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1.
Asian J Endosc Surg ; 16(3): 608-612, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37161600

ABSTRACT

Surgery for rectal cancer patients with an ileal conduit after total cystectomy is difficult because adhesions in the pelvis and around the ileal conduit are expected. In the present case, we performed robot-assisted low anterior resection of the rectum in a 69-year-old male patient with rectal cancer who underwent ileal conduit diversion after total cystectomy. In this procedure, the port was inserted into the left upper abdomen as a first step, and two additional ports were added on the left side. Low anterior resection was performed using two left hands to create more space in the abdominal cavity for the ileal conduit. We present this minimally invasive robotic procedure that is extremely useful for dissection of adhesions in a narrow pelvic cavity.


Subject(s)
Rectal Neoplasms , Robotics , Urinary Bladder Neoplasms , Urinary Diversion , Male , Humans , Aged , Rectum , Urinary Diversion/methods , Cystectomy/methods , Urinary Bladder Neoplasms/surgery , Rectal Neoplasms/complications , Rectal Neoplasms/surgery
2.
Asian J Endosc Surg ; 16(3): 563-566, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36958290

ABSTRACT

An 81-year-old man was referred to our hospital for anal bleeding. Colonoscopy revealed a type 3 tumor at the upper rectum and biopsy showed adenocarcinoma. An enhanced circumferential lesion at the upper rectum and a solitary soft-tissue shadow at the fifth sacral vertebra to the coccyx were detected on abdominal magnetic resonance imaging. Fluorodeoxyglucose uptake was observed at the same sites on positron emission tomography. The patient was diagnosed with rectal cancer with isolated sacrococcygeal metastasis and was treated with neoadjuvant chemoradiotherapy followed by robotic surgery. Hartmann's operation was performed in the lithotomy position. The left internal iliac artery and vein were then divided. The internal pudendal artery and vein, the piriformis muscle, and sacrospinous ligament were also divided while preserving the lumbosacral trunk. The scheduled transection line of the sacral surface was fully exposed to prevent massive bleeding during sacrectomy. The dorsal surface of the sacrum was then exposed in the prone position and communicated with the pelvic space. The sacrum was transected at the superior margin of S3 and a specimen was extracted. Pathological findings revealed the infiltration of cancer cells in the sacrococcygeal specimen. The postoperative course was uneventful and the patient was discharged on postoperative day 13.


Subject(s)
Rectal Neoplasms , Robotic Surgical Procedures , Male , Humans , Aged, 80 and over , Neoadjuvant Therapy , Rectal Neoplasms/surgery , Rectum/surgery , Pelvis , Chemoradiotherapy
3.
Mol Clin Oncol ; 18(2): 12, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36761387

ABSTRACT

Bevacizumab and eribulin are novel agents for the treatment of HER2-negative metastatic breast cancer (MBC); however, the choice between bevacizumab and eribulin for MBC can be difficult. The present study aimed to compare two treatment strategies, eribulin followed by bevacizumab and paclitaxel (BEV + PTX) versus BEV + PTX followed by eribulin, to determine whether the order of administration affects the outcome of MBC in the real world. A total of 180 patients who started BEV + PTX and eribulin treatment for HER2-negative MBC from August 2011 to June 2018 were selected. Of these, 84 patients were treated with both BEV + PTX and eribulin sequentially. To evaluate the influence of the sequential order, the efficacy of BEV + PTX followed by eribulin (B-E arm) was compared to treatment with the reverse sequence (E-B arm). The propensity score matching method (PSMA) was used to improve the robustness of the findings from the present study. A total of 60 cases analyzed received BEV + PTX or eribulin as either first- or second-line treatment. In the entire cohort, the median time to failure of strategy (TFS) was 16.8 and 9.9 months in the B-E and E-B arms, respectively [hazard ratio (HR)=0.515, 95% CI 0.298-0.889, P=0.017). A similar HR was derived from PSMA for TFS. Using PSMA, TFS was 16.9 and 9.9 months in the B-E and E-B arms, respectively (HR=0.491, 95% CI 0.253-0.952, P=0.031). These results suggested that when both bevacizumab and eribulin are administered, bevacizumab should be administered first and eribulin should be administered later to ensure the most effective use of each drug.

