Clinical, Functional, and Nutritional Efficacy of a Glutamine-Enriched Oligomeric Diet in Patients with Rectal Cancer.

AIMS: This work aims to evaluate the efficacy of nutritional supplementation with a glutamine-enriched oligomeric diet (GEOD) compared to a standard polymeric diet (SPD) in terms of oncology treatment-related diarrhea (OTRD) (frequency and consistency of stools), gastrointestinal toxicity, and functional and nutritional progress. METHODS: This prospective cohort study compared two groups of patients with rectal cancer in treatment with neoadjuvant chemotherapy and radiotherapy who were at risk of malnutrition. Patients were randomized to receive either 400 ml of GEOD or of SPD from the start of radiotherapy to 30 days after its completion. RESULTS: Eighty patients were recruited, 40 per arm. The GEOD arm had improved stool consistency and a greater reduction in the number of stools compared to the SPD arm (p < 0.001). The relative risk (RR) of developing diarrhea in the GEOD arm was 0.059 (95% CI 0.015-0.229). There was a reduced risk of developing intestinal mucositis in the GEOD arm compared to the SPD arm [RR 0.202 (95% CI 0.102 - 0.399)]. The GEOD arm had greater improvements in functional and nutritional status (p < 0.001). CONCLUSIONS: GEOD had a protective effect in terms of the development of gastrointestinal toxicity associated with chemotherapy and radiotherapy treatment in patients with rectal cancer.

Cytological features of diffuse and circumscribed gliomas.

The current World Health Organization classification of gliomas is based on morphological, genetic, and molecular parameters. In this review, we intend to present the most relevant cytological features of these tumours, with a particular focus on their analysis during intraoperative studies. Rapid diagnosis is required in this context, and at present it is not possible to evaluate the genetic or molecular profile of a tumour intraoperatively. New terminology and diagnostic parameters have been introduced, but the essence of intraoperative recognition remains the same. The main challenge in astrocytoma IDH-mutant, grade 2 is recognising the tissue as neoplastic. Since glioma grades 3 and 4 are assigned based on histological and genetic variables that are not necessarily measurable on cytology, the term high-grade glioma is often used for intraoperative diagnosis. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted shows peculiar cytological findings as well as the common subtypes of glioblastoma IDH-wildtype (giant cell, epithelioid, gliosarcoma and small cell). Many of the paediatric-type-diffuse gliomas have been described very recently and there are no cytological reports of proven cases. Finally, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, and astroblastoma MN1-altered constitute the group of circumscribed astrocytic gliomas. They are remarkable entities that the pathologist must be able to recognise since most are low-grade neoplasms that can show atypical morphological features.

A comprehensive review of the "tigroid" background cytological concept: what, when, where and why?

The concept of "tigroid" background is used in cytology to describe a peculiar smear background characterized by the presence of a relatively granular, reticulated material that was described as "foamy, lazy, tiger-striped or astrakhan". It was used to describe the background seen in smears obtained from seminoma. In addition to seminoma, we now know that it can be present in different tumours, mostly carcinomas and round cell sarcomas. These share with seminoma a cytoplasm with high glycogen content and many times clear cell morphology. The "tigroid" background is seen when smears are air-dried and Romanowsky-based stains are used (May-Grunwald-Giemsa and Diff-Quik stains). It is only seen in fine needle aspiration or intraoperative squashing or scrapping samples, but not in specimens obtained from effusions or liquid-based cytology. Wet-fixed cytologic samples with alcohol or with formaldehyde tend to dissolve the background so it is not usually present in Papanicolaou stained smears. In this review, we discuss tumours in which the "tigroid" background is observed and its potential diagnostic utility and aetiology. It is interesting to remark that except for parathyroid adenoma and adenomatoid tumour all the neoplasms in which this background has been observed are malignant.

GLUT-1 as a predictor of worse prognosis in pancreatic adenocarcinoma: immunohistochemistry study showing the correlation between expression and survival.

