Indocyanine Green Tattooing During Colonoscopy as a Guide to Laparoscopic Colorectal Cancer Surgery: A Literature Review.

BACKGROUND: Endoscopic tattooing of colorectal lesions has been performed employing several markers. The indocyanine green (ICG) that uses near infrared fluorescence technology, has been recently adopted in laparoscopic colorectal cancer surgery. This study aims to systematically review the international literature to validate the ICG in laparoscopic colorectal surgery, in order to include the ICG in the therapeutic protocol. METHODS: Following AMSTAR 2 criteria, we performed a systematic review to evaluate the use of green indocyanine as a marker for preoperative endoscopic tattooing and for lymph nodes mapping. The study selection was conducted using the PubMed database from January 1989 to July 2022. RESULTS: We identified 25 eligible studies. 13 based on fluorescent tumor localization in laparoscopic colorectal surgery using ICG while 12 of them reported the lymphatic road mapping and sentinel node identification by ICG using a near-infrared camera system. One study analyzed both topics. CONCLUSIONS: In laparoscopic colorectal cancer surgery indocyanine green can be used to localize fluorescent tumors and mapping fluorescence lymph node. The use of ICG appears to be a valid and safe technique that helps the surgeon to achieve a better oncological radicality. However, the protocols need to be clarified by further studies.

Sizzling Fat-Curative Endoscopic Resection of a Giant Lipoma Causing Colo-Colic Intussusception.

Giant colonic lipomas, tumors that infrequently occur in the gastrointestinal tract, can manifest as bleeding, abdominal pain and, in few cases, obstruction with intussusception. Surgery is usually the treatment of choice. We report the case of a 78 years-old woman with abdominal pain, constipation, and bleeding due to a giant lipoma of the sigmoid colon causing intussusception. After an initial diagnostic colonoscopy, the patient underwent an endoscopic mucosal resection (EMR) without complications. Even if surgery is traditionally the primary therapeutic approach for giant colonic lipomas, selected cases can be successfully treated with EMR.

Pesky Pesce: A Forgettable Fish Dinner with a Late Surprise, a Perianal Abscess.

Clinical presentation after ingestion of foreign body is a common finding in surgical practice. Perianal sepsis due to a foreign body is, usually, secondary to introduction via the trans-anal route. The case here reported is extremely rare since an ingested fishbone passed asymptomatically through most of the gastrointestinal tract, with resultant late-onset ischiorectal abscess. Moreover, clinical evidence of the perianal abscess manifested one month after the fishbone had been ingested. The final localization of the fishbone-lying anterior to the sacrum-complicated the preoperative and intraoperative detection of the ingested foreign body.

Thyroid diseases and skin autoimmunity.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Nodular thyroid disease in the elderly: novel molecular approaches for the diagnosis of malignancy.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

Management of concomitant hyperparathyroidism and thyroid diseases in the elderly patients: a retrospective cohort study.

BACKGROUND: Thyroid disease and hyperparathyroidism are the most common endocrine disorders. The incidence of thyroid disease in patients with hyperparathyroidism ranges in the different series from 17 to 84%, and thyroid cancer occurs with an incidence ranging from 2 to 15%. AIM: The aim of our study was to analyze the management of elderly patients with concomitant thyroid and parathyroid disease in order to define the best surgical therapeutic strategy and avoid reoperations associated with a higher risk of complications. METHODS: All consecutive patients (64 patients, age range 60-75 years), undergoing surgery for hyperparathyroidism, from January 2011 to June 2014, were retrospectively evaluated. Enrolled patients were divided into two study groups of patients affected by hyperparathyroidism with or without a concomitant thyroid disease. RESULTS: Out of 64 patients enrolled in our study (24 men, age range 60-75 years), affected by hyperparathyroidism, 34 had an associated thyroid disease and were treated with total thyroidectomy and parathyroidectomy. The group, who underwent parathyroidectomy associated with thyroidectomy, had no greater complications than the group receiving only parathyroidectomy. CONCLUSIONS: Thyroid disease must be excluded in patients affected by hyperparathyroidism. It is difficult to determine whether hyperparathyroidism can be considered a risk factor for thyroid disease, but an accurate preoperative study is essential for a surgery able to treat both thyroid and parathyroid disease. In this way, we avoid the elderly patient, with associated morbidity and increased surgical risk, to undergo a reoperation for thyroid disease, burdened with major complications.

The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer.

Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.

Transperineal excision of malignant peripheral nerve sheath tumors of the ischiorectal fossa: Case report of a rare tumor in a frequently forgotten anatomical region.

