Makoto Sohda

Gunma Prefectural Cancer Center, Maebashi, Gunma Prefecture, Japan

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Publications (89)212.79 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Hematogenous metastasis of esophageal adenocarcinoma to the skeletal muscle is uncommon. We report a rare case of esophageal adenocarcinoma with metastasis to the skeletal muscle. During pretherapeutic examination, a painful mass was detected in the left thigh of a 49-year-old man. Endoscopic biopsy identified poorly differentiated, advanced esophageal adenocarcinoma. Computed tomography (CT) revealed wall thickening in the distal esophagus. Two enlarged lymph nodes were detected-the middle thoracic paraesophageal lymph node in the mediastinum and the right cardiac lymph node. (18)F-fluorodeoxyglucose (FDG) positron emission tomography demonstrated left thigh metastasis, which had not been detected by CT 3 weeks previously, with increased accumulation of FDG. Therefore, ultrasound-guided core-needle biopsy was performed. Histologic and immunohistochemical findings supported a diagnosis of poorly differentiated adenocarcinoma. The final diagnosis was primary esophageal adenocarcinoma with distant metastasis to the skeletal (left thigh) muscle. The rate of disease progression in this case emphasizes the malignant potential of esophageal adenocarcinoma. A few cases of skeletal metastasis from advanced esophageal adenocarcinoma have been previously reported. However, rapid metastasis to a distant skeletal muscle with no other hematogenous metastasis is quite rare. Early detection and rapid treatment are especially important in cases of esophageal adenocarcinoma.
    International surgery. 09/2014; 99(5):650-655.
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    ABSTRACT: In recent years, the number of facilities performing thoracoscopic surgery of the esophagus has increased. Thoracoscopic surgery has many advantages, such as a magnification effect, good lighting, and a wide field of view. Esophagectomy requires fine manipulation within a deep and narrow space. Thus, thoracoscopic surgery is suitable for the performance of esophagectomy. The body position during this procedure may be either prone or left lateral decubitus. Because there are advantages in both cases, the relative merits are controversial. The operation time is longer than that of open thoracotomy, but the amount of bleeding is small in most cases of thoracoscopic esophagectomy. There are also some reports that thoracoscopic esophagectomy is comparable with open esophagectomy in terms of radicality and quality of lymph node dissection, and the intensive care unit and hospital stay durations are shortened. Robot-assisted esophagectomy is a promising technology for the fine manipulations and highquality 3-dimensional visualization required in the performance of esophageal thoracoscopic surgery. Thoracoscopic esophagectomy will become more widespread and undergo further development in the future with the spread of robotic surgery and 3-dimensional endoscopic surgery.
    Kyobu geka. The Japanese journal of thoracic surgery 07/2014; 67(8):773-7.
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    ABSTRACT: Background: [(18)F]-3-fluoro-alpha-methyl tyrosine ((18)F-FAMT) as an amino acid tracer in positron emission tomography (PET) has been widely investigated in several tumor types. Herein we investigated the clinical significance of (18)F-FAMT PET uptake as a prognostic marker together in our updated data of patients with esophageal cancer. Patients and Methods: We retrospectively assessed the treatment outcomes of 42 patients with histologically-confirmed esophageal cancer. The survival rate was analyzed using the median peak standardized uptake value (SUV) with 2.2 as the cut-off value. Results: FAMT uptakes were significantly correlated with factors reflecting tumor progression. Moreover, a significant correlation was observed between FAMT uptake and disease-free survival (p=0.023). Moreover, on evaluation of individual lymph node groups, the specificity and positive predictive value were significantly higher for (18)F-FAMT-PET than for (18)F-FDG-PET and computed tomography (CT). Conclusion: (18)F-FAMT is an important pre-treatment diagnostic modality and its accumulation is a good predictor of disease-free survival (DFS) in patients with operable esophageal cancer.
    Anticancer research 07/2014; 34(7):3623-8. · 1.71 Impact Factor
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    ABSTRACT: Purpose:(18)F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of (18)F-FAMT uptake in patients with oesophageal cancer.Methods:From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of (18)F-FAMT uptake.Results:High uptake of (18)F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that (18)F-FAMT was specifically transported by LAT1.Conclusions:The uptake of (18)F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of (18)F-FAMT accumulation.British Journal of Cancer advance online publication, 25 March 2014; doi:10.1038/bjc.2014.142
    British Journal of Cancer 03/2014; · 5.08 Impact Factor
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    ABSTRACT: Aims: L-[3-(18)F]-α-Methyltyrosine ((18)F-FAMT) has high specificity for malignant tumors on positron emission tomography (PET), and its role and potential usefulness has been previously investigated in operable esophageal carcinoma. We aimed to assess the ability of (18)F-FAMT PET to predict the response of esophageal cancer to definitive chemoradiotherapy. We retrospectively reviewed 40 patients with esophageal cancer imaged with (18)F-FAMT PET. The relationship between (18)F-FAMT PET uptake before chemoradiotherapy and clinical outcomes was assessed. The primary tumor was visualized in 95% patients. (18)F-FAMT uptake was significantly positively correlated with lymph node metastasis. The low-(18)F-FAMT accumulation group had significantly higher complete response (CR) rates than did the high-accumulation group. The addition of a lymph node metastasis category with low (18)F-FAMT uptake provides a more precise predictor of CR. (18)F-FAMT uptake prior to treatment is a good predictor of CR rate after CRT for esophageal cancer.
