Skin Malignant Melanoma and Matrix Metalloproteinases: Promising Links to Efficient Therapies.

Skin malignant melanoma (MM) is one of the most frequent and aggressive neoplasia worldwide. Its associated high mortality rates are mostly due to its metastases, while diagnosis and treatment of MM in its early stages is of favorable prognostic. Even skin superficial MMs at incipient local stages can already present with lymph node invasion and distant metastases. Therefore, knowledge of the controllable risk factors and pathogenic mechanisms of MM development, spreading, and metastatic pattern, as well as early diagnosis, are essential to decrease the high mortality rates associated with cutaneous malignant melanoma. Genetic factors are incriminated, although lifetime-acquired genetic mutations appear to be even more frequently involved in the development of MM. Skin melanocytes divide only twice per year and have time to accumulate genetic mutations as a consequence of environmental aggressive factors, such as UV exposure. In the search for more promising therapies, matrix metalloproteinases have become of significant interest, such as MMP-1, MMP-2, MMP-9, and MMP-13, which have been linked to more aggressive forms of cancer and earlier metastases. Therefore, the development of specific synthetic inhibitors of MMP secretion or activity could represent a more promising and effective approach to the personalized treatment of MM patients.

Osteoblast responsive biosilica-enriched gelatin microfibrillar microenvironments.

Engineering of scaffolds for bone regeneration is often inspired by the native extracellular matrix mimicking its composite fibrous structure. In the present study, we used low loadings of diatomite earth (DE) biosilica to improve the bone regeneration potential of gelatin electrospun fibrillar microenvironments. We explored the effect of increasing the DE content from 1 % to 3 % and 5 %, respectively, on the physico-chemical properties of the fibrous scaffolds denoted FG_DE1, FG_DE3, FG_DE5, regarding the aqueous media affinity, stability under simulated physiological conditions, morphology characteristics, and local mechanical properties at the surface. The presence of biosilica generated composite structures with lower swelling degrees and higher stiffness when compared to gelatin fibers. Increasing DE content led to higher Young modulus, while the stability of the protein matrix in PBS, at 37 °C, over 21 was significantly decreased by the presence of diatomite loadings. The best preosteoblast response was obtained for FG_DE3, with enhanced mineralization during the osteogenic differentiation when compared to the control sample without diatomite. 5 % DE in FG_DE5 proved to negatively influence cells' metabolic activity and morphology. Hence, the obtained composite microfibrillar scaffolds might find application as osteoblast-responsive materials for bone tissue engineering.

Pancreaticogastrostomy versus Pancreaticojejunostomy and the Proposal of a New Postoperative Pancreatic Fistula Risk Score.

Despite the substantial decrease in mortality rates following a pancreaticoduodenectomy to less than 5%, morbidity rates remain significant, reaching even 73%. Postoperative pancreatic fistula is one of the most frequent major complications and is significantly associated with other complications, including patient death. Currently, there is no consensus regarding the ideal type of pancreatic anastomosis, as the question of the choice between a pancreaticogastrostomy and pancreaticojejunostomy is still open. Furthermore, worldwide implementation of an ideal pancreatic fistula risk prediction score is missing. Our study found several significant predictive factors for the postoperative occurrence of fistulas, such as the soft consistency of the pancreas, non-dilated Wirsung duct, important intraoperative blood loss, other perioperative complications, preoperative patient hypoalbuminemia, and patient weight loss. Our study also revealed that for patients who exhibit fistula risk factors, pancreaticogastrostomy demonstrates a significantly lower pancreatic fistula rate than pancreaticojejunostomy. The occurrence of pancreatic fistulas has been significantly associated with the development of other postoperative major complications, and patient death. As the current pancreatic fistula risk scores proposed by various authors have not been consensually validated, we propose a simple, easy-to-use, and sensitive score for the risk prediction of postoperative pancreatic fistula occurrence based on important predictors from statistical analyses that have also been found to be significant by most of the reported studies. The new pancreatic fistula risk score proposed by us could be extremely useful for improved therapeutic management of cephalic pancreaticoduodenectomy patients.

