Histology for nephrology, from pre-implantation to post-transplant kidney biopsy. Lesson learned from ReBIrth (Renal BIopsy for Kidney Transplantation Therapy).

A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31st, 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management.

Hypothermic Machine Perfusion and Spontaneous Kidney Allograft Rupture: Causation or Correlation? A Case Report and Review of Pertinent Literature.

BACKGROUND: Spontaneous kidney allograft rupture (KAR) is a severe complication of kidney transplant. KAR occurs when no identifiable injuries noted at the time of the organ retrieval are present. KAR is associated with acute rejection, renal vein thrombosis, severe acute tubular necrosis, or trauma. In recent years, the introduction of hypothermic machine perfusion (HMP) has provided an excellent option for kidney allograft preservation reducing the incidence of delayed graft function. On the other hand, HMP can also represent a potentially traumatic event for a fragile graft, especially one belonging to expanded criteria donor. CASE PRESENTATION: Here, to our knowledge, we report the first case of KAR after the use of HMP, which occurred in 60-year-old women undergoing a single kidney transplant from a donation after brain death donor belonging to the expanded criteria donor category. The allograft was perfused for 240 minutes with HMP with passive oxygenation. The post-transplant course was unremarkable with early graft function, but on post operatory day 14 the patient complained of severe pain over the transplant site. A computed tomography scan showed a massive fluid collection in the perigraft region. Immediate surgical exploration showed 2 lacerations of 10 cm and 5 cm length at the upper and midpole of the kidney, requiring transplantectomy. Histologically, the graft did not show features of acute rejection. CONCLUSIONS: In the presented case, the repair and salvage of the kidney allograft was not possible. However, the review of the pertinent literature does not report another case linking HMP to KAR.

Oncofertility and Reproductive Counseling in Patients with Breast Cancer: A Retrospective Study.

INTRODUCTION: Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects induced by anticancer treatments. Fertility preservation and family planning are therefore crucial issues to be addressed in all cancer patients of reproductive age. Along those lines, a new branch of medicine with distinct multidisciplinary characteristics has developed over the years: oncofertility. Although both national and international guidelines value reproductive counseling as an essential aspect of the diagnostic-therapeutic pathway, part and parcel of the informed consent process, it is not included within the protocols adopted by the operating units for the care and management of neoplastic diseases. OBJECTIVE: This study aimed to evaluate the activity of the Breast Unit of the Policlinico Umberto I Hospital, Rome, Italy, and the degree of compliance with guidelines. By knowing the strengths and weaknesses of such approaches, the standards of care offered to breast cancer patients can be improved. MATERIALS AND METHODS: A retrospective study based on a review of medical records was conducted between 2014 and 2021. Patients under 40 years of age diagnosed with non-metastatic malignancies were included who received chemotherapy treatment, namely neoadjuvant, adjuvant or adjuvant hormone therapy. RESULTS: The data were extracted from the medical records of 51 patients who met the inclusion criteria, 41% of whom received reproductive counseling, and of these, 43% decided to undertake a path of fertility preservation. Factors such as the absence of children and young age reportedly favored both the interest in counseling proposals by the medical staff and the decision to undertake a path of fertility preservation. CONCLUSIONS: The study shows that there has been growing interest in the topic of oncofertility, especially in light of law 219/2017. Therefore, since 2018, multiple proposals for reproductive counseling have been set forth, but there was not an equally growing demand for fertility preservation practices, which can be explained by the invasive nature of such practices, the patients' concern about their own state of health, and poor or inadequate information. Such impediments highlight the importance of standardized counseling and the need for a multidisciplinary medical team to support the patient in the decision-making process. The study also revealed a drop in the number of patients receiving counseling due to the COVID-19 pandemic, contrary to the positive trend that was recorded prior to the pandemic.

Longitudinal monitoring of mRNA levels of regulatory T cell biomarkers by using non-invasive strategies to predict outcome in renal transplantation.

