Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy.

BACKGROUND/AIMS: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO). METHODS: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed. RESULTS: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients' survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387-17.110, p = 0.013) was the only independent factor influencing overall survival. CONCLUSION: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.

[A Case of Advanced Gastric Cancer with Multiple Bone Metastases, Virchow Lymph Node and Para-Aortic Lymph Node Metastases That Responded to Combined Modality Therapy and Underwent Conversion Surgery].

A 41-year-old woman with type 3 advanced gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple bone metastases was diagnosed with U-less cType 3 cT4aN3M1, cStage IV. We administered docetaxel, cisplatin, and S-1 (DCS)therapy for unresectable gastric cancer. After 11 courses of DCS, we confirmed that the distant lymph node metasta- ses were significantly reduced. We performed radiotherapy(30 Gy/10 Fr)on the thoracic lumber vertebrae. Because the patient was successfully downstaged, we performed total gastrectomy with Roux-en-Y reconstruction. The histopathological diagnosis was ypT3N2M0, ypStage III A. In this case, DCS therapy successfully treated gastric cancer with distant metastases, including multiple bone metastases.

Therapeutic strategy aiming at R0 resection for borderline-resectable esophageal squamous cell carcinoma using induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil.

OBJECTIVE: Treatment for borderline resectable (cT3br) esophageal squamous cell carcinoma (SCC) is currently undefined. This study aimed to analyze the outcome of treatment strategies including induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) against T3br esophageal SCC. METHODS: A total of 32 patients with cT3br esophageal SCC enrolled in this study were treated with two cycles of DCF induction therapy. RESULTS: The overall response rate to DCF induction therapy was 62.5%, while the disease control rate was 93.8% (complete response (CR), three; partial response (PR), 17; stable disease (SD), 10; progressive disease (PD), 2). After DCF induction chemotherapy, 27 patients underwent conversion surgery (CS) and five patients underwent definitive chemoradiotherapy (CRT). Out of 27 patients who underwent CS, 17 underwent transthoracic esophagectomy and 10 underwent thoracoscopic esophagectomy. Anastomotic leakage occurred in five patients (18.5%) and pneumonia in four (14.8%). Recurrent laryngeal nerve paralysis and arrhythmia were observed in two patients (7.4%). The R0 resection rate was 81.5%. Among the five patients who underwent definitive CRT, only one patient (20.0%) achieved CR. Two patients (40.0%) had PR and two (40.0%) had PD. Salvage esophagectomy was performed in one patient after definitive CRT. The 1-, 3-, and 5-year overall survival rates were 75.0, 50.6, and 46.4%, respectively, whereas the 1-, 3-, and 5-year disease-free survival rates were 54.9, 38.8, and 38.8%, respectively. CONCLUSION: DCF induction therapy and subsequent CS or definitive CRT are promising treatment strategies for cT3br esophageal SCC.

Segmental cervical esophagectomy with free jejunal flap reconstruction for cervical esophageal cancer in patients with previous history of gastric surgery: a report of two cases.

Although free-flap jejunal reconstruction is frequently performed after cervical esophagectomy for cervical esophageal cancer, the procedure after gastric surgery has not been reported. We encountered two patients with esophageal cancer and previous gastric surgeries who eventually underwent segmental esophagectomy with free-flap jejunal reconstruction. Case one involved a 75-year-old man who underwent abdominal abscess and duodenal ulcer perforation surgeries (abdominal drainage and subsequent gastrojejunal bypass). A type 0-IIa tumor was located posterior to the cervical esophagus's right wall, 21 cm from the incisor, without lymph node swelling or distant metastasis. The left lobe of the thyroid gland was mobilized to ensure an oral resection margin. Severe abdominal adhesions required careful adhesiolysis to harvest the jejunum (20 cm long) 40 cm from the jejunojejunostomy. An end-to-side and side-to-end esophagojejunostomy were performed for the proximal and distal ends, respectively. Case two involved a 75-year-old male with a history of distal gastrectomy with Billroth I reconstruction for early gastric cancer. A submucosal tumor-like lesion was located on the cervical esophageal wall on the left side, 21 cm from the incisor. The distal esophagus required additional segmental resection because the anal resection line was close to the tumor. Jejunum (10 cm long) 30 cm from Ligament of Treitz was harvested. An end-to-side and end-to-end esophagojejunostomy for the proximal and distal ends, respectively, was performed. This surgery requires a thorough preoperative examination to ensure an adequate surgical margin and a careful free-flap harvest based on post-gastric surgery anatomy.

