An atlas of gene expression and gene co-regulation in the human retina.

The human retina is a specialized tissue involved in light stimulus transduction. Despite its unique biology, an accurate reference transcriptome is still missing. Here, we performed gene expression analysis (RNA-seq) of 50 retinal samples from non-visually impaired post-mortem donors. We identified novel transcripts with high confidence (Observed Transcriptome (ObsT)) and quantified the expression level of known transcripts (Reference Transcriptome (RefT)). The ObsT included 77 623 transcripts (23 960 genes) covering 137 Mb (35 Mb new transcribed genome). Most of the transcripts (92%) were multi-exonic: 81% with known isoforms, 16% with new isoforms and 3% belonging to new genes. The RefT included 13 792 genes across 94 521 known transcripts. Mitochondrial genes were among the most highly expressed, accounting for about 10% of the reads. Of all the protein-coding genes in Gencode, 65% are expressed in the retina. We exploited inter-individual variability in gene expression to infer a gene co-expression network and to identify genes specifically expressed in photoreceptor cells. We experimentally validated the photoreceptors localization of three genes in human retina that had not been previously reported. RNA-seq data and the gene co-expression network are available online (http://retina.tigem.it).

Free flap reconstruction in patients with advanced oral squamous cell carcinoma: analysis of patient survival and cancer recurrence.

BACKGROUND: The purpose of this study was to compare the initial conditions and treatment outcomes of patients with advanced stage IV oral squamous cell carcinoma (OSCC) treated with or without free flap reconstruction following ablative tumor resection. METHODS: Two hundred forty-two pathological stage IV OSCC patients (without distant metastasis) treated by tumor ablation with free flap reconstruction (Group 1; n = 93) or without free flap reconstruction (Group 2; n = 149 treated with split-thickness skin grafts, primary closure of defects, secondary granulation of defects, and local or regional flaps) were recruited. We compared patient survival and cancer recurrence rates between these two groups. RESULTS: Group 1 had significantly more advanced tumor stage than group 2. Despite the unfavorably expected prognosis in group 1, both positive margin rate (17.2% in Group 1 versus 23.5% in Group 2, P = 0.213) and cancer recurrence rate (36.6% in Group 1 versus 38.3% in Group 2; P = 0.792) were not significantly different between the two groups. The 5-year disease-specific survival were also the same (51.4% in Group 1 versus 52.6% in Group 2; P = 0.493). CONCLUSIONS: Although cancer stages were more advanced in patients requiring free flap reconstruction, patient survival, and cancer recurrence in the patients with free flap reconstruction were maintained as patients without free flap.

Free medial plantar artery perforator flaps for the resurfacing of thumb defects.

BACKGROUND: Destruction of the thumb secondary to trauma presents a much more significant influence on daily living than do injuries to the other digits. Various surgical techniques contribute to repair distal defects of the fingers, especially thumb reconstruction. METHODS: Seven patients received free medial plantar artery perforator (MPAP) flaps to resurface the palmar defects of their thumbs. The flaps can be harvested with or without the main trunk of the medial plantar artery. The perforator of the MPAP flap was anastomosed to a proper digital artery, and the superficial vein of the flap was anastomosed to the dermal vein of the injured finger. These thumbs had no severe length discrepancy or metacarpophalangeal joint injuries. All patients underwent examinations including static 2-point discrimination, moving 2-point discrimination, and Semmes-Weinstein Test Score 6 months after reconstructive surgery. All tests were carried out by the same occupational therapist 6 months after reconstructive surgery. RESULTS: Five male and 2 female patients were selected for free MPAP flap reconstruction from May 2006 to September 2007. The mobility of the fingers was not restricted after surgery. Six flaps survived completely, and 1 flap partially failed because of venous congestion. Sensory restoration was ideal for all 7 MPAP flaps. CONCLUSION: The MPAP flap is a suitable choice for reconstructing palmar defects of the fingers, with less donor site morbidity. The cushiony character of the MPAP flap is anatomically similar to the pulp tissue of fingers, and sensory restoration is ideal compared with that of other reconstructive methods. Technical difficulty is focused on anastomosis of perforators (diameter ≤0.8 mm).

Free flap options for reconstruction of complicated scalp and calvarial defects: report of a series of cases and literature review.

