A.I. Lo Monte

Histological findings of the internal inguinal ring in patients having indirect inguinal hernia

BackgroundAiming to deepen the understanding of the factors involved in the genesis of groin hernia, this study is focused on identifying the histological changes within the muscle fibers of the internal inguinal ring in patients having indirect inguinal hernia.MethodsIn eight patients with primary or recurrent bilateral indirect inguinal hernia who underwent a Stoppa open posterior inguinal hernia repair, a tissue specimen from the edge of the internal inguinal ring was biopsied and histologically examined.ResultsIn all of the tissue samples, remarkable degenerative changes such as fibrohyaline degeneration of the muscle fibers, vascular congestion, and phlogistic infiltration through lymphohistiocytary elements was constantly detected. Also, in the patients with recurrent hernia, the key characteristic of the muscular change was that of fibrohyaline and, occasionally, myxoid degeneration of the myocytes. Nerve endings were frequently detected within the muscular structures of the internal inguinal ring.ConclusionThe degenerative fibrohyaline alteration, as well as the evidence of phlogistic elements within the examined structures, could represent a reason for a contractile incompetence of the internal inguinal ring. Consequently, the described findings lead the authors to depict this inflammatory degenerative structural weakness of the internal inguinal ring as a possible culprit of indirect inguinal hernia formation.

Sphincter-like motion following mechanical dilation of the internal inguinal ring during indirect inguinal hernia procedure.

IntroductionEven today, there is still great speculation as to the underlying pathogenesis of inguinal hernia. As a result, it could be extrapolated that the vast majority of repairs are based upon conjecture. Most current repairs are founded upon the principle of “closing the defect” in the anatomy, either by suturing closed under tension, covering with a mesh or obliterating the defect with a plug. Many variants of each method are refined to achieve better clinical outcomes. Yet few, if any, strive to understand a fundamental question: “What has gone wrong with the normal physiological and anatomical mechanisms that prevent abdominal structures protruding through the abdominal wall?” We consider, in the normal subject, the muscular structures that converge and wrap around the inguinal canal as a highly dynamic structure, which forms a reactive barrier to the augmentation of intra-abdominal pressures. In effect, the structures work together like a “striated sphincter complex.” Through years of surgical experience, we have seen the formation of adhesions and fibrosis in these delicate and key structures, and hypothesised that they may impair its shuttering action, thus, creating a patency of this jammed inguinal ring leading to hernia. Based upon these observations, we have created a hernia repair variant that tries to “unblock” the muscles prior to repair, thus, hopefully restoring a degree of physiologic function.MethodsA retrospective study describes the results of 47 patients operated for indirect inguinal hernia with a standardised procedure consisting of meticulous adhesiolysis of the hernia area and mechanical dilation (divulsion) of the inguinal orifice in order to break stiff fibres within the muscle, allowing viable muscle fibres to contract freely once more. After dilation, a proprietary lamellar-shaped implant was delivered into the canal. Its form and function are designed to eliminate impingement of the cord structures and give a gentle outwards force to induce a reactive contraction of the sphincter-like muscle complex during healing. This gentle contraction offers the possibility to eliminate fixation of the implant.ResultsThe removal of scar tissue, dilation and the introduction of the implant into the internal inguinal ring induced a forceful “gripping” contraction by the sphincter complex in all patients. Even without fixation, it became almost impossible to pull the implant out of the canal. After obliterating the orifice with the lamellar implant, it was clear that there was no dilative compression upon the cord structures.ConclusionThe results of this combined procedure, scar removal, dilation and implant delivery, led to thoughtful suggestions regarding the anatomy and the physiology of the inguinal canal. The procedural adhesiolysis during indirect inguinal hernia repair has always shown the well described concentric muscular arrangement formed by the internal oblique and transversus muscles. This circular-shaped muscular structure is often recognised as a static barrier that, due to weakness and/or together with other causes, fails in its role and allows indirect inguinal hernia protrusion. According to the results of our observations, we consider this concentric muscular complex as a dynamic formation: we will use the term “striated sphincter complex.” Its steady tightening motion after divulsion and the insertion of a lamellar implant is always accompanied by a strong gripping action, which is not seen prior to divulsion. This indicates that it could correspond to a sphincter: the “inguinal sphincter.” The impairment of this sphincter could be the cause of the inguinal canal’s patency and the development of hernia.

Use of tacrolimus and mycophenolate mofetil as induction and maintenance in simultaneous pancreas-kidney transplantation.

Abstract Clinical trials using quadruple immunosuppression that include the combination of tacrolimus and mycophenolate mofetil have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas‐kidney (SPK) transplantation. In an attempt to obtain a low rejection rate without antibody induction therapy, we undertook a prospective study of combined tacrolimus and mycophenolate mofetil and steroids as primary immunosuppression for SPK transplantation. In this study, we analyzed 17 patients who received low‐dose intravenous tacrolimus as induction therapy. This was combined with oral tacrolimus, mycophenolate mofetil, and steroids as the primary immunosuppression regimen. There was a significant reduction of empirically and biopsy‐proven rejection with an incidence of 23 % (4 patients). Leukopenia, gastroparesis, and gastrointestinal side‐effects were the cause of discontinuation of mycophenolate mofetil, or low tacrolimus trough level in those patients who developed rejection. All rejection episodes were easy to treat, and none of them required antibody therapy. The combination of tacrolimus with mycophenolate mofetil without antibody induction therapy is effective in preventing early acute rejection. This combination is safe and effective as an alternative immunosuppressive regimen after SPK transplantation.