4.
Asian J Endosc Surg ; 15(4): 832-835, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35765174

ABSTRACT

Double inferior vena cava (DIVC) is a rare but generally asymptomatic condition that is often detected incidentally by radiological examinations such as computed tomography (CT). Here, we describe the case of a 73-year-old woman with DIVC, who underwent robot-assisted surgery (RS) for rectal cancer. In this case, 3D CT angiography showed DIVC with an interiliac vein from the left common iliac vein and a tortuous aorta. Intraoperatively, we identified the presence of the left IVC in addition to the inferior mesenteric vein, gonadal vein, and ureter, which require meticulous attention during vascular processing. By optimizing the port placement, we were able to ensure mobility of the robotic arm and sufficient field of view to safely perform a robot-assisted anterior resection with lymph node dissection. Careful preoperative assessment and development of a strategy for port placement using CT imaging are essential in avoiding iatrogenic injury and performing safe RS.


Subject(s)
Rectal Neoplasms , Robotics , Abdomen , Aged , Female , Humans , Lymph Node Excision/methods , Rectal Neoplasms/surgery , Vena Cava, Inferior/diagnostic imaging , Vena Cava, Inferior/surgery
5.
Asian J Endosc Surg ; 15(4): 812-815, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35488505

ABSTRACT

A 69-year-old female underwent laparoscopic ileal partial resection for ileal adenocarcinoma. Pathological diagnosis was moderately differentiated tubular adenocarcinoma (UICC 8th; T4N0M0 StageIIB). The patient received adjuvant chemotherapy with modified 5-fluorouracil/leucovorin/oxaliplatin. Fourteen months after surgery, computed tomography revealed a mass in the upper rectum. Colonoscopy detected a submucosal protruding mass and a biopsy specimen showed moderately differentiated tubular adenocarcinoma. Robotic low anterior resection was performed. The tumor was located in the upper rectum and there was no macroscopic invasion or peritoneal dissemination. Pathologically, the tumor was moderately differentiated tubular adenocarcinoma located within the rectal wall with little evidence of a carcinoma component in the mucosal lining. Immunohistochemistry showed the same pattern as the previous ileal adenocarcinoma: negativity for cytokeratin 7 and positivity for cytokeratin 20 and caudal-type homeobox 2. In combination with the rectum showing no abnormalities in colonoscopy performed 15 mo previously, the mass was considered hematogenous metastasis from small bowel adenocarcinoma.


Subject(s)
Adenocarcinoma , Duodenal Neoplasms , Rectal Neoplasms , Robotic Surgical Procedures , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Female , Fluorouracil/therapeutic use , Humans , Keratin-20/therapeutic use , Keratin-7 , Leucovorin/therapeutic use , Oxaliplatin/therapeutic use , Rectal Neoplasms/pathology
6.
Asian J Endosc Surg ; 15(2): 397-400, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34874113

ABSTRACT

A 69-year-old woman underwent abdominoperineal resection for a gastrointestinal stromal tumor (GIST) of the rectum 15 years ago. She received adjuvant chemotherapy for 8 years. Seven years later, abdominal computed tomography revealed a soft-tissue shadow in the left lower abdomen, and fluorodeoxyglucose uptake was observed at the same site on positron emission tomography. The recurrence of GIST was suspected, and laparoscopic resection was performed. Laparoscopy showed that the tumor was located at the retroperitoneum near to the descending colon and invaded the left ovarian vessels. It also made contact with the left ureter; however, lighted ureteral catheters enabled us to identify and preserve the left ureter. An immunohistochemical examination revealed the recurrence of GIST. Recurrence may become apparent 15 years or more after GIST surgery, and, thus, a long-term follow-up is required. Lighted ureteral catheters were useful for identifying the ureter and preventing ureteral injury in a recurrent case suspected of invading the ureter.