BACKGROUND: Various parameters have been considered for predicting survival in pancreatic ductal adenocarcinoma. Information about western population is missing. The aim of this study is to assess the association between Glucose transporter type 1 (GLUT-1) expression and prognosis for patients with PDAC submitted for surgical resection in a European cohort. METHODS: Retrospective analysis of PDAC specimens after pancreatoduodenectomy assessing GLUT-1 expression according to intensity (weak vs strong) and extension (low if < 80% cells were stained, high if > 80%) was performed. Statistical analysis was performed using the exact Fisher test, Student t test or the Mann-Whitney U test. Survival was analysed using the Kaplan-Meier method and compared with the Log-rank test. The differences were considered significant at a two-sided p value of < 0.05. All statistical analyses were performed using SPSS® 23.0 for Windows (SPSS Inc., Chicago, IL, USA). RESULTS: Our study consisted of 39 patients of which 58.9% presented with weak and 41.1% with strong intensity. The median extension was 90%: 28.2% cases presented with a low extension and 71.8% with a high extension. No significant differences related to intensity were found. The high-extension group showed a higher percentage of T3 PDAC (92.9% vs 63.6%, p = 0.042) and LNR20 (35.7% vs 0%, p = 0.037) as well as shorter disease-free survival (17.58 vs 54.46 months; p = 0.048). CONCLUSIONS: Our findings suggest that GLUT-1 could be related to higher aggressivity in PDAC and could be used as a prognostic marker, identifying patients with a worse response to current therapies who could benefit from more aggressive treatments.

High Frequency of Severe Telaprevir-associated Skin Eruptions in Clinical Practice.

Since the introduction of telaprevir, administered in combination with pegylated interferon and ribavirin for the treatment of patients with chronic hepatitis C, the incidence and severity of skin eruptions have increased significantly. The aim of this prospective study is to assess the frequency of drug-induced skin eruptions and their clinical and histological characteristics in patients who received the above treatment in daily clinical practice at our hospital. A total of 60 patients were included. The frequency of telaprevir-associated skin eruptions was 48.3%, which is slightly below, but close to, previously described ranges. There was a predominance of an eczematous clinical pattern, and spongiotic dermatitis on histological examination. A slightly high frequency of severe skin eruptions (13.3%) was found in our study series, which may be explained by all our patients being assessed and closely monitored by one or more dermatologists.

Primary central neurocytoma of the mesencephalic tectum in a pediatric patient.

PURPOSE: Neurocytomas are tumors or neuronal differentiation, typically located within the supratentorial ventricular system. The extraventricular location is uncommon. A limited number of cases involving the brainstem have been reported and may be misdiagnosed as brainstem gliomas. Furthermore, midbrain neurocytomas are extremely rare, and no similar cases in pediatric patients have been reported in the literature to date. Brainstem location of neurocytomas often precludes gross total removal of the lesion, and in these cases, adjuvant therapies may be helpful. METHODS: We report a case of a 16-year-old child who presented with signs and symptoms of increased intracranial pressure. The magnetic resonance imaging study demonstrated the presence of a primary mesencephalic tectum lesion causing obstructive hydrocephalus. The patient underwent emergent ventriculoperitoneal shunt implantation, resolving the hydrocephalus and the clinical symptoms. The lesion was partially removed through a suboccipital craniotomy and supracerebellar infratentorial approach to the mesencephalic tectum, without intraoperative complications. RESULTS: Histological examination of the lesion was consistent with the diagnosis of extraventricular neurocytoma. The patient was referred to the oncology department for additional treatment with Gamma Knife radiosurgery. CONCLUSIONS: Although brainstem neurocytoma is rare, this case demonstrates that it should be included in the differential diagnosis of brainstem gliomas. Because of brainstem tumor location, complete surgical removal may be challenging or not possible, with a high risk of postoperative neurological deficits. Adjuvant therapies may prevent local tumor growth in cases of tumor remnants or recurrences following microsurgery in selected cases.

Starch/carbon nanofibers bionanocomposites via melt mixing: Effect of dispersion and compatibility on conductivity and mechanical properties.

Biodegradable polymers with conductivity and mechanical properties are required in several applications where it is necessary to substitute conductive synthetic plastics due to the high waste produced. In this study, bionanocomposites (BNCs) have been compounded by thermoplastification of rice starch via melt mixing with carbon nanofibers (NPs) and modified NPs (NPs [M]) using plasma of acrylic acid. Spectroscopy analysis, X-ray diffraction, and morphology were studied to elucidate the effect of dispersion and compatibility on the conductivity and mechanical properties. The incorporation of NPs promoted esterification reactions with starch during the melt mixing process, giving rise to changes in its crystal structure. NPs [M] showed better dispersion and compatibility because the plasma prevents reagglomeration and generates a stronger affinity. BNCs showed significative flexibility with remarked % elongation at break from 5.64 % to 248.60 %, and thermal conductivity increased from 0.10 to 0.58 W/m K, with NPs [M] at 5 %. In contrast, the electrical conductivity remained in the same magnitude order (10-4 S/cm). The better compatibility between starch-NPs [M] hinders electronic transport but increases the propagation of phonons to promote thermal conductivity. BNCs fabricated in this study by a dry and scalable process could be of interest in some application areas (intelligent food packing, electronics, textiles, etc.).

