulation, faster invasion through collagen matrix) and acquire increased proficiency to transmigrate through endothelial barrier (an obligatory step for vascular dissemination) when Pfn1 expression is suppressed. In Pfn1-deficient cells, hyperinvasiveness involves a phosphatidylinositol 3-kinase-PI(3,4)P2 signaling axis while augmented transendothelial migration occurs in a vascular endothelial growth factor-dependent manner. Contrasting these dissemination promoting activities, loss of Pfn1, however, dramatically inhibits metastatic outgrowth of disseminated BCCs, suggesting that Pfn1 has a key role in the metastatic colonization process. In summary, this study shows that Pfn1 has a dichotomous role in early vs late steps of breast cancer metastasis.

Small-incision cataract surgery in patients with Fuch's heterochromic iridocyclitis.

INTRODUCTION: Fuch's heterochromic iridocyclitis (FHI) is often complicated by cataract formation. OBJECTIVE: To assess the results of small-incision cataract surgery (SICS) in FHI and to study the effect of preoperative factors on postoperative vision. MATERIALS AND METHODS: Sixty-three eyes of 59 patients with Fuchs heterochromic iridocyclitis who had SICS with in-the-bag implantation of intraocular lens (IOL) were evaluated retrospectively; and the primary and secondary outcome measures evaluated were the postoperative vision and complication rate. RESULTS: The mean age was 39.22±4.95 years. The mean pre-operative vision was 0.75±0.24 Log MAR units. The mean final vision was 0.27±0.10 Log MAR units (P=less than 0.001). At the final follow-up, 84.1% of the patients had a final Snellen's vision of 6/12 or better. The mean follow-up period was 12.06±2.06 months. The causes of corrected distance visual acuity (CDVA) worse than 6/60 were vitreous opacities, posterior keratic precipitates (KPs), glaucoma, persistent uveitis and cystoid macular edema (CME). Preoperative factors like iris atrophy (P=0.973), heterochromia (P=0.10) and vessels in angle (P=0.074) did not have a significant effect on the final vision. On the contrary, vitreous opacities (P=0.002) and posterior KPs (P=0.009) had a significant effect on the final visual outcome. CONCLUSION: SICS with in-the-bag implantation of IOL in patients with Fuch's heterochromic iridocyclitis resulted in good visual outcomes. SICS in complicated cataracts can be performed in rural settings and eye camps with minimal instrumentation, obviating the need for referral to tertiary care centers. Pre-operative factors like vitreous opacities and posterior KPs have a significant effect on the final vision.

Lymphangioma circumscriptum of the tongue in children: successful treatment using intralesional bleomycin.

Lymphangioma circumscriptum is an uncommon congenital skin disorder occurring commonly in limbs and genitals, and is extremely rare in tongue. Although complete surgical excision is the most widely used treatment, more conservative procedures such as sclerotherapy are being increasingly used for treatment of lymphangiomas. We present a series of two cases of lymphangioma circumscriptum of tongue which were treated successfully with intralesional bleomycin injection.

AAV-based gene therapy prevents neuropathology and results in normal cognitive development in the hyperargininemic mouse.

Complete arginase I deficiency is the least severe urea cycle disorder, characterized by hyperargininemia and infrequent episodes of hyperammonemia. Patients suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation and seizures, and is associated with intellectual disability. In mice, onset is heralded by weight loss beginning around day 15; gait instability follows progressing to inability to stand and development of tail tremor with seizure-like activity and death. Here we report that hyperargininemic mice treated neonatally with an adeno-associated virus (AAV)-expressing arginase and followed long-term lack any presentation consistent with brain dysfunction. Behavioral and histopathological evaluation demonstrated that treated mice are indistinguishable from littermates, and that putative compounds associated with neurotoxicity are diminished. In addition, treatment results in near complete resolution of metabolic abnormalities early in life; however, there is the development of some derangement later with decline in transgene expression. Ammonium challenging revealed that treated mice are affected by exogenous loading much greater than littermates. These results demonstrate that AAV-based therapy for hyperargininemia is effective and prevents development of neurological abnormalities and cognitive dysfunction in a mouse model of hyperargininemia; however, nitrogen challenging reveals that these mice remain impaired in the handling of waste nitrogen.

Infrared microspectroscopy combined with conventional atomic force microscopy.

This paper reports nanotopography and mid infrared (IR) microspectroscopic imaging coupled within the same atomic force microscope (AFM). The reported advances are enabled by using a bimaterial microcantilever, conventionally used for standard AFM imaging, as a detector of monochromatic IR light. IR light intensity is recorded as thermomechanical bending of the cantilever measured upon illumination with intensity-modulated, narrowband radiation. The cantilever bending is then correlated with the sample's IR absorption. Spatial resolution was characterized by imaging a USAF 1951 optical resolution target made of SU-8 photoresist. The spatial resolution of the AFM topography measurement was a few nanometers as expected, while the spatial resolution of the IR measurement was 24.4 µm using relatively coarse spectral resolution (25-125 cm(-1)). In addition to well-controlled samples demonstrating the spatial and spectral properties of the setup, we used the method to map engineered skin and three-dimensional cell culture samples. This research combines modest IR imaging capabilities with the exceptional topographical imaging of conventional AFM to provide advantages of both in a facile manner.