Is Surgical Treatment for Obesity Able to Cure Urinary Incontinence in Women?-A Prospective Single-Center Study.

There is enough evidence to support weight loss in order to improve urinary incontinence. Nevertheless, weight loss and maintaining a lower weight are not easy to achieve in the general population. Our study aims to evaluate whether bariatric surgery has a positive effect on the symptoms of urinary incontinence in female patients. We performed a prospective study on obese female patients before and after bariatric surgery, over a period of 9 years. Patients with a BMI ≥ 33 kg/m2 were included if they described involuntary loss of urine and no previous surgery for urinary incontinence was performed. The patients underwent laparoscopic surgery, either gastric sleeve, bypass or banding, performed by four surgeons in our hospital. The type of incontinence was not assessed at the initial visit carried out by the surgeon. All patients who declared being incontinent were referred to the urologist where they received the ICIQ-UI-SF questionnaire before their bariatric surgery and during follow -up visits. The sum of points obtained at questions 3, 4 and 5 was used to evaluate the severity of incontinence, as well as the impact on the quality of life. Our evaluation collected data on age, time since onset of symptoms, pad usage, number and type of deliveries, concomitant conditions and medications. The type of incontinence was assessed by the urologist before bariatric surgery as urge, stress or mixed incontinence. At follow-up visits, the patients were also asked to fill out a 10-point VAS questionnaire evaluating their perception on the evolution of incontinence symptoms. Data were analyzed using t-test statistical analysis. Our objective defined changes in incontinence as cure, improved, no change and worse. We included 54 women from whom initial data and at least 18 months of follow-up were available. We observed that about 50% of all women undergoing bariatric surgery have some degree of urinary incontinence. The ICIQ score improved from 13.31 ± 5.18 before surgery to 8.30 ± 4.49 points after surgery (p < 0.0001). Before surgery, 38 patients (70%) described severe incontinence compared to only 20 patients (37%) after surgery. A total of 16 women (31%) reported complete cure of urinary incontinence after bariatric surgery. Data from the VAS questionnaire show improvement in 46 cases (85%). Pad usage improved from 7.04 ± 2.79 to 3.42 ± 2.77 (p < 0.001) per day. The number of patients using more than one pad per day decreased from 35 (65%) to 9 (17%). The type of incontinence did not seem to be relevant, but our sample size was too small to lead to statistically significant results. There was no impact on the outcome of incontinence of number/type of delivery, age or BMI. Our data show that bariatric surgery is able to cure urinary incontinence in one of three obese women. A significant improvement was obtained in more than two-thirds of the patients, regardless of the type of incontinence. For an obese female with urinary incontinence, treatment for obesity should prevail and incontinence should be treated only if symptoms remain.

Chronic Wound Management: From Gauze to Homologous Cellular Matrix.

BACKGROUND: Chronic wounds are a significant health problem with devastating consequences for patients' physical, social, and mental health, increasing healthcare systems' costs. Their prolonged healing times, economic burden, diminished quality of life, increased infection risk, and impact on patients' mobility and functionality make them a major concern for healthcare professionals. PURPOSE: This review offers a multi-perspective analysis of the medical literature focusing on chronic wound management. METHODS USED: We evaluated 48 articles from the last 21 years registered in the MEDLINE and Global Health databases. The articles included in our study had a minimum of 20 citations, patients > 18 years old, and focused on chronic, complex, and hard-to-heal wounds. Extracted data were summarized into a narrative synthesis using the same health-related quality of life instrument. RESULTS: We evaluated the efficacy of existing wound care therapies from classical methods to modern concepts, and wound care products to regenerative medicine that uses a patient's pluripotent stem cells and growth factors. Regenerative medicine and stem cell therapies, biologic dressings and scaffolds, negative pressure wound therapy (NPWT), electrical stimulation, topical growth factors and cytokines, hyperbaric oxygen therapy (HBOT), advanced wound dressings, artificial intelligence (AI), and digital wound management are all part of the new arsenal of wound healing. CONCLUSION: Periodic medical evaluation and proper use of modern wound care therapies, including the use of plasma-derived products [such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF)] combined with proper systemic support (adequate protein levels, blood sugar, vitamins involved in tissue regeneration, etc.) are the key to a faster wound healing, and, with the help of AI, can reach the fastest healing rate possible.