INTRODUCTION AND IMPORTANCE: Malignant peripheral nerve sheath tumor is an aggressive tumor that arises from peripheral nerves. Frequently associated with neurofibromatosis, its common localization is in the extremities, trunk (with paravertebral regions), neck and head. Some cases have been found in the pelvis or uterus. In this case report we illustrate one of the rarest localization of this type of tumor in the ischiorectal fossa, with the full recovery of the patient after surgical excision and radiotherapy. CASE PRESENTATION: A 61-year-old woman showed a lump near the anus which was initially diagnosed as a lipoma of the right ischiorectal fossa, by Computed Tomography scan. The tumor was completely removed with a minimal skin incision, and the patient had a complete recovery. Only the pathological examination determined the diagnosis of malignant peripheral nerve sheath tumor, in this unusual localization. In consideration of its high aggressiveness the patient underwent radiotherapy. After more than two years of follow-up there is no sign of recurrence. DISCUSSION: In sites far from branches of nerves, malignant peripheral nerve sheath tumors can be considered episodic. Ischiorectal fossa is a rare localization, and the differential diagnosis from benign mesenchymal cell tumors can be challenging. When possible, a biopsy should be performed before surgery. CONCLUSION: Surgical excision of tumors in ischiorectal fossa should be always complete, in consideration of possible histological surprise.

Perirectal hematoma after stapled surgery for hemorrhoidal prolapse and obstructed defecation syndrome: case series management to avoid panic-guided treatment.

Perirectal hematoma (PH) is one of the most feared complications of stapling procedures. Literature reviews have reported only a few works on PH, most of them describing isolated treatment approaches and severe outcomes. The aim of this study was to analyze a homogenous case series of PH and to define a treatment algorithm for huge postoperative PHs. A retrospective analysis of a prospective database of three high-volume proctology units was performed between 2008 and 2018, and all PH cases were analyzed. In all, 3058 patients underwent stapling procedures for hemorrhoidal disease or obstructed defecation syndrome with internal prolapse. Among these, 14 (0.46%) large PH cases were reported, and 12 of these hematomas were stable and treated conservatively (antibiotics and CT/laboratory test monitoring); most of them were resolved with spontaneous drainage. Two patients with progressive PH (signs of active bleeding and peritonism) were submitted to CT and arteriography to evaluate the source of bleeding, which was subsequently closed by embolization. This approach helped ensure that no patients with PH were referred for major abdominal surgery. Most PH cases are stable and treatable with a conservative approach, evolving with self-drainage. Progressive hematomas are rare and should undergo angiography with embolization to minimize the possibility of major surgery and severe complications.

Stapled and conventional Milligan-Morgan haemorrhoidectomy: different solutions for different targets.

PURPOSE: Haemorrhoidal disease is one of the most common anorectal disorders. The aim of this study is to compare the results, over the last 10 years, of stapled haemorrhoidopexy (SH) with those of standard Milligan-Morgan haemorrhoidectomy (M&M). Furthermore, we discuss the proper indications for each technique in terms of the lowest rate of complications and long-term results. METHODS: Three hundred forty-three patients with different degrees of symptomatic haemorrhoids underwent SH or M&M from January 2005 to December 2007. Patients were divided into two groups, age and sex matched. The administration of painkillers drugs, antibiotics and laxatives, complication symptoms and hospital stay in all the patients were recorded after surgical treatment. RESULTS: The mean operative time was shorter in the stapled group compared to that in the open group (31 min versus 40 min). Postoperative pain, hospital stay and return to full activity were shorter in the stapled group. There was a significant difference in the wound healing time between the two groups. We noticed a higher rate of recurrence in patients treated with stapled haemorrhoidectomy for fourth-degree haemorrhoids. CONCLUSIONS: According to our experience, the Longo technique is indicated for the treatment of haemorrhoids of second- and third degree. In the latter grades of prolapse, the Milligan-Morgan haemorrhoidectomy can also be applied with good outcomes. We believe that, in case of irreducible prolapse, the M&M is to be preferred. However, operative management varies according to surgeon's interest and is tailored to meet the individual patient's need.

Mesenchymal Stem Cells for Cryptoglandular Anal Fistula: Current State of Art.

Anal fistula is a common disease that needs surgical treatment to be resolved. Despite a variety of surgical options, the major problem is still to cure complex fistulas without any recurrence in the long-term follow-up but, at the same time, to avoid an impairment of continence. In recent years, one solution has been the application of mesenchymal stem cells derived from adipose tissue, especially in association with other treatments, such as the use of fibrin glue or the previous application of a seton. Their initial use in fistulas associated with Crohn's disease has shown encouraging results. In this non-systematic review our aim is to analyze the use in cryptoglandular fistulas: the rate of healing is not so high, and the number of studies is limited. Therefore, further randomized controlled trials are needed to establish their efficacy in the case of complex cryptoglandular anal fistulas and their possible complications.

SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity.

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable ß chain (TCRVß) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4+ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.

Clinical Effects of Oral Bacteriotherapy on Anal HPV Infection and Related Dysplasia in HIV-Positive MSM: Results from the "HPVinHIV" Trial.

