Automatic detection of midfacial fractures in facial bone CT images using deep learning-based object detection models.

BACKGROUND: Midfacial fractures are among the most frequent facial fractures. Surgery is recommended within 2 weeks of injury, but this time frame is often extended because the fracture is missed on diagnostic imaging in the busy emergency medicine setting. Using deep learning technology, which has progressed markedly in various fields, we attempted to develop a system for the automatic detection of midfacial fractures. The purpose of this study was to use this system to diagnose fractures accurately and rapidly, with the intention of benefiting both patients and emergency room physicians. METHODS: One hundred computed tomography images that included midfacial fractures (e.g., maxillary, zygomatic, nasal, and orbital fractures) were prepared. In each axial image, the fracture area was surrounded by a rectangular region to create the annotation data. Eighty images were randomly classified as the training dataset (3736 slices) and 20 as the validation dataset (883 slices). Training and validation were performed using Single Shot MultiBox Detector (SSD) and version 8 of You Only Look Once (YOLOv8), which are object detection algorithms. RESULTS: The performance indicators for SSD and YOLOv8 were respectively: precision, 0.872 and 0.871; recall, 0.823 and 0.775; F1 score, 0.846 and 0.82; average precision, 0.899 and 0.769. CONCLUSIONS: The use of deep learning techniques allowed the automatic detection of midfacial fractures with good accuracy and high speed. The system developed in this study is promising for automated detection of midfacial fractures and may provide a quick and accurate solution for emergency medical care and other settings.

Automatic orbital segmentation using deep learning-based 2D U-net and accuracy evaluation: A retrospective study.

The purpose of this study was to verify whether the accuracy of automatic segmentation (AS) of computed tomography (CT) images of fractured orbits using deep learning (DL) is sufficient for clinical application. In the surgery of orbital fractures, many methods have been reported to create a 3D anatomical model for use as a reference. However, because the orbit bone is thin and complex, creating a segmentation model for 3D printing is complicated and time-consuming. Here, the training of DL was performed using U-Net as the DL model, and the AS output was validated with Dice coefficients and average symmetry surface distance (ASSD). In addition, the AS output was 3D printed and evaluated for accuracy by four surgeons, each with over 15 years of clinical experience. One hundred twenty-five CT images were prepared, and manual orbital segmentation was performed in all cases. Ten orbital fracture cases were randomly selected as validation data, and the remaining 115 were set as training data. AS was successful in all cases, with good accuracy: Dice, 0.860 ± 0.033 (mean ± SD); ASSD, 0.713 ± 0.212 mm. In evaluating AS accuracy, the expert surgeons generally considered that it could be used for surgical support without further modification. The orbital AS algorithm developed using DL in this study is extremely accurate and can create 3D models rapidly at low cost, potentially enabling safer and more accurate surgeries.

Successful resection of growing teratoma syndrome in the abdominal wall with reconstruction using tensor fascia lata muscle flap: A case report and literature review.

While cancer cure is the primary goal, fertility preservation is also a cornerstone of the underlying principle of treatment for ovarian germ cell tumors. Growing teratoma syndrome (GTS) presents with growth of mature teratomas during or after chemotherapy. We report a case of successful treatment of GTS in the anterior abdominal wall involving reconstruction. A 23-year-old woman with a suspected right ovarian mature teratoma with torsion underwent emergency laparoscopically assisted extracorporeal ovarian cystectomy. Histopathological findings revealed a grade 1 immature teratoma. After two months, postoperative α-fetoprotein (AFP) levels increased, and disseminated lesions developed not only in the pelvic cavity but also in the abdominal wound where the tumor had been extracted using an extracorporeal technique at the time of primary surgery. The patient underwent laparoscopic right salpingo-oophorectomy, excision of multiple peritoneal nodules, and biopsy of abdominal wall mass. The left rectus abdominis muscle tumor could not be removed. All of these nodules were diagnosed as metastatic immature teratomas. Although the patient received three cycles of chemotherapy, the residual tumor in the abdominal wall grew remarkably despite post-chemotherapy normalization of AFP levels. Both rectus abdominis muscles involving the residual tumors were removed and reconstructed using a left tensor fascia lata muscle flap. Histopathologically, the residual tumors were identified as mature teratomas with no immature elements, resulting in GTS. The patient got pregnant without the need of fertility treatment and gave birth uneventfully by cesarean section. Thus, reconstruction with a tensor fascia lata muscle flap facilitated complete removal of GTS while preserving fertility.

