A New Method of Artificial-Intelligence-Based Automatic Identification of Lymphovascular Invasion in Urothelial Carcinomas.

The presence of lymphovascular invasion (LVI) in urothelial carcinoma (UC) is a poor prognostic finding. This is difficult to identify on routine hematoxylin-eosin (H&E)-stained slides, but considering the costs and time required for examination, immunohistochemical stains for the endothelium are not the recommended diagnostic protocol. We developed an AI-based automated method for LVI identification on H&E-stained slides. We selected two separate groups of UC patients with transurethral resection specimens. Group A had 105 patients (100 with UC; 5 with cystitis); group B had 55 patients (all with high-grade UC; D2-40 and CD34 immunohistochemical stains performed on each block). All the group A slides and 52 H&E cases from group B showing LVI using immunohistochemistry were scanned using an Aperio GT450 automatic scanner. We performed a pixel-per-pixel semantic segmentation of selected areas, and we trained InternImage to identify several classes. The DiceCoefficient and Intersection-over-Union scores for LVI detection using our method were 0.77 and 0.52, respectively. The pathologists' H&E-based evaluation in group B revealed 89.65% specificity, 42.30% sensitivity, 67.27% accuracy, and an F1 score of 0.55, which is much lower than the algorithm's DCC of 0.77. Our model outlines LVI on H&E-stained-slides more effectively than human examiners; thus, it proves a valuable tool for pathologists.

Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study.

BACKGROUND: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. METHODS: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. RESULTS: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0-5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). CONCLUSIONS: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.

Challenges in the Surgical Management of Patients with Diabetic Neuropathy.

Background: Diabetes Mellitus represents a major socio-economic issue both by influencing the patient's quality of life and also considering the impact on the healthcare system. Diabetic neuropathy is one of the main complications associated, in most cases being present from the moment of diagnosis. Considering the high incidence of diabetes among patients with biliodigestive surgical conditions, a thorough analysis of the evolution and management of these patients is necessary. Materials and Methods: The association between the evolution of diabetic patients with biliodigestive conditions and diabetic neuropathy as well as risk criteria and associated complications were analyzed in a descriptive, correlational study (314 patients) conducted in the Dr. I. Cantacuzino Clinical Hospital during 2020-2022. In the study, the patients were distributed into two groups, one consisting in patients without diabetes mellitus (control group) and the second further subdivided into two groups of study, first (2a) containing patients with type II with diabetic neuropathy and high and medium risk rate, and a second one (2b) including patients with diabetes mellitus type II with confirmed neuropathy and low risk rate. Clinical and laboratory evaluations were performed and management protocols applied. Results: Statistically significant correlations were highlighted between diabetic neuropathy and the variables tested which were subsequently combined to achieve a risk score and a management protocol. Conclusions: Diabetes mellitus associated with diabetic neuropathy represents a negative prognostic factor for the postoperative outcome being associated with high risk of morbidity and mortality. The risk score and the management protocol described as results of this study represent feasible solutions and a subservient instrument in preventing the occurrence of complications in patients with bilio-digestive surgical pathologies in order to improve the prognosis and survival of the patients.

A New Artificial Intelligence-Based Method for Identifying Mycobacterium Tuberculosis in Ziehl-Neelsen Stain on Tissue.

Mycobacteria identification is crucial to diagnose tuberculosis. Since the bacillus is very small, finding it in Ziehl-Neelsen (ZN)-stained slides is a long task requiring significant pathologist's effort. We developed an automated (AI-based) method of identification of mycobacteria. We prepared a training dataset of over 260,000 positive and over 700,000,000 negative patches annotated on scans of 510 whole slide images (WSI) of ZN-stained slides (110 positive and 400 negative). Several image augmentation techniques coupled with different custom computer vision architectures were used. WSIs automatic analysis was followed by a report indicating areas more likely to present mycobacteria. Our model performs AI-based diagnosis (the final decision of the diagnosis of WSI belongs to the pathologist). The results were validated internally on a dataset of 286,000 patches and tested in pathology laboratory settings on 60 ZN slides (23 positive and 37 negative). We compared the pathologists' results obtained by separately evaluating slides and WSIs with the results given by a pathologist aided by automatic analysis of WSIs. Our architecture showed 0.977 area under the receiver operating characteristic curve. The clinical test presented 98.33% accuracy, 95.65% sensitivity, and 100% specificity for the AI-assisted method, outperforming any other AI-based proposed methods for AFB detection.