Subject(s)
Gastrointestinal Stromal Tumors , Laparoscopy , Ureter , Aged , Female , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/surgery , Humans , Laparoscopy/methods , Retroperitoneal Space , Ureter/surgery , Urinary Catheters
7.
Surg Case Rep ; 7(1): 140, 2021 Jun 09.
Article in English | MEDLINE | ID: mdl-34106354

ABSTRACT

BACKGROUND: Median arcuate ligament syndrome (MALS), which results from compression of the median arcuate ligament (MAL), is a rare cause of abdominal pain and weight loss. Treatment is dissection of the MAL; however, the laparoscopic procedure is not yet established and it involves the risk of major vascular injury, especially in cases with an anomaly. CASE PRESENTATION: A 47-year-old man was evaluated at the hospital for epigastric pain. Contrast computed tomography scan revealed stenosis of the celiac artery origin due to the MAL. An Adachi V type vascular anomaly was also observed. Laparoscopic treatment was performed to release pressure on the celiac artery. Laparoscopic ultrasonography was used to less invasively confirm the release of the MAL. Despite a concomitant Adachi V type vascular anomaly, surgery was safely performed using the laparoscopic magnification view and intraoperative ultrasonography. Follow-up ultrasonography confirmed the celiac artery stenosis has not recurred. CONCLUSIONS: A rare case of MALS with an Adachi V type vascular anomaly is presented and the laparoscopic treatment is detailed.

8.
J Anus Rectum Colon ; 2(3): 77-82, 2018.
Article in English | MEDLINE | ID: mdl-31559347

ABSTRACT

OBJECTIVE: The use of laparoscopic surgery for rectal disease is expected to provide good cosmetic benefits for patients postoperatively. However, this expectation is significantly reduced when a diverting ileostomy is created. We present a new technique that reduces the size of the skin wound by constructing a diverting ileostomy in the umbilicus. This procedure, diverting umbilical ileostomy (umbistoma) does not require special tools for its construction and closure. METHODS: Twenty-nine patients underwent treatment with umbilical diverting stoma, including five women and 24 men, with a mean age of 70 years (range: 40-88 years). At the time of ostomy closure, a new umbilicus was formed by subcutaneously suturing the wound to the fascia. In addition, we did not close the new umbilical upper and lower spaces, so as to allow open drainage of the healing wound. RESULTS: All procedures were completed successfully without any perioperative complications. CONCLUSIONS: Our findings suggest that the umbilical diverting stoma could provide improved safety and cosmetic advantages in laparoscopic rectal resection.

9.
Clin J Gastroenterol ; 10(6): 530-534, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28913716

ABSTRACT

We report a case of a mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB) diagnosed over a period of 6 years. A 64-year-old man underwent follow-up evaluations for an abdominal aortic aneurysm at our hospital. In 2009, a computed tomography (CT) scan revealed a simple hepatic cyst in segment 3 of the liver. Annual CT scans initially showed almost no change in the size or shape of the cyst. The cystic lesion, which measured 5 cm in 2014, had increased to 11 cm by 2015, and a solid component was detected within the cyst. A biliary cystic tumor was suspected and we performed a left lateral hepatectomy. Pathological examination showed that the papillary lesion in the cyst included adenocarcinoma and adenoma components. We diagnosed M-IPNB in 2015. Identification of the solid component of the cyst, as well as an increase in cyst diameter in the image analyses, was critical for diagnosis of M-IPNB.


Subject(s)
Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cystadenocarcinoma, Mucinous/pathology , Cystadenocarcinoma, Papillary/pathology , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/surgery , Cystadenocarcinoma, Mucinous/diagnostic imaging , Cystadenocarcinoma, Mucinous/surgery , Cystadenocarcinoma, Papillary/diagnostic imaging , Cystadenocarcinoma, Papillary/surgery , Hepatectomy , Humans , Male , Middle Aged , Tomography, X-Ray Computed
10.
Asian J Endosc Surg ; 10(4): 430-433, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28612483

ABSTRACT

A 39 year-old woman with malignant foot melanoma underwent wide excision of the primary tumor with a safety margin and sentinel lymph node biopsy (SLNB) for the right inguinal lymph node. SLNB was positive and a computed tomography (CT) scan revealed right iliac lymph node swelling. Positron emission tomography computed tomography (PET-CT) scan of the lymph nodes revealed abnormal uptake of fluorodeoxyglucose (FDG). We performed a laparoscopic pelvic lymph node obturator, iliac lymph node) dissection. During the operation, several black lymph nodes were observed in the iliac lymph node. Pathologically, the iliac lymph node consisted of metastasized atypical melanocytes. This surgical method for pelvic lymph node dissection is not a standard procedure among institutions. There have been no reported cases of malignant melanoma with pelvic lymph node metastasis treated by laparoscopic surgery. However, due to the minimally invasive technique, this method is worth considering to be used for pelvic lymph node dissection in malignant melanoma as well as other cancers in the field of urology or gynecology.