Localization of Chronic Pain in Postmastectomy Patients: A Prospective Comparison Between Patients With and Without Breast Reconstruction.

BACKGROUND: After breast surgery with or without immediate reconstruction, chronic pain can be a major problem for patients. However, few studies have examined the details of the sites of long-lasting postoperative pain. In this study, we specified the postoperative pain location after breast surgery, including reconstruction, to find ways to improve surgical procedures or provide effective pain relief. METHODS: The subjects were 205 Japanese women undergoing mastectomy or breast reconstruction with a tissue expander (TE)/implant or a deep inferior epigastric perforator (DIEP) flap. Patients were asked whether they had pain in different parts of the body at 1 year after surgery. Differences were assessed by cross-tabulation and χ2 statistics. RESULTS: Surveys were completed by 157 subjects. Deep inferior epigastric perforator flap cases had significantly more pain and TE/Imp cases had significantly less pain in the medial breast, upper breast, breast upper medial quadrant, and abdomen (P = 0.006, P = 0.006, P < 0.001, P < 0.001, respectively). In the neck area, pain in TE/Imp cases was significantly worse than that in all other patients (P = 0.025). There was no significant difference in chronic pain in any other body regions among the mastectomy only, TE/Imp, and DIEP flap groups. CONCLUSIONS: The results of the present study revealed that the localization of prolonged postoperative pain after breast surgery differs depending on the surgical procedure. In DIEP flap reconstruction, there was a marked tendency for pain in the inner and upper chest and in the abdomen, whereas TE/IMP surgery resulted in pain around the neck of the affected side. These findings may help improve surgical methods and establish effective pain relief that focuses on the identified pain areas.

A Medical Tattooing Technique for Enhancing the Three-Dimensional Appearance of the Nipple-Areola Complex After Flap-Based Nipple Reconstruction.

INTRODUCTION: Medical tattooing is a critical reconstructive component in the surgical process for good esthetic outcomes and improved patient satisfaction. There are many nipple reconstruction methods that use a local flap, but reduced post-operative nipple projection is a common problem. Here, we report a modified tattooing method (3D-E tattoo) that enhances the three-dimensional appearance of the nipple-areola complex (NAC), including Montgomery glands, after flap-based nipple reconstruction. METHODS: The subjects were 110 consecutive patients who underwent nipple reconstruction using the C-V flap technique between April 2017 and June 2019. Of these patients, 49 received traditional medical tattooing (Group T) and 61 underwent 3D-E tattoo (Group 3D). A 10-point subjective evaluation of the 3D appearance of the reconstructed NAC was performed, and the scores were compared between the groups. RESULTS: The procedure time for 3D-E tattoo was about 5 minutes longer than that for traditional tattooing. The average score in Group 3D of 7.8/10 was significantly higher than that of 6.4/10 in Group T. CONCLUSION: Application of 3D techniques or "realism" in tattoo artistry has significant potential to improve the esthetic outcomes of reconstructive surgery. Adoption of simple technical skills to produce a more realistic 3D NAC permitted a symmetrical appearance to be reconstructed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Extension toward the Trapezius in a Transversely Oriented Latissimus Dorsi Flap for Breast Reconstruction.