Bcl-2 and p53 immunophenotypes in colorectal adenocarcinoma in type 2 diabetes mellitus versus non-diabetic patients.

We aimed to investigate immunohistochemical expression of the p53 tumor suppressor protein, and the B-cell lymphoma-2 (Bcl-2) apoptotic protein in colorectal adenocarcinoma patients with or without type 2 diabetes mellitus (T2DM). Tissue sections from 95 paraffin-embedded colorectal adenocarcinomas, originating from 52 T2DM and 43 non-diabetic patients, were immunostained for p53 [Ventana mouse monoclonal primary antibody (mAb) in vitro diagnostic (IVD) anti-p53, clone Bp53-11] and Bcl-2 (Ventana mAb IVD anti-Bcl-2, clone Bcl-2/124). Immunohistochemistry analysis did not find statistically significant differences between the two groups, but analysis on subgroups of patients in terms of presence or absence of obesity identified overexpression of p53 (>70% of cells) in the T2DM obese patients compared to non-diabetics. Overexpression of p53 was present in 80% of tumor cells coming from T2DM obese patients compared to 37.2% of tumor cells coming from non-diabetics obese and non-obese, and in 36.6% of tumor cells coming from non-diabetic non-obese patients (p=0.024). There was a single non-diabetic obese patient with p53 overexpression. Most cancer cells of T2DM obese patients presented more frequently p53 overexpression by comparison with cancer cells of the T2DM non-obese patients (80% vs 40.5%, p=0.028). Bcl-2/p53 co-expression was an infrequent event in T2DM patients' group. The results of this study suggest that patients with colorectal adenocarcinoma that associate T2DM and obesity exhibit higher p53 protein expression in malignant cells. In conclusion, our research highlights that obesity is a potential key factor in the relationship between T2DM and colorectal cancer.

Assessment of the Risk of Colorectal Cancer in Patients with Diabetes Mellitus.

Background: The increased incidence of both colorectal cancer and diabetes mellitus, as well as the fact that they are important causes of high morbidity and especially mortality, place the two pathologies on the list of priorities of the health system. There are studies which have observed that diabetes mellitus is directly involved in carcinogenesis and is an independent risk factor for colorectal cancer. The diabetic patient requires a complex medical-surgical approach, so setting the risk criteria for them can be the starting point for improving the survival rate. Materials and methods: The association between colorectal cancer and diabetes mellitus as well as screening criteria were analyzed in a descriptive prospective study (442 patients) conducted in the Dr. I. Cantacuzino Clinical Hospital during 2017-2018. In the study, patients were distributed in two clusters, one with diabetes mellitus (N = 194) and one without diabetes mellitus (N = 248) in which basic clinical and laboratory evaluations were performed followed by screening colonoscopies. Results: Statistically significant (p 0.005) correlations were highlighted between 7 of the variables tested and the positive results on colonoscopy, which were subsequently combined to achieve a risk score. Conclusions: Diabetes mellitus is an independent risk factor and a negative prognostic factor for colorectal cancer. The risk score described as a result of this study is a feasible, simple solution for early detection of precursor lesions or neoplasms with the ultimate goal of improving the prognosis and survival of these patient.

Diabetes Mellitus as a Risk-factor for Colorectal Cancer Literature Review - Current Situation and Future Perspectives.

Colorectal cancer and Diabetes Mellitus represent a major public health issue, first, by the number of new cases which are at an alarming rate. Secondly, by the negative effect over the quality of life, socio-economic status and lifespan, representing high morbidity and mortality causes. Diabetes Mellitus is the disease of the century with a global prevalence (standardised-age) which doubled since 1980, rising from 4,7% to 8,5% in adult population. In 2012, the estimated number of fatalities caused by Diabetes Mellitus and other related complications was at 3,7 million, out of which 43% were patients under the age of 70. Neoplasia represents the second cause of death, after cardiovascular disease. The occurrence of Colorectal cancer (CRCA) is rated for men and women at 3rd and 2nd place. However, the rate of mortality from CRCA is in the 4th place, representing 8,5% out of the total cancer related deaths. 52% of these cases are recorded in underdeveloped countries, considering their level, this reflects a very low survival rate. Moreover, every year, approximately 1.4 million cases are being diagnosed out of which 55% appear in overdeveloped countries. Screening for colorectal cancer refers to the periodical evaluation of the asymptomatic patients who are at a risk of developing this type of neoplasia. The colorectal cancer contains a series of particularities which makes it ideal for screening. Since the end of the 19th century there has been a high suspicion that type II diabetes, through direct etiological mechanisms, may play a part in carcinogenesis (breast, endometrium, colorectal, pancreas, liver, non-Hodgkin's lymphoma). At the moment, the relevant published literature presents type II diabetes as an independent risk factor for colorectal cancer. Although, despite experimental proof, many epidemiological studies, case-controlled studies and meta-analysis, there still is the necessity for prospective studies which can intensify the existing results and can allow the colorectal cancer screening to adapt to these patients.