Subject(s)
Laparoscopy , Lymph Node Excision , Melanoma/surgery , Pelvic Neoplasms/surgery , Skin Neoplasms/pathology , Adult , Female , Foot , Humans , Lymphatic Metastasis , Melanoma/secondary , Pelvic Neoplasms/secondary
11.
J Anus Rectum Colon ; 1(3): 84-88, 2017.
Article in English | MEDLINE | ID: mdl-31583306

ABSTRACT

OBJECTIVES: This study aimed to compare open stoma (OS) creation with laparoscopic stoma (LS) creation considering the operation time, blood loss, time of oral intake, and complications. We also compared multiport LS and single-incision laparoscopic stoma (SILS) creation. METHODS: We reviewed the demographic data, diagnosis, indications, operation time, blood loss, time of oral intake, operative procedure, and complications of 50 patients who underwent stoma creation between April 2014 and April 2016. RESULTS: The mean blood loss was significantly lower in the LS group (7.85±18.4 ml) than in the OS group (38.1±73.2 ml; P=0.02). There were no statistical differences between the groups in terms of the operation time (LS, 72.1±32.7 min; OS, 61.2±31.2 min; P=0.23) or time of oral intake (LS, 1.0±0 days; OS, 1.91±2.71 days; P=0.17). Peristomal skin problems occurred in 11 patients (47.8%) in the OS group and 5 patients (18.5%) in the LS group. There were no statistically significant differences between the SILS and multiport LS groups, considering the operation time, amount of bleeding, and time of oral intake. CONCLUSIONS: LS is comparable with OS in terms of operation time and time of oral intake and may cause lesser blood loss. Considering its advantages, LS is a useful approach for patients requiring biopsies or intra-abdominal inspection. SILS is a minimally invasive technique, suitable for patients in whom the stoma site is preoperatively decided.

12.
Surg Case Rep ; 2(1): 74, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27460130

ABSTRACT

A 59-year-old man presenting with fecal occult blood visited our hospital. He was diagnosed with advanced lower rectal cancer, which was contiguous with the prostate and the left seminal vesicle. There were no metastatic lesions with lymph nodes or other organs. We performed laparoscopic total pelvic exenteration (LTPE) using transanal minimal invasive surgery technique with bilateral en bloc lateral lymph node dissection for advanced primary rectal cancer after neoadjuvant chemoradiotherapy. The total operative time was 760 min, and the estimated blood loss was 200 ml. LTPE is not well established technically, but it has many advantages including good visibility of the surgical field, less blood loss, and smaller wounds. A laparoscopic approach may be an appropriate choice for treating locally advanced lower rectal cancer, which requires TPE.

