Maffucci's syndrome. Case reports and literature review

Maffucci syndrome is a rare, congenital disease, which is associated with the appearance of multiple enchondromas (possibility of malignant transformation in 20 to 100%), soft tissue hemangiomas and other mesenchymatous injuries. Case 1 is a 33-year-old female who presented with multiple nodules predominantly in upper extremities. Upon examination, there was deformity in articulation and nodules on the hands, which were soft and moveable. There were bony shavings in the second and fourth fingers of the left hand (enchondromas and atypical cells associated with hemangioma esclerosante). Maffucci syndrome was diagnosed. Later, excision of subcutaneous nodules in superior extremities was performed along with excision of nodules in both hands and hypochondrium (enchondroma injuries of left hand and hypochondrium, hemangioma in right hand). There was dysarticulation of the second finger at the metacarpal level of the phalanges of the left hand (chondrosarcoma). The patient is being followed up currently. Case 2 is a 26-year-old female. The patient had a history of subcutaneous abdominal tumor, exostosis, nodules and nodule in right breast. Upon examination, a tumor was found in the right breast, exostosis of right tibia, injury to the right wrist and left thyroid nodule. A simple mastectomy and axillary dissection was performed (fibroadenoma to intracanalicular and 14 negative lymph nodes). Later, left thyroidectomy and lumpectomy in right wrist were performed (hyperplasia to nodular thyroid and hemangioma cavernous). There was injury in the carpus of the right hand and elbow (hemangioma cavernous and synovial tissue with fibrosis and enchondroma). A diagnosis was made of Marffucci syndrome associated with mesenchymatous tumors. The patient was in poor general health and did not survive this hospitalization.     

The mechanism of microsatellite instability is different in synchronous and metachronous colorectal cancer

MLH1 promoter hypermethylation has been described as the primary mechanism for high-frequency microsatellite instability (MSI-H) in sporadic colorectal cancers (CRCs). The underlying molecular mechanism for microsatellite instability (MSI) in synchronous and metachronous CRCs is not well described. A total of 33 metachronous CRC patients and 77 synchronous CRC patients were identified from 2884 consecutive patients undergoing cancer surgery in an academic center. Evaluable tumors were tested for MSI, immunohistochemistry for MLH1 and MSH2 protein expression, and hypermethylation of the MLH1 promoter. MSI-H tumors were found in 12 (36%) metachronous CRC patients and 29 (38%) synchronous CRC patients. MSI-H metachronous CRC patients were younger at index cancer diagnosis (64 vs. 76 years, P = 0.01) and more often were diagnosed before 50 years of age (4 of 12 vs. 0 of 29, P = 0.005). Loss of MLH1 expression associated with promoter hypermethylation was common in all patients, although more common in MSI-H synchronous patients (50% metachronous vs. 83% synchronous, P = 0.03). Overall, MLH1 promoter hypermethylation was seen in 7 of 17 (41%) metachronous and 44 of 54 (81%) synchronous MSI-H CRCs tested (P = 0.004). Although MSI occurred with equal frequency among patients with synchronous and metachronous CRCs, the underlying mechanism for MSI was different. Observed differences in MLH1 promoter hypermethylation and patient characteristics suggest most MSI-H synchronous CRCs in our population were sporadic in origin. In contrast, more MSI-H metachronous CRCs were associated with patient and tumor characteristics suggestive of underlying hereditary nonpolyposis CRC. Presented as a poster at Digestive Disease Week 2001, Atlanta, Georgia, May 20–23, 2001.     

Reconstruction of the distal radius facet by a free vascularized osteochondral autograft: anatomic study and report of a patient

PURPOSE: Large chondral defects of the distal radius after fractures present a reconstructive challenge. The purpose of this study was to present the anatomic findings from a cadaver of a vascularized osteochondral autograft taken from the third metatarsal appropriate for reconstructing the distal radius articular facet. A patient is presented in whom 70% of the scaphoid fossa was reconstructed with this technique. METHODS: The base of the third metatarsal was studied in the feet of 20 cadavers. The size and shape of the cartilage were measured. Additionally vessel distribution was recorded and the diameters of vascular foramina were measured with Juch's method. RESULTS: The base of the third metatarsal is pear shaped and is wider dorsally than plantarly. It averages 19.2 mm long on its main axis. Its cartilaginous surface is minimally concave or flat and it is slanted slightly proximal-dorsal to distal-plantar and proximal-peroneal to distal-tibial. Nutrient foramina were found in every case in the dorsum and on both sides of the proximal shaft. At least 1 nutrient vessel could be tracked back to the dorsalis pedis in every dissected specimen. CONCLUSIONS: The anatomic features of the base of the third metatarsal make it a potential vascularized autograft to consider for osteochondral defects of the distal radius.     

