Showing papers by "Susumu Kobayashi published in 2010"
TL;DR: This review will summarize the current understanding of the functional role of activating mutations, key downstream signaling pathways and regulatory mechanisms, pivotal primary and acquired resistance mechanisms, structure-function relationships and ultimately the incorporation of molecular diagnostics and small molecule EGFR tyrosine kinase inhibitors into the authors' current treatment paradigms.
Abstract: The development of EGFR tyrosine kinase inhibitors for clinical use in non-small cell lung cancer and the subsequent discovery of activating EGFR mutations have led to an explosion of knowledge in the fields of EGFR biology, targeted therapeutics and lung cancer research. EGFR-mutated adenocarcinoma of the lung has clearly emerged as a unique clinical entity necessitating the routine introduction of molecular diagnostics into our current diagnostic algorithms and leading to the evidence-based preferential usage of EGFR-targeted agents for patients with EGFR-mutant lung cancers. This review will summarize our current understanding of the functional role of activating mutations, key downstream signaling pathways and regulatory mechanisms, pivotal primary and acquired resistance mechanisms, structure-function relationships and ultimately the incorporation of molecular diagnostics and small molecule EGFR tyrosine kinase inhibitors into our current treatment paradigms.
176 citations
TL;DR: It is demonstrated that D USP6 expression tracks in tandem with ERK inhibition and that regulation of DUSP6 is mediated at the promoter level by ETS1, a well-known nuclear target of activated ERK.
Abstract: Mitogen-activated protein kinase (MAPK) pathway signaling plays an important role in the majority of non-small-cell lung cancers (NSCLCs). In a prior microarray analysis of epidermal growth factor receptor (EGFR) inhibition in NSCLC cell lines, we noted that several dual specificity phosphatases (DUSPs) were among the most highly and immediately regulated genes. DUSPs act as natural terminators of MAPK signal transduction and therefore, we hypothesized a tumor suppressive role via feedback mechanisms. In the current study, we focus on the assessment of DUSP6, a cytoplasmic DUSP with high specificity for extracellular signal-regulated kinase (ERK). We demonstrate that DUSP6 expression tracks in tandem with ERK inhibition and that regulation of DUSP6 is mediated at the promoter level by ETS1, a well-known nuclear target of activated ERK. Small interfering RNA knockdown in DUSP6-high H441 lung cancer cells significantly increased ERK activation and cellular proliferation, whereas plasmid-driven overexpression in DUSP6-low H1975 lung cancer cells significantly reduced ERK activation and cellular proliferation and promoted apoptosis. Also, DUSP6 overexpression synergized with EGFR inhibitor treatment in EGFR-mutant HCC827 cells. Our results indicate that DUSP6 expression is regulated by ERK signaling and that DUSP6 exerts antitumor effects via negative feedback regulation, pointing to an important feedback loop in NSCLC. Further studies assessing the tumor suppressive role of DUSP6 and strategies aimed at modulation of its activity are warranted.
166 citations
TL;DR: It is demonstrated for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells.
Abstract: Coactivator-associated arginine methyltransferase I (CARM1; PRMT4) regulates gene expression by multiple mechanisms including methylation of histones and coactivation of steroid receptor transcription. Mice lacking CARM1 are small, fail to breathe and die shortly after birth, demonstrating the crucial role of CARM1 in development. In adults, CARM1 is overexpressed in human grade-III breast tumors and prostate adenocarcinomas, and knockdown of CARM1 inhibits proliferation of breast and prostate cancer cell lines. Based on these observations, we hypothesized that loss of CARM1 in mouse embryos would inhibit pulmonary cell proliferation, resulting in respiratory distress. By contrast, we report here that loss of CARM1 results in hyperproliferation of pulmonary epithelial cells during embryonic development. The lungs of newborn mice lacking CARM1 have substantially reduced airspace compared with their wild-type littermates. In the absence of CARM1, alveolar type II cells show increased proliferation. Electron microscopic analyses demonstrate that lungs from mice lacking CARM1 have immature alveolar type II cells and an absence of alveolar type I cells. Gene expression analysis reveals a dysregulation of cell cycle genes and markers of differentiation in the Carm1 knockout lung. Furthermore, there is an overlap in gene expression in the Carm1 knockout and the glucocorticoid receptor knockout lung, suggesting that hyperproliferation and lack of maturation of the alveolar cells are at least in part caused by attenuation of glucocorticoid-mediated signaling. These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells.