Successful combined laparoscopic and thoracoscopic surgery for esophago-mediastinal fistulae.

Minimally invasive surgeries have been developed, not only for gastrointestinal cancer, but also for benign or emergency cases. We report the case of a 62-year-old male who underwent laparoscopic and thoracoscopic combined surgery for an esophago-mediastinal fistula caused by a press-through package. In the initial laparoscopic phase, transhiatal dissection of the lower thoracic esophagus and harvesting of the greater omentum were performed. In the thoracoscopic phase, resection of the fistula and esophageal wall closure were performed. Thereafter, the greater omentum was lifted via the esophageal hiatus and wrapped around the repaired part of the esophagus for reinforcement. The total operative time was 371 min, with 163 and 208 min for the laparoscopic and thoracoscopic phases, respectively. In total, 20 ml of blood was lost. No perioperative complications or recurrences were observed. Laparoscopic and thoracoscopic combined omentoplasty was effective for refractory esophago-mediastinal fistula.

Dislocation of the gastric conduit reconstructed via the posterior mediastinal route is a significant risk factor for anastomotic disorder after McKeown esophagectomy.

BACKGROUND: Anastomotic disorder of the reconstructed gastric conduit is a life-threating morbidity after thoracic esophagectomy. Although there are various reasons for anastomotic disorder, the present study focused on dislocation of the gastric conduit (DGC). METHODS: The study cohort comprised 149 patients who underwent transthoracic esophagectomy. The relationships between DGC and peri- and postoperative morbidities were analyzed retrospectively. Data were analyzed to determine whether body mass index (BMI) and extension of the gastric conduit were related to DGC. Uni- and multivariate Cox regression analyses were performed to identify the factors associated with anastomotic disorder. RESULTS: DGC was significantly related to anastomotic leakage (P < .001), anastomotic stricture (P = .018), and mediastinal abscess/empyema (P = .031). Compared with the DGC-negative group, the DGC-positive group had a significantly larger mean preoperative BMI (23.01 ± 3.26 kg/m2 vs. 21.22 ± 3.13 kg/m2, P = .001) and mean maximum cross-sectional area of the gastric conduit (1024.75 ± 550.43 mm2 vs. 619.46 ± 263.70 mm2, P < .001). Multivariate analysis revealed that DGC was an independent risk factor for anastomotic leakage (odds ratio: 4.840, 95% confidence interval: 1.770-13.30, P < .001). Body weight recovery tended to be better in the DGC-negative group than in the DGC-positive group, although this intergroup difference was not significant. CONCLUSION: DGC reconstructed via the posterior mediastinal route is a significant cause of critical morbidities related to anastomosis. In particular, care is required when performing gastric conduit reconstruction via the posterior mediastinal route in patients with a high BMI.

Strategy Treatment of cT4b Esophageal Squamous Cell Carcinoma Using Docetaxel, Cisplatin, and 5-Fluorouracil.

BACKGROUND/AIM: This study analyzed the outcomes of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy and DCF plus concurrent radiotherapy (DCF-RT), both followed by conversion surgery, if possible, in patients with cT4b esophageal cancer. PATIENTS AND METHODS: Forty-six patients with cT4b esophageal cancer, including borderline cT4b lesions, were eligible. Borderline cT4b lesions were treated with induction DCF therapy. For definitive cT4b lesions, definitive DCF-RT was administered. Patients unsuitable for induction DCF therapy or DCF-RT were treated with other therapies. After treatment, conversion surgery (CS) was performed for the residual tumor in resectable cases. RESULTS: Induction DCF therapy was administered to 12 patients (group A), and DCF-RT was provided to 18 patients (group B). Meanwhile, other therapies were provided to 16 patients (group C). The 1-, 3-, and 5-year overall survival (OS) rates were 66.7, 30.0, and 15.0%, respectively, in group A; 66.7, 37.5, and 37.5%, respectively, in group B; and 62.5, 0, and 0%, respectively, in group C. DCF-RT tended to prolong survival, albeit without significance (p=0.1040). The group A + B had significantly better overall survival than group C (p=0.0437). Fourteen patients underwent CS (30.4%), and patients who underwent CS had significantly better overall survival than those who did not undergo surgery (p=0.0291). CONCLUSION: Induction DCF or DCF-RT is promising for the treatment of cT4b esophageal cancer. Effective CS including combined resection of the invaded organ can contribute to improved therapeutic outcomes.

The Prognostic Significance of Plakophilin-1 Expression in Esophageal Cancer.

BACKGROUND/AIM: Plakophilin 1 (PKP1) expression is inversely related to cancer grade. This study aimed to evaluate whether PKP1 is a prognostic marker for esophageal cancer (EC). MATERIALS AND METHODS: We tested immunohistochemically for PKP1 in squamous cell carcinoma EC specimens from 99 patients, including cytoplasmic (C), membrane (M), and nuclear (N) cellular areas, and analyzed their relationships with clinicopathological factors. RESULTS: PKP1stains were stratified into strong and weak for all three cellular areas. Staining was inversely related to tumor depth (C: p=0.002, M: p=0.00007, N: p=0.02), lymph node metastasis (C: p=0.003, M: p=0.001, N: p=0.004) and pathological stage (C: p=0.0004, M: p=0.0001, N: p=0.006). Cytoplasmic and membrane staining were inversely related to vessel invasion. Patients with strong C stain had a better overall survival than those with weak C stains (p=0.01). Disease-free survival of patients with strong M stains was better than that of those with weak staining (p=0.01). CONCLUSION: Cytoplasmic and membrane PKP1 expression is a possible prognostic marker for EC.

Treatment strategy for brain metastases from esophageal cancer.

BACKGROUND: This study aimed to examine the treatment outcomes of patients with brain metastases from esophageal cancer. Brain metastases from esophageal cancer are rare and have a poorer prognosis than brain metastases from lung and breast cancer. METHODS: This study included patients who were diagnosed with and treated for esophageal cancer in our department and subsequently developed brain metastases between April 2010 and December 2014. We examined the differences in survival in patients based on receiving chemotherapy. RESULTS: In total, 8 patients (7 men and 1 woman) with a mean age of 65 years (range 51-73) were included. Seven presented with neurologic symptoms. Two were diagnosed via computed tomography (CT), 5 via magnetic resonance imaging, and 1 via positron emission tomography/CT. They were treated using whole-brain irradiation or with a gamma knife. In 5 patients, chemotherapy was administered after treatment of the brain metastases. The mean survival from the start of treatment was 358 days (range 31-1196). CONCLUSION: The relatively successful local control of brain metastases in these patients indicates that long-term survival may be attainable via concomitant chemotherapy.

Nutritional status predicts adjuvant chemotherapy outcomes for stage III colorectal cancer.

OBJECTIVES: Previously, adjuvant chemotherapy using oxaliplatin was a standard treatment for patients with node-positive colorectal cancer (CRC) who underwent curative surgery. The factor predicting adverse events and therapeutic effect have not yet been established. METHODS: A retrospective cohort of 42 patients diagnosed with stage III CRC between April 2009 and March 2013 in our institution were included in this study. The indicators of host nutritional status were body weight (BW), body mass index (BMI), serum albumin, Onodera's prognostic nutritional index (OPNI), and Glasgow Prognostic Score (GPS). The indicators of host immunocompetence was total lymphocyte counts, total neutrophil counts, granulocytes/lymphocytes ratio (G/L ratio). RESULTS: The overall recurrence rate was 26.1%. Patients who had a recurrence were more likely to be older. The recurrence was not associated with type of regimen or adverse events. The cases with a few cumulative doses and relative dose intensity of oxaliplatin experienced significantly more recurrence. Nutritional status indicators, such as the serum albumin level, OPNI, and the modified Glasgow prognostic score (mGPS) were associated with the adjuvant chemotherapy outcome. Our study results indicated worse nutritional status induced worse disease-free survival (DFS) and more recurrence. CONCLUSION: The host's nutritional status associated with outcomes in stage III CRC patients.

18 F-Fluorodeoxyglucose positron emission tomography can be used to determine the indication for endoscopic resection of superficial esophageal cancer.