13.
World J Gastroenterol ; 14(20): 3269-72, 2008 May 28.
Article in English | MEDLINE | ID: mdl-18506939

ABSTRACT

We described a patient with adenocarcinoma of the stomach combined with choriocarcinoma and neuroendocrine cell carcinoma. An 85-year-old man visited our hospital because of appetite loss. Gastric fiberscopy revealed a large tumor occupying the cardial region and anterior wall of the gastric body. The patient underwent total gastrectomy with lymphnode dissection and partial resection of the liver. Choriocarcinoma, small cell carcinoma and tubular adenocarcinoma existed in the gastric tumor. The choriocarcinomatous foci contained cells positive for beta-subunit of human chorionic gonadotropin (B-hCG) and human placental lactogen mainly in syncytiotrophoblastic cells. The small cell carcinomatous foci contained cells positive for synaptophysin, neuron-specific enolase (NSE), and chromogranin A. The prognosis for gastric adenocarcinoma with choriocarcinoma and neuroendocrine cell carcinoma is exceedingly poor. This patient died about 2 mo after the first complaint from hepatic failure. This is the first reported case of gastric cancer with these three pathological features.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Neuroendocrine/pathology , Choriocarcinoma/pathology , Liver Neoplasms/secondary , Stomach Neoplasms/pathology , Adenocarcinoma/surgery , Aged, 80 and over , Carcinoma, Neuroendocrine/surgery , Choriocarcinoma/surgery , Fatal Outcome , Gastrectomy , Hepatectomy , Humans , Immunohistochemistry , Liver Failure/etiology , Liver Neoplasms/complications , Lymph Node Excision , Male , Stomach Neoplasms/surgery
14.
Anticancer Res ; 26(5B): 3729-32, 2006.
Article in English | MEDLINE | ID: mdl-17094392

ABSTRACT

BACKGROUND: p16(INK4a) is a tumor suppressor gene frequently inactivated by aberrant promoter hypermethylation. In the present study, p16(INK4a) methylation was evaluated in non-small cell lung cancer (NSCLC) using a quantitative assay and the clinical significance of the methylation was explored. MATERIALS AND METHODS: A total of 244 tumor samples from formalin-fixed paraffin-embedded archives were examined in this study. p16(INK4a) methylation was analyzed by the fluorescence-based, real-time methylation-specific PCR assay, MethyLight. The quantitative methylation value was expressed as the percentage of methylated reference (PMR). RESULTS: The median level of p16(INK4) methylation was 0.55 PMR (range 0.00-503.4). The p16(INK4) methylation value was significantly higher in males (p = 0.005) and in squamous cell carcinoma (p = 0.018). Prognostic analysis using the Cox proportional hazard model showed that the p16(INK4a) methylation value was a significant prognostic factor (odds ratio, 1.005; 95% CI, 1.003 to 1.008; p < 0.0001). The p16(INK4a) methylation value remained a significant prognostic factor (p = 0.0004) in multivariate analysis including age, gender, histological type and clinical stage. Specimens were then classified into hypermethylated or non-hypermethylated groups based on the p16(INK4a) methylation value using various cut-offs from 1 to 100 PMR. There was no significant difference in prognosis between the two groups using a cut-off value of 1 PMR. On the other hand, there was a significant difference using 6 PMR or more as the cut-off value (p < 0.01). CONCLUSION: These results provide clear evidence for the prognostic significance of p16(INK4a) methylation in NSCLC using quantitative DNA methylation analysis. Careful assessment of DNA methylation is needed because qualitative methylation analysis may overestimate low levels of methylation, which have less clinical significance.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Methylation , Lung Neoplasms/genetics , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Promoter Regions, Genetic , Survival Analysis
15.
World J Gastroenterol ; 12(4): 662-4, 2006 Jan 28.
Article in English | MEDLINE | ID: mdl-16489689

ABSTRACT

We report a case of surgically proved left-sided torsion of the greater omentum that caused secondary by untreated inguinal hernia. Case A 36-year-old man presented to our hospital with abdominal pain. He had been diagnosed with a left inguinal hernia, but he had not received any treatments. Contrast-enhanced computed tomography (CT) of the abdomen showed a large fat density mass below the Sigmoid colon and left inguinal hernia with incarcerated fat. Exploratory laparotomy revealed torsion of the greater omentum with small bloody ascites. The greater omentum was twisted into one and a half circles and entered into a left inguinal hernia. An omentectomy with a repair of left inguinal hernia was performed. A resected omentum was submitted for pathological examination, which showed hemorrhagic infarction. Omental torsion is a rare cause of acute abdominal pain but should be included in the differential diagnoses of acute abdomen, especially in patients with untreated inguinal hernia.