76 citations
TL;DR: In patients with NSCLC and EGFR-activating mutations, a dose of erlotinib at 25mg/d (equivalent to gefitinib 250 mg/d) leads to impressive response rates and progression-free survival similar to the growing experience with the approved doses of gef itinib (250 mg/D) and erlot inib (150 mg /d).
72 citations
TL;DR: It is shown that JAK2 inhibition-induced apoptosis correlated with up-regulation of the nonphosphorylated form of the BH3-only protein Bim in hematopoietic cell lines bearingJAK2 mutations, and that targeting this apoptotic pathway could be a novel therapeutic strategy for patients with activating JAK1 mutations.
54 citations
TL;DR: A “tailor-made virtual lung” of patients that was constructed using three-dimensional multidetector computed tomography (3D-MDCT) angiography was reviewed, and common ostia was observed more frequently on the left side than on the right.
Abstract: Little information is available regarding the variations in pulmonary vein anatomy for the purpose of thoracic or video-assisted thoracoscopic surgery (VATS). To learn about the types and frequency of pulmonary vein variations for VATS, we reviewed a “tailor-made virtual lung” of patients that was constructed using three-dimensional multidetector computed tomography (3D-MDCT) angiography. We reviewed routine 64-row 3D-MDCT pulmonary angiography of 140 patients before surgery between June 2006 and February 2009. We observed that most patients had the expected anatomy (98%) on the left side and on the right side (86%). On the right side, 10% of patients had three branches, and 4% patients had four or five branches. Independent drainage of the middle lobe vein directly into the left atrium was observed in 8% patients. Common ostia were observed on the left side in 33% and on the right side in 13% of the patients. The right inferior pulmonary veins branched immediately in 23% of the patients. Right isolated superior posterior branches were observed occasionally (2%). We observed common ostia more frequently on the left side than on the right. The middle lobe variations were frequent, and the right inferior pulmonary vein often divided at the root. Preoperative 3D-MDCT presented correct pulmonary vein anatomy of the patients.
54 citations
TL;DR: A concise synthesis of a highly functionalized chloropupukeananin skeleton via a reverse electron-demand Diels-Alder reaction and intramolecular carbonyl-ene reaction sequence based on the proposed biosynthetic pathway is described.
36 citations
TL;DR: A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured broth of a fungus, Verticillium sp.
Abstract: A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1033. It is a 24-membered ring cyclic depsipeptide, its structure being elucidated as cyclo[(2R)-2-hydroxyheptanoyl-N-methyl- L-alanyl]4. Verticilide inhibited ryanodine binding to ryanodine receptors in the cockroach at an IC50 value of 4.2 μM, whereas inhibition against mouse ryanodine receptors was weak (IC50=53.9 μM).
33 citations
TL;DR: The synthesis of R-3-CCPA and S-3 -CCPA are described along with their pharmacological properties as inhibitors of lysophospholipase D/autotaxin, agonists of the LPA(5) GPCR, and blockers of lung metastasis of B16-F10 melanoma cells in a C57BL/6 mouse model to extend the potential utility of these compounds as potential lead compounds warranting evaluation as cancer therapeutics.
32 citations
TL;DR: In this paper, a remarkable enhancement in the rate of a TiCl4-mediated stereoselective Mukaiyama aldol reaction (VMAR) using vinylketene silyl N,O-acetal 1 was observed in the presence of water.
31 citations
TL;DR: The reaction affords siladioxocine derivatives with (Z)- or (E)-geometry at the endocyclic double bond, strongly depending on the sterical and configurational vicinity as discussed by the authors.
Abstract: The reaction affords siladioxocine derivatives with (Z)- or (E)-geometry at the endocyclic double bond, strongly depending on the sterical and configurational vicinity.
TL;DR: A new strategy for synthesizing the labeled saccharides, in which the labeling unit, the 2-aminopyridine moiety, is coupled with a spacer unit derived from D-mannitol, indicates that Galbeta1-4Fuc is the endogenous glyco-epitope present in C. elegans N-glycans.
