Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers.

Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this "unseen organ"-the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers.

Is Marginal Donor an Efficient Solution for Expanding the Donor Pool for Liver Transplant?

Once the techniques of hepatobiliopancreatic surgery improved, liver transplantation widely extended in different hospitals; therefore, the need of grafts and automatically of liver donors reported a significant increase in the last decade. In this respect, attention was focused on increasing the liver donor pool. The aim of this review is to study the benefits of using marginal grafts in liver transplantation. With the advent of multiple methods of liver preservation, the use of grafts previously considered unsuitable has become possible. Thus, extended allocation criteria have emerged. However, the allocation of these grafts must be carefully considered and analyzed in the context of both recipient and donor factors.

Recurrence and Carcinogenetic Rates of Colorectal Polyps.

AIM: to determin the recurrence rate of benign recto-colonic polyps in a 5-year interval, and compare the development rate of intrapolypoid carcinomatous lesions in polypectomized versus nonpolypectomized subjects. MATERIAL AND METHOD: a group of 77 patients diagnosed with recto-colonic polypoid lesions during the period 2014-2019 underwent colonoscopy at the time of study initiation and then annually during a five-year interval. Results: The recurrence rate of polyps increased annually from 5 to 12.5%; the highest rate was noted in the last two years. The five-year cumulative risk of neoplastic lesions was 73% in patients without polypectomy and 20% among those with endoscopic resection (p 0.05). Comparing the recurrence rate of benign lesions (60%) in patients without neoplastic findings with the recurrence rate of adenomas in patients with benign lesions (40%), a higher risk of recurrence was found in the first category, and seemed to be influenced by the personal history of pre-existing adenomatous lesions. CONCLUSION: an increased risk of colorectal polyps recurrence was reported during five year follow up; moreover, during the first three years an increased risk of malignant transformation was observed among cases in which endoscopic resection was not feasible when compared to those in which complete excision was feasible.

Prognostic Factors in Intrahepatic Cholangiocarcinoma - A Systematic Review.

Introduction: intrahepatic cholangiocarcinoma (ICCA) are rare, aggressive cancers that develop in second order or smaller bile ducts. The aim of this review is to systematically review the most important prognostic factors affecting the long-term outcomes of these patients. Material and Methods: articles conducted on this issue, written in English, published between from January 2000 to December 2023 in Cochrane Library, PubMed, Embase, MedLine, Web of Science, Elsevier, Google Scholar were systematically researched and reviewed. Results: ICCA are usually late diagnosed cancers because of the asymptomatic character, and curative procedures are often not feasible, only 20 to 30% of patients being fit for surgery. With the prognostic of this aggressive malignancy being baleful, the most important risk factors but also prognosis factors seem to be represented by socioeconomic factors, morphological presentation, dimensions, number and extension of the tumor as well as resection margins. Conclusions: once these factors are widely recognized and identified in each case, the clinician will be able to find the best treatment for these patients in order to improve the long-term outcomes.

Prognostic Significance of Preoperative Inflammation Markers on the Long-Term Outcomes in Peritoneal Carcinomatosis from Ovarian Cancer.

Ovarian cancer remains one of the most lethal gynaecological malignancies affecting women worldwide; therefore, attention has been focused on identifying new prognostic factors which might help the clinician to select cases who could benefit most from surgery versus cases in which neoadjuvant systemic therapy followed by interval debulking surgery should be performed. The aim of the current paper is to identify whether preoperative inflammation could serve as a prognostic factor for advanced-stage ovarian cancer. Material and methods: The data of 57 patients who underwent to surgery for advanced-stage ovarian cancer between 2014 and 2020 at the Cantacuzino Clinical Hospital were retrospectively reviewed. The receiver operating characteristic curve was used to determine the optimal cut-off value of different inflammatory markers for the overall survival analysis. The analysed parameters were the preoperative level of CA125, monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII). Results: Baseline CA125 > 780 µ/mL, NLR ≥ 2.7, MLR > 0.25, PLR > 200 and a systemic immune inflammation index (SII, defined as platelet × neutrophil-lymphocyte ratio) ≥ 84,1000 were associated with significantly worse disease-free and overall survival in a univariate analysis. In a multivariate analysis, MLR and SII were significantly associated with higher values of overall survival (p < 0.0001 and p = 0.0124); meanwhile, preoperative values of CA125, PLR and MLR were not associated with the overall survival values (p = 0.5612, p = 0.6137 and p = 0.1982, respectively). In conclusion, patients presenting higher levels of MLR and SII preoperatively are expected to have a poorer outcome even if complete debulking surgery is performed and should be instead considered candidates for neoadjuvant systemic therapy followed by interval surgery.