A transverse paddle latissimus dorsi (LD) flap has the advantage that if the skin paddle is placed in the transverse bra line, the donor site scar is well hidden by underwear. With this transfer, medial back tissues are usually moved to the medial area of the reconstructed breast following 180 degree rotation. Because these tissues are thinner than the lateral thoracic area, the medial part of the reconstructed breast sometimes becomes flatter than expected. METHODS: To add bulk in the medial lower quadrant for giving an impression of an outward-expanding breast, we modified the LD flap by adding a part of the trapezius muscle. Seven patients underwent mastectomy and simultaneously received a modified LD flap. To hide the donor site scar beneath underwear, the skin paddle needed to be oriented transversely. The additional harvested tissues were tested for vascularity by fluorescence following intravascular injections of indocyanine green. If this was negative, the tissue was not used for breast reconstruction. Postoperatively, another surgeon judged whether this modification had contributed favorably to the reconstructed medial lower quadrant. RESULTS: Indocyanine green testing was positive in six cases. The shape of the lower medial quadrant was judged as good in five of the seven cases. Complications included an animation deformity of the LD muscle, donor site seroma, and donor site wound dehiscence. CONCLUSION: This transversely oriented LD flap with extension to the trapezius muscle placed at the bra-line is one option to add bulk to the medial lower quadrant of the reconstructed breast when an additional scar is not desired for cosmetic reasons.

Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.

The influence of venous system patterns on DIEP flap viability for breast reconstruction.

A deep inferior epigastric artery perforator (DIEP) flap has unique variations in the anatomy of the vascular supply, and this idea has been adapted to the venous system. Venous system patterns, including connections between the superficial and deep inferior epigastric vein (SDC) or connections of the superficial inferior epigastric vein across the midline-crossing linking veins (MCLV), have gradually become recognized as a cause of fat necrosis and induration due to venous congestion. Therefore, it is important to select patients who are appropriate for transplantation by evaluating blood flow in the flap based on these patterns. The subjects were 52 consecutive patients who underwent DIEP flap breast reconstruction. Relationships of fat necrosis and induration of a transplanted flap and venous system patterns (presence of SDC on the contralateral side: cSDC or MCLV, direction and diameter of perforator vein) in the flap were investigated. Logistic regression and univariate and multivariate analyses were used to identify predictors of fat necrosis and induration of the flap. Fat necrosis and induration were detected in 17.4 and 34.8% of cases, respectively. These incidences were significantly linked to the absence of cSDC and MCLV patterns in the flap. Patients without a cSDC or MCLV pattern had harder fat tissue in Zone II, especially in the distal portion. These results suggest that the absence of a cSDC or MCLV pattern causes complications such as fat necrosis and induration in a transplanted flap. If neither pattern is detected before surgery, improvement of venous drainage is recommended.

Can Lymph Transportation Capacity Predict Treatment Efficacy of Lower Extremity Lymphedema by LVA?

Treatment outcomes for lower extremity lymphedema (LEL) using multiple lymphaticovenular anastomoses (LVA) are still uncertain. Classification of progression of lymphedema by disease staging is a potential preoperative predictor of the efficacy of treatment, but it is difficult to judge progression of lymphedema objectively. Recent studies have indicated that lymph pump dysfunction, which reflects lymph transportation capacity, is associated with lymphedema progression. Indocyanine green (ICG) lymphography, a minimally invasive modality for pathophysiological assessment of lymphedema, can be used for rapid and objective measurement of ICG velocity (ICGv) and transit time to the knee (TTk), which are parameters of lymph transportation capacity, over a certain period. In the current study, we analyzed the relationship between these parameters and outcomes for LEL treated by multiple LVA. Thirty-four consecutive patients who underwent multiple LVA and ICG lymphography were enrolled in the study. The relationship of ICGv and TTk with the efficacy of treatment by LVA (LEL index reduction) was investigated using Pearson correlation coefficient analysis. LEL index reduction was more strongly correlated with ICGv than with TTk, whereas it was weakly correlated with both quantification methods of lymph pump function (r > 0.6). Both ICGv and TTk are objective and simple parameters that can measure lymph pump functions quickly. Lymph pump function, especially calculated with ICGv, might help predict the treatment efficacy and objective evaluation after therapeutic intervention using multiple LVA.