BACKGROUND: Acute T-cell mediated rejection (aTCMR) is still an issue in kidney transplantation, for it is associated with chronic rejection, graft loss, and overall worse outcomes. For these reasons, a standard non-invasive molecular tool to detect is desirable to offer a simpler monitoring of kidney transplant recipients (KTRs). The purpose of our study was to examine, in peripheral blood before and after transplantation, the expression patterns of regulatory T cell (Treg)-related genes: the forkhead box P3 (FOXP3) and the two CTLA-4 isoforms (full-length and soluble) to predict acute rejection onset, de novo donor-specific antibodies (DSA) development and renal dysfunction 1 year after transplantation. METHODS: We profiled by using a relative quantification analysis (qRT-PCR) circulating mRNA levels of these biomarkers in peripheral blood of 89 KTRs within the first post-transplant year (at baseline and 15, 60 and 365 days, and when possible at the acute rejection) and compared also the results with 24 healthy controls. RESULTS: The three mRNA levels drastically reduced 15 days after transplantation and gradually recovered at 1 year in comparison with baseline, with very low levels at the time of aTCMR for FOXP3 (RQ = 0.445, IQR = 0.086-1.264, p = 0.040), maybe for the pro-apoptotic role of FOXP3 during inflammation. A multivariate Cox regression analysis evidenced a significant relation between aTCMR onset and thymoglobuline induction (HR = 6.749 p = 0.041), everolimus use (HR = 7.017, p = 0.007) and an increased risk from the solCTLA-4 expression at 15 days, mainly considering recipients treated with Mycophelolic acid (HR = 13.94 p = 0.038, 95%CI:1.157-167.87). Besides, solCTLA-4 also predisposed to graft dysfunction (eGFR< 60 mL/min/1.73m2) at 1 year (AOR = 3.683, 95%CI = 1.145-11.845, p = 0.029). On the other hand, pre-transplant solCTLA-4 levels showed a protective association with de novo DSAs development (HR = 0.189, 95%CI = 0.078-0.459, p < 0.001). CONCLUSIONS: mRNA levels of Treg-associated genes, mainly for solCTLA-4, in peripheral blood could put forward as candidate non-invasive biomarkers of cellular and humoral alloreactivity in clinical transplantation and might help shape immunosuppression, tailor monitoring and achieve better long-term outcomes of kidney transplantation in the wake of "precision medicine".

Early-Isolated V Lesion in Kidney Allograft: Acute Rejection or Ischemic Injury? A Case Report of Primary Nonfunction and Graft Loss.

Intimal arteritis (v-lesion) is a negative prognostic factor for kidney allograft survival. Early isolated v-lesions do not always represent a pathologic marker of acute T cell- or antibody-mediated rejection. In particular, in the case of transplant negative for C4d and donor-specific antibodies, such a finding can suggest an ischemic-reperfusion injury. There is an intense debate in the literature concerning the origin of this histologic feature. In the present study, we analyze how this argument can have a clinical relevance. Here we report a case of a 61-year-old woman with end-stage renal disease due to autosomal dominant polycystic kidney disease. The patient underwent kidney transplant from expanded criteria donor. Organs from expanded criteria donors are more prone to ischemic-reperfusion injury. Postoperative course was characterized by primary nonfunction of the graft. A first biopsy showed early isolated v-lesion in otherwise normal renal parenchymal. Simultaneously, a computed tomography scan revealed stenosis of the main renal artery. An endovascular stent was placed. Despite improved vascularization of the graft, no clinical response was observed and the patient remained anuric. A second biopsy was performed, showing T-cell mediated rejection (Banff Classification 1A). Despite pulse steroid, the patient lost the graft.

Transplant Renal Artery Stenosis: A Case Report of Functional Recovery Six Months After Angioplasty.

Transplant renal artery stenosis (TRAS) is a common vascular complication after kidney transplantation, leading to worsening or refractory hypertension, deterioration in renal function, and possible cause of graft loss. Early diagnosis and an appropriate treatment are crucial for organ preservation. Endovascular treatment, including percutaneous transluminal angioplasty and stent implantation, is considered the first-line therapy for TRAS. Here we report the case of a 69-year-old woman with end-stage renal disease for chronic kidney disease not biopsy proven, who underwent a kidney transplant from expanded criteria donors on December 2018. Postoperative course was characterized by delayed graft function. Doppler ultrasonography (US) showed an increase of peak systolic velocity at the origin of the renal artery, and parvus-tardus waveform in periferic graft arteries and an abdominal computed tomography scan confirmed a stenosis at the origin of the main renal artery (TRAS). The patient underwent a percutaneous transluminal angioplasty. It was not possible to place a stent at the particular location of the stenosis at the anastomosis. Despite the improvement of the graft's perfusion, monitored with Doppler US, the patient showed a very poor improvement in renal function and remained on hemodialysis for months. A percutaneous needle biopsy reported a normal renal parenchyma and excluded acute rejection. During this period, the patient received immunosuppressive therapy. About 6 months after the transplant, the patient had an unexpected and slow renal function recovery until she was weaned completely from hemodialysis.