Hyponatremia as a Prognostic Factor in Advanced Stage Ovarian Cancer Patients.

Background: hyponatremia represents one of the most commonly encountered conditions in hospitalized patients, multiple mechanisms being cited so far, neoplastic syndromes being an important cause. The aim of the current paper is to analyse the presence and influence of the short- and long-term outcomes of hyponatremia on ovarian cancer patients submitted to surgery for advanced stage ovarian cancer. Method: 57 patients diagnosed with advanced stage ovarian cancer were submitted to surgery between 2014-2020. The patients were further classified according to the preoperative value of sodium into two groups. Results: there were 21 cases with preoperative normal values of sodium and respectively 36 cases with hyponatremia. Patients with preoperative hyponatremia associated a significantly higher rate of early postoperative complications and a significantly poorer long-term outcome. Therefore, cases with hyponatremia reported a mean disease-free survival of 10.8 months and respectively a mean overall survival of 18.5 months while cases with normal natrium levels reported a mean disease-free survival of 31.4 months and respectively a mean overall survival of 49.7 months (p=0.0001 and p 0.001). Conclusions: patients with lower preoperative values of sodium have a higher risk of developing postoperative complications and a significantly poorer outcome when compared to cases presenting normal levels of sodium preoperatively.

A Review of Abdominal Meshes for Hernia Repair-Current Status and Emerging Solutions.

Abdominal hernias are common issues in the clinical setting, burdening millions of patients worldwide. Associated with pain, decreased quality of life, and severe potential complications, abdominal wall hernias should be treated as soon as possible. Whether an open repair or laparoscopic surgical approach is tackled, mesh reinforcement is generally required to ensure a durable hernia repair. Over the years, numerous mesh products have been made available on the market and in clinical settings, yet each of the currently used meshes presents certain limitations that reflect on treatment outcomes. Thus, mesh development is still ongoing, and emerging solutions have reached various testing stages. In this regard, this paper aims to establish an up-to-date framework on abdominal meshes, briefly overviewing currently available solutions for hernia repair and discussing in detail the most recent advances in the field. Particularly, there are presented the developments in lightweight materials, meshes with improved attachment, antimicrobial fabrics, composite and hybrid textiles, and performant mesh designs, followed by a systematic review of recently completed clinical trials.

Novel Material Optimization Strategies for Developing Upgraded Abdominal Meshes.

Over 20 million hernias are operated on globally per year, with most interventions requiring mesh reinforcement. A wide range of such medical devices are currently available on the market, most fabricated from synthetic polymers. Yet, searching for an ideal mesh is an ongoing process, with continuous efforts directed toward developing upgraded implants by modifying existing products or creating innovative systems from scratch. In this regard, this review presents the most frequently employed polymers for mesh fabrication, outlining the market available products and their relevant characteristics, further focusing on the state-of-the-art mesh approaches. Specifically, we mainly discuss recent studies concerning coating application, nanomaterials addition, stem cell seeding, and 3D printing of custom mesh designs.

Revisiting the Intestinal Microbiome and Its Role in Diarrhea and Constipation.

The gut microbiota represents a community of microorganisms (bacteria, fungi, archaea, viruses, and protozoa) that colonize the gut and are responsible for gut mucosal structural integrity and immune and metabolic homeostasis. The relationship between the gut microbiome and human health has been intensively researched in the past years. It is now widely recognized that gut microbial composition is highly responsible for the general health of the host. Among the diseases that have been linked to an altered gut microbial population are diarrheal illnesses and functional constipation. The capacity of probiotics to modulate the gut microbiome population, strengthen the intestinal barrier, and modulate the immune system together with their antioxidant properties have encouraged the research of probiotic therapy in many gastrointestinal afflictions. Dietary and lifestyle changes and the use of probiotics seem to play an important role in easing constipation and effectively alleviating diarrhea by suppressing the germs involved. This review aims to describe how probiotic bacteria and the use of specific strains could interfere and bring benefits as an associated treatment for diarrhea and constipation.

Platelet to Lymphocyte Ratio as a Predictive Tool for the Perioperative and Postoperative Outcomes in Advanced Stage Ovarian Cancer.

