Paclitaxel-related dermatological problems: Not only alopecia occurs.

OBJECTIVE: Dermatological problems after chemotherapy are often neglected with gynecological oncologists. Since paclitaxel is one of most popular agents for gynecology organ-related cancers, dermatologic change after paclitaxel treatment is seldom reported before. CASE REPORT: Two patients with gynecological organ malignancy who underwent the postoperative dose-dense weekly schedule of paclitaxel 80 mg/m2 plus carboplatin (area of curve 5) every three weeks had repeat dermatological problems (skull, facial and upper trunk areas) during the treatment. They included dermatitis, eczema, and folliculitis. Topical use of anti-fungal cream and oral anti-histamine agents stopped the disease progression and all had completed their chemotherapy without interruption. CONCLUSION: Clinicians should be aware of paclitaxel-induced skin toxicities, especially on the skull, face and upper trunk areas to minimize the occurrence of severe morbidity and to provide the better quality of life when cure is our primary priority in the management of gynecological organs-related malignancies.

Pain after laparoscopic surgery: Focus on shoulder-tip pain after gynecological laparoscopic surgery.

Laparoscopy, one of minimally invasive procedures, is a commonly used procedure in diagnosis and management of various kinds of clinical problems, including gynecologic organ-related diseases. Compared with conventional exploratory laparotomy, the benefits of laparoscopic surgery include reduction of surgical wound, decreasing in postoperative pain, shortening hospital stay, rapid recovery, and a better cosmetic result. However, there are still up to 80% of patients after laparoscopic surgery complaining of high levels of pain and needing pain relief. Postlaparoscopic pain can be separated into distinct causes, such as surgical trauma- or incision wound-associated inflammatory change, and pneumoperitoneum (carbon dioxide [CO2])-related morphological and biochemical changes of peritoneum and diaphragm. The latter is secondary to irritation, stretching, and foreign body stimulation, leading to phrenic neuropraxia and subsequent shoulder-tip pain (STP). STP is the most typical unpleasant experience of patients after laparoscopic surgery. There are at least 11 strategies available to attempt to decrease postlaparoscopic STP, including (1) the use of an alternative insufflating gas in place of CO2, (2) the use of low-pressure pneumoperitoneum in place of standard-pressure pneumoperitoneum, (3) the use of warmed or warmed and humidified CO2, (4) gasless laparoscopy, (5) subdiaphragmatic intraperitoneal anesthesia, (6) local intraperitoneal anesthesia, (7) actively expelling out of gas, (8) intraperitoneal drainage, (9) fluid instillation, (10) pulmonary recruitment maneuvers, and (11) others and combination. The present article is limited in discussing postlaparoscopic STP. We extensively review published articles to provide a better strategy to reduce postlaparoscopic STP.

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells.

BACKGROUND: Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo. OBJECTIVE: IMQ has been reported to promote the apoptosis of THP-1-derived macrophages through an ER stress-dependent pathway. However, the role of ER stress in IMQ-induced autophagy is unknown. In this study, we investigated the relationship between ER stress and IMQ-induced autophagy. METHODS: The expression of LC3, P62, p-PERK, Grp78, p-elF2α and IRE1α proteins were determined by immunoblotting. The relationship between ER stress and IMQ-induced autophagy were analyzed by ER stress inhibitors, a PERK inhibitor and the genetic silencing of PERK. The role of double-strand RNA-dependent protein kinase (PKR) activation in IMQ-induced autophagy was assessed by inhibiting PKR and genetically silencing PKR. The IMQ-induced autophagy was evaluated by immunoblotting and EGFP-LC3 puncta formation. RESULTS: IMQ induced reactive oxygen species (ROS) production in cancer cells. Additionally, IMQ markedly induced ER stress via ROS production and increased autophagosome formation in a dose- and time-dependent manner in both TLR7/8-expressing and TLR7/8-deficient cancer cells. Pharmacological or genetic inhibition of ER stress dramatically reduced LC3-II expression and EGFP-LC3 puncta formation in IMQ-treated cancer cells. IMQ-induced autophagy was markedly reduced by depletion and/or inhibition of PKR, a downstream effector of ER stress. CONCLUSION: IMQ-induced autophagy is dependent on PKR activation, which is mediated by ROS-triggered ER stress. These findings might provide useful information for basic research and for the clinical application of IMQ.