Abstract: To search for the endogenous glyco-epitope in Caenorhabditis elegans, we synthesized labeled Galbeta1-3Fuc and Galbeta1-4Fuc and examined their binding affinity for C. elegans galectin LEC-6 using frontal affinity chromatography analysis. We developed a new strategy for synthesizing the labeled saccharides, in which the labeling unit, the 2-aminopyridine moiety, is coupled with a spacer unit derived from D-mannitol. Our results indicate that Galbeta1-4Fuc is the endogenous glyco-epitope present in C. elegans N-glycans.
TL;DR: The results confirm that aspergione A and B are in fact ustusorane C and pseudodeflectusin, respectively.
Abstract: The syntheses of racemic and optically active pseudodeflectusin and ustusorane C are described. The 1H- and 13C-NMR data for our synthetic pseudodeflectusin and ustusorane C were identical to those of the corresponding natural products. We also synthesized the proposed structure of aspergione A and B whose 1H- and 13C-NMR data were identical to those of ustusorane C and pseudodeflectusin. The 1H- and 13C-NMR spectra of our synthetic aspergione A and B were different from those of the natural compounds. Our results confirm that aspergione A and B are in fact ustusorane C and pseudodeflectusin, respectively.
TL;DR: A retrospective evaluation of seven patients with advanced EGFR mutated NSCLC that were given erlotinib at 25 mg/day as their first EGFR TKI and generated similar inhibitory concentrations of gefitinib and erlot inib.
Abstract: 7572 Background: The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are effective in non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) gene mutations. The...
TL;DR: In this paper, the authors demonstrate that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells during embryonic development, and they show that the lungs of newborn mice lacking CARM 1 have substantially reduced airspace compared with their wild-type littermates.
Abstract: Coactivator-associated arginine methyltransferase I (CARM1; PRMT4) regulates gene expression by multiple mechanisms including methylation of histones and coactivation of steroid receptor transcription. Mice lacking CARM1 are small, fail to breathe and die shortly after birth, demonstrating the crucial role of CARM1 in development. In adults, CARM1 is overexpressed in human grade-III breast tumors and prostate adenocarcinomas, and knockdown of CARM1 inhibits proliferation of breast and prostate cancer cell lines. Based on these observations, we hypothesized that loss of CARM1 in mouse embryos would inhibit pulmonary cell proliferation, resulting in respiratory distress. By contrast, we report here that loss of CARM1 results in hyperproliferation of pulmonary epithelial cells during embryonic development. The lungs of newborn mice lacking CARM1 have substantially reduced airspace compared with their wild-type littermates. In the absence of CARM1, alveolar type II cells show increased proliferation. Electron microscopic analyses demonstrate that lungs from mice lacking CARM1 have immature alveolar type II cells and an absence of alveolar type I cells. Gene expression analysis reveals a dysregulation of cell cycle genes and markers of differentiation in the Carm1 knockout lung. Furthermore, there is an overlap in gene expression in the Carm1 knockout and the glucocorticoid receptor knockout lung, suggesting that hyperproliferation and lack of maturation of the alveolar cells are at least in part caused by attenuation of glucocorticoid-mediated signaling. These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells.
TL;DR: This operation can be performed much more comfortably if another port is inserted in the right lower quadrant, as opposed to surgery with only three ports, so-called single-incision laparoscopic surgery.
Abstract: Background: A high surgical technique is required for laparoscopic anterior resection using single-incision laparoscopic surgery such as multiport surgery. We report a novel surgical technique of umbilical incision laparoscopic surgery with one assist port which could be performed like conventional multiport surgery. Methods: With the patient in the lithotomy position, a 3-cm longitudinal skin incision is made at the umbilicus and carried down to the peritoneum. A 12-mm and two 5-mm trocars are placed through the incision. Another 12-mm trocar is placed for the insertion of laparoscopic coagulation shears and a stapler in the right lower quadrant. After surgery, the trocar in the right lower quadrant is removed and a drain is replaced through the insertion site. The operator mainly uses two trocars, a 5-mm trocar placed at the umbilicus and a 12-mm trocar in the right lower quadrant, making it like conventional laparoscopic surgery. Results: The median operation time was 195 (range 180–205) min, intraoperative blood loss was 20 (range 0–60) ml, and none of the 3 patients had any complications postoperatively. Conclusion: As opposed to surgery with only three ports, so-called single-incision laparoscopic surgery, this operation can be performed much more comfortably if another port is inserted in the right lower quadrant.