THE ROLE OF BUTYRIC ACID AS A OPROTECTIVE AGENT AGAINST INFLAMMATORY BOWEL DISEASE

SUMMARY Inflammatory bowel diseases (IBD), such as Crohns disease and ulcerative colitis, are pa- thologies characterized by a chronic inflammation of the gastrointestinal tract. Their etiopathogenesis is not yet fully understood. Immune system and heat shock proteins (Hsps) dysfunctions are considered to be among the most likely causes of these diseases. Butyrate is a short-chain fatty acid mainly produced by intestinal microflora. It has a tro- phic, beneficial and protective role in the colonic mucosa, and it also induces changes in Hsp levels and localization. It may therefore be a valuable complementary therapeutic agent when used alongside traditional drugs (mesalazine and corticosteroids) to treat such conditions. The administration of specific probiotic formulations in order to increase the production of butyrate in the endoluminal environment may promote clinical remis- sion in IBD patients. Due to these characteristics, there has been keen interest in the use of butyrate as a novel therapeutic supplement in the recent years. The current findings need to be validated through further clinical trials to better define the biomolecular dy- namics of butyrate in the colonocytes of IBD patients.

Isolation and Culture of β-Like Cells From Porcine Wirsung Duct

We sought to develop a protocol to isolate and culture porcine Wirsung duct cells in order to determine their potency to differentiate into insulin-expressing beta-like cells. The porcine Wirsung duct isolated by a surgical microdissection was digested with collagenase P and trypsin to dissociate ductal cells. These elements were cultured in serum-free supplemented media: for 2 weeks. Thereafter the cells were exposed to varying concentrations of glucose (0, 5.6, 17.8, and 25 mmol/L) to induce a beta-like phenotype, as identified by immunohistochemical staining. Cell growth proceeded slowly for the first 2 weeks of culture. After glucose induction for 2 weeks, they formed pancreatic islet-like structures. These cells were stained for the pancreatic ductal cell marker cytokeratin-19 (CK-19) and the pancreatic endocrine markers insulin and glucagon. After the second week, 90% of cells were positive for CK-19. Up to 20.1% of the cells in pancreatic 3-dimensional structures induced by 17.8 mmol/L glucose were positive for insulin, and <3.2%, for glucagon. The positive ratio of immunoreactive staining was dependent on the glucose concentration; 17.8 mmol/L glucose effectively stimulated insulin- and glucagon-secreting cells. We concluded that porcine Wirsung duct cells were capable of proliferation with the potential to differentiate toward beta cells upon glucose induction in vitro.

Use of Intraperitoneal ePTFE Gore Dual-Mesh Plus in a Giant Incisional Hernia After Kidney Transplantation: A Case Report

We evaluated the incidence of and predisposing factors for an incisional hernia after kidney transplantation. Numerous techniques have been used to repair postoperative fascial dehiscences or simple incisional hernias, but no clear treatment exists for giant hernias. Our aim was to obtain (1) a safe procedure to repair a large abdominal defect and reinforce the surrounding, fragile zones and (2) a simple, rapid technique to reduce the operative time. Herein we have described the surgical repair of a giant incisional hernia using intraperitoneal Gore ePTFE dual-mesh plus (Gore-Tex; W. L. Gore, Flagstaff, Ariz, USA) in a 55-year-old man status-post renal transplantation. Total necrosis of distal graft ureter had caused a giant urinoma. The patient was reexplored on day 2 posttransplantation with a primary fascial approximation. Thirty days after transplantation we discovered a large incisional hernia and performed a repair. No drain was used. The patient continued immunosuppressive therapy (cyclosporine, mycophenolate mofetil, prednisolone) and was discharged on postoperative day 4 with no complications. An ultrasonographic follow-up at 1 year revealed the prosthesis to be correctly positioned. Incisional hernia is not rare after renal transplantation but the real incidence is unknown. Immunosuppressive therapy, prolonged pretransplantation dialysis, obesity, and diabetes are probably the major causes of incisional hernias in these patients. Surgical complications of renal transplantation surgery, such as wound hematoma, urinoma, and lymphocele, are the most important predisposing factors for an incisional hernia. The use of intraperitoneal ePTFE dual-mesh is feasible, safe, and easy to repair a large incisional hernia in a kidney transplant patient.