Subject(s)
Abdomen, Acute/etiology , Hernia, Inguinal/complications , Peritoneal Diseases/complications , Adult , Humans , Male , Omentum , Tomography, X-Ray Computed , Torsion Abnormality
16.
Anticancer Res ; 25(6C): 4455-61, 2005.
Article in English | MEDLINE | ID: mdl-16334126

ABSTRACT

BACKGROUND: Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) play important roles in folate metabolism. Previous studies have suggested that TS expression is a prognostic factor in non-small cell lung cancer (NSCLC). The TS gene has a variable number of tandem repeats (VNTR) and single nucleotide polymorphism (SNP) in the 5'-untranslated region, which are associated with TS expression. This association suggests that the TS polymorphism is a novel prognostic factor in NSCLC. In the present study, multiple genetic polymorphisms, TS VNTR, TS SNP and MTHFR C677T, were analyzed in NSCLC and compared with clinicopathological features and patients' prognoses. MATERIALS AND METHODS: Genomic DNA was isolated from 294 surgically resected NSCLC tissues. The genotypes were determined by PCR and PCR-RFLP. The TS VNTR and SNP were combined, followed by functional stratification of H/H (3G/3G), H/L (2R/3G, 3G/3C) and L/L (2R/2R, 2R/3C, 3C/3C). Patients' prognoses were compared with TS and/or MTHFR genotype groups. TS was divided into the H- (H/H, H/L) and L-groups (L/L) according to functional stratification and MTHFR C677T was divided into C- (C/C) and T-groups (C/T, T/T). RESULTS: TS VNTR, the SNP and the TS functional type, along with MTHFR C677T, showed no significant association with clinicopathological factors. There were no differences in prognosis between each genotype or functional group when the TS and MTHFR groups were considered separately. However, we found a unique association between prognosis and the TS functional group in stage I NSCLC, taking both TS and MTHFR groups into consideration. The patients in the TS L-group survived longer than those in the H-group when limited to stage I and MTHFR C-group (p = 0.086). This relationship between the TS genotype group and prognosis was statistically significant in the subgroup of stage IB and MTHFR C-group (p = 0.030). In contrast, the patients in the TS H-group survived longer than those in the L-group when limited to stage I and MTHFR T-group (p = 0.052). CONCLUSION: The TS and MTHFR genotypes can be prognostic factors in NSCLC, where gene-gene interactions between the genotypes may occur. Further validation and investigation of the involvement of genotypes of folate metabolizing enzymes in the prognosis of NSCLC patients are required.


Subject(s)
Carcinoma, Non-Small-Cell Lung/enzymology , Lung Neoplasms/enzymology , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Thymidylate Synthase/genetics , Aged , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , DNA, Neoplasm/genetics , Female , Genotype , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Prognosis
17.
Gan To Kagaku Ryoho ; 32(6): 829-31, 2005 Jun.
Article in Japanese | MEDLINE | ID: mdl-15984525

ABSTRACT

A 48-year-old man underwent subtotal esophagectomy for pStage III (pT 3 pN 3) thoracic esophageal carcinoma on June 20, 2002, in combination with chemotherapy (5-FU 500 mg/day day 1-14, CDDP 10 mg/day day 1-14, VDS 3 mg on days 1 and 8) before and after the operation. Recurrence was seen 7 months after the operation in right pleura and lower mediastinum. Chemo (same regimen)-radiotherapy (50 Gy) was then performed but without effect. Thereafter, lung and upper mediastinal metastases were found, and weekly administration of paclitaxel (70 mg/m2, day 1, 8, 15, q 4w) was initiated in combination with radiotherapy (40 Gy). Two cycles of treatment resulted in PR, and CR was achieved after the 8th cycle was completed. Although treatment was terminated after the 12 th cycle due to development of peripheral neuropathy (grade 2), CR was still maintained 8 months after the completion of treatment. These results suggested the effectiveness of the treatment in cases that show resistance to conventional 5-FU-based chemotherapy.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Squamous Cell/secondary , Esophageal Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Mediastinal Neoplasms/drug therapy , Mediastinal Neoplasms/radiotherapy , Paclitaxel/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Drug Administration Schedule , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophagectomy , Humans , Lung Neoplasms/secondary , Male , Mediastinal Neoplasms/secondary , Middle Aged , Peripheral Nervous System Diseases/chemically induced , Radiotherapy Dosage , Remission Induction
18.
Anticancer Res ; 24(2B): 649-54, 2004.
Article in English | MEDLINE | ID: mdl-15161007

