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[³»°úÇÐȸ ·±Ãµ °­ÀÇ K-CAB : GERD Ä¡·áÀÇ ÃֽŠÁö°ß ¹× P-CABÀÇ ¿ªÇÒ]

Potassium competitive acid blocker, P-CAB °è¿­ÀÇ ±¹³» ½Å¾à TegoprazanÀ» ¼Ò°³ÇÏ°Ú½À´Ï´Ù. CJ¿¡¼­ °³¹ßÇÏ¿´°í K-CABÀ̶ó´Â »óÇ°¸íÀ¸·Î °ð launchingµÉ ¿¹Á¤ÀÔ´Ï´Ù. (¾¾Á¦ÀÌÇコÄɾî Kolmar, 2019³â 3¿ù?)

Tegoprazan J Pharmacol Exp Ther 2018

À§»ê°ú À§»êºÐºñ¾ïÁ¦Á¦ÀÇ ¿ª»ç¿¡´Â µÎ ¸íÀÇ À¯¸íÇÑ À̸§ÀÌ ³ª¿É´Ï´Ù. ÇѸíÀº ÀÇ»çÀÌ°í ÇѸíÀº ȯÀÚÀÔ´Ï´Ù. Alexis St. MartinÀ̶ó´Â ¹Ì±¹ º´»ç´Â ±º´ë¿¡¼­ Å« »ç°í¸¦ ´çÇÑ ÈÄ °Ü¿ì ¸ñ¼ûÀ» °ÇÁ³Áö¸¸ º¹ºÎ¿¡ fistula°¡ ³²¾Ò½À´Ï´Ù. ±×ÀÇ ÁÖÄ¡ÀÇ William Beaumant´Â ÀÌ fistula¸¦ ÅëÇÏ¿© À§ÀÇ physiology¸¦ ¿¬±¸ÇÏ¿´°í, ÀÌ µÑÀÇ ¸¸³²À» ÅëÇÏ¿© À§ÀÇ ³»ºÎ°¡ acidicÇÏ´Ù´Â °ÍÀÌ ¹àÇôÁ³½À´Ï´Ù. À§»ê, gastric acid¶ó´Â °³³äÀÌ ¼¼»ó¿¡ óÀ½ ¼Ò°³µÈ °ÍÀÔ´Ï´Ù. 1822³â 6¿ù »ç°í ÈÄ Ã¹ ¸¸³²¿¡ ´ëÇÑ Beaumont ¹Ú»çÀÇ Áõ¾ðÀÔ´Ï´Ù. ³»ÀåÀÌ ´Ù Æ¢¾î³ª¿Â ²ûÁ÷ÇÑ »óȲÀ¸·Î À§¿¡ perforationÀÌ ÀÖ¾ú´Âµ¥ ±× Å©±â´Â µÎ¹ø° ¼Õ°¡¶ôÀÌ µé¾î°¥ Á¤µµ¿´°í, À̸¦ ÅëÇÏ¿© À½½Ä¹°ÀÌ ³ª¿À°í ÀÖ¾ú´Ù´Â °ÍÀÔ´Ï´Ù.

»ç°í 3³â ÈÄÀÎ 1825³âºÎÅÍ 13³â¿¡ °ÉÃÄ 238°¡Áö ¿¬±¸¸¦ ÁøÇàÇÑ Beaumont ¹Ú»ç´Â 1833³â Experiments and observations on the gastric juice¶ó´Â 280ÆäÀÌÁö ³í¹®À» ¹ß°£ÇÏ¿´½À´Ï´Ù. ÀÌ ³í¹®Àº ÇöÀç Google¿¡¼­ e-bookÀ¸·Î º¸½Ç ¼ö ÀÖ½À´Ï´Ù. Fistula¸¦ ÅëÇÏ¿© ¿©·¯ ÃøÁ¤ ±â±¸¸¦ ³Ö°í »©¸é¼­ ÁøÇàµÇ¾ú´ø Èï¹Ì·Î¿î ½ÇÇè°úÁ¤ÀÌ »ó¼¼È÷ ±â¼úµÇ¾î ÀÖ½À´Ï´Ù.

À§Ã¼ºÎ fundic glandÀÇ neck ºÎÀ§¿¡ À§Ä¡ÇÑ parietal cellÀÌ histamine, acetylcholine, gastrin¿¡ ÀÚ±ØÀ» ¹ÞÀ¸¸é ±×¸²°ú °°ÀÌ ¸ð¾çÀÌ º¯Çϸ鼭 À§»êÀÌ ºÐºñµË´Ï´Ù. ±× °úÁ¤¿¡¼­ hydrogen-potassium pump°¡ Áß¿äÇÑ ¿ªÇÒÀ» ÇÕ´Ï´Ù. À§»êºÐºñ ¾ïÁ¦Á¦ÀÇ È¿½Ã´Â cimetidine°ú °°Àº histamine antagonistÀÌÁö¸¸, ÇöÀç ¸¹ÀÌ »ç¿ëµÇ´Â Á¾·ù´Â 1¼¼´ë ¹× 2¼¼´ë proton pump inhibitorÀ̸ç, ¿À´Ã ¼Ò°³µå¸®´Â Á¾·ù´Â Potassium competitive acid blocker, P-CABÀÔ´Ï´Ù.

PPI¿Í P-CABÀº ¾î¶² Â÷ÀÌ°¡ ÀÖ´ÂÁö »ìÆ캸°Ú½À´Ï´Ù. ´ç¿¬ÇÑ À̾߱âÀÌ°ÚÁö¸¸ proton pump¿¡¼­ÀÇ binding site°¡ ¼­·Î ´Ù¸£°í mode of action¿¡ Áß¿äÇÑ Â÷ÀÌ°¡ ÀÖ½À´Ï´Ù. PPI´Â ±× ÀÚü°¡ prodrugÀÔ´Ï´Ù. µû¶ó¼­ reactive formÀ¸·Î º¯ÇüµÈ ÈÄ ÀÛ¿ëÇÒ ¼ö ÀÖÀ¸¸ç ºñ°¡¿ªÀûÀ¸·Î °áÇÕÇÕ´Ï´Ù. À̸¦ À§ÇÏ¿© proton pump ÀÚü°¡ stimulation µÇ¾î¾ß ÇÕ´Ï´Ù. ÀÌ ¶§¹®¿¡ ½ÄÀü¿¡ Åõ¿©ÇÏ´Â °ÍÀÌÁö¿ä. ¹Ý¸é P-CABÀº prodrugÀÌ ¾Æ´Ï¹Ç·Î proton pumpÀÇ stimulation ¾øÀÌ Á÷Á¢ reversible bindingÀ» ÇÕ´Ï´Ù. µû¶ó¼­ ½Ä»ç¿Í ¹«°üÇÏ¿¡ Åõ¿©ÇÒ ¼ö ÀÖ½À´Ï´Ù.

(1) ¿©·¯ Á¾·ùÀÇ PPI´Â ºÐÀÚ ±¸Á¶°¡ ¼­·Î ºñ½ÁÇÕ´Ï´Ù. ¹Ý¸é ÇöÀç±îÁö ½ÃÆÇµÈ ¼¼ Á¾·ùÀÇ P-CABÀº ºÐÀÚ ±¸Á¶¿¡ »ó´çÇÑ Â÷ÀÌ°¡ ÀÖ½À´Ï´Ù. ±âÁ¸¿¡ °³¹ß ȤÀº ½ÃÆǵǾú´ø P-CABÀº hepatotoxicity°¡ ¹®Á¦¿´´Âµ¥ ¿À´Ã ¼Ò°³µå¸®´Â tegoprazan, Áï K-CABÀº ºÐÀÚ±¸Á¶°¡ ÀüÇô ´Ù¸£±â ¶§¹®¿¡ ºÎÀÛ¿ë profile¿¡µµ Â÷ÀÌ°¡ À־ hepatotoxicity ¹®Á¦°¡ ¾ø¾ú´ø °ÍÀ¸·Î »ý°¢µË´Ï´Ù. (2) TegoprazanÀÇ half life´Â 3.7¿¡¼­ 7.1½Ã°£À¸·Î PPIº¸´Ù´Â ±æ°í ´Ù¸¥ P-CABº¸´Ù´Â ª½À´Ï´Ù. (3) ±âÁ¸¿¡ ±¹³»¿¡ ½ÃÆǵǾú´ø rebaprazanÀº À§»êºÐºñ¾ïÁ¦´ÉÀÌ ±âÁ¸ÀÇ PPIº¸´Ù ¾àÇÏ¿© peptic ulcerÀÇ ÀûÀÀÁõÀÌ ÀÖÀ» »Ó, GERD¿¡¼­´Â ÀûÀÀÁõÀ» ¹ÞÁö ¸øÇÏ¿´½À´Ï´Ù. µÚ¿¡¼­ ÀÚ¼¼È÷ ¸»¾¸µå¸®°ÚÁö¸¸ tegoprazan, Áï K-CABÀº °­·ÂÇÑ À§»ê ºÐºñ ¾ïÁ¦´ÉÀ» °¡Áö°í À־ ÁÖ·Î GERD¿¡¼­ »ç¿ëÇϵµ·Ï ¿¬±¸°³¹ßµÇ°í ÀÖ½À´Ï´Ù.

P-CAB, ƯÈ÷ TegoprazanÀÇ ÀåÁ¡Àº ¾Æ·¡¿Í °°½À´Ï´Ù.

Benefits of K-CAB compared to PPI
More potent acid suppression
More rapid acid inhibition
Less dependent on CYP2C19
No food effect
Optimal for H. pylori eradication
Excellent safety profile

pH 4ÀÌ»óÀ¸·Î ºñ±³ÇÒ ¶§º¸´Ù pH 6ÀÌ»óÀ¸·Î ºñ±³Çϸé ÇöÀúÇÑ Â÷ÀÌ°¡ ³³´Ï´Ù.

1ÀÏ, 7ÀÏ ¸ðµÎ 1½Ã°£ À̳»¿¡ pH 4ÀÌ»óÀ¸·Î ¿Ã¶ó°©´Ï´Ù.

Tegoprazan 50mgÀ¸·Î ¾ß°£¿¡¼­ pH 4ÀÌ»çÀ¸·Î À¯ÁöµË´Ï´Ù.

TegoprazanÀÌ ½ÄÀü°ú ½ÄÈÄ Åõ¾à ½Ã Å« Â÷ÀÌ°¡ ¾ø´Ù´Â ÀÚ·áÀÔ´Ï´Ù.

TegoprazanÀÇ Åë»ó ¿ë·®Àº 50mg/dayÀÔ´Ï´Ù. À̸¦ ÇÏ·ç µÎ ¹ø Åõ¾àÇÏ¸é °ÅÀÇ ÇÏ·ç Á¾ÀÏ pH°¡ 6ÀÌ»óÀ¸·Î À¯ÁöµË´Ï´Ù. ÀÌ¿Í °°Àº °­·ÂÇÑ À§»ê¾ïÁ¦´Â Ç︮ÄÚ¹ÚÅÍ Á¦±ÕÄ¡·á¿¡ À¯¿ëÇÏ¿¡ ÀÛ¿ëÇÒ °ÍÀ¸·Î ¿¹»óÇÏ°í ÀÖ½À´Ï´Ù.

±¹³» Àӻ󿬱¸ °á°ú´Â 2018³â 9¿ù 19ÀÏ conference¿¡¼­ ¿ø±¤´ë ÃÖ¼®Ã¤ ±³¼ö´Ô²²¼­ ¹ßÇ¥ÇÑ ¹Ù ÀÖ¾î ÀÌ ³»¿ëµµ ¼Ò°³ÇÏ¿´½À´Ï´Ù.

2»ó key °á°ú

3»ó key °á°ú

2,3»ó ÀڷḦ ¸ðÀº ºÐ¼®Àε¥, LA-B,C,D¿¡¼­ ´ëÁ¶¾à¿¡ ºñÇÏ¿© tegoprazanÀÇ È¿°ú°¡ ´õ ÁÁ¾Ò´Ù´Â Èï¹Ì·Î¿î ºÐ¼®ÀÌ °¡´ÉÇß½À´Ï´Ù.

NERD¿¡ ´ëÇÑ placebo controlled data¿¡¼­ 4ÁÖ¿¡ À¯ÀÇÇÑ È¿°ú°¡ ÀÖ¾ú½À´Ï´Ù.

Safety profileÀº ´ëÁ¶¾à°ú Â÷ÀÌ°¡ ¾ø¾ú´Ù°í ÇÕ´Ï´Ù. LFT »ó½Âµµ ´ëÁ¶¾à°ú Â÷ÀÌ°¡ ¾ø¾ú½À´Ï´Ù. °ú°Å ·¹¹Ù³Ø½º(rebaprazan)¿¡¼­ Á¾Á¾ hepatotoxicity°¡ ÀÖ¾ú´Ù´Â °Í°ú È®¿¬ÇÑ Â÷ÀÌÀ̸ç tegoprazanÀÇ Æ¯ÀåÁ¡ÀÎ °ÍÀ¸·Î »ý°¢µË´Ï´Ù.

[2018-10-27. ÁÂÀå Áú¹®]

P-CABÀÌ PPI¸¦ replaceÇÒ ¼ö ÀÖÀ» °ÍÀ¸·Î »ý°¢ÇϽʴϱî?

[2018-10-27. ÀÌÁØÇà ´äº¯]

P-CABÀÌ PPIÀÇ unmet need¿¡ ´ëÇÑ ÁÁÀº ´ë¾ÈÀÌ µÉ °ÍÀº Ʋ¸²¾ø´Ù°í »ý°¢ÇÕ´Ï´Ù. Áö±Ý±îÁöÀÇ ¿¬±¸ °á°ú¿Í ÀϺ»ÀÇ ½ÃÀå ÇöȲÀ» »ìÆ캼 ¶§, Helicobacter Á¦±ÕÄ¡·á¿Í NERD¿¡¼­ ¿ì¼±ÀûÀ¸·Î »ç¿ëµÉ ¼ö ÀÖÀ» °ÍÀÔ´Ï´Ù. ±×·¯³ª À§»êÀÇ °úµµÇÑ ¾ïÁ¦µµ ³ª¸§´ë·Î ¶Ç ´Ù¸¥ ¹®Á¦¸¦ ¹ß»ý½Ãų ¼ö Àֱ⠶§¹®¿¡ ȯÀÚÀÇ »óȲ¿¡ µû¶ó µÎ Á¾·ùÀÇ ¾àÁ¦°¡ »óÈ£ º¸¿ÏÀûÀ¸·Î ¾²ÀÌÁö ¾ÊÀ»±î ¿¹»óÇÏ°í ÀÖ½À´Ï´Ù.

À§»ê ºÐºñ ¾ïÁ¦ Ä¡·á°¡ ÇÊ¿äÇÑ È¯ÀÚ¸¦ Ä¡·áÇÏ´Â ÀÇ»ç·Î¼­ »õ·Ó°í ¾ÈÀüÇÏ°í °­·ÂÇÑ Ä¡·á¾àÁ¦°¡ ³ª¿Ô´Ù´Â Á¡¿¡¼­ ¸Å¿ì ¹Ý°¡¿î ÀÏÀÔ´Ï´Ù. ¾àÁ¦ launching ÈÄ ÀÓ»ó °æÇèÀÌ ½×À̸é Á» ´õ ¼¼ºÎÀûÀÎ ÀÇ°ßÀ» µå¸± ¼ö ÀÖÀ» °Í °°½À´Ï´Ù.


[Selected posters]

Cribriform-morular variant papillary thyroid cancerÀÇ Àý¹ÝÀº familial adenomatous polyposisÀÔ´Ï´Ù. 2017³â 7¿ù 27ÀÏ ¸ñ¿äÁý´ãȸ¿¡¼­ ÇÑ Áõ·Ê¸¦ ³íÇÑ ¹Ù ÀÖ¾î ¾Æ·¡¿¡ ¿Å°Ü ¼Ò°³ÇÕ´Ï´Ù.

°©»ó¼±¾ÏÀ¸·Î ¼ö¼ú ÈÄ ´ëÀå °Ë»ç¸¦ ÅëÇÏ¿© FAP·Î È®ÁøµÈ ȯÀÚÀÔ´Ï´Ù. º´¸® °á°ú´Â ¾Æ·¡¿Í °°½À´Ï´Ù.