Temporary banking of the nipple-areola complex in breast reconstruction following mastectomy for gigantomastia.

INTRODUCTION: Gigantomastia is a breast disorder characterized by exaggerated rapid growth of the breasts, generally bilaterally. In some severe cases, mastectomy is required to ensure safe delivery or control disease progression or recurrence. Subsequently, most patients want to undergo breast reconstruction, including the nipple-areola complex (NAC). PRESENTATION OF CASE: Here, we report our experience with temporary banking of the NAC in a patient who underwent mastectomy for severe Gigantomastia. Each NAC was temporarily transplanted into the axilla as banking tissue for NAC reconstruction at a later date. Although the color of the NAC was slightly lighter after reconstruction, it mainly kept its original color and texture in addition to medical tattooing technique. At present, there has been no recurrence and the patient is fully satisfied with her appearance. DISCUSSION: In this case, mastectomy was recommended because of an unbearable breast size that disturb a safety delivery, as well as respiratory and cardiac complications and skin ulcer control. Because the disease is not pathologically malignant, temporary preservation of NAC allows it to be safely used again for later nipple reconstruction. CONCLUSION: Temporary banking of the nipple-areola complex in breast reconstruction following breast resection including NAC, would be one of good surgical options for benign breast tumors like　gigantomastia.

Innovative CAD/CAM Guide for Mandibular Reconstruction with Metallic Condylar Head and Free Fibular Flap.

In reconstructions of mandibles and condyles, free fibular flaps and metallic condylar heads (CH) are often used after resection. However, in conventional reconstructions, it is difficult to fix the metallic CH on the same preoperative position because the position is determined visually. Therefore, we have made an original computer-aided design and manufacture (CAD/CAM) guide for mandibular condyle reconstruction, combining a metallic CH with a free fibular flap. A 71-year-old woman with gingival carcinoma underwent hemimandibulectomy. We reconstructed the mandible and condyle with a metallic CH and a free fibular flap. We placed a mark on the CAD/CAM guide showing the correct position for fixing the CH to the fibular blocks. We also designed a surface for attaching to the healthy edge of the mandible. The fibular blocks and metallic CH were fixed as 1 unit before separating the flap from the leg and replacing the diseased tissue. Reconstruction was completed by fixing the attachment surface to the healthy side of the mandible. The guide marks solved the difficulty of conventional reconstruction; during surgery, we fixed the metallic CH to the same position as the original bone using these marks. The postoperative deviation of the condyle from the virtual plan was 4.3 mm, whereas the reported deviation of such prostheses was 3.8 mm (range 1.3-6.7); so our guide was acceptably accurate. Furthermore, it appears that the CAD/CAM guide is more useful for reconstruction after hemimandibulectomy including the condyle than after segmental resection without including condyle.

Does an In-House Computer-Aided Design/Computer-Aided Manufacturing Approach Contribute to Accuracy and Time Shortening in Mandibular Reconstruction?

Mandibular reconstruction using computer-aided design and computer-assisted manufacturing (CAD/CAM) techniques has received recent attention. This technique has theoretical advantages, although this approach can be commercially used in the limited area of the world.The aim is to describe our experience using in-house CAD/CAM guides and the situations in which CAD/CAM may present benefit in the region where commercial guides are unavailable.The authors developed our In-house CAD/CAM approach for mandibular reconstructions with a free fibular flap. Patients were divided into 2 group; CAD/CAM and conventional groups. In the CAD/CAM group, reconstructions were planned virtually using CAD/CAM; these CAD/CAM guides were used in the surgery. In the conventional group, free-hand cutting and fitting of the fibular segments were performed as reconstructions. Later, the bone computed tomographic image was compared with the plan. The averaged deviations and the percentages of the points within 1 mm, 2 mm, and 3 mm deviations were recorded. Total and ischemic time were also recorded.Reconstruction points within 1 mm deviation were 59% of CAD/CAM group (n = 9) and 42% of conventional group (n = 10, P = 0.04), within 2 mm 82% and 69% (P = 0.03). Total time were 1012 and 911 minutes, while flap ischemic time were 147 and 175 minutes (P = 0.03), respectively.In-house CAD/CAM mandibular reconstruction also supported accuracy and shorter flap ischemic time. For a detailed accurate reconstruction, CAD/CAM showed superiority than conventional method. Use of the In-house CAD/CAM guides might be an option where commercial guides are not available.