18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful imaging modality that reflects the tumor activity. However, FDG-PET is mainly used for advanced cancer, not superficial cancer. In this study, we investigated the relationship between the superficial tumor depth of esophageal cancer and the FDG uptake to determine the indications for endoscopic resection (ER). From 2009 to 2017, 444 patients with esophageal cancer underwent esophagectomy or endoscopic submucosal dissection (ESD), and 195 patients were pathologically diagnosed with superficial cancer. Among them, 146 patients were examined by FDG-PET before esophagectomy or ESD. In these 146 patients, the relationship between the pathological tumor depth and FDG uptake was analyzed. The mean maximum standardized uptake value in pT1a-EP/LPM tumors was 1.362 ± 0.890, that in pT1a-MM/pT1b-SM1 tumors was 2.453 ± 1.872, and that in pT1b-SM2/SM3 tumors was 4.265 ± 3.233 (P < .0001). Among 51 pT1a-EP/LPM tumors, 10 (19.6%) showed positive detection of FDG. For pT1a-MM/pT1b-SM1 and pT1b-SM2/SM3 tumors, the detection rate was 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate of pT1a-EP/LPM was significantly lower than in the other two groups (P < .0001). Among 10 FDG-PET-positive lesions, only 1 had no apparent reason for PET positivity; however, 9 of 10 had a suitable reason for detectability by PET and inadequacy for ER. Negative detection of superficial esophageal squamous cell carcinoma by FDG-PET is useful to determine the indication for ER when the tumor depth cannot be diagnosed even after performing magnifying endoscopy with narrow band imaging and endoscopic ultrasonography. When FDG uptake is recognized, a therapeutic modality other than ER should be considered.

Laparoscopic surgery for a Bochdalek hernia triggered by pregnancy in an adult woman: A case report.

INTRODUCTION: A Bochdalek hernia (BH) is a type of congenital diaphragmatic hernia. We herein describe an adult woman with a BH triggered by pregnancy and treated by laparoscopic surgery. PRESENTATION OF CASE: A 26-year-old woman was referred to our hospital because of abdominal pain and dyspnea resulting from a left diaphragmatic hernia. She was diagnosed with a BH and underwent laparoscopic surgery. Her postoperative progress was satisfactory, and no recurrence was found at follow-up approximately 1 year later. DISCUSSION: A recently published study reviewing detailed cases of laparoscopic and/or thoracoscopic repair of adult BH from 1999 to 2016 identified 30 cases. A laparoscopic approach for treatment of BH has recently attracted increasing interest. CONCLUSION: Laparoscopic surgery can be safely performed on adults with BH without complications.

Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil.

BACKGROUND/AIM: The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). PATIENTS AND METHODS: The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. RESULTS: Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. CONCLUSION: Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUVmax DCF therapy are associated with early disease relapse and death.

Salvage esophagectomy combined with partial aortic wall resection following thoracic endovascular aortic repair.

OBJECTIVE: Definitive chemoradiotherapy is useful for locally advanced esophageal cancer. However, salvage esophagectomy is required when residual or recurrent tumor is evident after chemoradiotherapy. We performed salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair for aortic invasion, and we evaluated the results. METHODS: Four patients underwent esophagectomy combined with aortic wall resection after thoracic endovascular aortic repair because the lesion was diagnosed as stage T4b. We evaluated short-term outcomes, including duration of thoracic surgery, blood loss, duration of intubation, intensive care unit stay, and postoperative morbidity, as well as survival after salvage surgery. RESULTS: Lesions were resected with no intraoperative procedural adverse events. Mean thoracic operation time was 444 min, and mean thoracic blood loss was 506 g. In all patients, complete resection of the lesion was possible with no intraoperative adverse events. All patients were extubated on postoperative day 0, and all were discharged from the intensive care unit on postoperative day 1. One patient experienced grade II wound pain (bilateral chest pain), and another patient experienced difficult sputum expectoration (grade IIIA). The mean follow-up time was 19.8 months, and two patients were alive with no disease recurrence at the time of this report. However, the remaining two patients had died secondary to lymph node metastasis. CONCLUSIONS: Salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair provides acceptable short-term outcomes. Future studies are needed to evaluate long-term survival and patient selection criteria.

Significance of Expression of Complement C4d in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to cure. C4d is a degradation product of the classical complement pathway and is suggested as an early diagnostic marker for other SCCs. The purpose of this study was to clarify the association of complement C4d with ESCC. PATIENTS AND METHODS: Immunohistochemical staining for C4d was performed on surgical specimens obtained from 114 patients with ESCC. RESULTS: Positive C4d expression was observed in 70 (61.4%) cases and negative expression in 44 (38.6%) cases. There was a significant inverse correlation between C4d expression and depth of tumor invasion (p=0.0001), lymph node metastasis (p=0.011), lymphatic invasion (p=0.033), and TNM stage (p=0.0021). Kaplan-Meier analysis showed that negative C4d expression tended to lead to shorter overall survival (p=0.232). CONCLUSION: C4d expression in ESCC might be useful in developing treatment strategies or suppression of ESCC.