Thyroid gland, lymph node, total thyroidectomy with central(anterior compartment) neck dissection: Papillary carcinomas (x3):
1) Subtype: Cribriform-morular variant
2) Tumor location: Both lobes
3) Tumor size: 0.8x0.8x0.8cm (lower pole, right), 0.3x0.3x0.2cm (mid pole, left), 1.5x1.2x1.1cm (lower pole, left)
4) Lymph vessel invasion: Absent
5) Blood vessel invasion: Absent
6) Extrathyroid extension: Present (minimal)
7) Surgical margins: Negative
8) Tumor multicentricity: Present
9) Lymph nodes ; No regional lymph node metastasis (0/2: "right central LN", 0/1; "left central LN", 0/1)
10) Other pathology: None
11) Parathyroid glands: No
12) pT1b N0
¥â-catenin: Positive in tumor cells
p27: Positive (1+, 5%)
Cyclin D1: Positive (2+, 25%)
Note: This tumor is associated with germline mutations in APC gene (e.q, familial adenomatous polyposis) although rarely associated with somatic mutations. Clinical work up is recommended.
±× ¸¹Àº °©»ó¼±¾Ï ȯÀÚ Áß ¿Ö ÀÌ È¯ÀÚ¸¸ FAP °Ë»ç¸¦ ÇßÀ»±î¿ä? °©»ó¼±¾ÏÀÇ º´¸®ÇÐÀû Ư¼º ¶§¹®À̾ú½À´Ï´Ù. Cribriform-morular variant´Â FAP¿Í µ¿¹ÝµÇ´Â °æ¿ì°¡ ¸¹´Ù°í Àß ¾Ë·ÁÁø º´ÀÔ´Ï´Ù. ÀÌ È¯ÀÚ´Â º´¸®°ú¿¡¼­ FAP °¡´É¼ºÀ» ¾ð±ÞÇÏ¿´°í, ³»°ú¿¡¼­ À̸¦ È®ÀÎÇÑ °æ¿ìÀÔ´Ï´Ù. ¾Æ·¡ ¹®ÇåÀ» Âü°íÇϽñ⠹ٶø´Ï´Ù.
*Âü°í: Cribriform-morular variant of papillary thyroid carcinoma: a distinctive type of thyroid cancer.
The aim of this systematic review is to study the features of cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) by analysing the 129 documented cases in the English literature. The disease occurred almost exclusively in women. The median age of presentation for CMV-PTC was 24 years. Slightly over half of the patients with CMV-PTC had familial adenomatous polyposis (FAP). CMV-PTC presented before the colonic manifestations in approximately half of the patients with FAP. Patients with FAP often have multifocal tumours in the thyroid. Microscopic examination of CMV-PTC revealed predominately cribriform and morular pattern of cancer cells with characteristic nuclear features of papillary thyroid carcinoma. Psammoma body is rare. On immunohistochemical studies, ¥â-catenin is diffusely positive in CMV-PTC. The morular cells in CMV-PTC are strongly positive for CD10, bcl-2 and E-cadherin. Pre-operative diagnosis of CMV-PTC by fine-needle aspiration biopsy could be aided by cribriform architecture, epithelial morules and ¥â-catenin immunostaining. Mutations of APC gene are found in the patients with CMV-PTC associated with FAP. In addition, mutations in CTNNB1, RET/PTC rearrangement and PI3K3CA mutations have been reported. BRAF mutation is negative in all CMV-PTC tested. Compared to conventional papillary thyroid carcinoma, CMV-PTC had a lower frequency of lymph node metastases at presentation (12%) and distant metastases (3%) as well as lower recurrence rates (8.5%) and patients' mortality rates (2%). To conclude, patients with CMV-PTC have distinctive clinical, pathological and molecular profiles when compared to conventional papillary thyroid carcinoma.
[Áú¹®] Cribriform-morular variantÀÎ thyroid papillary cancer¿¡¼­´Â FAP¸¦ ÀǽÉÇØ¾ß ÇÏ´Â °ÍÀº Àß ¾Ë°Ú½À´Ï´Ù. ±×·¸´Ù¸é FAP ȯÀÚ¿¡¼­ ¹ß»ýÇÏ´Â thyroid cancer Áß cribriform-morular variantÀÇ ºñÁßÀº ¾î´À Á¤µµÀԴϱî?
[´äº¯] FAP ȯÀÚÀÇ °©»ó¼±¾Ï¿¡ ´ëÇÑ ÃÖ±Ù Å« ±Ô¸ðÀÇ ¿¬±¸ °á°úÀÔ´Ï´Ù (J Clin Endocrinol Metab 2016). 11¸í Áß 8¸íÀÌ Cribriform-morular variant¿´½À´Ï´Ù.