Beyond Islet Transplantation in Diabetes Cell Therapy: From Embryonic Stem Cells to Transdifferentiation of Adult Cells

Exogenous insulin is, at the moment, the therapy of choice of diabetes, but does not allow tight regulation of glucose leading to long-term complications. Recently, pancreatic islet transplantation to reconstitute insulin-producing β cells, has emerged as an alternative promising therapeutic approach. Unfortunately, the number of donor islets is too low compared with the high number of patients needing a transplantation leading to a search for renewable sources of high-quality β-cells. This review, summarizes more recent promising approaches to the generation of new β-cells from embryonic stem cells for transdifferentiation of adult cells, particularly a critical examination of the seminal work by Lumelsky et al.

Double Endocrine Neoplasia in a Renal Transplant Recipient: Case Report and Review of the Literature

INTRODUCTION The incidence of cancer compared for age groups is 3-4 times higher in transplant recipients than the general population. The increased risk is related to immunosuppressive therapy as well as the use of increasingly older donors and recipients. Although cardiovascular disease with a functioning transplant is the leading cause of death (47%), cancer mortality is significant especially among older patients. However, the most frequent posttransplantation cancers relate to hemolymphopoietic organs and skin, whereas the occurrence of solid tumors elsewhere is rare. Herein we have described a rare case of synchronous double malignancy of endocrine organs (thyroid-adrenal) in a young woman who underwent renal transplantation. CASE REPORT A 37-year-old woman with end-stage renal disease for 18 years underwent transplantation when she was 30 years old with a 17-year-old standard cadaveric donor receiving immunosuppressive therapy with mycophenolate mofetil, cyclosporine, and steroids. Follow-up demonstrated good indices of renal function with negative tumor pathology at 79 months when, at an annual ultrasound monitoring, we found a lesion in the right lobe of the thyroid and left adrenal neoplasm of dubious interpretation. The cytology for the thyroid was highly suspicious of papillary carcinoma, whereas the histological examination after surgery diagnosed a thyroid multifocal papillary microcarcinoma (mpT1NxMx) and an oxyphil cell adrenocortical carcinoma (pT2, N0). RESULTS Six months after total thyroidectomy with central lymphadenectomy and left kidney and adrenal gland removal the patient showed no evidence of recurrent lesions and stable graft function. CONCLUSIONS The rare occurrence of solid tumors after transplantation has no known etiopathogenetic relation. Despite the young age of the patient and the double neoplasm that could have produced an unfavorable outcome for the patient and the graft, careful follow-up for tumor pathologies and multidisciplinary management achieved an early diagnosis of both tumors with a surgical eradication without adjuvant therapy, preserving the life of the patient and the function of the graft.

A Good Breath of Oxygen for Beta-Like Cells Obtained From Porcine Exocrine Pancreatic Tissue

Ischemia is the most important factor that affects organ survival during harvesting. The two-layer method (TLM) is one of several cold storage solutions that seeks to preserve organs and cells avoiding in vivo and in vitro ischemia. We compared the retrieval of beta-like elements from exocrine pancreatic cells using TLM versus University of Wisconsin (UW) solutions. For this purpose pancreata laparoscopically harvested from 20 female pigs were preserved in UW solution or TLM before digestion. The resulting exocrine cells were divided into 2 groups: the first was cultured in a designed medium to allow differentiation into beta-like cells and the second was cryopreserved before the differentiation process at -196 °C for 8 weeks before culture in the same medium. The results revealed that TLM was better than UW as a preservation solution in terms of beta-cell viability and insulin secretion. We suggest that the use of TLM solution allows one to obtain less damaged cells for research purposes.

Bone Resorption in Kidney Transplant Recipients

Early diagnosis of persistent hyperparathyroidism (HP) following kidney transplantation may prevent worsening of osteodystrophy and potential damage to the graft. We evaluated the utility of collagen pyridinoline (PYD) and deoxypyridinoline (DPD) urinary cross-links beyond the common HP markers to evaluate 70 selected stable recipients between 1997 and 2006 who were divided into 2 group depending on the immunosuppressive protocol. All patients showed elevated levels of urinary cross-links even though calcemia and phosphoremia values were normal. Their mean creatinine level was slightly increased. Data were assessed as mean values +/- SD. All variables underwent a correlation matrix analysis and a stepwise regression, with posttransplant intact parathyroid hormone (iPTH) as the dependent variable and other variables as regressors. A statistically significant correlation was observed between PYD and alkaline phosphatase (ALP; P = .0026, r = .41); PYD and DPD (P = .015, r = .34); pre- and posttransplant iPTH (P = .024, r = .31); and creatinine and ALP (P = .024, r = .31). Taking the groups separately, there were significant correlations between PYD and ALP (P = .0076, r = .42); PYD and DPD (P = .017, r = .38); ALP and posttransplant iPTH (P = .038, r = .33); osteocalcin (OC) and posttransplant iPTH (P = .048, r = .32); and pre- and posttransplant iPTH (P = .019, r = .37) among subjects in the first group, whereas subjects in the second group showed a correlation between posttransplant iPTH and age at transplantation (P = .032, r = .61). In conclusion, we showed that urinary cross-links may be helpful to reveal bone resorption in kidney recipients when usual bone metabolism parameters do not demonstrate hyperparathyroidism.