    Anticancer research 02/2014; 34(2):909-13. · 1.71 Impact Factor
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    ABSTRACT: Aim: We investigated the significance of pre-treatment screening by (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET) in patients with esophageal cancer. We retrospectively evaluated the clinical significance of screening in 200 patients with primary esophageal cancer using FDG-PET. Out of 200 patients, 34 (17%) had synchronous multiple primary tumors; 31 patients had two types of cancers (15.5%) and three patients had three types (1.5%). The 37 second and third primary tumors were 13 stomach cancers (35.1%), 13 head and neck cancers (35.1%), seven colon (18.9%) and two lung (5.4%) cancers. When PET was performed at initial treatment for esophageal cancer, the diagnostic sensitivity of FDG-PET/Computed tomography (CT) for the second and third synchronous primary cancer were 53.8% (7/13) for the stomach; head and neck, 61.5% (8/13); colon, 42.9% (3/7); and lung, 50% (1/2), for an overall sensitivity of 54.1% (20/37 sites). FDG-PET/CT for patients with esophageal cancer may find both metastases from the primary esophageal cancer and other types of synchronous primary cancers.
    Anticancer research 01/2014; 34(1):283-287. · 1.71 Impact Factor
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    ABSTRACT: Aim: The objective of the present study was to evaluate the significance of pre-treatment screening for patients with esophageal cancer. A retrospective evaluation of the clinical significance of total colonoscopy in 136 patients with primary esophageal cancer was performed. Twenty-three patients (16.9%) had diverticula, and five (3.7%) had colon cancer. Benign polyps were present in 57 patients (41.9%); 37 of these patients underwent endoscopic treatment, one underwent surgery (esophagectomy). Twenty-seven out of 32 patients (84.4%) who underwent histopathological studies had tubular adenoma. Significant associations were found between presence of colorectal lesions and body weight, body-mass index (p<0.001), Brinkman index (p<0.001), and the Sake index (p<0.05). Screening for colorectal lesions using total colonoscopy is important in patients with esophageal cancer, especially for those with a high body-mass index, and those who smoke or drink heavily.
    Anticancer research 11/2013; 33(11):5113-7. · 1.71 Impact Factor
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    ABSTRACT: A 64-year-old man was diagnosed with advanced gastric cancer type 3 and regional celiac trunk lymph node metastases. We performed preoperative chemotherapy with docetaxel, cisplatin, and S-1(DCS therapy). Total gastrectomy with lymph node dissection was performed after 2 courses of DCS. Pathologically, no viable cells were found in the primary lesion or in the dissected lymph nodes. The pathological response to preoperative DCS therapy was classified as grade 3. The postoperative course was uneventful; the patient is currently healthy and receives periodic medical examinations.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2013; 40(11):1537-1540.
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    ABSTRACT: Esophageal carcinosarcoma (ECS) is a rare malignant neoplasm associated with a poor patient prognosis. It is characterized by the presence of both malignant epithelial and mesenchymal components. Molecular-targeted therapy of several receptor tyrosine kinases (RTKs) has been reported to be effective in the treatment of various malignant tumors, including carcinosarcoma of several organs. This study aimed to assess the therapeutic potential of targeting RTKs in ECS. Overexpression of RTKs was assessed in 21 ECS cases by immunohistochemistry (IHC). Positively stained cases were further examined for RTK gene mutations and amplifications by direct sequencing analysis and fluorescence in situ hybridization. In epithelial components, KIT, platelet-derived growth factor receptor (PDGFR)A, PDGFRB, MET, epidermal growth factor receptor (EGFR) and HER-2 were overexpressed in 1 (4.8%), 1 (4.8%), 0 (0%), 11 (52.4%), 13 (61.9%) and 2 (9.5%) cases, respectively. In the mesenchymal components the corresponding numbers of cases were 2 (9.5%), 2 (9.5%), 0 (0%), 12 (57.1%), 11 (52.4%) and 0 (0%). No mutations in the c-kit, PDGFRA and c-met genes were found. Among 19 EGFR-positive tumors, 2 had EGFR missense mutations (T790A, exon 20) only in the mesenchymal component. Gene amplification or high polysomy of c-kit, PDGFRA, c-met and EGFR was observed in 1 (33.3%), 0 (0%), 3 (18.8%) and 10 (52.6%) cases, respectively. In conclusion, various RTKs, particularly MET and EGFR were overexpressed in ECSs suggesting that molecular-targeted therapies directed to MET, EGFR or other RTKs may be effective in inhibiting the growth or progression of the epithelial and/or mesenchymal component of ECS.