Two Cases of the Vascular Territory of a Single-pedicled Deep Inferior Epigastric Perforator Flap with a Vertical Midline Abdominal Scar.

: The deep inferior epigastric perforator (DIEP) flap is becoming the gold standard for breast reconstruction using autologous tissue. If there are scars in the abdomen from previous surgery, it is necessary to judge the indication for using this flap carefully. Particularly in cases with vertical midline scars, the blood flow supply to the zone II can be compromised. Even when patients have a median abdominal scar, it has been reported that the blood flow can extend beyond the scar and reach several centimeters to about half of zone II. We performed breast reconstruction using DIEP flaps for 2 patients with vertical midline scars in the lower abdomen. Indocyanine green angiography was conducted intraoperatively to confirm the vascular territory with a single pedicle before cutting off the flap. One patient showed fluorescence contrast on the contralateral side across the midline scar. However, the fluorescence contrast was absent across the midline scar in the other patient. Based on this result, we investigated the possible vascular territory of a single pedicled DIEP flap in patients with vertical midline abdominal scars. We suggest that successful blood supply to zone II of a single-pedicled DIEP flap in a patient with a vertical midline abdominal scar is related to the location of the perforator and the property of the tissue in the midline near the perforator. However, because it is difficult to predict the vascular territory of a single pedicle before surgery, intraoperative evaluation using such techniques such as indocyanine green fluorescence imaging is important.

Factors associated with chronic pain following breast reconstruction in Japanese women.

Chronic pain after breast surgery including breast reconstruction is a major concern for patients. However, the factors associated with chronic pain after breast surgery are uncertain in Japanese population. The aim of this study was to identify patient-specific and medical/surgical factors that predict chronic pain after breast surgery in Japanese patients. The subjects were 189 Japanese women undergoing breast surgery including tissue expander/implant (TE/implant), deep inferior epigastric perforator (DIEP) procedures and mastectomy only. Pain was assessed at one year postoperatively using a validated survey instrument: the Japanese version of the Short-Form McGill Pain Questionnaire (SF-MPQ-JV). A multiple linear regression model was used to examine the relationships of clinical factors with postoperative pain. Surveys were completed by 141 subjects. A younger age (p = .04) and bilateral procedures (p < .05) were both closely associated with the extent of increased postoperative pain at 1 year using the MPQ-Total pain rating. Compared to total mastectomy only, TE/implant procedures showed a significantly lower visual analog scale (VAS) (p = .04) and present pain index (PPI) (p = .03) scores. No factor related to chronic pain was also significantly related to the frequency of pain medication use postoperatively or the effect of social life of the patients. This study identified patients at risk for greater chronic pain after breast surgery. These findings will allow surgeons to improve patient comfort, reduce clinical morbidity and enhance patient satisfaction with their surgical outcome. Abbreviations: BMI: body mass index; CI: confidence interval; DIEP: deep inferior epigastric perforator flap; MPQ: McGill pain questionnaire; PPI: present pain index; SD: standard deviation; SF-MPQ-JV: Japanese version of the short-form McGill pain questionnaire; TE: tissue expander; VAS: visual analog scale.

The HDAC inhibitor OBP-801 suppresses the growth of myxofibrosarcoma cells.