Background: platelet to lymphocyte ratio remains a significant prognostic factor in different malignancies. The aim of the current paper is to study the correlation between the preoperative values of platelet to lymphocyte ratio (PLR) and the postoperative outcomes in ovarian cancer patients. Method: we conducted a retrospective study on 57 patients submitted to cytoreductive surgery between 2014-2020. We determined the optimal cut off value of PLR for predicting survival outcomes by using the Receiver Operating Characteristic curve a value of 350 being obtained. The patients were further classified in two groups according to the PLR value. Results: there were 37 patients with PLR 350 and respectively 20 patients with PLR 350. Patients in the second group were significantly older and presented significantly higher rates of perioperative complications, a significantly higher level of circulating platelets, of CA125 and respectively a significantly lower level of circulating lymphocytes and of preoperative hemoglobin level. Meanwhile, patients in the second group reported a significantly poorer disease free and overall survival. Conclusions: ovarian cancer patients with higher preoperative levels of PLR trend to have a poorer early and long-term postoperative outcome. Therefore, in such cases more aggressive systemic therapies might be needed.

An Occlusive Form of Acute Gangrenous Appendicitis With Periappendicular Abscess in an Elderly Patient: A Case Report and Literature Review.

Acute appendicitis represents one of the common causes of admission to the emergency department. In rare cases, patients with appendicitis can suffer complications such as intestinal obstruction. These particular cases of occlusive appendicitis with a periappendicular abscess usually occur in elderly patients and can develop in an aggressive form, nonetheless with a favorable evolution. We present a case of an 80-year-old male patient, reporting symptoms similar to an occlusive digestive pathology: abdominal pain, intestinal transit disorders, and fecal vomiting. A computerized tomography scan suggested a mechanical bowel obstruction. The patient had an exploratory laparotomy indication to find the cause of the obstruction. The peritoneal cavity inspection revealed an occlusive form of acute gangrenous appendicitis with a periappendicular abscess. An appendectomy was performed. In conclusion, as surgeons, we must always take into consideration that acute appendicitis can represent a cause of intestinal obstruction, especially in elderly patients.

Chitosan and Cyclodextrins-Versatile Materials Used to Create Drug Delivery Systems for Gastrointestinal Cancers.

Gastrointestinal cancers are characterized by a frequent incidence, a high number of associated deaths, and a tremendous burden on the medical system and patients worldwide. As conventional chemotherapeutic drugs face numerous limitations, researchers started to investigate better alternatives for extending drug efficacy and limiting adverse effects. A remarkably increasing interest has been addressed to chitosan and cyclodextrins, two highly versatile natural carbohydrate materials endowed with unique physicochemical properties. In this respect, numerous studies reported on fabricating various chitosan and cyclodextrin-based formulations that enabled prolonged circulation times, improved cellular internalization of carried drugs, preferential uptake by the targeted cells, reduced side effects, enhanced apoptosis rates, and increased tumor suppression rates. Therefore, this paper aims to briefly present the advantageous properties of these oligo- and polysaccharides for designing drug delivery systems, further focusing the discussion on nanocarrier systems based on chitosan/cyclodextrins for treating different gastrointestinal cancers. Specifically, there are reviewed studies describing promising solutions for colorectal, liver, gastric, pancreatic, and other types of cancers of the digestive system towards creating an updated framework of what concerns anticancer chitosan/cyclodextrin-based drug delivery systems.

Intrahepatic Cholangiocarcinoma - Where Do We Stand Today? Literature Review.

Intrahepatic cholangiocarcinomas represent rare and aggressive malignancies developing from the second order bile ducts to the smaller biliary branches. The aim of this narrative review is to discuss about the main diagnostic and therapeutic challenges in order to help medical and surgical oncologists to gain familiarity in regard to this subject. Articles discussing about epidemiology, histology, diagnostic, perioperative management and surgery which were published from January 2000 to September 2023 included in Cochrane Library, PubMed, Embase, MedLine, Web of Science, Elsevier, Google Scholar databases were reviewed. Articles reviewed in the current paper came to demonstrate that the main problem in such cases is related to the fact that most cases remain asymptomatic for a long period of time and therefore are diagnosed in advanced stages of the disease when curative procedures are feasible after performing extended visceral sacrifice or even worse, are no longer possible; however, the most efficient therapeutic strategy in order to improve the long term outcomes remains radical surgery. In this respect, attention was focused on improving the accuracy of the diagnostic tools and on identifying non-surgical therapeutic options which might increase the chances of achieving complete resection. Intrahepatic cholangiocarcinoma represent rare aggressive tumors with poor outcomes especially if radical surgery is not feasible.