Complicated Clinical Course of a Patient with Multivisceral Cystic Echinococcosis Requiring Extensive Surgical and Medical Treatment.

Cystic echinococcosis is an often-overlooked condition that otherwise negatively impacts both the individual and the community, prompting major public health concerns. Early diagnosis and treatment, as well as collaboration between specialties including surgery and parasitology, are essential for avoiding complications and disease relapse. To better illustrate this, we present the case of an elderly person with a rare localization of the disease at the muscular level. The patient underwent numerous surgical interventions, and received multiple courses of antiparasitic treatment over the course of 40 years as a result of the multivisceral dissemination of the parasite.

Gossypiboma, the Hidden Enemy of an Emergency Cesarean Hysterectomy-Case Report and Review of the Literature.

Gossypiboma or textiloma is a rare medical situation that can complicate the favorable evolution of a surgical case, with repercussions for the patient's prognosis. The diagnosis can be difficult due to various clinical symptoms, the time elapsed since the surgical intervention, and the imaging often not being precise in detecting textilomas. Due to the medicolegal implications, the reporting of this event is inconsistent. We present a rare case of a 28-year-old woman who presented with vague pain in the left iliac fossa 11 months after an emergency cesarean hysterectomy was performed. The preoperative imaging examination identified the presence of a subhepatic mass with dimensions of 10 × 8 cm2 and another formation in the right iliac fossa with dimensions of 11 × 9 cm2. Exploratory laparotomy found the presence of a large subhepatic gossypiboma, intimately adherent to the hepatic angle of the colon and omentum and a second one adherent to the sigmoid colon, small intestine, and parietal peritoneum. The particularity of this case is given by the simultaneous presence of two textilomas with inconclusive evolution, which can make the differential diagnosis difficult to achieve. For a better assessment of the risk of occurrence of this pathology and the identification of a correct prevention strategy, we performed an extensive search and a review of all the articles published in the PubMed database, identifying 57 articles. In conclusion, emergency surgery increases the risk of this complication, and, as a result, prevention can be achieved by following existing protocols in the operating room.

Coexistence of Trisomy 8 and 13 in a Newly Diagnosed Patient With Diffuse Large B Cell Non-Hodgkin Lymphoma and Acute Myeloid Leukemia Secondary to Primary Myelofibrosis.

Concomitant diagnosis of non-Hodgkin lymphoma (NHL) and acute myeloid leukemia secondary to chronic myeloproliferative neoplasms (MPNs) is rarely reported. Patients with MPNs may have a second neoplasm, and the risk of lymphoid line neoplasms is 2.5-3.5 times for lymphoid line neoplasms. The explanation for this association is the genetic instability of hematopoietic progenitors in MPNs. An 80-year-old Caucasian man, with many comorbidities, presents for physical asthenia, sweating. The right inguinal adenopathy was known one month before the examination. The patient was diagnosed concomitantly with diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) secondary to primary myelofibrosis (PMF) and presented trisomy 8, trisomy 13, and triple-negative PMF status. The patient initially received two well-tolerated R mini CHOP series. This type of treatment was selected to treat DLBCL for one unfit patient for intensive chemotherapy due to his age and comorbidities. R mini CHOP administration was followed by severe aplasia that lasted approximately two weeks followed by severe thrombocytosis that reached 4000 x109/L, and Thromboreductin recommendation was mandatory. The result of the treatment was a partial response but with severe adverse events like neutropenia G4, due to the delay of the treatment the patient lost the response. It was mandatory to select another treatment line and the chosen was venetoclax; it was selected for the simultaneous treatment of DLBCL and the underlying AML. It was obtained a significant reduction in the size of the inguinal lymph node block in two weeks of treatment. Severe neutropenia was diagnosed and complicated with sepsis. The evolution is unfavorable with the installation of multiple organ dysfunction. The presence of a complex karyotype (trisomy 8, trisomy 13) in a patient with myeloid metaplasia with triple-negative PMF was associated with blast transformation and severe thrombocytosis. The patient was diagnosed concomitantly with DLBCL, making the therapeutic decision difficult. Venetoclax has been shown to be useful in the treatment of DLBCL but has been associated with severe neutropenia, which has led to infectious complications.

