Thomas Diflo

Bone Marrow-Derived Cells Contribute to Epithelial Engraftment during Wound Healing

Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels (</= 1%) in the absence of injury. Here we show that skin damage affects the degree of engraftment of BMDC as keratinocytes and that the keratinocytes are actively cycling. Female mice reconstituted with sex-mismatched BM were wounded by punch biopsy and incision. At the wound site, engraftment of BMDC as epidermal cells increased within 1 day, and continued to increase to approximately 4% by 3 weeks after injury. Using a Cre-lox system, fusion of BMDC with epithelial cells was ruled out. BMDC-derived epithelial cells at the wound edges expressed Ki67, a marker for actively cycling cells, and this proliferation correlated with an increase in the number of donor-derived cells within the wound. Donor-derived cytokeratin 5-expressing cells were rare, suggesting that BMDC do not engraft as epidermal stem cells, and the level of engraftment peaked and then decreased over time, further suggesting that BMDC may assist in early wound healing by engrafting as transit-amplifying cells, which then differentiate into keratinocytes.

Quantitative Evaluation of Acute Renal Transplant Dysfunction with Low-Dose Three-dimensional MR Renography

PURPOSE To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22-71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTT(A)), the tubular compartment (MTT(T)), and the collecting system compartment (MTT(C)) were calculated. Also derived was MTT for the whole kidney (MTT(K) = MTT(A) + MTT(T) + MTT(C)) and fractional MTT of each compartment (MTT(A/K) = MTT(A)/MTT(K), MTT(T/K) = MTT(T)/MTT(K), MTT(C/K) = MTT(C)/MTT(K)). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. RESULTS There were significant differences in GFR and MTT(K) between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTT(A/K) was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTT(T/K) was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group (mean, 69.2% ± 6.1; P = .003). CONCLUSION Low-dose MR renography analyzed by using a multicompartmental tracer kinetic renal model may help to differentiate noninvasively between acute rejection and ATN after kidney transplantation.

Intrahepatic portal cavernoma as an indication for liver transplantation

Cavernous transformation of the portal vein (portal cavernoma) consists of a periportal or/and intrahepatic venous collateral network, developed as a result of acute or long‐standing portal vein thrombosis. Better control of hemorrhagic and thrombotic complications in the patients with portal cavernoma substantially improves their life span and the clinical outcome. However, biliary complications that occur in the late stages of this disease have been recently recognized as challenging management issues because they recur and are difficult to treat. Because of the relatively small number of the patients with cholangiopathy due to portal cavernoma, there is no current standardized treatment approach. We report the case of a predominantly intrahepatic portal cavernoma occurring in a patient with chronic idiopathic portal vein thrombosis, which led to severe cholangiopathy that mimicked primary sclerosing cholangitis and cholangiocarcinoma, was unresponsive to endoscopic stent placement, and finally required liver transplantation. Liver Transpl 13:1312–1316, 2007,

Graft-versus-host Disease In Fully Allogeneic Small Bowel Transplantation In The Rat

Small bowel and its mesentery contain considerable amounts of lymphoid tissue that can mediate graft-versus-host disease in small bowel transplant (SBT) recipients. Present studies determined the existence of GVHD in a fully allogeneic SBT model and examined the effect of donor pretreatment with ALS in eliminating GVHD. Adult male Lewis (Lew) rats received orthotopic small bowel transplants from untreated (LewxBN)F1 (LBNF1) donors (group 1) or Brown Norway (BN) donors that were untreated (group 2) or pretreated with ALS (days -2 and -1) (group 3). All recipients were treated with cyclosporine 15 mg/kg/day i.m. on days 0-6 postoperatively. Animals were weighed and examined daily for signs of rejection and GVHD. No animals in groups 1 or 3 showed any physical signs of GVHD, but all of those in group 2 had characteristic weight loss, diarrhea, and dermatitis between 4 and 6 weeks postoperatively, from which they all recovered. Histologic examination of skin and spleen at this time confirmed the presence of GVHD. The relative spleen weight [( spleen weight/body weight] x 100) of group 2 animals was also significantly greater than that of unoperated control Lew animals. Spleen cells obtained from group 2 animals at the time of subclinical GVHD, but not cells from group 1 or 3 animals, caused enlargement of popliteal lymph nodes when they were injected into the footpads of Lew rats. This study shows that GVHD can manifest itself in recipients of a fully allogeneic small bowel transplant even when rejection is prevented by effective immunosuppression with CsA. However, combined use of recipient treatment with CsA and pretreatment of donor animals with ALS eliminates all manifestations of GVHD.

