BACKGROUND:The prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancers in the Japanese population have scarcely been investigated.METHODS:Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary epithelial ovarian cancers in patients who underwent oophorectomy at our institution between April 2005 and September 2014. Genetic and/or epigenetic alterations of the mismatch repair genes were investigated in patients with loss of any mismatch repair proteins in the tumor.RESULTS:There were 305 patients with a median age of 54 years (range, 18-83 years). Loss of expression in the ovarian tumor of one or more mismatch repair proteins was observed in 3 of the 305 patients (0.98%): 2 patients MLH1/PMS2 loss and 1 patient showed MSH2/MSH6 loss. Genetic testing of these three patients failed to reveal any pathogenic germline mutations of MLH1 or MSH2. One patient with MLH1/PMS2 loss showed hypermethylation of the promoter region of MLH1. Somatic mutations were found in each of the alleles of MLH1 (c.545dupG and deletion of exons 2-19) in the other patient with MLH1/PMS2 loss. In the patient with MSH2/MSH6 loss, two somatic mutations were detected in MSH2 (c.229_230delAG and c.1861C>T), although we could not determine whether these mutations were biallelic or not.CONCLUSIONS:The prevalence of defective mismatch repair epithelial ovarian cancer in the Japanese hospital-based population was extremely low. Molecular mechanism involved in such defective mismatch repair ovarian cancers seems to be epigenetic events through MLH1 promotor hypermethylation or somatically mutated mismatch repair genes without germline mismatch repair mutation.
A 43-year-old woman underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrioid adenocarcinoma of the uterine body(Stage ⅢC)at 40 years of age. Screening of the adenocarcinoma samples for Lynch syndrome by immunohistochemistry for mismatch repair proteins indicated a loss of MSH2/MSH6 proteinexpression . A genetic test revealed a deletion of about 20 kb, including exons 8 and 9 of the EPCAM gene. Colonoscopy revealed a type 1 tumor in the cecum. The risk of developing metachronous colorectal cancer and postoperative survival according to the extent of colectomy(total colectomy versus segmental colectomy)and her marked obesity were considered collectively. The patient subsequently selected total colectomy with ileorectal anastomosis. Pathological findings revealed mucinous carcinoma(Stage Ⅱ). Patients with Lynch syndrome caused by deletion of EPCAM are not usually at a high risk of uterine body cancer, but the risk of developing uterine body cancer should be noted when the range of EPCAM deletion extends near to MSH2, as inthis case.
In the original publication, surname of first author is misspelt as “Amamo”. It should be “Amano” as given in this Correction.
The aim of this study was to investigate the prevalence of Lynch syndrome among Japanese patients with surgically resected colorectal cancer at a single institution.
A 39-year-old woman underwent right colectomy for type-3 transverse colon cancer, which was histologically identified as well-differentiated stage II A adenocarcinoma with a mucinous component and tumor-infiltrating lymphocytes. The patient was suspected of having Lynch syndrome(LS)since she fulfilled 2 of the revised Bethesda criteria, even though there was no family history of LS. Twelve months after colectomy, abdominal CT revealed thickening of the uterine endometrium. Histopathological examination of biopsy specimens revealed well-differentiated endometrioid carcinoma. Extended hysterectomy with bilateral oophorectomy was performed. Histological examination of the resected specimen revealed well-differentiated endometrioid carcinoma of stage I . Immunohistochemistry analysis of mismatch repair proteins demonstrated loss of MLH1/ PMS2 expression in the colon cancer, but normal expression in the uterine cancer. Genetic testing identified duplication of exons 10-15 of the MLH1 gene, leading to a definitive diagnosis of LS. The patient has not shown any evidence of recurrence or new LS-associated tumors in the 12 years since the last surgery. There is an ongoing debate regarding the pathogenesis of endometrioid cancer, and this case emphasizes the importance of surveillance for gynecological malignancies after colon cancer surgery in female LS patients.
To validate the usefulness of sennoside as a substitute for polyethylene glycol (PEG) as a mechanical bowel preparation (MBP) for elective colon cancer surgery.
To investigate the recent incidence of malignant tumors associated with Peutz–Jeghers syndrome (PJS) in Japan to clarify if there are any differences in malignant tumor risk and the spectrum of malignancies by reviewing the literature on this subject.