Surgical Complications of Peritoneal Dialysis.

Peritoneal dialysis (PD) is a method of renal function replacement which has a series of advantages like greater autonomy of the patient with fewer hospital visits and better preservation of residual renal function, but it has also disadvantages. The main disadvantages are a limited life-time due to peritoneal membrane failure and the risk of infections. The main complication of PD remains peritonitis, which is responsible for the most cases of method failure. There are also other complications which incorrect treated may lead to failure of the method: mechanical complications, abdominal wall defects, exit site and tunnel infections. Encapsulating peritoneal sclerosis is a rare entity found in PD patients but with high morbidity and mortality. We have retrospectively analyzed the patients with end stage renal disease under peritoneal dialysis which were admitted to Surgical Clinic "I. Juvara" of the Clinical Hospital "Dr. I. Cantacuzino" between 2007 and 2017 for surgical complications related to PD. The patients were assigned in two groups: with non-infectious and infectious complications. We have found 109 patients which have had 126 surgical interventions related to peritoneal dialysis. Out of these, 30 interventions consisted in catheter removal for loss of ultrafiltration capacity, so these were excluded from analysis. The lot resulted consisted in 80 patients with 91 complications: 42 non-infectious and 49 infectious. Mean age was 60.5 (+-12.3) years. Sex distribution was 2.75/1 male/female. Diabetes mellitus was present at 45 (56,25 %) patients. Comparing the patients with non-infectious with those with infectious complications we found significant association between type of complications and the length of PD in the sense that infectious complications tend to appear later than the non-infectious. Also, the loss of peritoneal dialysis is strongly associated with infectious complications. Looking inside groups we found that abdominal wall defects are associated with the history of previous abdominal surgery (p 0,001). Regarding the morbidity and mortality only infectious complications had associated mortality in our study, there were no significant differences in morbidity rate between groups. Between all these patients we have also identified 16 with encapsultating peritoneal sclerosis. In most cases the diagnosis was established during the intervention for another complication. We have registered a 20% morality rate at these patients. Conclusions: Noninfectious surgical complications are not raising problems for diagnosis or surgical treatment, but an incorrect treatment may lead to failure of the PD. Infectious complications and especially peritonitis remains the main cause of method failure. These are generating the highest rates of morbidity and mortality from peritoneal dialysis complications. Even if the immediate surgical intervention for peritonitis related to peritoneal dialysis is usually unnecessary, surgical observation is absolutely mandatory in every case. The absence of a response to the proper medical treatment is an indication for peritoneal cavity exploration inclusive by laparoscopy/laparotomy. Any delay in diagnosis and definitive treatment can lead to loss of peritoneal membrane function and even death of the patient. Encapsulated peritoneal sclerosis is a rare but serious complication of PD. The risk for developing EPS increases with the duration of PD treatment. No predictive and reliable screening tests especially in the early stages of EPS were found. So, it is important not to underestimate the clinical symptoms, diagnosis being based on a high index of suspicion. The only established basic treatment of EPS is enterolysis of peritoneal adhesions, and time should not be unnecessarily wasted on conservative treatment.

Surgical Management of Diabetic Neuropathy Foot Complications.