Journal Article•
TL;DR: It is revealed that morbidity and mortality for pulmonary resection on HD are 74% and 11%, respectively, and Thoracoscopic operations for lung cancer patients on HD may minimize the operative invasiveness.
Abstract: There have been a few reports of pulmonary resection for lung cancer in patients on hemodialysis (HD), but no reports of video-assisted thoracoscopic surgery (VATS) in these patients have been submitted. We describe two patients on HD undergoing thoracoscopic resection for lung cancer. For the thoracoscopic operation, anatomies of the patients were confirmed by three-dimensional multidetector computed tomography (3D-MDCT). The first patient underwent a right lower lobectomy thoracoscopically, and the second patient underwent a resection of the superior segment of the right lower lobe thoracoscopically. They were discharged on postoperative days 10 and 4, respectively. A review of the literature reveals that morbidity and mortality for pulmonary resection on HD are 74% and 11%, respectively. Thoracoscopic operations for lung cancer patients on HD may minimize the operative invasiveness. Preoperative 3D-MDCT angiography was useful because it supports understanding of the patient's personal anatomy for VATS.
TL;DR: It is recommended that patients without clinical findings except for axillary lymph node metastasis, especially post-breast-conserving surgery followed by radiation therapy, should be considered not only as having ipsilateral but also contralateral occult breast cancer.
Abstract: We report a rare case of a 64-year-old female with metachronous secondary primary left occult breast cancer initially presenting right axillary lymph node metastases. The patient, who had received breast-conserving therapy for left breast cancer at another hospital about 4.5 years ago, came to our hospital complaining of right axillary node swelling. After both breast and systemic examination, she received complete right axillary lymph node dissection. Just after the operation, she was diagnosed with right occult breast cancer by a review of the right axillary lymph nodes and previous left breast cancer. She was followed by radiation and systemic chemoendocrine therapies. One year after axillary lymph node dissection, mammography and ultrasonography showed a new lesion in her left breast. Core needle biopsy revealed similar findings to right axillary lymph node metastasis. After salvage surgery, the diagnosis was revised. We recommend that patients without clinical findings except for axillary lymph node metastasis, especially post-breast-conserving surgery followed by radiation therapy, should be considered not only as having ipsilateral but also contralateral occult breast cancer. If there is no evidence of a primary lesion, axillary lymph node dissection needs to be carried out, and the patient should be offered the choice of radiation therapy or mastectomy followed by proper systemic therapy.
Journal Article•
TL;DR: A 36-year-old male with Crohn's disease who had undergone partial resection of the small intestine twelve years ago developed recurrent disease in the terminal ileum in March, 2009 and underwent laparoscopic right colectomy using single incision lapARoscopic surgery (SILS) for the recurrent lesion in May, 2009.
Abstract: A 36-year-old male with Crohn's disease who had undergone partial resection of the small intestine twelve years ago developed recurrent disease in the terminal ileum in March, 2009. He was referred to our department for the second operation because his abdominal pain and appetite loss were progressively worse. He underwent laparoscopic right colectomy using single incision laparoscopic surgery (SILS) for the recurrent lesion in May, 2009. The duration of the operation was 130 min, and perioperative blood loss was 100 ml. His postoperative course was uneventful and was transferred to the Department of Internal Medicine ten days after the operation for the chemotherapy with infliximab. SILS has been performed since the late 1990s for a wide variety of surgical procedures. We describe the reported first case of single incision laparoscopic right colectomy for recurrent Crohn's disease.
TL;DR: In this paper, the synthesis of (+)-cacospongionolide B was achieved by highly stereoselective C-glycosidation of a glycal derived from D-arabinose with 3-furyl boronic acid in the presence of a palladium catalyst.