    Oncology Reports 03/2013; · 2.30 Impact Factor
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    ABSTRACT: More effective protocols are needed for unresectable and recurrent esophageal cancer. Therefore, we conducted a phase I trial to establish the recommended dose of docetaxel, nedaplatin, and 5-fluorouracil (DNF) as combination chemotherapy. Fourteen patients with esophageal cancer were enrolled and received DNF combination therapy at different dose levels according to the treatment and examination plan. Dose-limiting toxicities (DLTs) included febrile neutropenia. DLTs occurred in 3/5 patients at level 4. The recommended doses (level 3) of DNF were 60 mg/m(2) (day 1), 70 mg/m(2) (day 1), and 700 mg/m(2) (days 1-5), respectively, given at 3-week intervals. In conclusion, DNF combined chemotherapy for advanced esophageal cancer was associated with relatively minor adverse events and was safely administered at the recommended dose. A phase II study is now underway.
    Cancer Chemotherapy and Pharmacology 01/2013; · 2.80 Impact Factor
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    ABSTRACT: Barrett's esophagus (BE) is the premalignant lesion from which esophageal adenocarcinoma near the esophagogastric junction arises. The management of BE and the treatment of Barrett's esophageal adenocarcinoma (BEA) are important clinical issues in Europe and the United States. As the Helicobacter pylori infection rate in Japan is decreasing in the younger population, the incidence of BE and adenocarcinoma arising from BE may start increasing. Thus, we review the current status of BEA and its management. Magnifying endoscopy with narrow-band imaging is important for diagnosing dysplasia arising from BE. In Japan, adenocarcinoma arising from BE is managed the same way as squamous cell carcinoma in the same location. Strategies to prevent BEA may include medication such as non-steroidal anti-inflammatory drugs and proton pump inhibitors, and anti-reflux surgery. Understanding the pathophysiology of BE will help to reduce the incidence of BEA.
    Surgery Today 01/2013; · 0.96 Impact Factor
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    Cancer Science 01/2013; 104(1):Januarycover. · 3.48 Impact Factor
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    ABSTRACT: PURPOSE: Nonspecific esophageal motility disorder (NEMD) is a vague category that includes patients with poorly defined contraction abnormalities observed during esophageal manometry. This study investigated the therapeutic effects of the video-assisted thoracoscopic surgery (VATS) approach using long myotomy and fundopexy for NEMD. METHODS: The VATS approach using myotomy and fundopexy was performed for 4 patients of NEMD between 2005 and 2008. A total of 4 patients with NEMD that underwent treatment at our institution were analyzed retrospectively. RESULTS: The patients included 2 males and 2 females with a median age of 48 years (range 21-74 years). The median duration of NEMD symptoms was 58 months (range 4-108 months). Dysphagia was a primary symptom in all patients. Chest pain was a primary symptom in 3 of 4 patients (75 %). Treatment with medication was attempted before the operation. The median operative time was 344.5 min (range 210-476 min). The median time before starting oral feeding was 2.5 days (range 2-22 days). All patients achieved a significant improvement of their previous condition. CONCLUSIONS: The VATS approach using myotomy and fundopexy for NEMD is a good treatment in cases resistant to medication and balloon dilation.
    Surgery Today 12/2012; · 0.96 Impact Factor
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    ABSTRACT: The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression of miR-150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial-mesenchymal-transition (EMT)-inducers, as target genes of miR-150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR-150 in ESCC, and to investigate miR-150's EMT-regulatory ability. Quantitative RT-PCR was used to evaluate miR-150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR-150 via degradation of ZEB1. MiR-150 expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (p<0.001). Low expression of miR-150 in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (p<0.05). In vitro assays showed that EMT-inducer-ZEB1 is a new direct target of miR-150. Moreover, miR-150 induced MET-like changes in TE-8 cells through ZEB1 degradation (e.g., E-cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation of ZEB1 by miR-150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC.