OBJECTIVE: The advent of free tissue transfer has offered several options that allow the restoration of both the structural and functional defects of the scalp and calvaria caused by malignant tumors or sequelae after trauma. This study aims to investigate the free flap options for complicated scalp and calvarial reconstructions. METHODS: There were 12 free tissue transfers used to reconstruct scalp and calvarial defects in this study, with nine acute or subacute wounds resulting from trauma or cranietomy, two congenital hydrocephalus post ventriculo-peritoneal shunting and one primary cancer. They consisted of five fasciocutaneous flaps (four anterolateral thigh fasciocutaneous flaps and one deep inferior epigastric perforator flap) and seven myocutaenosu flaps (five anterolateral thigh myocutaneous flaps and two rectus abdominis myocutaneous flaps). RESULTS: The overall flap success rate was 100%. There were no major complications except for one where wound dehiscence was caused by hematoma accumulation and was healed by local debridement. All donor sites underwent primary closure except for three receiving split-thickness skin grafting after bulky anterolateral thigh flap harvest. No major donor-site morbidity was observed except for one patient with some graft loss. CONCLUSIONS: With its evident structural and functional advantages, fasciocutaneous flaps were suitable for larger scalp defect only and myocutaneous flaps can be considered as an excellent reconstructive option for complicated scalp and calvarial defects, especially where dead space coexists.

Free medial plantar artery perforator flap for finger pulp reconstruction: report of a series of 10 cases.

PURPOSE: Treatment of composite tissue loss in the finger pulp is often difficult. The purpose of this report is to present our experience on using medial plantar artery perforator flap for repair of finger pulp defects and to restore fingertip sensation after traumatic injury. PATIENTS AND METHODS: The free medial plantar artery perforator (MPAP) flaps were performed for digital pulp reconstruction in ten patients (eight fingertips and two thumbtips) between June, 2006 and December, 2007. This flap blood supply was perforator vessel of medial plantar artery, which was through the intermuscular septum between the abductor hallucis muscle and the flexor digitorum muscle. The recipient vessels were digital artery and dorsal digital vein. The flap was not reinnervated during transfer procedures. The donor sites were closed primarily in all cases. RESULTS: Flap size ranged from 15 x 25 mm to 60 x 20 mm. All flaps were survival. Partial loss occurred in one flap, due to venous congestion caused by excessive stitch tension. The donor sites healed unevenfully in eight cases, but mild wound dehiscence occurred in two cases. The follow-ups ranged from 6 to 29 months with the mean of 18.1 months. The mean of s-2PD and m-2PD were 8.8 mm and 6.8 mm at patients' last visits, respectively. CONCLUSION: MPAP flaps are good in terms of general morbidity, cosmetic results, and durability. This flap is a valuable alternative method of repairing the glabrous finger pulp and tip defects.

A dynamic technique for the treatment of severe or recurrent blepharoptosis: frontalis-orbicularis oculi muscle flap shortening.

BACKGROUND: Severe or recurrent blepharoptosis remains a great challenge to most plastic surgeons. A variety of techniques have been developed according to the function of the levator palpebrae superioris and frontalis muscles. In this study, the frontalis-orbicularis oculi (FOO) muscle flap is designed as an entity to treat severe or recurrent blepharoptosis with satisfactory results. METHODS: Between January 1997 and July 2007, FOO muscle flap shortening was applied to correct severe or recurrent blepharoptosis in 29 patients (38 eyelids), aged from 3 to 77 years. There were 11 males and 18 females, with bilateral ptosis in 9 patients. The follow-up period ranged from 10 to 52 months. RESULTS: Twenty-four patients (82%) had good results, with the degree of ptosis less than 2 mm. The remaining 5 patients had fair results, and received readjustment in 2 cases. CONCLUSION: In our study, fresh cadaver dissection revealed that the frontalis muscle is connected and interdigitated very closely with the orbicularis oculi muscle. Based on the anatomic study and literature review, we suggest that the FOO muscle flap shortening is a good alternative to treat severe or recurrent blepharoptosis.

Forehead osteoma excision by endoscopic approach.

Six cases of frontal osteoma had been operated with assistance of endoscopic surgery. Patient age ranged from 34 to 59 years. The diameter of the masses varies from 8 to 14 mm. The access incision was hidden behind the frontal hairline and the dissection plane went in the subperiosteal layer. The injury of the nerve branch and vessel can be easily avoided and endorsed by manipulating the endoscope. The average length of the procedure was 59.5 minutes. There is no complication such as scalp sensation impairment or hematoma over the forehead or scalp area. The elimination of the forehead osteoma can be executed at the forehead area scarlessly by the assistance of the endoscopic-assisted surgery.

Ocular surface area changes after double eyelidplasty.

INTRODUCTION: Double eyelidplasty is one of the most common cosmetic surgeries in Asia. Subjective enlargement of the ocular surface area (OSA) after double eyelidplasty was appreciated by patients. Objective measurement of the OSA provides a more scientific result. We introduce a relatively precise method, using iris as a scale combined with the digital photography and software calculation, to measure the OSA before and after double eyelidplasty. MATERIALS AND METHODS: One hundred and nineteen patients (108 females and 11 males) were enrolled in this study. Ninety-two patients received minimally invasive double eyelidplasty without other procedures and 27 patients received medial epicanthoplasty with modified Z-plasty besides double eyelidplasty. Digital photographs of the operative eyes in all patients were obtained preoperatively and postoperatively. The image processing software we used was ImageJ (v1.43, National Institutes of Health, United States). Preoperative and postoperative OSAs were measured. The percentage of difference of the OSA between two eyes in same patient before and after the operation was calculated and compared. RESULTS: The average increase of the OSA among 238 operative eyes was 12.5 ± 8.2%. Preoperative and postoperative OSA differences between two eyes in same patients were significantly decreased after surgery. CONCLUSION: Digital photography using iris as a scale combined with software calculation is an easy and convenient method to measure the OSA; it provides quantitative information for both preoperative and postoperative evaluation. Our study revealed that double eyelidplasty not only increased OSA but also improved ocular asymmetry after surgery.

Salvage for pectoralis major myocutaneous flap failure in head and neck reconstruction by microvascular flap.

The pectoralis major myocutaneous pedicled flap (PMMPF) - the "workhorse" for head and neck reconstruction - is associated with a high incidence of complications in certain cases. This study presents free tissue transfer as an alternative salvage technique after PMMPF failure in head and neck reconstruction. It includes seven consecutive patients who underwent free tissue salvage after PMMPF failure in head and neck reconstruction from January 2008 to September 2010 at Kaohsiung Medical University Hospital, Taiwan. Four vertical rectus abdominis myocutaneous (VRAM) flaps were applied for tongue and mouth floor defects, while three anterolateral thigh (ALT) flaps were used for mouth floor, buccal, and cheek defects. All flaps survived uneventfully, and normal oral feeding was achieved without major complications. Free tissue transfer has several advantages and can be successfully employed in head and neck reconstruction, and it is also a reliable salvage procedure after PMMPF failure in such cases.

Medial epicanthoplasty based on anatomic variations.

The presence of epicanthal folds is a unique appearance in the eyelids of Asians. Various medial epicanthoplasty techniques have been discussed to achieve a better aesthetic result. Owing to the complexity of the surgery, a design based on anatomic variations of the epicanthal fold is imperative. From September 2006 to November 2010, the author performed medial epicanthoplasty procedures on 86 Asian patients. The whole procedure, including discrepant Z skin incision, myotomy and the plication of the medial canthal ligament (MCL), was performed layer by layer. The inner canthal distance (ICD) was measured and calculated by software ImageJ before and 3 months after surgery. All patients were satisfied with the long-term results and there were no recurrences of the epicanthal fold. The shortening ratios of the ICD ranged from 7.2% to 13.7% (average 10.78%) in the group without the plication of the MCL (57/86). In addition, the ICD shortening ratio ranged from 9.1% to 17.7% (average 15.66%) in the group with the MCL plication (29/86). The technique we described is aimed to correct layered structures including skin, muscle and the MCL of the medial epicanthus. Satisfactory results were ideally achieved with finer scar and natural cosmetic appearance in this series.

Alternative reconstruction of donor defect of free radial forearm flap in head and neck cancer.

We report our method of restoration of the radial artery in the use of the anterolateral thigh (ALT) flap to overcome the important drawback of sacrificing the radial artery in cases of free radial forearm flap (FRFF), which is indicated for reconstruction of the tongue and other intraoral defects. There were 12 patients in our series, but only seven completed their postoperative evaluations. We harvested FRFF and ALT flaps simultaneously. The former was used for palatal or lip reconstruction and the latter was anastomosed as a flow-through flap to salvage the radial artery. All major donor site problems of the FRFF were solved by coverage by the ALT flap, except for abnormal sensation on the radial side of the donor hand. The FRFF is a proper choice for small tongue or lip defects. When it is chosen for its unique merits, the ALT flap can also serve as an alternative in reconstructing the donor site with least morbidity, including the restoration of patency to the radial artery.