Primary malignant melanoma of the bowel diagnosed following a bowel intussusception in an adult patient. A case report and review of the literatureport.

AIM: Primary small bowel melanoma is a very rare clinical entity with a paucity of publications in literature. Most cases of gastrointestinal melanomas are metastatic lesions arising generally from primary lesion of the skin, eyes, or anus. We present a case of a small bowel intussusception with primary malignant melanoma as lead point and a gluteal melanoma metastasis after four years free from disease. CASE REPORT: A 77-year-old female has come to our attention with signs and symptoms of intestinal occlusion. She was subjected to a computerized tomography (CT) of the abdomen and pelvis that revealed small bowel intussusception caused by intestinal polypoid lesion. She was treated with a bowel resection. The histological exam has shown the presence of an amelanocytic malignant melanoma. The examination of skin, eyes, esophagus, colon and anus, a tot al body contrast- enhanced CT and a bone scintigraphy were negative for primary melanoma. So, the final diagnosis was primary melanoma of the ileum. After four-years disease-free survival, the patient came back to our attention for a gluteal melanoma metastasis, that was surgically removed. Afterwards she started immunotherapy, that is still ongoing. DISCUSSION AND CONCLUSION: The diagnosis and the treatment of primary intestinal melanoma is a challenging due to the lack of scientific indications. Our case shows how an early diagnosis, although accidental, can offer a good survival free from disease. Moreover, a careful follow-up of our patients allows us to promptly identify neoplasm recurrence or distant metastasis that can be treated with surgery and systematic therapy. KEY WORDS: Intussusception, Primary bowel melanoma.

Follow-up and Management of Kidney Transplant Recipients During the COVID-19 Lockdown: The Experience of an Italian Transplant Center, Including Two Cases of COVID-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new infectious disease that emerged in China in late 2019 and is now spreading around the world. Social distancing measures were needed to reduce transmission, and lockdown included restricted access to health care facilities. The impact of COVID-19 on transplant recipients is unknown, but considering their immunosuppression status and associated comorbidities, they should be considered a high-risk population. METHODS: A kidney transplant center in Central Italy implemented a strategy to maintain follow-up of kidney transplant recipients by phone and e-mail during lockdown. Telephone interviews were used to administer a clinical questionnaire to patients, and e-mail was used to receive the results of diagnostic tests conducted in outpatient settings. RESULTS: From March 17 to April 23, 2020, a total of 143 kidney transplant recipients were contacted. Twenty-eight patients needed in-hospital consultation for problems unrelated to COVID-19, 3 of whom needed hospitalization. Eleven patients were managed at home for mild urinary or respiratory diseases, and 1 was referred to the hematologist. We identified 2 suspected cases of COVID-19 infection, and the patients were referred to hospital care. Immunosuppressive therapy was modulated, and intravenous corticosteroids and potentially effective antiviral therapy were administered with a favorable outcome. CONCLUSIONS: In the context of a lockdown, such as that occurring in response to COVID-19, we suggest implementing remote surveillance programs in kidney transplant recipients with the help of any available technology and offering medical consulting and logistic support as needed.

Standard stapled transanal rectal resection versus stapled transanal rectal resection with one high-volume stapler to prevent complications in the elderly.