PURPOSE: Myxofibrosarcoma is characterized by a high rate of recurrence after surgery. Since myxofibrosarcoma is refractory to conventional cytotoxic chemotherapy, the established radical treatment is primary wide resection. The effects of histone deacetylase (HDAC) inhibitors on myxofibrosarcoma have not yet been investigated. Therefore, the main purpose of the present study was to examine the effects of a HDAC inhibitor on myxofibrosarcoma. METHODS: The effects of the HDAC inhibitor OBP-801 on human myxofibrosarcoma cells were examined using cell viability assay, flow cytometric analysis of the cell cycle and apoptosis, and Western blotting. The effects of combinations of OBP-801 with pazopanib or Akt-mTOR inhibitors were also investigated using cell viability assay. RESULTS: OBP-801 inhibited the growth of myxofibrosarcoma NMFH-1 and NMFH-2 cells. It also induced cell cycle arrest at the G2 phase and apoptosis in both cell lines. The inhibitory effects of pazopanib and Akt-mTOR inhibitors on the growth of myxofibrosarcoma cells were enhanced by the combination with OBP-801. CONCLUSIONS: The present results demonstrated that OBP-801 exerted therapeutic effects in myxofibrosarcoma in both single and concomitant administrations. Therefore, OBP-801 has potential as a novel treatment for myxofibrosarcoma.

Involvement of PDGF-BB and IGF-1 in Activation of Human Schwann Cells by Platelet-Rich Plasma.

BACKGROUND: Platelet-rich plasma contains high concentrations of growth factors that stimulate proliferation and migration of various cell types. Earlier experiments demonstrated that local platelet-rich plasma administration activates Schwann cells to improve axonal regeneration at a transected peripheral nerve lesion. However, the optimal concentration of human platelet-rich plasma for activation of human Schwann cells has not been determined, and mechanisms by which platelet-rich plasma activates Schwann cells remain to be clarified. METHODS: Human Schwann cells were cultured with various concentrations of platelet-rich plasma in 5% fetal bovine serum/Dulbecco's Modified Eagle Medium. Cell viability, microchemotaxis, flow cytometry, and quantitative real-time polymerase chain reaction assays were performed to assess proliferation, migration, cell cycle, and neurotrophic factor expression of the human Schwann cells, respectively. Human Schwann cells were co-cultured with neuronal cells to assess their capacity to induce neurite extension. Neutralizing antibodies for platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor-1 (IGF-1) were added to the culture to estimate contribution of these cytokines to human Schwann cell stimulation by platelet-rich plasma. RESULTS: An addition of platelet-rich plasma at 5% strongly elevated proliferation, migration, and neurotrophic factor production of human Schwann cells. Both PDGF-BB and IGF-1 may be involved in mitogenic effect of platelet-rich plasma on human Schwann cells, and PDGF-BB may also play an important role in the migration-inducing effect of platelet-rich plasma. Neutralization of both PDGF-BB and IGF-1 cancelled the promoting effect of platelet-rich plasma on neurite-inducing activity of human Schwann cells. CONCLUSION: This study may suggest the optimal concentration of platelet-rich plasma for human Schwann cell stimulation and potential mechanisms underlying the activation of human Schwann cells by platelet-rich plasma, which may be quite useful for platelet-rich plasma therapy for peripheral nerve regeneration. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Medial Upper Lip Vermillion Reconstruction with a Labial Artery-based Cross-lip Vermillion Flap.

A defect of the central upper lip vermillion generally requires "like for like" reconstruction because this part of the upper lip can attract attention and has a unique structure and color. In this article, we report use of a labial artery-based horizontal long cross-lip flap for central upper lip vermillion reconstruction. In the first stage of surgery, a horizontal long vermillion flap from the lower lip starting at the left commissure with a vascular pedicle containing an inferior labial artery was raised and transposed to the upper vermillion defect. In the second stage, 12 days later, the pedicle was divided to complete the reconstruction. There were no postoperative complications in articulation or eating, and the patient was satisfied with the esthetic outcome. This surgical technique reduces microstomia and inconvenience in eating and speaking compared with a common horizontal cross-lip flap and provides better color- and texture-matched tissue compared to reconstruction using a tongue flap or mucosal flap. The technique is simple, requires a relatively short surgical time, has minimum donor-site morbidity and permits good esthetic and functional reconstruction of the central upper lip vermillion for a relatively small defect.