A new trend for the treatment of blepharoptosis: frontalis-orbicularis oculi muscle flap shortening technique.

Operation techniques for blepharoptosis have been a great challenge for plastic surgeons. Complications and recurrence in conventional operations of eyelid ptosis cannot be neglected. The finding of the close linkage between the longitudinal-oriented frontalis muscle (FM) and the horizontal-orientated orbicularis oculi (OOM) muscle convinced us of the efficacy to develop the dynamic and powerful Frontalis-Orbicularis Oculi Muscle (FOOM) flap-shortening technique which corrects blepharoptosis with good biomechanics in place of the traditional frontalis muscle sling. From January 2003 to September 2007, the FOOM flap shortening technique was applied on 35 ptotic eyelids of 31 patients, age ranging from 18 year to 77 years. All FOOM flaps were harvested and adjusted depending on the severity of the blepharoptosis. The follow up period ranged from 5 to 55 months. Thirty eyelids had good results, with the degree of ptosis less than 2mm. There were only five recurrent ptotic eyelids due to technical undercorrection. The estimation of resected length is measured when the FOOM flap is fully stretched and the length is approximately 22.0-23.0 mm for mild cases, 23.0-24.0 mm for moderate cases, and 25.0-26.0 mm for severe blepharoptosis. The FOOM flap-shortening technique was developed and corrected blepharoptosis with good results compared to conventional operation techniques. It achieves antagonistic equilibrium with ideal biomechanics by debilitating eye-closing power and enhancing eye-opening power.

Contour refinements of free flaps for optimal outcome in oral reconstruction: combination of modified liposuction technique and w-plasty in one-stage procedure.

BACKGROUND: Bulkiness and unsightly scarring are the major complaints after oral cancer reconstruction with free flap transfer. Some debulking procedures, such as blunt-tipped cannula liposuction or staged excision, can result in some improvement, but these methods do not provide a one-stage procedure for flap thinning and scar revision due to the concern of flap ischemic change. All suction lipectomy methods were applied on flap resurfacing cases; no through-and-through defect case was used. The author used a nonstandard open-tip cannula for liposuction and w-plasty for scar revision in a one-stage operation in oral through-and-through defect cases. This method achieved excellent aesthetic results without complications. MATERIAL AND METHODS: From January of 2004 to October of 2006, secondary debulking procedures were performed on 22 patients who had undergone reconstruction with free anterolateral thigh flaps. All flaps were on the cheek for oral cancer through-and-through defect reconstruction. Suction lipectomy with nonstandard open-tip cannula and w-plasty were performed. RESULTS: All flaps survived well without any partial skin necrosis. Over 85% of patients were satisfied with the outcome. CONCLUSIONS: This method can provide a one-stage debulking procedure for the cheek through-and-through defect after free flap reconstruction, and it achieves good aesthetic outcomes.

Downregulation of Janus kinase 3 expression by small interfering RNA in rat composite tissue allotransplantation.

RNA interference (RNAi) has recently emerged as an efficient method to silence gene expression in mammalian cells by transfection of small interfering RNAs (siRNAs). The Janus kinase 3 (JAK3) is also pertinent to the development of a new immuno-suppressant. This study aimed to inhibit JAK3 expression using RNAi to determine allograft tolerance. To silence JAK3 expression, one dsRNA was tested to incorporate the JAK3 mRNA sequence. The expression vector containing the pre-mRNA expression cassette was transfected into rat basophilic leukemia cell line, RBL-2H3, for RNAi analysis (in vitro). The alloskin and composite tissue allograft were then transplanted to recipients using RNAi protocol to determine the allograft tolerance (in vivo). The results showed effective in vitro and in vivo downregulation of JAK3 expression by RNAi. Moreover, the histology of alloskin graft and composite tissue allograft (in vivo) under the siRNA showed more prominently diminished inflammatory infiltration than the control group. This is the first time in the literature that the suppressive effect of JAK3 silenced by siRNA has been tested both in vitro and in vivo, and shows that siRNA is capable of specific and functional silencing in allograft rejection.

Refinement of reverse digital arterial flap for finger defects: surgical technique.

We have designed a refinement of the reverse digital artery flap technique for soft-tissue defects on the dorsum of the fingers. In contrast with the traditional reverse digital artery flap it reduces the morbidity at the donor site and increases the ease and availability of resurfacing the defect. We suggest it is an alternative for the resurfacing of finger defects, especially over the dorsum.