BACKGROUND: The causes of obstructed defecation syndrome (ODS) can actually be either functional or mechanical (primary or secondary deficit of the sensitivity, slow bowel transit, pelvic floor dyssynergia, internal and external rectal prolapse, recto-anal intussusceptions, anterior or posterior rectocele and pelvic prolapse of the bladder, uterus, bowel or sigma). The aim of our study was to evaluate the safety, efficacy and feasibility of stapled transanal rectal resection (STARR) procedure performed by a single or double stapler through clinical and functional outcomes for transanal stapled surgery. METHODS: From January 2016 to October 2017, ninety patients with ODS secondary to rectal prolapse, anal-rectal intussusception and anterior rectocele, that underwent to a STARR procedure were enrolled. Thirty of these underwent a STARR procedure with double circular stapler PPH-01 (Group A); 30 with single circular stapler CPH34HV with a purse string suture (Group B); and 30 with single circular stapler CPH34HV with a "parachute technique" (Group C). All patients were selected with clinical examination, Wexner score for fecal incontinence and ODS score for constipation. Patients also underwent a Defeco RMN for an anatomical and dynamic evaluation of the pelvic floor. RESULTS: No recurrence rates were observed in the three groups. The mean operative time was 46.3 minutes in group A; 34.5 minutes in group B; and 37.6 minutes in Group C. The volume of the resected specimen was 17 mL in group A; 15 mL in group B; and 16 mL in Group C. Complications were bleeding (3.3% in group A); fecal urgency (6.6% in group A, 10% in group B and 3.3% in group C); rectal hematoma (3.3% in group A). all symptoms significantly improved after the operation without differences between groups. CONCLUSIONS: The STARR technique performed with a single stapler CPH34HV is safe, faster and less expensive than the STARR performed by a double PPH01. Besides, with the parachute technique, it is possible to resect asymmetric prolapses.

Cancer stem cells as functional biomarkers.

According to the American Association of Cancer Research (AACR), a Cancer Stem Cell is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that constitutes the tumor [1]. Cancer Stem Cells (CSCs) are involved in the metastatic process, in the resistance to therapeutic treatments of many types of human cancers and consequently in the onset of recurrences. Numerous translational studies have been conducted to understand CSC characteristics and evaluate association between CSC-related biomarkers and clinical outcomes. The CSC theory can explain also a tumor relapse after that a tumor has been completely surgically removed (R0 macroscopical zero residual resection) or after an apparently complete response to chemotherapy. CSCs, in fact, showed a marked ability to reduce intracellular accumulation of chemotherapic agents by active drug extrusion, increased chemoresistance and survival, as well as elevated membrane transporter activity. In addition, it is possible that these cancer stem cells may nest in the "secured" (niche) sites of our body, where they may remain undisturbed for a long time, even years, until a stimulus arrives to awaken them, causing the disease to resume. CSCs, in fact, are able to use a variety of cellular pathways to survive to anticancer treatments. More recently CSCs have been described in several solid tumors, expressing specific biomarkers. Another field of research should be focused on the realization of diagnostic instruments to follow up patients after R0 surgical resection or after a complete response for an early detection and management of relapse and metastasis.

Total fistulectomy, sphincteroplasty and closure of the residual cavity for trans-sphincteric perianal fistula in the elderly patient.

BACKGROUND: Perianal fistula is a complex and frequent disease. At present, no treatment nor technique has shown an absolute superiority in terms of efficacy and recurrence rate. The technique has to be chosen considering the balance between faecal continence preservation and disease eradication. Rarely concomitant perianal abscess and fistula are treated at the same time, and often time to complete recovery is long. AIMS: The aim of this study was to evaluate the possibility of treating the abscess and the fistula tract in one procedure with total fistulectomy, sphincteroplasty and an almost complete closure of the residual cavity, thus reducing the healing time in older patients. METHODS: A non-randomized single-centre series of 86 patients from 2007 to 2012 with low-medium trans-sphincteric perianal fistula (< 30% of external sphincter involvement) with or without synchronous perianal abscess were treated with total fistulectomy, sphincteroplasty and closure of the residual cavity technique. RESULTS: Success rate was 97.7% with a healing time of 4 weeks; overall morbidity was 16.2%; recurrence rate was 2.3%; no major alterations of continence were observed. DISCUSSION: Fistulectomy, sphincteroplasty and closure of the residual cavity are associated with a low rate of recurrence and good faecal continence preservation in older patients. This technique can be safely used even with a concomitant perianal abscess, with reduction in healing time and in the number of surgical procedures needed. CONCLUSIONS: Total fistulectomy with sphincteroplasty and partial closure of the residual cavity, as described, is a safe procedure but has to be performed by dedicated colorectal surgeons.

