Severe fibrosis contributed to both incomplete resection and difficult colorectal ESD. Larger tumor size and paradoxical movement during the procedure were independent factors contributing to the difficulty of colorectal ESD. These factors might enable endoscopists to develop strategies for treating colorectal ESD.

Paclitaxel is a chemotherapeutic agent that causes peripheral neuropathy as its major dose-limiting side effect. However, the peripheral neuropathy is difficult to manage. A study we recently conducted showed that repetitive administration of aucubin as a prophylactic inhibits paclitaxel-induced mechanical allodynia. However, the mechanisms underlying the anti-allodynic activity of aucubin, which is a major component of Plantaginis Semen, was unclear. In addition to mechanical allodynia, aucubin inhibited spontaneous and mechanical stimuli-induced firing in spinal dorsal horn neurons; however, catalpol, a metabolite of aucubin, did not show these effects. Furthermore, paclitaxel induced the expression of CCAAT/enhancer-binding protein homologous protein, a marker of endoplasmic reticulum (ER) stress, in the sciatic nerve and a Schwann cell line (LY-PPB6 cells); however, this effect was inhibited by aucubin. These results suggest that aucubin inhibits paclitaxel-induced mechanical allodynia through the inhibition of ER stress in peripheral Schwann cells. Key words paclitaxel; mechanical allodynia; aucubin; firing; Schwann cell; stressPaclitaxel is an anti-microtubule agent originally isolated from the bark of the Pacific yew tree (Taxus brevifolia) and is wildly used to treat solid neoplasms such as breast, ovarian, and lung cancers.1,2) However, in spite of its useful anticancer effect, paclitaxel causes peripheral neuropathy, which is characterized by mechanical allodynia, spontaneous pain, shooting and burning pain, tingling, and numbness, with a stocking-and-glove distribution.3) The peripheral neuropathy is a major dose-limiting side effect, which disturbs cancer treatment with paclitaxel. Therefore, relief of the neuropathy is very important for improving both the QOL and cancer treatment with paclitaxel. Several drugs, including gabapentin and amifostine, have failed to relieve paclitaxel-induced peripheral neuropathy [4][5][6] ; therefore, alternative therapeutic agents are need.Goshajinkigan is a traditional herbal formulation that consists of 10 herbal medicines (Rehmanniae Radix, Achyranthis Radix, Corni Fructus, Dioscoreae Rhizoma, Plantaginis Semen, Alismatis Rhizoma, Poria, Moutan Cortex, Cinnamoni Cortex, and Processi Aconiti Radix). It has been shown to attenuate the progression of peripheral neuropathy induced by docetaxel and paclitaxel/carboplatin treatments in cancer patients.7,8) Our previous study has been shown that repetitive administration of goshajinkigan extract as a prophylactic inhibits the exacerbation of paclitaxel-induced mechanical allodynia in mice.9) We also showed that aucubin, which is an iridoid glycoside and the main component of Plantaginis Semen, plays an important role in the anti-allodynic action of goshajinkigan.10) However, the mechanisms underlying the anti-allodynic activity of aucubin are not understood completely. It was reported in a previous study that paclitaxel decreased peripheral blood flow and induced mechanical allodynia in mice.11) The study also demonstra...

The chemotherapeutic agent paclitaxel (PTX) causes peripheral neuropathy as a major dose-limiting side effect, and this peripheral neuropathy is difficult to control. Our previous report showed that prophylactic repetitive administration of goshajinkigan (牛車腎氣丸 niú chē shèn qì wán), but not hachimijiogan (八味地黃丸 bā wèi dì huáng wán), which lacks two of the constituents of goshajinkigan, inhibited PTX-induced mechanical allodynia in mice. Thus, the herbal medicines Plantaginis Semen (車前子 chē qián zǐ) or Achyranthis Radix (牛膝 niú xī) may contribute to the inhibitory action of goshajinkigan on the exacerbation of PTX-induced mechanical allodynia [Andoh et al, J. Tradit. Complement. Med. 2014; 4: 293–297]. Therefore, in this study, we examined whether an extract of Plantaginis Semen (EPS) or Achyranthis Radix (EAR) would relieve PTX-induced mechanical allodynia in mice. A single intraperitoneal injection of PTX caused mechanical allodynia, which peaked on day 14 after injection. Repetitive oral administration of EPS, but not EAR, starting from the day after PTX injection significantly inhibited the exacerbation of PTX-induced mechanical allodynia. Repetitive intraperitoneal injection of aucubin, one of the main components of EPS, starting from the day after PTX injection also significantly reduced PTX-induced mechanical allodynia. However, repetitive intraperitoneal injection of geniposide acid (a precursor of aucubin) or catalpol (a metabolite of aucubin) did not prevent the exacerbation of mechanical allodynia. These results suggest that prophylactic administration of EPS is effective for preventing the exacerbation of PTX-induced allodynia. Aucubin may contribute to the inhibitory action of EPS on the exacerbation of PTX-induced allodynia.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is difficult to manage with currently available therapeutic drugs. Therefore, there is a need for novel therapeutic agents for treating CIPN. Goshajinkigan (GJG) is a Kampo formula composed of ten crude drugs. While GJG has been used for the treatment of CIPN, the active constituents of GJG and their underlying mechanisms of pharmacological effects are still unknown. Our previous study revealed that repetitive oral administration of the water extract of Plantaginis Semen, a crude drug ingredient of GJG, inhibited the mechanical allodynia induced by an intraperitoneal injection of paclitaxel in mice. To elucidate the active compounds of Plantaginis Semen, activity-guided separation of the water extract of Plantaginis Semen was performed. From the active fraction, four iridoids (1-4) were identified. Repetitive oral administration of aucubin (1) at 100 or 30 mg/kg and 100 mg/kg of the fraction crude 3 [primarily comprised of pedicularis-lactone (3)], showed anti-allodynic activity, suggesting 1 and 3 could be some of the active compounds responsible for the anti-allodynic property of Plantaginis Semen and GJG. Our study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously. Identification of active anti-allodynic compounds found in Kampo formulations will support the development of novel therapies for the management of CIPN in cancer patients.

P i c t u r e 1 . A: T r a n s v e r s e s e c t i o n o f c h e s t a n d a b d o mi n a l CT s h o wi n g h y p o d e n s e l e s i o n o v e r t h e l e f t l o b e o f t h e l i v e r a n d ma s s i v e p e r i c a r d i a l e f f u s i o n . B : Ve r t i c a l s e c t i o n o f CT . PICTURES IN CLINICALPerforation into the pericardium is an uncommon complication of liver abscess (3,4). In the previous literature, some