¹8F-Fluorodeoxyglucose Positron Emission Tomography for Evaluating the Response to Neoadjuvant Chemotherapy in Advanced Esophageal Cancer.

BACKGROUND/AIM: The purpose of the present study was to improve the diagnostic precision of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) after neoadjuvant chemotherapy (NAC) in patients with advanced esophageal cancer. PATIENTS AND METHODS: Thirty patients underwent FDG-PET/CT before and after NAC. The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) were measured. Patients were divided into two pathological response groups: "responders" (grades 1b-3) or "non-responders" (grades 0-1a). RESULTS: Overall, 11 patients were responders. Significant differences were present for the post-NAC SUVmax (p=0.070), %decrease in SUVmax (p=0.017), post-NAC MTV (p=0.014), and %decrease in MTV (p=0.003). CONCLUSION: Receiver operating characteristic curve analysis showed that the %decrease in MTV of the primary tumor was the best indicator of response to NAC. We are currently striving to improve the accuracy of this assessment method.

Effective Mediastinal Lymphadenectomy for Esophageal Cancer Using Slender Tracheal Forceps in Prone Position Thoracoscopic Esophagectomy.

BACKGROUND/AIM: Adequate mediastinal lymphadenectomy during thoracoscopic esophagectomy (TE) requires an extensive operating field. In order to rectify this problem, we developed slender tracheal forceps that can pass through a 12-mm trocar. PATIENTS AND METHODS: TE in the prone position was performed in 58 patients with esophageal cancer using slender tracheal forceps. Perioperative and postoperative clinical data were compared against those of 61 patients who underwent transthoracic open esophagectomy (OE). RESULTS: The mean duration of thoracic manipulation was significantly longer in the TE than OE group: 226.2 versus 171.3 minutes (p<0.0001). Mean blood loss was significantly lower in the TE than OE group: 39.9 versus 176.8 g (p<0.0001). A mean of 23.4 mediastinal lymph nodes were dissected in the TE group and 25.1 in the OE group. The timing of extubation tended to be earlier in the TE group. Postoperative morbidity did not differ between groups. CONCLUSION: Slender tracheal forceps are acceptable for fine mediastinal lymphadenectomy in thoracoscopic surgery for esophageal cancer, and the technique could contribute to development of minimally invasive surgery.

Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma.

A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil (5-FU; DCF combination regimen) was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled and received DCF combination therapy at different dose levels. DLTs included febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at level 2 and 3. The study proceeded to level 4, according to the protocol. The level 4 dose was defined as the MTD and the level 3 dose was defined as the RD. The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the present study was 70 mg/m(2) DOC plus 70 mg/m(2) CDDP on day 1 plus 700 mg/m(2) 5-FU on days 1-5 at 4-week intervals. This regimen was tolerable and highly active. A phase II study has been started.

Aldehyde dehydrogenase, Ald4p, is a major component of mitochondrial fluorescent inclusion bodies in the yeast Saccharomyces cerevisiae.

When Saccharomyces cerevisiae strain 3626 was cultured to the stationary phase in a medium that contained glucose, needle-like structures that emitted autofluorescence were observed in almost all cells by fluorescence microscopy under UV excitation. The needle-like structures completely overlapped with the profile of straight elongated mitochondria. Therefore, these structures were designated as mitochondrial fluorescent inclusion bodies (MFIBs). The MFIB-enriched mitochondrial fractions were successfully isolated and 2D-gel electrophoresis revealed that a protein of 54 kDa was only highly concentrated in the fractions. Determination of the N-terminal amino acid sequence of the 54-kDa protein identified it as a mitochondrial aldehyde dehydrogenase, Ald4p. Immunofluorescence microscopy showed that anti-Ald4p antibody specifically stained MFIBs. Freeze-substitution electron microscopy demonstrated that cells that retained MFIBs had electron-dense filamentous structures with a diameter of 10 nm in straight elongated mitochondria. Immunoelectron microscopy showed that Ald4p was localized to the electron-dense filamentous structures in mitochondria. These results together showed that a major component of MFIBs is Ald4p. In addition, we demonstrate that MFIBs are common features that appear in mitochondria of many species of yeast.