Abstract: Total synthesis of (+)-cacospongionolide B was achieved. The synthesis involved highly stereoselective C-glycosidation of a glycal derived from D-arabinose with 3-furyl boronic acid in the presence of a palladium catalyst and B-alkyl Suzuki-Miyaura coupling of in situ generated alkylborane prepared by the reaction of vinyl trans-decalin with alkenyl triflate.
TL;DR: A second generation total synthesis of (−)-diversifolin has been achieved by a more straightforward strategy, involving a highly stereochemistry-dependent 10-membered ring-closing metathesis and a stereoselective dihydroxylation/lactone transposition sequence as discussed by the authors.
TL;DR: In this paper, the clinical efficacy of erlotinib at a dose of 25 mg daily for patients with metastatic non-small cell lung cancers (NSCLCs) with somatic mutations in the epidermal growth factor receptor (EGFR) gene was reported.
Journal Article•
TL;DR: VATS is the preferred surgical choice for lung cancer patients with IP and it is found that surgery-related exacerbation of preoperative IP or development of postoperative IP was found in either group.
Abstract: Purpose A serious complication following primary lung cancer surgery on patients with interstitial pneumonia (IP) is the postoperative acute exacerbation of IP. Because few studies have examined the feasibility of using video-assisted thoracic surgery (VATS) on these patients, we reviewed our experience with this technique. Methods We examined 78 patients; 11 had IP (IP group) and 67 did not (non-IP group). Results Patients in the IP group were older than those in the non-IP group (p = 0.097), and they had a significantly higher incidence of squamous cell carcinoma than patients in the non-IP group (p = 0.002). Dominating the IP group, though not statistically significant, were males, the intention to undergo VATS, and limited surgery. VATS was performed on 10 lesions in the IP group and on 45 in the non-IP group. No surgery-related exacerbation of preoperative IP or development of postoperative IP was found in either group. Conclusion VATS is the preferred surgical choice for lung cancer patients with IP.
TL;DR: The structure-activity relationships for the cytoprotective activity against cytotoxicity induced by 3-morpholinosydnonimine (SIN-1) in nerve growth factor (NGF)-differentiated PC12 cells was examined and the C-8/C-9 double bond, but not the stereogenic center derived from alanine, was found to play a key role in the cytopsized activity.
Abstract: We developed an efficient, stereoselective synthetic method for the diketopiperazine moiety of neoechinulin A and its derivatives. The intramolecular cyclization at 80 oC proceeded with minimal racemization of the stereogenic center at C-12 on neoechinulin A, even though the cyclization at 110 oC caused partial racemization. In contrast with these results, the cyclization on diketopiperazine of 8,9-dihydroneoechinulin A derivatives did not cause epimerization of the stereogenic centers, even at 110 °C. We examined the structure-activity relationships for the cytoprotective activity against cytotoxicity induced by 3-morpholinosydnonimine (SIN-1) in nerve growth factor (NGF)-differentiated PC12 cells. The C-8/C-9 double bond, but not the stereogenic center derived from alanine, was found to play a key role in the cytoprotective activity.
Journal Article•
TL;DR: A new technique which allows lateral pelvic lymph node dissection like in open surgery for advanced rectal cancer to be reported, by which the obturator space is skeletonized and anatomical structures are identified clearly.
Abstract: In Japan, there has been no indication of laparoscopic surgery for advanced lower rectal cancer because of the problem about the treatment of lateral pelvic lymph node metastasis. We report a new technique which allows lateral pelvic lymph node dissection like in open surgery for advanced rectal cancer. After laparoscopic total mesorectal excision for rectal cancer, a surgical incision of approximately 8 cm is placed in the supra-pubic area. Then, the latero-vesical area of the retroperitoneum, latero-vesical space is dissected bluntly with forceps. The external iliac artery and vein are taped and lymph node dissection is performed. As the external iliac vein is pulled internally, fatty tissue including lymph nodes in the obturator space is separated from the psoas major muscle. After completing of such a procedure, the obturator nerve is indentified in the fatty tissue with surrounding lymph nodes. As the external iliac vein is pulled laterally, fatty tissue including lymph nodes in the oburator space is dissected by fat aspiration procedure (FAP) using a suction tip. FAP is helpful to confirm the vascular system, by which the obturator space is skeletonized and anatomical structures are identified clearly.