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.

Use of the circular compression stapler and circular mechanical stapler in the end-to-side transanal colorectal anastomosis after left colon and rectal resections A single center experience.

AIM: The aim of our study was to compare the efficacy of the circular compression stapler and the circular mechanical stapler in transanal colorectal anastomosis after left colectomy or anterior rectal resection. MATERIALS AND METHODS: We performed a retrospective analysis of 10 patients with disease of the, sigmoid colon or rectum (carcinoma or diverticular disease) who underwent left colectomy or anterior rectal resection with end-to-side transanal colorectal anastomosis. A follow-up was planned for all patients at 1, 3 and 6 months after surgery and the anastomosis was evaluated by colonoscopy at 1 year. RESULTS: In all patients an end-to-side transanal colorectal anastomosis was performed using a circular compression stapler (CCS group) or circular mechanical staplers with titanium staples (CMS group). The mean distance of the anastomosis from the anal margin was 6.4 ± 1.5 cm in the CCS group and 18.2 ± 11.2 cm in the CMS group. All patients in the CCS group expelled the ring after a mean time of 8.2 postoperative days. At 12 months colonoscopy revealed that all CCS patients had a satisfactory anastomosis with mean size of the colic lumen at the level of anastomotic line of 26.3 mm. CONCLUSIONS: In our experience the circular compression stapler a valuable alternative to the circular mechanical stapler for the creation of transanal colorectal anastomosis, in line with the relevant literature. KEY WORDS: Anastomotic leakage, Anastomotic stenosis, Circular compression stapler, Circular mechanical stapler, Transanal colorectal anastomosis.

Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers.

BACKGROUND: The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. MATERIALS AND METHODS: The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. RESULTS: Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. CONCLUSIONS: The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

Chievitz' juxtaparotid organ, free from cancer.

INTRODUCTION: Up to the half of twentieth century, Chievitz organ was considered an embryonal organ, disappearing with growth. But Zenker, in 1953, demonstrated the existence of this organ in adult life, too4. REVIEW: In this article we review the embryology, the macroscopic and microscopic anatomy, the ultrastructure, the functional significance and the pathology of the Chievitz'Juxtaparotid Organ (CJO). The CJO is not a macroscopic apparent organ, but it looks like a nerve. The CJO takes connections with buccinator muscle, at the level of the parotid duct, and the medial pterygoid muscle. The cell parenchyma is enveloped by the connective tissue, that is divided into three layers15, 16: the inner layer -"stratum fibrosum internum"-, composed of collagenous and elastic microfibrils; the middle layer - "stratum nervosum" - containing a lamellar inner core and Ruffini SNF5; the external layer - "stratum fibrosum externum", that is a collagen capsule. The parenchymal cells show a rich enzyme activity. The parenchymal cells may play the same role as glomus cells of the 1st type and Merkel cells20, 21. When a surgical resection is performed for an oral carcinoma, the CJO may be present in the specimen25. The CJO may be wrongly diagnosed as perineural invasion by carcinoma26, 27, 28. CONCLUSION: We report that Chievitz' organ is the only organ in which the cancer does not occur. KEY WORDS: Chievitz' organ, Juxtaoral organ, Parotid gland.

A case of symptomatic mass in the right iliac fossa: a Bermuda Triangle which often lies the right diagnosis.

Disease of the iliac fossa can often be accompanied by non-specific symptoms and some of these are exclusively caused by the compression of bulky masses of other neighboring structures. In young women a differential diagnosis is a non trivial task as several possible causes have to be taken into account. Thus, intraligamentary tumors, which are extremely rare finding, are frequently confused with uterus, ovary or intestinal tumors. Even if myomas are the most benign tumors of the female genital tract, broad ligament leiomyomas are an unusual finding in women of reproductive age. These tumors are often asymptomatic until they reach a volume likely to cause symptoms related to the mass pressure. An accurate patient's anamnesis and examination serve as a guide to further examinations. Ultrasound is the first line imaging as it can show ovarian or other pelvic mass and doesn't involve exposure to radiations in young patients, who can be pregnant. We describe the clinical presentation and imaging features of a broad ligament leiomyoma, which presented as an inguinal mass in a patient with a right iliac fossa pain. We also report our diagnostic process performing the differential diagnosis with other potential pathologies of RIF. In these cases, a preoperative disease classification discriminating the benign or malignant tumor nature is closely linked to the proper patient management.