[The most common benign cutaneous neoplasms of vascular, muscular, and adipose tissue and their treatment]. / Häufigste benigne Gefäß­, Muskel- und Fettgewebstumoren der Haut und ihre Therapie.

Benign cutaneous vascular and cutaneous neoplasms arising from muscle or adipose tissue are rare. Their definition and classification are still controversially discussed. Histopathological and immunohistochemical studies, together with the new genetic tests, contribute significantly to the correct description of the various benign neoplasms of cutaneous origin. Clarifying whether a lesion is benign is fundamental for prognosis and therapeutic management. In most cases, surgical excision is the treatment of choice. Dermatologists should be familiar with the classifications of the most common benign cutaneous neoplasms of vascular, muscular, and adipose tissue and be able to recommend the procedures currently used for an accurate diagnosis. Ensuring that a lesion is benign and a good surgical outcome are essential for the patient.

Experience of the Colentina Clinical Hospital Surgery Clinic in the Treatment of COVID-19 Patients Hospitalised in the Period March - August 2020.

Introduction: SARS-CoV-2 is a Betacoronavirus belonging to the Sarbecovirus subgenus of the Coronavidae family, antigenically distinct from SARS CoV, with which it has a genetic similarity of about 76% of nucleotides (1). It causes the Covid-19 disease in humans, which mainly affects the respiratory system, through inflammatory and procoagulant mechanisms at the level of alveolar microcirculation. Material and method: There are 145 patients infected with SARS-CoV-2, treated in the Colentina Surgery Clinic during March-August 2020, whose cases were analysed to identify some elements that would help to improve the medical management of these patients from multiple perspectives. Discussion: There was a slight predominance of male impairments, and the ages of interest were mostly over 60 years. The cases that required surgery were in an absolute minority (14 cases). The operations were performed only in conditions of a surgical emergency. Mortality was high (24,13%).

Severe Bleeding Complications Resulting in Death Following Anticoagulant Treatment in COVID-19 Surgical Patients.

Microthrombi formation in the pulmonary circulation is one of the main pathophysiological mechanisms responsible for the unfavorable respiratory evolution of CoViD-19 patients. Low molecular weight heparin (LMWH) anticoagulant therapy is a major pillar of treatment. But sometimes LMWH causes severe complications that can result in death. This is a retrospective, descriptive study, covering September 2020 and presenting 3 cases of severe hemorrhages followed by death in COVID-19 anticoagulated patients in therapeutic doses with LMWH in the hospital units of origin. Patients had hematomas of the rectus abdominal muscles and hemoperitoneum (2 cases) respectively hematoma of left gluteal muscles (1 case). The 2 patients with hematoma of rectus abdominal muscles were operated. The death occurred between 1-4 days after hospitalization.

Bioinspired Hydrogel Coating Based on Methacryloyl Gelatin Bioactivates Polypropylene Meshes for Abdominal Wall Repair.