Effects of PEEP on residual vascularization in oesophageal substitution gastroplasty by surface oximetry-capnometry and photoplethysmography: an experimental study

OBJECTIVE: To evaluate the effects of positive end-expiratory pressure (PEEP) on residual vascularization in gastric tubes for oesophageal replacement. DESIGN: Experimental open study. MATERIALS: Eleven mongrel dogs. METHODS: Intestinal parietal blood flow was evaluated by photoplethysmography (PPG) and measurement of surface oxygen (PsO(2)) and carbon dioxide (PsCO(2)) tensions under basal conditions. After Akiyama's tubular gastroplasty, three levels of PEEP were administered. At each level, fluids were infused to counter the drop in cardiac output. PPG, surface gas tensions, arterial pressure, cardiac output and arterial blood gas tensions were monitored. Control sections of the bowel were also monitored by PPG. RESULTS: Cardiac output dropped for each level of PEEP and returned to basal levels on volume restabilization and on removal of PEEP. Central venous pressure and pulmonary arterial and capillary pressures increased for each level of PEEP and only returned to basal levels on removal of PEEP. PsO(2) values dropped for each level of PEEP and returned to basal levels on volume restabilization and on removal of PEEP. PsCO(2) levels rose, and PPG wave amplitude dropped, for each level of PEEP; these two variables only returned to basal levels on removal of PEEP. PPG values for the control sections reflected those of the anastomotic area. CONCLUSIONS: PEEP affects surface oxygen values at the level of the gastroplasty by means of its effect on cardiac output. PEEP also creates a venous return compromise and PPG wave amplitude and surface carbon dioxide values are related to this compromise. All three variables could be significant in anastomotic wound healing.     

Medical co-morbidities,secondary complications,and mortality in elderly with acute spinal cord injury

Despite an increasing incidence of spinal cord injury (SCI) in the elderly and evidence that age appears to influence outcome after neurotrauma, surprisingly little is known regarding clinical outcomes and secondary complications in elderly with an acute SCI. This study was undertaken to evaluate the effect of age on clinical outcomes after acute traumatic SCI managed in an acute care unit by a multidisciplinary team. A retrospective chart review of all patients with acute SCI admitted to an acute care unit at a university hospital between 1998 and 2000 was performed. Data on clinical outcomes and secondary complications in younger individuals (group 1: age < 60 years) were compared to elderly subjects (group 2: age > or = 60 years). There were 28 elderly (age 60-89 years) and 30 younger (age 17-56 years) individuals. The severity and level of SCI were similar in both groups (p = 0.11; p = 0.93). Co-morbidities were more frequent in the elderly (p < 0.01). There was a trend, which did not achieve significance, for an increased incidence of secondary complications in the elderly (57.1% versus 33.3%; p = 0.11). The most common secondary complications in both groups were infections, psychiatric disorders, pressure sores, and cardiovascular complications. Mortality rates in elderly and younger individuals with acute SCI (p = 0.41) were not significantly different. Our data suggest that rigorous attention to principles of acute SCI care can minimize previously reported higher susceptibility for secondary complications in the elderly. A multidisciplinary team approach to the management of the elderly with acute SCI is essential to minimize or prevent secondary complications.     

Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma

OBJECTIVES

To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).

MATERIALS AND METHODS

Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.

RESULTS

MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.

CONCLUSIONS

Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.     

The risk of cardiovascular disease associated with proteinuria in renal transplant patients

Proteinuria in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplantation. We investigated the effect of proteinuria on cardiovascular disease after renal transplantation in 532 renal transplant patients with functioning grafts for more than 1 year. Patients were classified into two groups depending on the presence of persistent proteinuria. We analyzed graft and patient survival, posttransplantation cardiovascular disease, and main causes of graft loss and death. Five- and 10-year graft and patient survival rates were lower in the group with proteinuria. The main cause of death was vascular disease in both groups. The presence of posttransplantation cardiovascular disease was higher in the group with proteinuria. Persistent proteinuria was associated with graft loss (RR=4.18), patient death (RR=1.92), and cardiovascular disease (RR=2.45). In conclusion, persistent proteinuria was an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.     

Return to dialysis after renal transplantation. Which would be the best way?

The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hospital admissions during the first year after initiation of dialysis were considerably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss.