Hereditary and non-hereditary branches of family eligible for BRCA test: cancers in other sites.

BACKGROUND: The analysis of relationships of BRCA alterations with cancer at sites other than breast/ovary may provide innovative information concerning BRCA pathogenic role and support additional clinical decisions. Aim of this study is to compare presence of cancers in other sites in members of hereditary (H) and not-hereditary (nH) branches of families of patients eligible to BRCA test. METHODS: We retrospectively analyzed the incidence of cancer in other sites in members of 136 families eligible for hereditary breast/ovarian cancer genetic counseling at Centro Studi Tumori Eredo-familiari of our Institute; we compared the frequency of other cancer types in 1156 members of the H-branch with respect to 1062 members of nH-Branch. The families belonging to a proband case and with informative members in at least three generation entered the present study. RESULTS: The frequency of other Cancers in members of H-branch was significantly higher than that in members of nH-branch (161 vs 75 cancers; p < 0.0001). In specific, members of H-branch had a significantly higher probability to have more lung cancer (38 vs 9;p < 0.0006), kidney cancer (23 vs 5;p < 0.0005), liver cancer (13 vs 3;p < 0.02) and larynx cancer (14 vs 4;p < 0.03). Interestingly, to belong to H-branch resulted significantly associated with a higher probability of lung cancer (OR 4.5; 2.15-9.38 95%C.I.), liver cancer (OR: 4.02; 1.14-14.15 95% C.I.) and larynx cancer (OR:3.4; 1.12-10.39 95%C.I.) independently from Gender and Age. CONCLUSIONS: Members belonging to the H-branch of families of patients eligible to BRCA test have a higher risk of tumors in lung, larynx and liver. Clinicians should consider the increased risk for these cancers to activate prevention/early diagnosis practices in members of families with breast/ovarian familial cancer syndrome.

Abdominal wall dysfunction in adult bladder exstrophy: a treatable but under-recognized problem.

PURPOSE: Bladder exstrophy is defined by urogenital and skeletal abnormalities with cosmetic and functional deformity of the lower anterior abdominal wall. The primary management objectives have historically been establishment of urinary continence with renal function preservation, reconstruction of functional and cosmetically acceptable external genitalia, and abdominal wall closure of some variety. The literature has focused on the challenges of neonatal approaches to abdominal wall closure; however, there has been a paucity of long-term followup to identify the presence and severity of abdominal wall defects in adulthood. Our goal was to characterize the adult disease and determine effective therapy. METHODS: A retrospective review of a consecutive series of six patients was performed. RESULTS: We report and characterize the presence of severe abdominal wall dysfunction in these adult exstrophy patients treated as children. We tailored an abdominal wall and pelvic floor reconstruction with long-term success to highlight a need for awareness of the magnitude of the problem and its solvability. CONCLUSIONS: The natural history of abdominal wall laxity and the long-term consequences of cloacal exstrophy closure have gone unexplored and unreported. Evaluation of our series facilitates understanding in this complex area and may be valuable for patients who are living limited lives thinking that no solution is available.

Proteomic profile in familial breast cancer patients.

OBJECTIVES: Breast cancer is the most common form of cancer affecting women, and the strongest risk factor remains family history. Although screening in asymptomatic women seems able to reduce breast-cancer related mortality, it is of limited usefulness in young women and patients with familial breast cancer syndrome. New diagnostic tools useful for breast cancer management are urgently needed. The aim of the present paper is to look for new candidate tumor markers useful for diagnosis in these patients. DESIGN AND METHODS: In this prospective study 292 serum samples (100 from healthy people, 100 from sporadic breast cancer patients and 92 from familial breast cancer patients) were analyzed by SELDI-TOF-MS. All samples both from cancer patients and healthy subjects were run in duplicate and randomly spotted on CM10 and IMAC30 protein chip array. Data were analyzed using the expression differential mapping (EDM) tool, decisional tree and multivariate analysis. A further in silico investigation was performed in order to hypothesize the identity of evidenced peptides. RESULTS: EDM highlighted thirteen and sixteen significant differentially expressed peaks by CM10 and IMAC30 protein chip respectively. Subsequent analysis showed that two peaks at m/z 11730 and 5066 were differentially expressed in sporadic and familial breast cancer patients respectively, while a peak at m/z 8127 was overexpressed only in familial breast cancer patients. The diagnostic power of protein peaks was tested by decisional tree; sensitivity and specificity ranged from 17% to 91.67%. CONCLUSIONS: We show that the serum profile of familial breast cancer patients was different when compared with that of sporadic breast cancer patients. We hypothesized the identity of the most significant peaks, and further studies are now planned in order to definitively establish the identity.

Craniofacial distraction osteogenesis: a review of 3278 cases.

The nascent field of craniofacial distraction osteogenesis has not yet been subjected to a rigorous evaluation of techniques and outcomes. Consequently, many of the standard approaches to distraction have been borrowed from the experience with long bones in orthopedic surgery. The ideal "latency period" of neutral fixation, rate and rhythm of distraction, and consolidation period have not yet been determined for the human facial skeleton. In addition, because the individual craniofacial surgeon's experience with distraction has generally been small, outcomes and meaningful complication rates have not yet been published. In this study, a four-page questionnaire was sent to 2476 craniofacial and oral/maxillofacial surgeons throughout the world, asking about their experiences with distraction osteogenesis. Information about the types of cases, indications for surgery, surgical techniques, postoperative management, outcomes, and complications were tabulated. Of 274 respondents (response rate, 11.4 percent), 148 indicated that they used distraction in their surgical practice. One hundred forty-five completed surveys were entered into a database that provided information about 3278 craniofacial distraction cases. Statistical analyses were performed comparing the rates of premature consolidation, fibrous nonunion, and nerve injury, on the basis of the use of a latency period and different rates and rhythms of distraction. In addition, the rates of all complications were determined and compared on the basis of the number of distraction cases performed per surgeon. The results of the study clearly show a wide variation in the surgical practice of craniofacial distraction osteogenesis. Although the cumulative complication rate was found to be 35.6 percent, there is a pronounced learning curve, with far fewer complications occurring among more experienced surgeons (p < 0.001). The presence of inferior alveolar nerve injury as a result of mandibular distraction was much lower for respondents whose distraction regimens consisted of no more than 1 mm of distraction per day (19.5 percent versus 2.4 percent; p < 0.001). No evidence was found to support the use of a latency period or to divide the daily distraction regimen into more than one session per day. Conclusions could not be drawn from this study regarding the length of the consolidation period. Overall, the surgeon-reported outcomes are comparable with those published for other craniofacial procedures, despite the higher incidence of complications. Although conclusions made on the basis of a subjective questionnaire need to be interpreted cautiously, this study has strength in the large numbers of cases reviewed. Because of the anonymity of responses, it has been assumed that surgeons who responded to the survey reported accurate numbers of complications and successful outcomes. Finally, additional clinical and animal studies that will be of benefit in advancing the field of craniofacial distraction osteogenesis are outlined.

Improved mandible function after hemimandibulectomy, condylar head preservation, and vascularized fibular reconstruction.

Temporomandibular joint dysfunction after tumor extirpation of the hemimandible is a frequent sequela after condylar head reconstruction. Condylar head resection is often performed because of oncological and vascular considerations. Recent studies have demonstrated that malignancies of the mandibular ramus and body rarely involve the condylar head, and that the vascularity and supportive structures of the condylar head are sufficient to maintain viability and function. This study demonstrates that temporomandibular joint function is preserved after hemimandibulectomy without resection of the condylar head. Fixation of a vascularized fibular flap to the condylar head is performed in situ. Condylar viability and growth is maintained with painless incisal opening. The condylar head is a growth center for the mandible in the pediatric population. Its preservation in these patients will avoid the long-term problems associated with growth center loss such as malocclusion and concomitant maxillary deformity.

Multiple-component tissue reconstruction of a complex dorsal foot wound through a single gracilis muscle donor incision.

The authors describe the ability of the gracilis muscle to provide multiple tissue components- skin, muscle, nerve, and tendonin the reconstruction of a complex dorsal foot wound resulting from a sarcoma resection. The deficits of skin, deep peroneal nerve, anterior tibialis tendon, and dorsal extensor retinaculum were all reconstructed with the gracilis component flap through one medial thigh incision. This case illustrates two important points: (1) the gracilis flap is tremendously versatile and can serve as the donor for multiple tissue components in complex reconstructions, and (2) donor site morbidity can and should be minimized even in complex reconstructions.

Adverse outcome of nonoperative management of intimal injuries caused by penetrating trauma.

PURPOSE: The objective of this study was to determine adverse outcomes associated with the nonoperative management of intimal injuries. METHODS: A five-year retrospective review of 118 patients admitted with soft signs of vascular injury to two level I trauma centers was conducted. All injuries evaluated were isolated penetrating injuries. The number of major arteries at risk were 16 axillary, 31 brachial, 36 common femoral, 22 superficial femoral, and 13 deep femoral. Twenty-three angiographic abnormalities were identified in 23 limbs. Seven injuries were categorized as "minor" intimal flaps and treated with observation alone. The remainder were explored during operation. RESULTS: During the follow-up period, six of the seven patients treated without operation returned to either the outpatient clinic or emergency department with acute onset of pain or paresthesia in the previously injured limb. The following abnormalities were identified with angiography: one axillary artery thrombosis, one brachial artery pseudoaneurysm, two common femoral thromboses, two superficial femoral artery/superficial femoral vein fistulas, and one deep femoral artery pseudoaneurysm. All the abnormalities were repaired with operation. CONCLUSION: The benign nature of intimal injury identified with angiography may be overemphasized. The results of long-term follow-up in patients with this type of injury must be reviewed before "observation alone" can be recommended as standard treatment.