Considering the potential of hydrogels to mimic the cellular microenvironment, methacryloyl gelatin (GelMA) and methacryloyl mucin (MuMA) were selected and compared as bioinspired coatings for commercially available polypropylene (PP) meshes for ventral hernia repair. Thin, elastic hydrated hydrogel layers were obtained through network-forming photo-polymerization, after immobilization of derivatives on the surface of the PP fibers. Fourier transform infrared spectroscopy (FTIR) proved the successful coating while the surface morphology and homogeneity were investigated by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). The stability of the hydrogel layers was evaluated through biodynamic tests performed on the coated meshes for seven days, followed by inspection of surface morphology through SEM and micro-CT. Taking into account that platelet-rich plasma (PRP) may improve healing due to its high concentration of growth factors, this extract was used as pre-treatment for the hydrogel coating to additionally stimulate cell interactions. The performed advanced characterization proved that GelMA and MuMA coatings can modulate fibroblasts response on PP meshes, either as such or supplemented with PRP extract as a blood-derived bioactivator. GelMA supported the best cellular response. These findings may extend the applicative potential of functionalized gelatin opening a new path on the research and engineering of a new generation of bioactive meshes.

Hepatic hydatid cyst - diagnose and treatment algorithm.

Introduction: the hydatic disease, caused by the larvae of Echinococcus granulosus, is a serious disease, potentially lethal, which can be found anywhere in the world, but especially in endemic areas such as the Mediterranean Basin, Australia, New Zealand, North Africa, Eastern Europe, the Balkans, Middle East and South America. The hydatic cyst is mainly found in the liver (75% of the cases), being asymptomatic in most cases and discovered accidentally on a routine abdominal ultrasound or an ultrasound performed for diagnosing other pathologies. The hepatic hydatid cyst therapy is multimodal, including medical, surgical, and, lately, minimally invasive techniques. Materials and methods: 88 patients were diagnosed with liver hydatid cyst at the General Surgery Clinic of the Colentina Hospital in Bucharest where they were admitted from January 2014 to July 2017. Data collection was realized by consulting the patients' observation sheets, followed by organizing a database of clinical, paraclinical and treatment parameters. Age, gender, place of origin, year and duration of admission, symptoms and signs at admission, paraclinical serological tests relevant for liver function and E. granulosus infection, imaging investigations performed and their results, type of treatment received and post-treatment progress with the complications that occurred were taken in account. Results: some of the results of the study showed some differences comparing to the data from specialty literature, the possible causes being the small number of patients, the paraclinical examinations that were not sufficiently detailed to allow the study of a phenomenon in all its complexity, the lack of information from the patients' first presentation to a doctor or from their previous admissions. Conclusions: patients with hepatic hydatid cyst form a heterogeneous group, semiology being poor and unspecific. Among the laboratory examinations, eosinophilia is a sign of concern but is present in less than half of the patients. Imaging findings are the basis for the diagnosis of hepatic hydatid cysts. Surgical treatment remains the "gold standard" in therapy, but minimally invasive methods with high applicability, less frequent complications and lower hospital requirements are starting to gain ground.

New Options in the Management of Cystic Echinococcosis - A Single Centre Experience Using Minimally Invasive Techniques.

OBJECTIVE: The aim of this study is to verify if the experience on 4 years in using minimally invasive techniques in the treatment of CE could match regarding the indications and results with the major studies on topic. METHOD: During 03.2014 - 03. 2018 period, 38 PAIR, 28 MoCaT procedures and 7 percutaneous drainages have been performed at 51 patients from 76 cases of hydatid hepatic cysts (67,1%). There were 26 men and 25 women, and the age ranged from 19 to 78. 7 patients have had 2 hydatid hepatic cysts or more and 2 procedures were performed at 3 of those patients; other 11 patients needed the second procedure during the surveillance. Results: The evolution of the patients was favorable, and the surveillance was 2 years postintervention at least. There were no major surgical adverse effects. We defined as an expected result obtaining a scar lesion or a small cavity with calcified walls (hyperechoic). Only 2 (3,9%) patients needed conversion to open surgery. The complications we have faced were represented by the cystic-biliary fistula in 15 cases (29,4%) and the re-opening of the cyst's cavity in 11 cases (21,67%). Conclusions: The percutaneous treatment of CE is safe and effective, following the correct assignation according with the cysts type. The percutaneous treatment of CE is an easier alternative to the open surgery and has lower rate of complications and relapses, and a shorter hospitalisation. Now routine, it becomes slighty the first option for invasive treatment of CE. The role of open surgery is restricted to CE with severe complications.