Accurate and safe diagnosis and treatment of neoplastic biliary lesions using a novel 9F and 11F digital single-operator cholangioscope.

Background and study aims Digital single-operator cholangioscopy (DSOC) allows the diagnosis of biliary duct disorders and treatment for complicated stones. However, these technologies have limitations such as the size of the probe and working channel, excessive cost, and low image resolution. Recently, a novel DSOC system (eyeMAX, Micro-Tech, Nanjing, China) was developed to address these limitations. We aimed to evaluate the usefulness and safety of a novel 9F and 11F DSOC system in terms of neoplastic diagnostic accuracy based on visual examination, ability to evaluate tumor extension and to achieve complete biliary stone clearance, and procedure-related adverse events (AEs). Patients and methods Data from ≥ 18-year-old patients who underwent DSOC from July 2021 to April 2022 were retrospectively recovered and divided into a diagnostic and a therapeutic cohort. Results A total of 80 patients were included. In the diagnostic cohort (n = 49/80), neovascularity was identified in 26 of 49 patients (46.9%). Biopsy was performed in 65.3% patients with adequate tissue sample obtained in 96.8% of cases. Biopsy confirmed neoplasia in 23 of 32 cases. DSOC visual impression achieved 91.6% sensitivity and 87.5% specificity in diagnosing neoplasms. In the therapeutic cohort (n = 43/80), 26 of 43 patients required lithotripsy alone. Total stone removal was achieved in 71% patients in the first session. Neither early nor late AEs were documented in either the diagnostic or therapeutic cohort. Conclusions The novel DSOC device has excellent diagnostic accuracy in distinguishing neoplastic biliary lesions as well as therapeutic benefits in the context of total stone removal, with no documented AEs.

Visual Acuity Improvement in Low, Moderate and High Myopia After Posterior-Chamber Phakic Implantable Collamer Lens Surgery in a Large Patient Cohort.

Purpose: To compare best-corrected visual acuity (BCVA) before and after implantable collamer lens (ICL) surgery in patients with low, moderate and high myopia. Methods: A single-centre, prospective, registry-based study involving patients with myopia who received ICLs between October 2018 and August 2020. The study population was divided into three groups of subjects with low (from 0 to -6 D), moderate (-6 to -10 D) and high myopia (more than -10 D). We analysed uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical equivalent (SE), differences between BCVA pre- and 1-month postoperative, and line gain in BCVA 1 month after surgery. Results: A total of 770 eyes belonging to 473 patients were surgically intervened during the study period, of which 692 eyes completed 1 month of postoperative follow-up and were included in the study population. At 1-month follow-up, 478 eyes (69%) achieved a BCVA of 20/20, 599 (87%) obtained 20/25 or better, and 663 (96%) had a BCVA of 20/40 or better. We identified a significant improvement in BCVA (baseline 0.15±0.2 logMAR vs follow-up 0.07±0.2 logMAR, p<0.0001) and a significant reduction in SE (baseline -9.23±4.1 D, vs follow-up -0.21±0.8 D, p<0.0001), with a significant relationship between preoperative SE and line gain (r = -0.46, p<0.0001). We identified a significantly higher line gain among eyes with higher degrees of myopia (low myopia 0.22±0.69 lines compared to moderate myopia 0.56±1.1 lines and high myopia 1.51±1.9 lines, p<0.0001). Notably, 99.6% of eyes with a high grade of myopia achieved improvement to a low degree (less than -6 D) at follow-up. The safety and efficacy indexes were 0.083±0.1 and -0.001±0.1, respectively. Conclusion: In this large patient cohort, ICL surgery was related to a significant line gain in BCVA, particularly among eyes with higher degrees of myopia.

PLA/modified-starch blends and their application for the fabrication of non-woven fabrics by melt-blowing.

Blends of polylactic acid (PLA) and thermoplastic starch (TS) with and without chemical modification were obtained by melt extrusion and used to obtain non-woven fabrics by melt-blowing for the first time. Different TS were obtained by reactive extrusion from native cassava, oxidized, maleated, and dual modified (oxidized and maleated) starch. The chemical modification of starch decreases the difference in viscosity and favors blending, resulting in more homogeneous morphologies, unlike the blends with unmodified TS, which displayed a visible phase separation with large TS droplets. The dual modified starch showed a synergistic effect to process TS by melt-blowing. Regarding non-woven fabrics, values in diameter (2.5-82.1 µm), thickness (0.4-0.6 mm), and grammage (49.9-103.8 g/m2) were explained due to differences in viscosity of the components, and to the fact that during melt the hot air preferentially stretches and thins the areas without large droplets of TS. Moreover, plasticized starch acts as a flow modifier. The porosity of the fibers increased with the addition of TS. Further studies and optimization of blends with low contents of TS and type starch modification will be necessary to completely understand these systems with very complex behavior to obtain non-woven fabrics with improved properties and application.