Scirrhous changes in dysplastic nodules do not indicate high‐grade status

Background and Aims: Dysplastic nodules (DN) may be divided into high‐grade and low‐grade, and the former has been known as a precancerous or borderline lesion. Recently many morphological characteristics concerning these types of DN have been reported. In the present study we attempted to evaluate the scirrhous change in DN as an indicative feature of high‐grade DN, based on the morphological and cell‐kinetic analyses using immunohistochemical stains for Ki‐67.

Uterine Transplantation, Abdominal Trachelectomy, and Other Reproductive Options for Cancer Patients

More and more women with cancer issues are now raising fertility concerns as survival improves and childbearing is delayed. Pregnancy is no longer contraindicated in cancer patients including breast and endometrial cancer survivors. In fact, survival in patients treated for breast cancer who subsequently become pregnant is actually higher than that in patients who do not become pregnant. “Therapeutic” abortions are no longer recommended. Assisted reproductive technology (ART) have been associated with ovarian neoplasms, but the association is probably not causal. Neither ART nor hormone replacement is contraindicated in cancer patients. Our institution is very supportive of patients and the difficult decisions cancer survivors face. Using a program of counseling and close collaboration between oncologists, perinatologists, and reproductive endocrinologists, informed patients are offered every possible option, including ART and uterine transplantation, to achieve their family planning objectives.

Selection and imaging of the living liver donor

Primum non nocere—First, do no harm: this is one of the basic tenets of medical practice. The very act of living donation violates this age-old edict. The rapidly increasing number of adult recipients and the critical shortage of cadaveric organs have forced transplant surgeons and physicians to search for suitable grafts elsewhere. The use of living liver donors for children has already had a significant impact on the pediatric waiting list. There has been considerable concern, however, regarding the rapidity with which adult-to-adult living donor transplantation has been embraced by transplant centers throughout the country compared with the very cautious and calculated start-up witnessed when living liver donation was first introduced for pediatric recipients. Children needing livers have greatly benefited from living donation and, to a lesser degree, from split-liver transplantation. The splitting of cadaveric livers has become more common, but unfortunately relatively few cadaveric organs are suitable for splitting and the procedure generally benefits an adult and a pediatric recipient and so does nothing extra to reduce the numbers of adults on the waiting list. The number of adults on the waiting list is, however, increasing at a tremendous rate, and thus the demand for solutions is great. Most living donor grafts given to adult recipients are right lobes. Left lobe grafts are not discussed in this review. The risks are considerable. Right hepatic lobectomy is a formidable procedure even in the most skilled hands. Proper donor selection is critical. The donor selection practices of four leading transplant centers are reviewed in the first segment of this review. In the second section, the imaging of potential donors is examined in more detail. Curr Opin Organ Transplant 2001, 6:350–354

A Decade of Change: An Institutional Experience with Breast Surgery in 1995 and 2005

Introduction With the adoption of routine screening mammography, breast cancers are being diagnosed at earlier stages, with DCIS now accouting for 22.5% of all newly diagnosed breast cancers. This has been attributed to both increased breast cancer awareness and improvements in breast imaging techniques. How have these changes, including the increased use of image-guided sampling techniques, influenced the clinical practice of breast surgery? Methods The institutional pathology database was queried for all breast surgeries, including breast reconstruction, performed in 1995 and 2005. Cosmetic procedures were excluded. The results were analysed utilizing the Chi-square test. Results Surgical indications changed during 10-year study period, with an increase in preoperatively diagnosed cancers undergoing definitive surgical management. ADH, and to a lesser extent, ALH, became indications for surgical excision. Fewer surgical biopsies were performed for indeterminate abnormalities on breast imaging, due to the introduction of stereotactic large core biopsy. While the rate of benign breast biopsies remained constant, there was a higher percentage of precancerous and DCIS cases in 2005. The overall rate of mastectomy decreased from 36.8% in 1995 to 14.5% in 2005. With the increase in sentinel node procedures, the rate of ALND dropped from 18.3% to 13.7%. Accompanying the increased recognition of early-stage cancers, the rate of positive ALND also decreased, from 43.3% to 25.0%. Conclusions While the rate of benign breast biopsies has remained constant over a recent 10-year period, fewer diagnostic surgical image-guided biopsies were performed in 2005. A greater percentage of patients with breast cancer or preinvasive disease have these diagnoses determined before surgery. More preinvasive and Stage 0 cancers are undergoing surgical management. Earlier stage invasive cancers are being detected, reflected by the lower incidence of axillary nodal metastases.