Thymectomy and systemic lupus erythematosus (SLE).

UNLABELLED: Dear Sir The thymus plays a crucial role in the context of cellmediated immunity in the differentiation of T lymphocytes, not only during the embryogenesis and fetal period but also during the adulthood, even after its involution 1,2,3. It has been proved, indeed, that thymectomy in adult rat entails a decrease of the T-lymphocite response to mitogens and eventually its abolition 4,5,6. The removal of the thymus can decrease the activity of T-helper cells but in the same time it might enhance the activity of T-suppressor whose function is depressed in autoimmune diseases 7. The therapeutic role of thymectomy is proved in Myasthenia Gravis even if the exact mechanism underlying its effect remains largely unknown. The role of thymectomy as a treatment of autoimmune diseases other than Myasthenia Gravis (i.e. sistemic lupus erythematosus, rheumatoid arthritis, autoimmune hemolytic anemia, multiple sclerosis) has been investigated but the results of these studies are questionable 7. Our aim is to evaluate the role of thymectomy in order to clarify whether it may be regarded not just as therapeuytic, but, on the contrary, as a factor paving the way to the onset of autoimmune diseases. Therefore, the relevant literature has been taken into account along our study. Thymus has an important role in regulating immune reaction through its control on T-cell differentiation of both T-helper and T-suppressor/cytotoxic cells. That is the reason why thymectomy produces a shift in autoimmune diseases with disregulation of the immune networks2. After thymectomy, indeed, an induction and an acceleration of autoimmune processes has been observed. A relevant work focusing on those mechanisms was written by Gerli et al1 . In their work, the authors consider the long term immunologic effects of therapeutic thymectomy in patients with Myasthenia Gravis comparing 16 patients with Myasthenia Gravis and previous Thymectomy (at least 8 years before), 6 patients with Myasthenia Gravis and recent Thymectomy (<1year) and 13 with Myasthenia Gravis non Thymectomized and 32 healthy subjects used as control. The study shows that the long term thymectomized patients had mild T-cell lymphopenia and an expansion of CD4+ and CD8+ cells. These serologic abnormalities were not detectable in not and recently thymectomized patients. Myasthenia Gravis and SLE are autoimmune disorders. They have positivity for antinuclear antibodies (ANA) and thymus hyperplasia. SLE is characterized by an alteration of the immune system that involves B cells and T lymphocites, resulting in polyclonal B cell activation and autoantybody production. The thymus deletes self-reactive T-cells with high avidity T-cell receptors for self antigens expressed in the thymus 8,9. This, hence, means that thymus has a protective role against autoimmunity. The prevalence of SLE in pts with Myasthenia Gravis has been reported 0,2%-2,7% 10. Cases in which the SLE has developed after thymectomy for Myasthenia Gravis have been reported in the literature, but there are also cases in which SLE developed before thymectomy in pts with both SLE and MG. Iwadate at al reported from a review of the literature in a period of 40 years (1963- 2004) 21 patients in whom LES developed after thymectomy. Their ages ranged from 11 to 66 years (mean 40.4 years) with SLE developing from 2 months to 13 years (mean 4.9 years) after thymectomy. Polyarthritis was the most common manifestation of SLE 11. The proof that thymectomy can facilitate the development of SLE can be traced in the cases reported by the literature. The prevalence of SLE among patients with thymoma varies between 1,5 and 10% 12. Boonen et al identified in a period of 20 years (1975-1998) 18 new cases of thymoma and SLE. In 39% of the patients SLE was diagnosed before detection of thymoma. In 33% of the patients, thymoma and SLE was found simultaneously and in 28% SLE was discovered after thymoma. In five cases thymectomy had no clear effect on SLE. In two cases an exacerbation was reported and in one case SLE was attenuated 11,13. However, Vaiopoulos et al 14 described in a series of 28 patients with both LES and Myasthenia Gravis, 17 cases in which LES developed before thymectomy. CONCLUSIONS: Thymectomy may thus be a precipitating factor for the development of SLE due to the loss of central tolerance and the overproduction of antibodies. Therefore, after a thymectomy, it is important to perform a timely follow up of the patient.