Embedded Graphite and Carbon Nanofibers in a Polyurethane Matrix Used as Anodes in Microbial Fuel Cells for Wastewater Treatment.

Composites of polyurethane and graphite and polyurethane and carbon nanofibers (PU/Graphite 0.5% and PU/CNF 1%) were synthesized and used as anodes in dual-compartment microbial fuel cells (MFCs) for municipal wastewater treatment; electrical energy generation and organic matter removal were assessed. The maximum power density, coulombic efficiency and chemical oxygen demand (COD) removal efficiency in the MFCs packed with the PU/Graphite 0.5% and PU/CNF 1% composites were 232.32 mW/m3 and 90.78 mW/m3, 5.87 and 4.41%, and 51.38 and 68.62%, respectively. In addition, the internal resistance of the MFCs with the best bioelectrochemical performance (PU/Graphite 0.5%) was 1051.11 Ω. The results obtained in this study demonstrate the feasibility of using these types of materials in dual-compartment MFCs for wastewater treatment with electric power generation.

Newly proposed quantitative criteria can assess chronic atrophic gastritis via probe-based confocal laser endomicroscopy (pCLE): a pilot study.

Background and study aims Probe-based confocal laser endomicroscopy (pCLE) can provide high magnification to evaluate chronic atrophic gastritis (CAG), but the current pCLE criteria are qualitative and prone to variability. We aimed to propose a quantitative CAG criterion based on pCLE to distinguish non-atrophic gastritis (NAG) from CAG. Patients and methods This observational, exploratory pilot study included patients with NAG and CAG evaluated via esophagogastroduodenoscopy, pCLE, and histology. We measured the gastric glands density, gastric gland area, and inter-glandular distance during pCLE. Results Thirty-nine patients (30/39 with CAG) were included. In total, 194 glands were measured by pCLE, and 18301 were measured by histology, with a median of five glands per NAG patient and 4.5 per CAG patient; pCLE moderately correlate with histology (rho = 0.307; P  = 0.087). A gland area of 1890-9105 µm 2 and an inter-glandular distance of 12 to 72 µm based on the values observed in the NAG patients were considered normal. The proposed pCLE-based CAG criteria were as follows: a) glands density < 5; b) gland area < 1/16 the pCLE field area (< 1890 µm 2 ) or > 1/4 the pCLE field area (> 9105 µm 2 ); or c) inter-glandular distance < 12 or > 72 µm; CAG was diagnosed by the presence of at least one criterion. The proposed criteria discriminated CAG with a ranged sensitivity of 76.9 % to 92.3 %, a negative predictive value of 66.6 % to 80.0 %, and 69.6 % to 73.9% accuracy. Conclusions The proposed pCLE criteria offer an accurate quantitative measurement of CAG with high sensitivity and excellent interobserver agreement. Larger studies are needed to validate the proposed criteria.

Fine needle aspiration cytology of a myxoid adrenocortical adenoma. A case report.

The myxoid variant of adrenocortical (AC) tumors is characterized by peculiar histologic features that differ from conventional ones. It shows a prominent myxoid stromal component and is composed of small cells with mild atypia arranged in cords, pseudoglandular structures and microcysts. Reflecting the rarity of this variant, very few cytologic descriptions are available. We describe one case in a 41-year-old woman with a previous diagnosis of breast carcinoma and BRCA1 mutation. During follow-up controls, an adrenal tumor was discovered. Fine needle aspiration cytology and Tru-Cut biopsies were performed simultaneously. Smears showed numerous groups of cohesive cells of intermediate to small size. Within the largest groups, aggregates of myxoid metachromatic material were evident. This myxoid material could also be observed as isolated acellular fragments. While the cytoplasm of most tumoral cells was homogenously stained some showed small vacuoles. Histologically, the tumor grew, forming anastomosing cords, separated by myxoid material that determined microcystic spaces. Immunohistochemistry was characteristic of AC myxoid tumor. After surgery, pathologic analysis confirmed this diagnosis. The tumor showed no necrosis or invasion, had a low mitotic index (3/50 high power fields) and Ki-67 proliferative index of 15%. According to the different diagnostic systems the tumor was classified as an adenoma. In conclusion, the myxoid variant of AC tumors shows peculiar cytologic features. If unaware of the existence of this variant, it can easily be misinterpreted as a metastatic tumor.