Prediction and Management of Surgical Site Infections in Hybrid Vascular Surgery for Peripheral Artery Disease.

OBJECTIVES: Postoperative complications are an important problem that all surgeons face. Among all possible complications, local and systemic infections are one of the most prevalent postprocedural adverse events. It is difficult to assess whether or not a patient will develop a surgical site infection (SSI), but there are certain basic investigations that can suggest the probability of such an event. We also investigated some clinically assessable signs to help us better predict the occurrence of SSIs. Every bit of information brings us closer to an ideal where we can bring postoperative complications to a minimum. Close examination and attention to detail is crucial in the prediction and prevention of SSIs. Methods: A multicenter, retrospective and prospective observational study was carried out between 01.01.2019 â?" 01.09.2021. All adult patients with peripheral artery disease (PAD) who had disabling intermittent claudication or rest pain, were included in this study. We excluded minor or vascular surgery emergencies (ruptured aneurysms, acute ischemia or vascular trauma). We followed the postoperative complications as well as their management with an emphasis on surgical site infections (SSIs). Receiver Operating Characteristic (ROC) curves were used to determine key values of statistical relevance by calculating the Area Under the Curve (AUC). Multivariate analysis was used to assess the statistical relevance of our data. Results: The study evaluates 128 patients diagnosed with PAD, aged between 47 and 97, with a mean age of 71.26 Ã+- 10.8 years. There were significantly more male than female patients 71.09% vs. 28.91% (p 0.01). All patients were treated using hybrid vascular techniques. All complication rates were recorded but we focused on SSIs, which was the most prevalent complication (25%). C-Reactive Protein with values higher than 5 mg/dl, was confirmed as a positive predictive factor for postoperative surgical site infections (AUC = 0.80). Another positive predictive factor for SSIs is hyperglycemia. Glycemic values higher than 140mg/dl are more frequently associated with postoperative infections (p = 0.02), a predictability curve of statistical significance was also obtained (AUC = 0.71). Postoperative SSIs were more prevalent in patients with preoperative distal trophic lesions (p 0.01). The presence of other complications such as edema and lymphoceles were also linked to SSIs (p 0.01). Nevertheless, patients who underwent surgery over negative wound pressure therapy (NWPT) for infection management had significantly shorter hospital stays (p 0.01). Conclusions: There are multiple clinical or paraclinical predictors of SSIs. The coexistence of several such factors can carry an additional risk of developing a SSI and should be evaluated and controlled separately in the preoperative phase as much as possible. Admission to a diabetes center and regulation of glycemic values prior to elective vascular surgery, for patients who can be surgically postponed is an effective method of preventing infections. Surgical management remains the most reliable form of treatment of SSIs, being the most efficient therapy and offering immediate results, while simultaneously shortening hospital stays.

Gut Microbiome Changes in Gestational Diabetes.

Gestational diabetes mellitus (GDM), one of the most common endocrine pathologies during pregnancy, is defined as any degree of glucose intolerance with onset or first discovery in the perinatal period. Physiological changes that occur in pregnant women can lead to inflammation, which promotes insulin resistance. In the general context of worldwide increasing obesity in young females of reproductive age, GDM follows the same ascending trend. Changes in the intestinal microbiome play a decisive role in obesity and the development of insulin resistance and chronic inflammation, especially in patients with type 2 diabetes mellitus (T2D). To date, various studies have also associated intestinal dysbiosis with metabolic changes in women with GDM. Although host metabolism in women with GDM has not been fully elucidated, it is of particular importance to analyze the available data and to discuss the actual knowledge regarding microbiome changes with potential impact on the health of pregnant women and newborns. We analyzed peer-reviewed journal articles available in online databases in order to summarize the most recent findings regarding how variations in diet and metabolic status of GDM patients can contribute to alteration of the gut microbiome, in the same way that changes of the gut microbiota can lead to GDM. The most frequently observed alteration in the microbiome of patients with GDM was either an increase of the Firmicutes phylum, respectively, or a decrease of the Bacteroidetes and Actinobacteria phyla. Gut dysbiosis was still present postpartum and can impact the development of the newborn, as shown in several studies. In the evolution of GDM, probiotic supplementation and regular physical activity have the strongest evidence of proper blood glucose control, favoring fetal development and a healthy outcome for the postpartum period. The current review aims to summarize and discuss the most recent findings regarding the correlation between GDM and dysbiosis, and current and future methods for prevention and treatment (lifestyle changes, pre- and probiotics administration). To conclude, by highlighting the role of the gut microbiota, one can change perspectives about the development and progression of GDM and open up new avenues for the development of innovative therapeutic targets in this disease.