ABSTRACT

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in folate metabolism, which is an important pathway of the methyl donor for DNA methylation. The MTHFR gene has genetic variants (C667T and A1298C), which cause reduced enzyme activity. Impaired folate metabolism by these genetic variants of MTHFR could change the methylation pattern of DNA including promoter hypermethylation, which has been frequently observed in cancer. In this study, we compared the MTHFR genotypes and haplotype to the features of colorectal cancer focusing on the promoter methylation of tumor DNA. MATERIALS AND METHODS: Genomic DNA was isolated from 194 colorectal cancer tissues and subjected to MTHFR genotyping by PCR-based restriction fragment length polymorphism analysis. The MTHFR haplotype was determined by combination of C667T and A1298C genotype and classified into 2 groups, high (H-haplotype) or low (L-haplotype) enzymatic activity of MTHFR. The methylation level of tumor suppressor genes (CDKN2A, hMLH1, ARF and TIMP3) was measured by a fluorescence-based, real-time methylation specific PCR method. RESULTS: There was no significant association of the clinicopathological features with either C667T genotype, A1298C genotype or haplotype of MTHFR. The methylation level of CDKN2A was higher in cancer with the L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal origin were considered (p=0.029). hMLH1 methylation also tended to be higher in proximal colon cancers of MTHFR L-haplotype (p=0.059). In addition, the proximal colon cancers showing CpG island methylator phenotype (CIMP) were significantly more frequent in L-haplotype than in H-haplotype. CONCLUSION: These results suggest that the haplotype with low enzymatic activity of MTHFR is linked with promoter hypermethylation and consequently modifies the risk of CIMP(+) proximal colon cancer development in the Japanese people. The relationship between MTHFR polymorphism and DNA methylation in the Japanese is contrary to the previous results in Caucasians. Further study is needed focusing on ethnic variations in the relationships among MTHFR polymorphism, DNA methylation and the development of CIMP(+) colorectal cancer.


Subject(s)
Colonic Neoplasms/enzymology , Colonic Neoplasms/genetics , DNA Methylation , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Adaptor Proteins, Signal Transducing , Adult , Aged , Aged, 80 and over , Carrier Proteins , Female , Genes, p16 , Haplotypes , Humans , Male , Middle Aged , MutL Protein Homolog 1 , Neoplasm Proteins/genetics , Nuclear Proteins , Polymorphism, Genetic , Promoter Regions, Genetic , Tissue Inhibitor of Metalloproteinase-3 , Tissue Inhibitor of Metalloproteinases/genetics , Tumor Suppressor Protein p14ARF/genetics
19.
Int J Mol Med ; 13(3): 413-7, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14767572

ABSTRACT

MYOD1 promoter methylation occurs in various malignancies including colorectal cancer. We analyzed MYOD1 methylation in 80 colorectal cancer and 74 adjacent normal tissues using MethyLight, which enabled quantitative DNA methylation analysis. The measured methylation value was expressed as a percentage of methylated reference (PMR). The results were compared with clinicopathological features and patient prognosis in order to investigate whether MYOD1 methylation may serve as an independent prognostic factor of colorectal cancer. MYOD1 promoter methylation was detectable in all samples and was significantly higher in tumor compared to normal mucosa, where the median level of methylation was 5.3 PMR (range 0.03-133.4) in normal mucosa and 42.3 PMR (range 0.44-742.9) in tumor. The methylation value of MYOD1 was higher with elder patients both in normal colonic mucosa (p=0.034) and in cancer tissues (p=0.0012). Patients without MYOD1 hypermethylation showed significantly longer survival than those with hypermethylation (p=0.0077). In multivariate analysis of prognostic factors, MYOD1 hypermethylation was a significant prognostic factor (p=0.015) independent to patients' age. These results suggest that MYOD1 hypermethylation plays an important role in colorectal cancer and may be a novel prognostic factor. In addition, quantitative methylation analysis by MethyLight is encouraged for other genes showing age-related and non-cancer-specific methylation.


Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation , DNA, Neoplasm/chemistry , DNA, Neoplasm/genetics , MyoD Protein/genetics , Aged , Colorectal Neoplasms/chemistry , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction/methods , Prognosis , Promoter Regions, Genetic
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