When we perform stapled ileal pouch anal anastomosis (IPAA) for familial adenomatous polyposis (FAP), some rectal mucosa persists. There is no consensus on surgical treatment when cancer develops at the residual mucosa. We report the case of a 43-year-old woman who repeatedly underwent endoscopic resection for intramucosal cancer that developed in the residual rectal mucosa 6 years after stapled IPAA, which she received at age 33. She was referred to our department for surgical treatment. We performed mucosectomy for the residual rectum mucosa, including a 0-Ⅱa lesion at the anterior wall. Two months later, stenosis was observed at the anastomotic site. We repeatedly conducted balloon expansion of the stenotic lesion. Six months later, the resected lesion was covered with white epithelium, and columnar epithelium was confirmed by step biopsy of the epithelium from the dentate line to the ileoanal pouch anastomotic site. This finding indicated that the regenerating epithelium was derived from the epithelium from the anal side. The patient remains well after 2 year 4 months with no complaints.
A 21-year-old woman who underwent laparoscopic total colectomy for familial adenomatous polyposis (FAP) 1 year 3 months previously presented with a mass larger than 10 cm around the ileostomy. Multiple tumors in the mesentery around the ileostomy and anterior to the sacrum, accompanied by bilateral hydronephrosis, were detected by computed tomography. The patient was diagnosed with intraabdominal desmoid tumors, stage Ⅳ according to the Church's classification. The desmoid tumor (15×9 cm) around the ileostomy was completely resected surgically, whereas another desmoid tumor (5×4 cm) was incompletely resected. We found a desmoid tumor of more than 10 cm in size and many fibromatous plaques in the mesentery. We then performed 4 courses of systemic chemotherapy with dacarbazine and doxorubicin in for the residual desmoid tumors after surgery. There was no growth of the residual desmoid tumors for 12 months after chemotherapy. Genetic tests detected a pathogenic germline mutation of the APC gene in the high-risk region of the desmoid tumor. We also confirmed somatic mutations in the resected specimens.
We report a case of 4 carcinomas of the uterine body, right ovary, and duodenum in a patient with familial adenomatous polyposis (FAP). Her mother's family line carries FAP. She underwent proctocolectomy with ileoanal anastomosis for FAP when she was 20 years old. She was diagnosed with carcinoma of the uterine body and right ovary, and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy at 48 years of age. The pathological examination revealed endometrioid adenocarcinoma of the uterine body (Stage ⅠB) and endometrioid adenocarcinoma of the right ovary (Stage ⅠA). Her diagnosis was Stage Ⅳ according to the Spigelman classification of duodenal polyposis, and she underwent pancreas-preserving total duodenectomy at 50 years of age. The pathological examination was conclusive for 2 carcinomas in the adenoma, which were 20 mm and 25 mm in diameter, respectively. She has been well without any evidence of cancer recurrence 20 months after the pancreas-preserving total duodenectomy.
家族性大腸腺腫症に合併する胃底腺ポリポーシスや胃腺腫はmalignant potentialが低く,予防的胃切除の対象とならないが,東アジアでは一般集団に比べ胃癌のリスクが高いことに注意する.十二指腸癌(乳頭癌を含む)は予防的大腸切除後の死因の第1位を占めるため,前癌病変への対応が重要である.Spigelman分類stage IVの十二指腸ポリポーシスでは癌化のリスクが高まるため,綿密な内視鏡的サーベイランス,あるいは膵温存十二指腸切除術などの外科治療を考慮する.乳頭部の腺腫には内視鏡的あるいは外科的局所切除術が選択肢となる.デスモイド腫瘍は大腸切除後に発生することが多い.腹壁に発生した場合には切除が推奨される.腹腔内デスモイド腫瘍の治療方針の決定にはChurchの病期分類を参考にし,病期IIIないしIVではダカルバジン・ドキソルビシンなどを用いた化学療法が有効な選択肢となる.