Focus on PD-1/PD-L1 as a Therapeutic Target in Ovarian Cancer.

Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a high number of intra tumor infiltrating lymphocytes (TILs). Therefore, immunomodulation is considered to have an important role in cancer treatment, and immune checkpoint inhibitors may be useful for restoring T cell-mediated antitumor immunity. However, the data presented in the literature until now are not sufficient to allow for the identification and selection of patients who really respond to immunotherapy among those with ovarian cancer. Although there are some studies with favorable results, more prospective trials are needed in this sense. This review focuses on the current and future perspectives of PD-1/L1 blockade in ovarian cancer and analyzes the most important immune checkpoint inhibitors used, with the aim of achieving optimal clinical outcomes. Future studies and trials are needed to maximize the efficacy of immune checkpoint blockade therapy in ovarian cancer, as well as in all cancers, in general.

Emergency Surgery for Small Bowel Hemangioma. A review of the literature.

Background: Hemangiomas of the small intestine are tumors rarely found in practice. Patients usually present in emergency settings with anemia, gastrointestinal bleeding or abdominal pain. The purpose of this review of the literature is to evaluate the diagnostic modalities, therapeutic options and their results in cases of intestinal hemangiomas. Methods: This is a review of the recent literature concerning intestinal hemangioma with bleeding in the last five years including one case from our institution. Search criteria were defined using MeSH terms. The descriptive analysis was performed accordingly. Results: In the last five years there was a total of 24 cases ours being the 25th with a predominance of male patients (20 cases). Literature search found a low threshold for preoperative diagnostic (only in 28% of the cases). More than half of the tumors were in the ileum. Surgery is the main therapeutic option (in 88% of the cases). Nonsurgical treatment (endoscopic or radiological) can rarely be employed successfully. Conclusions: Surgery is the main treatment for larger hemangiomas while for smaller ones nonsurgical treatment methods are available.

Polytrauma: The European Paradigm.

This review of the literature aims to describe the main advantages and disadvantages of the trauma systems in Europe. Moreover, the purpose of this article is to present the last concepts regarding the management of the polytrauma patients and the newest sets of measures to prevent car crashes in European Union. The articles published regarding the management of the polytrauma patient and trauma systems were identified using PubMed search. Optimal management of major polytrauma requires a national trauma system which should detail every level of organization from the trauma centers to the every member of the trauma team. European trauma systems varies a lot depending on the country and the specialized trauma surgery training programs are more advanced in countries with complex trauma systems. Introducing road safety performance indicators for trauma management decreased the rate of deaths by car crashes in Europe.

Vulvar and Vaginal Melanomas-The Darker Shades of Gynecological Cancers.

Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect.

Use of a Tumor Bed Boost in the Radiotherapy after Oncoplastic Breast Conserving Surgery.

AIM OF THE STUDY: Use of a radiotherapy (RT) tumor bed boost in addition to whole breast irradiation (WBI) after oncoplastic breast conserving surgery (OBCS) can be very challenging due to the massive tissue displacements. The aim of our study is to present relevant RT data regarding the use of a boost RT in patients who underwent OBCS and received adjuvant RT at Neolife Medical Center Bucharest. Materials and Methods: 12 patients treated with intensity modulated radiotherapy (IMRT), after OBCS, using conventional or hypofractionated schedules, between 10/2018 and 12/2020 were included in the study. Pre- and postoperative CT images and surgical clips when available were used for tumor bed (TB) localization and definition of the boost volume. Results: One or more risk factors associated with local recurrence (age under 51 years, high grade tumors, associated ductal carcinoma in situ) were present in 10 patients. Boost RT was delivered in 3 patients. Conclusions: TB localization for the boost RT is difficult without an appropriate marking. Surgical clips and communication between the surgeon and the radiation oncologist are essential for treatment success.