Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation in the absence of GAD and IA-2 autoantibodies.

We report herein the patterns of type 1 diabetes recurrence in a simultaneous pancreas-kidney transplant (SPK) recipient, in the absence of rejection. A 38-year-old female underwent SPK for end-stage nephropathy secondary to type 1 diabetes. Fasting blood glucose, HbA1c, fructosamine, C-peptide and autoantibodies (GAD-65, IA-2) were monitored throughout follow-up. At 3.5 years post-SPK, HbA1c and fructosamine increased sharply, indicating loss of perfect metabolic control, despite C-peptide levels in the normal-high range. Exogenous insulin was restarted 4 months later. C-peptide levels abruptly fell and became undetectable at 5.5 years. Autoantibody levels, which were undetectable at the time of SPK, never converted to positivity. Pancreas retranspantation was performed at 6 years. The failed pancreas graft had a normal macroscopic appearance. On histology, there were no signs of cellular or humoral rejection in the kidney or pancreas. A selective peri-islet lymphocytic infiltrate was observed, together with near-total destruction of ß cells. At 2.5 years post retransplantation, pancreatic graft function is perfect. This observation indicates unequivocally that pancreas graft can be lost to recurrence of type 1 diabetes in the absence of rejection. GAD-65 and IA-2 autoantibodies are not reliable markers of autoimmunity recurrence.

[Lynch syndrome: when pathologist and clinician have the opportunity to reduce the risk of developing cancer]. / Le syndrome de lynch: pathologiste et praticien peuvent ensemble éduire le risque de cancer.

Lynch syndrome is an autosomal dominant disease associated with an important risk of cancer, mainly endometrial and colorectal-cancer. This risk can be efficiently lessen by an appropriate screening as far as the mutations carriers are identified. As current clinicopathological recommendations lack sensitivity, a systematic pre-screening of every patient with a colorectal or endometrial cancer can be proposed. Oncogenetic units of the HUG in Geneva and ICHV in Valais have set up a population-based study to evaluate the efficacy of such a strategy. Whatever the approach, the pathologist is directly implicated as Lynch syndrome harbors specific histological aspects that can help to its identification, but also as pre-screening tests are directly realized on tumor-tissue.

Cytology of benign multicystic peritoneal mesothelioma in peritoneal washings.

OBJECTIVE: To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM). METHODS: Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy. RESULTS: The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells. CONCLUSION: The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).

Use of collagen for standardization of PBSC graft quality evaluation: a multicenter comparative analysis of commercial collagen-based and methylcellulose-based colony-forming unit (CFU) assay kits.

The colony-forming unit-granulocyte-macrophage (CFU-GM) assay, an essential test in evaluation of the quality of autologous grafts of hematopoietic stem cells, has yet to be standardized. With this aim in view, we carried out a multicenter study of five commercially available culture kits for CFU-GM evaluation. Four kits were methylcellulose-based (H4431, H4434, H4435, StemBio1d) and one was collagen-based (EasyClone-Multi). Using fresh and frozen samples of PBSC grafts, we compared CFU-GM and burst-forming unit-erythrocytes (BFU-E) growth using the EasyClone kit to each of the methylcellulose kits. BFU-E and CFU-GM clonogenicity of both fresh and frozen PBSC was clearly inferior with the H4431 kit, which provides conditioned medium only. CFU-GM numbers obtained with fresh and frozen PBSC samples were significantly higher with the EasyClone kit than with the H4434 and StemBio kits. BFU-E numbers were also higher with the EasyClone kit, but only when colonies were scored after May-Grünwald-Giemsa (MGG) staining. Finally, although the H4435 kit provides higher doses of recombinant cytokines than the EasyClone kit, CFU-GM and BFU-E numbers obtained for fresh or frozen PBSC with both kits were similar. In addition, CFU-GM and BFU-E numbers correlated well with CD34+ cell numbers for all five kits for both fresh and frozen PBSC. In summary, our study shows that the EasyClone-Multi and H4435 kits provide the best CFU-GM growth. The collagen-based EasyClone kit has the additional advantage of allowing gel staining and storage, which facilitates colony identification and, more importantly, makes gel exchange possible for standardization of the CFU-GM assay.

The synthetic tetrapeptide AcSDKP protects cells that reconstitute long-term bone marrow stromal cultures from the effects of mafosfamide (Asta Z 7654).

The tetrapeptide AcSDKP (Seraspenide) has been described as an inhibitor of CFU-S entry into DNA synthesis; as a result, its administration can protect mice against lethal doses of cytosine arabinoside. We have studied the ability of AcSDKP to protect and promote the growth of early CD34+ human bone marrow (BM) stem cells in Dexter long-term cultures following exposure to a toxic concentration of mafosfamide. The protection assay was based on the preincubation of CD34+ BM cells with or without AcSDKP at 10(-10)M or 10(-8)M followed by exposure to a toxic dose of mafosfamide (100 micrograms/mL). The production of granulomonocytic progenitor cells (CFU-GM) was subsequently studied in long-term bone marrow cultures (LTBMC) of the samples exposed to mafosfamide and preincubated or not (control) with AcSDKP. After a lag of 2 to 3 weeks, the number of CFU-GM peaked at the 4th to 5th week in both the supernatant and the adherent layers. A greater production of granulomonocytic progenitor cells was observed in LTBMC from the samples preincubated with AcSDKP compared with control cells. Depending on the BM samples, enhanced production of CFU-GM in the AcSDKP-treated cell cultures was observed at either the 10(-10)M or 10(-8)M concentration. These results suggest that AcSDKP can protect in vitro human long-term culture-initiating cells (LTC-IC) from mafosfamide, resulting in an increased production of CFU-GM from this early stem cell compartment.