BACKGROUND: Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men. METHODS: In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented. RESULTS: 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression (p = 0.002), lower rate of onset of new anal dysplasia (p = 0.023) and lower rates of worsening of persistent lesions (p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group (p = 0.067). CONCLUSION: Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

Expression and Clinical Utility of Transcription Factors Involved in Epithelial-Mesenchymal Transition during Thyroid Cancer Progression.

The transcription factors involved in epithelial-mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients' clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

A large Brunner's gland adenoma: an unusual cause of gastrointestinal bleeding. Case report and literature review.

Brunner's gland adenoma is a rare benign tumour of the duodenum. His most common location is the posterior wall of the duodenum near the junction of its first and second portion. It is usually small and asymptomatic often discovered incidentally with upper gastrointestinal endoscopy, but sometimes may become large causing symptoms (haemorrhage or intestinal obstruction). We report a rare case of a very large Brunner's gland adenoma in a 38-year-old female presenting with severe anaemia but without obstructive symptoms and detected by ultrasonography. The tumour was managed by surgical removal and during a six month follow-up the patient remained symptom-free without any recurrence. The literature on Brunner's gland adenoma is reviewed.

CD28 Autonomous Signaling Orchestrates IL-22 Expression and IL-22-Regulated Epithelial Barrier Functions in Human T Lymphocytes.

IL-22 is a member of the IL-10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL-22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. Here we characterized the role of CD28 autonomous signaling in regulating IL-22 expression in human CD4+ T cells. We show that CD28 stimulation in the absence of TCR strongly up-regulates IL-22 gene expression and secretion. As recently observed for IL-17A, we also found that CD28-mediated regulation of IL-22 transcription requires the cooperative activities of both IL-6-activated STAT3 and RelA/NF-κB transcription factors. CD28-mediated IL-22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28-associated class 1A phosphatidylinositol 3-kinase (PI3K) as a pivotal mediator of CD28-mediated IL-22 expression and IL-22-dependent epithelial cell barrier functions.

CD28 Individual Signaling Up-regulates Human IL-17A Expression by Promoting the Recruitment of RelA/NF-κB and STAT3 Transcription Factors on the Proximal Promoter.

CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, multiple sclerosis, and type 1 diabetes patients. Due to the relevance of IL-17A in the pathophysiology of several inflammatory and autoimmune diseases, we characterized the mechanisms and signaling mediators responsible for CD28-induced IL-17A expression. Here we show that CD28-mediated up-regulation of IL-17A gene expression depends on RelA/NF-κB and IL-6-associated STAT3 transcriptions factors. In particular, we found that CD28-activated RelA/NF-κB induces the expression of IL-6 that, in a positive feedback loop, mediates the activation and nuclear translocation of tyrosine phosphorylated STAT3 (pSTAT3). pSTAT3 in turn cooperates with RelA/NF-κB by binding specific sequences within the proximal promoter of human IL-17A gene, thus inducing its expression. Finally, by using specific inhibitory drugs, we also identified class 1A phosphatidylinositol 3-kinase (PI3K) as a critical upstream regulator of CD28-mediated RelA/NF-κB and STAT3 recruitments and trans-activation of IL-17A promoter. Our findings reveal a novel mechanism by which human CD28 may amplify IL-17A expression in human T lymphocytes and provide biological bases for immunotherapeutic approaches targeting CD28-associated class 1A PI3K to dampen IL-17A-mediated inflammatory response in autoimmune/inflammatory disorders.

Laparoscopic diagnosis and treatment of diaphragmatic Morgagni hernia. Case report and review of the literature.

BACKGROUND: Morgagni's hernia is a rare and congenital type of diaphragmatic hernia. The majority of these are asymptomatic and diagnosed incidentally during evaluation or treatment for other conditions. When diagnosis is made surgery is mandatory. The Authors report the laparoscopic repair of small Morgagni hernia, followed by review of the literature. MATERIALS AND METHODS: A case of 55-year-old woman complaining a sensation of tightness in her chest, but especially an oppressive epigastric pain with episodes of fainting fit and breathless is described. The definitive diagnosis was confirmed by laparoscopy. The hernia was repaired laparoscopically using a mesh fixed by hernia stapler after excision of the sac. RESULTS: In the postoperative patients has presented an episode of heart condition due to pericarditis treated pharmacologically. The patient was discharged on the seventh postoperative day symptom-free. CONCLUSIONS: Laparoscopic technique must be considered as a first line approach for the treatment of Morgagni hernia, easy and safe by carry out. We recommend do not excise hernia sac, even if small, and particular cure in the use of the mesh fixed by metal staples.

CTLA-4 and PD-1 Ligand Gene Expression in Epithelial Thyroid Cancers.

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80, and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.

[Thyreopathy associated with vagus schwannoma]. / Tireopatia associata a schwannoma del vago.

We report the case of a young woman who underwent total thyroidectomy for a suspect nodular thyreopathy and occasionally happened to be affected simultaneously by vagus nerve schwannoma. Symptomatology is discussed and we propose a review of the literature about this non frequent pathology and discuss the latest diagnostic procedures and surgical indications and treatment.