Background: Diabetic foot complications result from the association between peripheral vascular disease, neuropathy and a precarious healing process. Peripheral neuropathy observed in diabetics affects all components of the nervous system, contributing to the occurrence of leg ulcers, musculoskeletal changes, resulting in severe deformities. The clinical manifestation of these complications ranges from simple lesions to complex entities threatening the loss of pelvic limb or even life (1,2). Methods: In our surgery department, a significant number of patients with diabetic foot lesions are hospitalized and treated annually, 40% having clinical manifestations of diabetic neuropathy associated. In 2017, a total of 448 patients were hospitalized for complications of diabetes. We performed a retrospective analysis of 150 consecutive patients who underwent surgery for neuropathic diabetic foot lesions. Results: The analyzed patients had a favorable postoperative progression, benefiting from distal perfusion. Ray resection was the preferred surgical intervention. Major amputation was performed in 10% of cases with extensive gangrene and sepsis, amputation of the calf being preferred in all situations. Conclusions: The management of these patients is delicate, often multidisciplinary approach being necessary. A well-managed therapeutic attitude can make the difference between preserving or losing the pelvic limb.

Soft Tissue Infections in Diabetic Patients.

Background: the patient with diabetes has an increased susceptibility to infections, with negative evolutionary potential leading to increased morbidity and mortality compared to the general population. The cause is the alteration of immune defense mechanisms, the hyperglycemic environment leading to alteration of neutrophil function, suppression of the antioxidant system and humoral activity, systemic micro and macroangiopathy, neuropathy, depression of antibacterial activity of the genitourinary and digestive tract. Infections localized at the soft tissue (skin, fascia and aponeurosis, subcutaneous tissue, muscles) in the diabetic patient require a complex medico-surgical approach in which aggressive surgical treatment should be complemented by metabolic balancing and sustained antibiotic therapy. Materials and methods: these peculiarities will be exposed and analyzed in a retrospective descriptive study performed at the General Surgery Clinic. Juvara of the clinical hospital Dr. I. Cantacuzino, during the period of Jan. 2013- Dec.2017, which followed the type of lesions, their localization, the germs involved, the comorbidities, the biologic parameters, the antibiotic and surgical treatment as well as the postoperative evolution. The study does not include patients with localized infections in the diabetic foot, a particular pathological entity that will be analyzed separately in a separate study. Results: 150 diabetic patients with soft tissue infections localized in the upper limb, calf, thigh, perineum, abdominal and thoracic wall were identified. The most frequent localization was found in the lower limb (54%). The incidence of these infections was higher in males (55%), and the most affected age group was 60-69 years (38%). Most patients had type II diabetes (93%). Among the associated comorbidities, cardiovascular diseases and obesity are the most common, explaining to a large extent the complicated evolution, potentially lethal of this pathology. From the bacteriological perspective, a plurimicrobian flora is identified, staphylococcus aureus being most frequently encountered. The antibiotic treatment was initiated immediately empirically, subsequently according to the antibiogram; the most commonly used antibiotic classes being cephalosporins and carbapenems. Surgical interventions were in their majority of debridement and necrectomy, but in a few cases limb amputation was necessary. In particular, the number of surgical interventions performed in the same patient and in the same hospital stay was between 1 and 7 interventions. Conclusions: Soft tissue infections in the diabetic patient have a heterogeneous aspect with specific particularities requiring careful clinical examination, multidisciplinary treatment including rapid, serial surgical interventions to control the growing aggression of the germs involved. Fast and caseadapted therapeutic decisions, careful observation of the patient's general condition and of the wound several times a day are essential to achieving favorable postoperative outcomes.

Variation in Expression of Inflammation-Related Signaling Molecules with Profibrotic and Antifibrotic Effects in Cutaneous and Oral Mucosa Scars.

Wound healing is a complex biologic process evolving in three phases: inflammation, proliferation, and tissue remodeling controlled by numerous growth factors and cytokines. Oral mucosa wounds heal with significantly less important scars with less numerous macrophages and mast cells and more numerous myofibroblasts than cutaneous counterparts. We analyzed 32 cutaneous and 32 oral mucosa scars for TGFbeta1, TGFbeta2, TGFbeta3, TNFalpha, PDGF BB and FGF1 expression in mesenchymal cells, endothelial cells, macrophages, and multinucleated giant cells. We identified differences in the expression of profibrotic and antifibrotic factors in oral mucosa and skin scars; TGFbeta2 was positive in cutaneous multinucleated giant cells, TNFalpha was positive in cutaneous macrophages, and both were negative in oral mucosa while TGFbeta3 was positive in oral macrophages and mostly negative in cutaneous ones. PDGF BB and FGF1 were positive in oral endothelial cells and oral macrophages and negative in macrophages with opposite positivity pattern in cutaneous scars. Based on these findings, macrophage seems to be the key player in modulating pro- and antifibrotic processes in wound regeneration.