Gastrointestinal Tract Epithelial Changes Associated With Taxanes: Marker of Drug Toxicity Versus Effect

Daniels, Jason; Gibson, Michael K.; Li, Xu; Sun, Shaoli; Canto, Marcia I.; Heath, Elisabeth I.; Wang, Jean; Brock, Malcolm V.; Montgomery, Elizabeth A.

doi:10.1097/pas.0b013e3181582331

Cited by 63 publications

(31 citation statements)

References 12 publications

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“…In the context of taxane therapy, cells in the proliferative compartment of the gastrointestinal tract appear hyperchromatic and display numerous mitotic figures, many of ''ring'' appearance. 13 Nuclei in the gastrointestinal tract also show marked loss of polarity. Interestingly, the taxane-associated epithelial changes noted in gastrointestinal biopsy specimens have been reported to mimic epithelial dysplasia.…”

Section: Discussionmentioning

confidence: 95%

“…Interestingly, the taxane-associated epithelial changes noted in gastrointestinal biopsy specimens have been reported to mimic epithelial dysplasia. 13 The dermatopathologic effects of taxane cytotoxicity are also reminiscent of changes induced by podophyllin resin, its homologs, and certain derivatives, such as etoposide. 14 Podophyllin resin is used to topically treat cutaneous and mucosal warts caused by human papillomavirus infection.…”

Section: Discussionmentioning

confidence: 99%

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Dermatopathologic effects of taxane therapy

Plummer

Shea

2011

Journal of the American Academy of Dermatology

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Dermatopathologic effects of taxane therapy

Plummer

Shea

2011

Journal of the American Academy of Dermatology

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“…The pathophysiologic mechanism is thought to begin with a predisposition to mucosal damage through mitotic arrest of rapidly dividing cell types and mitotic arrest in otherwise normal esophageal, gastric, small bowel, and colonic mucosa [3,4]. Bacterial translocation, proliferation, and production of endotoxins ensue in the setting of decreased immunocompetence.…”

Section: Discussionmentioning

confidence: 99%

Collateral Damage: Taxane-Induced Colonic Perforation

Erdrich¹,

Kastenberg²,

DiMaio³

et al. 2014

Dig Dis Sci

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A 70-year-old woman with history of multifocal right breast cancer (ER-/PR-/Her2neu?) was evaluated in the emergency department for acute abdominal pain. Her past medical history was notable for well-controlled asthma and pulmonary sarcoidosis treated with prednisone 6 years earlier. She had no significant surgical history. Three days prior to initial evaluation she had completed the fifth of six planned cycles of neoadjuvant chemotherapy with docetaxel, carboplatin, and trastuzumab. She recalled mild cramping pain after the last few cycles that was sometimes associated with diarrhea but had always self-resolved. The fifth cycle was followed by more severe and progressive pain.She arrived to the emergency department afebrile with normal vital signs. Her abdomen was firm and diffusely tender with rebound in the left lower quadrant. Although her WBC count was 8.4 9 10 9 /L with 70 % neutrophils, she had received pegfilgrastim that week. Lactate and electrolytes were normal. A computed tomography scan was interpreted as showing free intraperitoneal air and fluid in addition to peritoneal enhancement, thickening of the small bowel, and thickening from the distal transverse through the sigmoid colon. A 3-cm fluid collection was identified adjacent to the sigmoid. Additionally, free fluid was visualized near the duodenum (Fig. 1). The site of enteric perforation was not apparent.Based on her examination and imaging, she was brought to the operating room directly from the emergency department for exploratory laparotomy, during which peritonitis was identified with a purulent exudate in the right upper quadrant including the perihepatic and pericholecystic spaces with intact duodenum and stomach. Extensive pus was found in the pouch of Douglas surrounding a focally necrotic, free and well-circumscribed perforation on the anti-mesenteric surface of the sigmoid colon, remote from perforating blood vessels or the sparse diverticula present (Fig. 2), confirmed intraoperatively. A sigmoid resection with end colostomy was performed to enable the resumption of chemotherapy.Her postoperative course was unremarkable, with early return of bowel function and rapid toleration of a regular diet. She was treated with piperacillin/tazobactam while inpatient and discharged to home on the fifth postoperative day with amoxicillin/clavulanic acid in order to complete a total antibiotic course of 10 days for the intraabdominal perforation and extensive purulence. Gross and histopathologic examination of the surgical specimen backed by a detailed operative report conclusively excluded a ruptured diverticulum as the cause of perforation. Since striking mitotic arrest was present in the enteric epithelium with numerous mitotic spindles arranged in ring forms (Fig. 3), taxane-related enteric perforation was diagnosed.Trastuzumab without docetaxel or carboplatin was given for her breast cancer, given the previous consequences of taxane toxicity. Six weeks following perforation, she underwent wire localized lumpectomy and sentinel node biopsy, wh...

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“…12 The mitotic arrest peaks at 3e12 h after Taxol administration, and is followed by an increase in apoptosis 6e36 h later. 13 The differential diagnosis for apoptotic injury includes cytomegalovirus infection and other drug or radiation induced injury.…”

Section: Changes Induced By Drugs and Toxinsmentioning

confidence: 99%