Correction to: Hepatic hydatid cyst - diagnose and treatment algorithm.

[This corrects the article on p. 203 in vol. 11, PMID: 30364592.].

Therapy of Stenosing Rectal Cancer.

Develop a rectal cancer management aims to establish an algorithm diagnostic, surgical treatment strategy implementation, strategy and neoadjuvant and adjuvant treatment response and optimal methods for assessing response to specific treatment. In trying to track this management, we studied the issues listed above, we conducted a retrospective clinical study, descriptive and included the analysis of data obtained on a sample selected 90 patients diagnosed with stenosing rectal cancer between January 2008 and December 2012 treated on the General Surgery Clinic I of "Prof. Dr. Al. Trestioreanu" Oncology Institute and on the General Surgery Clinic of Colentina Clinical Hospital, in Bucharest and aimed at analyzing the therapeutic attitudes of stenosing rectal cancer. Choosing the surgery, especially when applying preoperative and postoperative radiotherapy, with or without concomitant chemotherapy, it took into account the presence of stenosis (obstruction complete or incomplete) and the evolutionary stage locally and remotely disease.

Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors.

Regression in melanoma is a frequent biological event of uncertain prognostic value as the lesion exhibits heterogeneous phenotypical features, both at the morphological and immunohistochemical level. In the present study, we examined the expression of tissue inhibitors of metalloproteinases (TIMP1, TIMP2 and TIMP3) in melanoma with regression. We specifically examined the expression levels of these TIMPs in regressed components (RC) and non-regressed components (NRC) of the tumor and compared their expression levels with those in non-regressed melanomas. We found that TIMP1 was overexpressed in the NRC of melanomas with partial regression (PR) compared with the NRC in melanomas with segmental regression (SR) (P=0.011). TIMP2 was overexpressed in the NRC of melanomas with PR compared with the NRC in melanomas with SR (PR/SR, P=0.009); or compared with the NRC in melanomas with simultaneous SR-PR (P=0.002); or compared with melanomas without regression (absence of regression) (P=0.037). Moreover, TIMP3 was overexpressed in the NRC of all melanomas with SR as compared to the RC component (P=0.007). Our findings on the differential expression of TIMP1, TIMP2 and TIMP3 in melanomas with regression support the hypothesis that the morphological differences identified in the melanoma regression spectrum may have a correlation with prognosis. This may explain the controversial findings within the literature concerning the biological and prognostic role of regression in melanoma.

Medical and surgical management of a rare and complicated case of multivisceral hydatidosis; 18 years of evolution.

Hydatidosis (echinococcosis) is a parasitic disease caused by the development in the human host of the larval form of the Echinococcus spp. tapeworm. Among the parasitic diseases transmitted from animal to human, hydatidosis represents the main Romanian helminthic zoonosis in humans, due to the severity of the clinical presentation and the complications of this illness. Before 1995-2000, surgical care was considered the only treatment available for the disease in Romania. Recently, the association of surgical procedures with pre and postoperative benzimidazolic drugs has been imposed. We describe the case of a patient diagnosed in 1995, when he had already presented a form of multivisceral hydatidosis, and we also emphasize the development of this disease in this transition period, which concerns the change in the hydatidosis approach.