Intraoperative enteroscopy by standard colonoscope with a minimal contamination technique.

About 5% of occult gastrointestinal bleeding derives from small intestinal lesions. The intraoperative enteroscopy (IOE), although the development of double-balloon enteroscopy and capsule endoscopy reduced the indications, is still valid to locate the bleeding site in some selected cases. An 88-year-old woman presenting to the emergency department with a severe anemia underwent the laparotomic exploration and IOE. A 15-mm laparoscopy trocar with a sterile camera drape was adopted to introduce a standard colonoscope through an enterotomy. The operation was safe and effective, without intraoperative morbidity and early complications related to surgery or endoscopy. We propose a technical solution during the IOE to minimize contamination of the surgical field. Although this technique is safe and feasible, further studies are needed to evaluate the method effectiveness.

Chronic radiation-induced proctitis: the 4 % formalin application as non-surgical treatment.

PURPOSE: Radiation proctitis is a known complication following radiation therapy for pelvic malignancy. The majority of cases are treated nonsurgically. Rectal instillation of formalin solution has been described as a successful treatment for chronic radiation-induced hemorrhagic proctitis resistant to medical treatment. We present our results in patients undergoing treatment with application of 4 % formalin for radiation-induced injury to the rectum. METHODS: All patients were treated under anesthesia by direct application of 4 % formalin solution to the affected rectal areas. Patient gender, initial malignancy, grade of proctitis, need for blood transfusion, previous therapy, number of applications and response to treatment with formalin, complications, and length of follow-up were reviewed. RESULTS: A total of 15 patients with a mean age of 68.9 (range, 48-77) years were followed for 31.3 (range, 18-51) months. The mean interval from the conclusion of radiotherapy and the onset of symptoms was 6.9 months. The mean duration of hemorrhagic proctitis before formalin application was 7.9 months. Ten patients had only one formalin application and five patients required a second application because of the persistent bleeding. Thirteen patients (87 %) had complete cessation of bleeding. No complications related to the formalin treatment were observed. CONCLUSIONS: According to a revision of the literature and our experience, despite the small number of patients in our trial, we can state that the application of 4 % formalin solution is an effective, safe, and well-tolerated treatment for chronic radiation-induced hemorrhagic proctitis with minimal discomfort and no severe complications.

Combined Burch urethropexy and anterior rectopexy in pelvic organ prolapse: skip the mesh.

PURPOSE: Pelvic organ prolapse (POP) is a common accompaniment of advancing age. Current repair techniques incorporate transvaginal and transabdominal approaches with or without prosthetic mesh insertion. In this paper, we present the short- and medium-term results of a unit policy directed at patients with POP of combined abdominal rectopexy and Burch retropubic urethropexy without the use of prosthetic mesh assessing its safety profile in selected cases. METHODS: Between January 2009 and January 2011, 16 women with tri-compartmental prolapse who had all undergone prior hysterectomy underwent combined surgical pelvic floor repair. Preoperative symptom assessment by validated questionnaires and clinical examination were pre- and postoperatively recorded. Cures were defined as either optimal or satisfactory outcomes based on combined clinical, radiological examinations and reported patient satisfaction. RESULTS: The mean age of the 16 patients was 57.2 years, and their mean BMI was 28.6 (±5 SD). Pelvic examination revealed a POP-Q stage III prolapse in 12 patients and stage IV in 4 patients. The mean operating time was 57.5 min (range 40-85), with a mean length of hospital stay of 4.5 days. Cystocele and enterocele resolution was noted in every case on dynamic magnetic resonance imaging (MRI). CONCLUSIONS: Our results in a small patient cohort employing a simple 'all-in-one' repair approach combining a retropubic colposuspension with an anterior rectopexy appear to be satisfactory. Further larger randomized studies are required, incorporating a laparoscopic arm in order to determine the longer-term effectiveness of this approach.