【目的】直腸癌の括約筋温存手術における,closed suction drainの縫合不全に対する意義について後方視的に検討した.さらに,縫合不全の危険因子についても検討した.【対象・方法】直腸癌に対する括約筋温存手術において,仙骨前面にclosed suction drainを留置した連続151例を対象.縫合不全の頻度,治療,ドレーン排液量の推移,縫合不全の危険因子について検討した.縫合不全の分類はInternational Study Group of Rectal Cancer(ISREC)groupのGrade分類に従った.【結果】縫合不全は6例(4.0%)に認めた.縫合不全のGradeはA 3例,B 1例,C 2例であった.縫合不全の部位が吻合部後壁の3例ではすべてGrade A,側端吻合の口側大腸断端の1例ではGrade B,吻合部前壁の2例ではいずれもGrade Cであった.ドレーン排液量は,縫合不全症例の方が,非縫合不全症例より第1病日までの排液量が多かった(p=0.04)が,第2病日,第3病日の排液量に差はなかった.縫合不全の危険因子について,ロジスティック回帰分析を行ったところ,単変量解析では側方郭清施行(p<0.01),ドレーン抜去日6日目以降(p=0.06)が選択され,多変量解析では側方郭清(p=0.04)のみが縫合不全の危険因子として同定された.【結語】直腸癌に対する括約筋温存手術においてclosed suction drainは,縫合不全発生率とのバランスから考えれば有用性は限定的である.
Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.
2005年に臨床導入された内痔核に対するALTA療法は,その簡便さと安全性から広く普及してきたが,治療成績の報告は少ない.当科でALTA療法を行った310例の治療成績は,観察期間32(5-65)カ月,手術時間15(4-27)分,ALTA総注射量は25(6-40)mL,一痔核あたりの注射量は10(6-15)mLであった.合併症は28例(9%)に認められ,いずれも対症療法で軽快した.再発は10例(3.2%)に認められ,再発の形態は8例が内痔核の再脱出,2例が外痔核成分の腫脹であった.再発例と非再発例を比較した結果,年齢・性別・Goligher分類・手術時間・痔核処理数・ALTA注射量について有意差を認めなかった.再発例の検討で再発部位は右前方に多く,再発時期は術後5カ月以内の早期再発と,17カ月以降の晩期再発の二峰性を示した.これら再発例に対しても再治療を行った.ALTA療法は良性疾患である内痔核に対する治療法で,再発に対しても再治療が可能であり,その優れた低侵襲性や安全性から標準治療の一つに適すると考えられた.
The interleukin (IL)-6 concentration in plasma or serum has been considered to represent the degree of stress resulting from surgery. However, IL-6 in peritoneal fluid has rarely been considered. The aim of this study was to assess the concentration and amount of IL-6 in peritoneal fluid as indicators of surgical stress. To obtain basic data on peritoneal release of IL-6 during gastric cancer surgery, we measured IL-6 in peritoneal drainage samples, stored for up to 72 hours postoperatively, from patients who had undergone conventional open (ODG group, n = 20) and laparoscopic-assisted (LADG group, n = 19) distal gastrectomy. Within 24 hours, 61 and 77% of the IL-6 was released into the peritoneal cavity in the LADG and ODG groups, respectively. In both groups, the concentration and amount of peritoneal fluid IL-6 were significantly correlated with each other (LADG group: Spearman's rank correlation test [rS] = 0.48, P = 0.04; ODG group: rS = 0.58, P = 0.01). The concentration and amount of IL-6 in peritoneal fluid was 2.8- and 3.6-fold higher in the ODG than in the LADG group, respectively (P < 0.01). With regard to the relationship between the serum C-reactive protein (CRP) peak and the concentration or amount of peritoneal fluid IL-6 released within 24 hours, only the concentration of peritoneal fluid IL-6 in the LADG group was significantly correlated (rS = 0.60, P = 0.01) with the serum CRP peak. Our findings suggest that the amount and concentration of IL-6 released into the peritoneal cavity for up to 24 hours after surgery can each be a reliable parameter for assessment of surgical stress.
Purpose: To evaluate the validity of avoiding placement of surgical drain in elective curative colectomy for cancer. who need placement of surgical Patients and methods. The subjects were consecutive 50 colonic cancer patients undergoing elective curative resection without routine placement of surgical drains since June 2010. Forty-six patients who underwent similar surgery with routine placement be-fore May 2010 were served as a control. Results: Surgical drain was placed in 5 patients (10%) be-cause of intraoperative spillage of stool in one and information for postoperative hemorrhage in 4, even though no postoperative complications occurred in such patients. There were no significant differenc-es in the incidence anastomotic leakage (0% vs. 2.2%, p=0.14), incisional site infection (4.4% vs. 4.4%, p>0.99), organ/space infection (0% vs. 2.2%, p=0.14), maximal postoperative body temperature, and changes in C-reactive protein levels between patients without subsequent drain placement (n=45) and those with routine drain placement (n=45). Conclusion: Avoiding routine placement of surgical drain in elective curative colectomy is acceptable in terms of validity. Further collection of data is needed to identify candidates suitable for drain placement.
The safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer patients ≥ 75 years was retrospectively evaluated. We analyzed 106 patients, who received FOLFIRI or a combination of FOLFIRI and bevacizumab following oxaliplatin-based first-line chemotherapy. The clinical characteristics and outcome in elderly patients ≥75 years(elderly[EP]group; n=18)were compared with those in patients aged<75 years(control group; n=88). The number of patients treated by a combination of FOLFIRI and bevacizumab in the EP group was lower than that in the control group (27.8% vs 55.7%; p=0.03). The comparison revealed no significant differences in response rate, progression-free survival, overall survival, and the frequency of overall adverse events after the start of second-line chemotherapy, although the frequency of anemia(Bgrade 3, p=0.07)and alopecia(grade 1/2, p=0.054)tended to be higher in the EP group than in the control group. Although this study retrospectively analyzed a limited number of patients, our results indicate that the safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer are almost equal in patients ≥ 75 years and those aged<75 years.
The correlation between the amount of peritoneal fluid and clinical parameters in patients with perforated peptic ulcer (PPU) has not been investigated. The authors' objective was to derive a reliable formula for determining the amount of peritoneal fluid in patients with PPU before surgery, and to evaluate the correlation between the estimated amount of peritoneal fluid and clinical parameters. We investigated 62 consecutive patients who underwent emergency surgery for PPU, and in whom prediction of the amount of accumulated intraperitoneal fluid was possible by computed tomography (CT) using the methods described by Oriuchi et al. We examined the relationship between the predicted amount of accumulated intraperitoneal fluid and that measured during surgery, and the relationship between the amount of fluid predicted preoperatively or measured during surgery and several clinical parameters. There was a significant positive correlation between the amount of fluid predicted by CT scan and that measured during surgery. When patients with gastric ulcer and duodenal ulcer were analyzed collectively, the predicted amount of intraperitoneal fluid and the amount measured during surgery were each associated with the period from onset until CT scan, perforation size, the Mannheim peritoneal index, and the severity of postoperative complications according to the Clavien-Dindo classification. Our present results suggest that the method of Oriuchi et al is useful for predicting the amount of accumulated intraperitoneal fluid in patients with PPU, and that this would be potentially helpful for treatment decision-making and estimating the severity of postoperative complications.
PURPOSE:Peritoneal dissemination is expected to be present in P1, P2, and P3 according to the 8th edition of colon cancer handling convention. The peritoneal carcinomatosis index (PCI) plays a central role in classification of peritoneal metastases.PATIENTS AND METHODS:Peritoneal dissemination was examined during surgery in patients with colon cancer and peritoneal metastasis undergoing treatment with oxaliplatin-based chemotherapy.RESULTS:Correlation between PCI and P1, P2, and P3 was found. Moreover, using a PCI cut-off value of 6 for peritoneal dissemination, there was a significant difference in survival.CONCLUSION:Positive correlation was found between PCI and P classification of colon cancer. Regardless of the presence metastases to other organs, there is a possibility that PCI is effective in predicting prognosis of patients with peritoneal dissemination- positive colon cancer.
The KRAS status in cancer tissue with submucosal or deeper invasion was investigated in patients with familial adenomatous polyposis (FAP). Fifteen cancerous lesions in 10 FAP patients were subjected to analysis for KRAS status. The clinical features of FAP were the dense type in 2 patients and the sparse type in 8 patients. Of the 15 cancerous lesions, 6 (40%) were identified as having wild-type KRAS and the remaining 9 (60%), as having mutated KRAS. Of the 9 mutated lesions, the G13D mutation was recognized in 4 patients and was the most frequent pattern. With regard to the KRAS status in patients with multiple cancerous lesions, 1 patient had 3 cancerous lesions of which 2 were of the mutated type and 1 was of the wild type and another patient had 4 cancerous lesions of which 3 were of the mutated type and 1 was of the wild type. These results suggest that the frequency of wild-type KRAS in cancer associated with FAP was approximately 40%, although it was lower than that in sporadic cancer. Moreover, we need to analyze the KRAS status in all cancerous lesions in clinical practice when chemotherapy with anti-epidermal growth factor receptor (EGFR) antibody is required for the treatment of FAP patients with unresectable advanced multiple cancers.