Journal Article•
TL;DR: Preoperative serum p53 Abs do not seem to be a marker of tumor progression but may be a useful marker for detecting high risk of lymph node metastasis in T1 colorectal cancer.
Abstract: The aim of this study was to evaluate the significance of preoperative serum p53 antibodies (Abs) in patients with colorectal cancer. Between 2007 and 2008, serum p53 Abs were measured by enzyme-linked immunoabsorbent assay in 100 consecutive patients with colorectal cancer. Relationships between clinicopathologic features and the preoperative presence of serum p53 Abs were evaluated. Serum p53 Abs were positive in approximately 30%, regardless of the depth of tumor invasion--sm (submucosa), mp (muscularis propria), or ss (subserosa). Two patients among 23 T1 patients (9%) had lymph node metastasis. These 2 patients belonged to a group of 7 patients who were determined positive for serum p53 Abs (29%), although none of 16 patients negative for serum p53 Abs had lymph node metastasis, regardless of vascular invasion. Preoperative serum p53 Abs do not seem to be a marker of tumor progression but may be a useful marker for detecting high risk of lymph node metastasis in T1 colorectal cancer.
Patent•
26 Nov 2010
TL;DR: In this paper, the authors provided a novel nerve cell death inhibitor which has an effect of inhibiting delayed NCL death caused by transient ischemia, which contains cyclic phosphatidic acid (CPA) or carbacyclic (CPA) or a salt thereof.
Abstract: Provided is a novel nerve cell death inhibitor which has an effect of inhibiting delayed nerve cell death caused by transient ischemia. Specifically provided is a drug for inhibiting delayed nerve cell death caused by transient ischemia, which contains cyclic phosphatidic acid or carbacyclic phosphatidic acid or a salt thereof.
TL;DR: A new strategy for synthesizing the labeled saccharides, in which the labeling unit, the 2-aminopyridine moiety, is coupled with a spacer unit derived from D-mannitol, indicates that Galbeta1-4Fuc is the endogenous glyco-epitope present in C. elegans N-glycans.
Abstract: To search for the endogenous glyco-epitope in Caenorhabditis elegans, we synthesized labeled Galbeta1-3Fuc and Galbeta1-4Fuc and examined their binding affinity for C. elegans galectin LEC-6 using frontal affinity chromatography analysis. We developed a new strategy for synthesizing the labeled saccharides, in which the labeling unit, the 2-aminopyridine moiety, is coupled with a spacer unit derived from D-mannitol. Our results indicate that Galbeta1-4Fuc is the endogenous glyco-epitope present in C. elegans N-glycans.
TL;DR: The first catalytic, enantioselective Simmons-Smith cyclopropanation of an allylic alochol has been achieved by the reaction of an alcohol with Et 2 Zn and CH 2 I 2 in the presence of a catalytic amount of chiral disulfonamide as mentioned in this paper.
Abstract: The first catalytic, enantioselective Simmons-Smith cyclopropanation of an allylic alochol has been achieved by the reaction of an allylic alcohol with Et 2 Zn and CH 2 I 2 in the presence of a catalytic amount of chiral disulfonamide 1 .
TL;DR: It’s time to dust off the gloves and get ready for winter.
Abstract: 症例は64歳，男性．腹部不快感を主訴に他院を受診，注腸検査で横行結腸に約6cmの腫瘍性病変がみられたため当科に紹介された．糖尿病のコントロールが不良であったため，術前2週間の糖尿病教育入院の後に手術を予定した．手術前日は水分のみ摂取可とし，昼よりニフレック2,000mlを内服させた．手術4日前のCT検査では横行結腸に腫瘍による腸重積様の像が認められたが，開腹時腹腔内を検索すると横行結腸には腫瘍がみられず，術中大腸鏡検査で術前腫瘍が位置していた部位に潰瘍性病変を確認した．それ以外に粗大病変がみられなかったため，潰瘍性病変を含む腸管を約10cm切除してD2郭清を施行した．手術切除標本には癌の遺残はなくリンパ節転移もみられなかった．有茎性大腸ポリープの自然脱落はまれであるが，巨大ポリープの場合，手術前処置が脱落を誘発する可能性があるので注意を要すると考えられた．