Mesothelial-to-Mesenchymal Transition Contributes to the Generation of Carcinoma-Associated Fibroblasts in Locally Advanced Primary Colorectal Carcinomas.

During peritoneal metastasis, cancer cells spread from abdominal solid tumors, disseminate through the peritoneal fluid and attach to and invade through mesothelial cells (MCs) that line the peritoneum. Intestinal adenocarcinomas originating in the mucosa infiltrate the submucosa, muscle layer, and serosa in order to finally colonize the peritoneal cavity. However, the mechanism by which metastatic cells leave the primary tumor and reach the peritoneal cavity has not been previously described. Hence, we investigate whether MCs lining visceral peritoneum, through a mesothelial-to-mesenchymal transition (MMT), are a source of carcinoma-associated fibroblasts (CAFs), which could contribute to cancer progression toward the peritoneal cavity. CAFs detected in biopsies from patients with superficially invasive colorectal cancer differed from locally advanced tumors. An aberrant accumulation of myofibroblasts expressing mesothelial markers was found in the stroma of deeply infiltrative tumors located in the neighborhood of a frequently activated mesothelium. We suggest that MMT is a key event in the early stages of peritoneal dissemination.

Fine needle aspiration cytology of polymorphous adenocarcinoma of the salivary glands: A report of 11 patients and review of the literature.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is a rare malignant tumor of the minor salivary glands. It has an infiltrative growth, variable architectural patterns, neurotropism and cellular monomorphism. Approximately 75% of the cases show a specific mutation in the protein kinase D1 (PRKD1) gene. Reflecting the rarity of the tumor and intraoral location, the cytologic experience is limited with few reported series. In this study we analyze our cytologic experience to determine if a preoperative diagnosis is possible. METHODS: A retrospective study of 11 patients with PAC in which a cytologic study was available. A review of the literature was also performed. RESULTS: Our study shows that PAC has relatively constant cytological features. The analysis of the cytological literature although it shows some heterogeneity, also reveals repetitive cytological findings. Smears are cellular with irregular groups some showing pseudopapillary branching morphology. Monolayered clusters and small acinar structures are also present. Most cases have small metachromatic globules embedded within the groups determining a cylindromatous pattern. Tumoral cells are small and uniform with scarce to moderate cytoplasm. Nuclei are round and oval with occasional grooves and small nucleoli. CONCLUSION: PAC has characteristic cytological features that together with its location in minor salivary gland must make us consider it preoperatively. It may resemble basal cell adenoma and epithelial-rich pleomorphic adenoma so we should be cautious in the final diagnosis. Whenever possible, the characteristic cytomorphology of PCA should make us evaluate the mutational status of PRKD1 gene since it may permit a more accurate diagnosis.

Peripheral Reconstructive Lamellar Keratoplasty for Late Ectasia After Penetrating Keratoplasty in Keratoconus Eyes.

PURPOSE: To describe outcomes of customized peripheral anterior lamellar keratoplasty (PALK) for late ectasia of the donor-recipient junction after penetrating keratoplasty (PK) for keratoconus. METHODS: This was a single-center, retrospective review of 33 eyes (28 patients) that developed ectasia restricted to the graft-host junction; 17 eyes underwent PALK using lamellar resections of 8- to 11-mm width starting at the external margin of the previous PK and suturing a same-size donor graft (annular or segmental). Five eyes were excluded from analysis because of postoperative complications unrelated to the technique. RESULTS: The average time between PK and diagnosis of secondary ectasia was 28 years (range 9-49 years). Slit-lamp examination showed localized thinning and elongation of the scar at the graft-host junction with well-defined biomicroscopic limits. Preoperatively, the mean keratometric measures were K1: 44.8 ± 4.8 D and K2: 54.1 ± 4.8 D and postoperatively K1: 47.5 ± 3.5 D and K2: 50.8 ± 2.6 D. The mean improvement in corrected visual acuity was 10 lines, and mean cylinder improved from 9.3 ± 2.1 D to 3.3 ± 1.4 D. All cases showed anatomical and refractive improvement. CONCLUSIONS: With long-term follow-up, late post-PK ectasia becomes an increasing problem. PALK can be a successful surgical option to reinforce the ectatic area while preserving a functional clear PK. By adding donor corneal tissue, PALK restores the ectatic area, improves visual acuity, keratometric values, and astigmatism, and preserves the functional graft while avoiding the higher risks of a larger diameter PK.