    Cancer Science 09/2012; · 3.48 Impact Factor
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    ABSTRACT: CD47 inhibits phagocytosis and its overexpression is correlated with poor prognosis in patients with several types of cancer. It has also been reported that CD47 expression in multiple sclerosis is regulated by microRNAs. However, the regulatory mechanism of CD47 in cancer tissues has not been yet clarified. Re-analysis of a public microarray database revealed that miR-133a is downregulated in esophageal squamous cell carcinoma (ESCC). Moreover, in silico algorithms predicted that miR-133a is a regulator of CD47. The purpose of this study was to clarify the clinical significance of CD47 and its regulatory mechanism by miR-133a in ESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR-133a expression in 102 cases of curative resected ESCC and adjacent non-cancerous tissue. The regulation of CD47 by miR-133a was examined with precursor miR-133a-transfected cells. A mouse xenograft model was used to investigate the ability of miR-133a to suppress tumor progression. High expression levels of CD47 were associated with lymph node metastasis (P=0.049). Multivariate analysis showed that CD47 expression was an independent prognostic factor (P=0.045). miR-133a expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P<0.001). In vitro assays showed that miR-133a is a direct regulator of CD47. miR‑133a significantly inhibited tumorigenesis and growth in vivo. CD47 expression is a novel prognostic marker in ESCC that is directly inhibited by the miR-133a tumor suppressor. This correlation could provide new insight into the mechanism of cancer progression and a promising candidate for target therapy in ESCC.
    Oncology Reports 05/2012; 28(2):465-72. · 2.30 Impact Factor
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    ABSTRACT: Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.
    Annals of Surgical Oncology 01/2012; 19(6):1911-7. · 4.12 Impact Factor
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    ABSTRACT: We report two cases of rectal malignant melanomas. The patients were an 84-year-old male and a 66-year-old female who had blood in their stools. They were preoperatively diagnosed with poorly differentiated adenocarcinoma of the rectum. The clinical diagnosis for each was rectal carcinoma at stage IIIc according to the tumor-node-metastasis classification (6th edition), and the patients underwent abdominoperineal resection with dissection of lymph nodes. Pathological examination of the resected specimens revealed a malignant melanoma. Immunohistochemical analysis results were positive for HMB-45 and negative for cytokeratin AE1/AE3, CD45, and synaptophysin. Primary anorectal melanoma is an uncommon and aggressive disease that carries a poor prognosis. Therefore, it is necessary to provide systemic treatment. To improve prognosis, it is important to detect anorectal melanoma at an early stage.
    Case reports in surgery. 01/2012; 2012:247348.
  • Journal of the American College of Surgeons 12/2011; 213(6):e35-7. · 4.50 Impact Factor
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    ABSTRACT: Heat shock proteins (HSPs) are well known as tumor rejection antigens, most notable of which is HSP70. HSP110 is classified as a member of the HSP70/DnaK superfamily. The objective of this study was to clarify the clinicopathological and prognostic significance of Heat Shock Protein 110 expression and T lymphocyte infiltration in esophageal cancer. Immunohistochemical staining of HSP110, CD4 and CD8 were performed on surgical specimens obtained from 124 patients with esophageal cancer. The expression of HSP110 correlated inversely with depth of invasion (p<0.0001), lymph node metastasis (p=0.0163), pathological stage (p<0.0001), lymphatic invasion (p=0.0104), blood vessel invasion (p=0.0027), infiltrative growth pattern (p=0.0368) and correlated positively with CD4+ T lymphocyte infiltration (p=0.0018). Reduction of HSP110 expression was significantly correlated with poor prognosis (p=0.0010). The present findings suggest that HSP110 expression and T lymphocyte infiltration is a significant prognostic factor for esophageal cancer.
    Hepato-gastroenterology 11/2011; 58(110-111):1555-60. · 0.77 Impact Factor
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    ABSTRACT: Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a suppressor of TNF-α mediated apoptosis, and its expression is induced by NF-κB activation. TNFAIP8 expression is significantly increased in various cancer cell lines. A correlation between TNFAIP8 overexpression, cancer progression, and poor prognosis has been described in many reports of human solid cancers. To clarify the functional and clinical significance of the cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC. Next, TNFAIP8 expression was depleted by using siRNA to examine the function of TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines. We detected correlations between TNFAIP8 expression and TNM stage (P < 0.001), tumor depth (P = 0.002), lymph node metastasis (P = 0.013), distant metastasis (P = 0.001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.001) among the clinicopathological characteristics of ESCC patients, and high TNFAIP8 expression was found in poor survival. TNFAIP8 depletion was significantly associated with apoptosis induction after cisplatin administration and reduced proliferation. Our results suggest that TNFAIP8 might be an effective therapeutic target for ESCC in the future.
    Annals of Surgical Oncology 10/2011; 19 Suppl 3:S589-96. · 4.12 Impact Factor

Publication Stats

947 Citations
212.79 Total Impact Points


  • 2013
    • Gunma Prefectural Cancer Center
      Maebashi, Gunma Prefecture, Japan
  • 2003–2013
    • Gunma University
      • • Department of General Surgical Science
      • • Graduate School of Medicine
      Maebashi-shi, Gunma-ken, Japan