Results: Twenty-one patients (16.3%) had solid nodules, and 24 patients (18.6%) had benign cystic nodules. In total, PTC was found in 11 patients (16% of the women and 0%of the men), 8 of which were CMV-PTC and the rest were classical PTC. In 17 female patients with thyroid nodules, CMV-PTC occurred in 8 of 9 patients who were 35 years age or younger but in none of the 8 patients who were older than 35 (P .0004 by Fisher¡¯s exact test). The APC germline mutations in 8 patients with CMV-PTC were present at the 5 side of the profuse type of FAP region (codons 1249-1330).
Conclusions: The prevalence of CMV-PTC in FAP patients was higher than previously reported and this type of tumor was found preferentially in younger (under age 35) female patients with FAP.
* Âü°í: EndoTODAY °¡Á·¼º ¼±Á¾¼º ¿ëÁ¾Áõ FAP

´ëÇÑÇ×°ø Àǹ«½Ç¿¡¼­ ¹ßÇ¥ÇÑ Èï¹Ì·Î¿î ÀÚ·áÀÔ´Ï´Ù. 95ȸ ºñÇà ´ç 1°ÇÀÇ È¯ÀÚ°¡ ¹ß»ýÇÏ°í Àִµ¥, ½Ç½Å (21%) ´ÙÀ½À¸·Î ¼ÒÈ­±â°è Áõ»ó(18%)ÀÌ ¸¹¾Ò½À´Ï´Ù. ±â³» »ç¸Á »ç°ÇÀº 2017³â¿¡ 4°ÇÀ̾ú°í ±× Áß ÇÑ ¸íÀº ¿øÀÎ ¹Ì»óÀ̾ú½À´Ï´Ù. 1031°Ç Áß Ç×°ø±â ȸÇ×Àº 5°ÇÀ̾ú½À´Ï´Ù.

'¸¸¼º À§¿°Àü'ÀÇ µå¹® Áõ·ÊÀÔ´Ï´Ù. EndoTODAY¿¡¼­µµ gastric volvulus¿Í diaphragmatic evantrationÀ» ¼Ò°³ÇÑ ¹Ù ÀÖÀ¸´Ï Âü°íÇϽñ⠹ٶø´Ï´Ù.

Foreign body¿¡ ÀÇÇÑ ½Äµµ actinomycosis Áõ·ÊÀÔ´Ï´Ù. ¸ñ¿ä³»½Ã°æÁý´ãȸ¿¡¼­ actinomycosis Áõ·Ê¸¦ ³íÀÇÇÑ ¹Ù ÀÖÀ¸´Ï Âü°íÇϽñ⠹ٶø´Ï´Ù.

ÇǺΠÀüÀÌ·Î Áø´ÜµÇ Á÷ÀåÀÇ ¹ÝÁö¼¼Æ÷¾Ï 1¿¹

Pyogenic liver abscess·Î ÀÎÇÑ hepatogastric fistula

Malignant mesothelioma of peritoneum (tuberculous peironitis¿Í ±¸ºÐÀÌ ¾î·Á¿ü´ø °æ¿ì)


[Pictures]


[References]

1) EndoTODAY P-CAB

© ÀÏ¿ø³»½Ã°æ±³½Ç ¹Ù¸¥³»½Ã°æ¿¬±¸¼Ò ÀÌÁØÇà. EndoTODAY Endoscopy Learning Center. Lee Jun Haeng.