Naldemedine-induced opioid withdrawal syndrome with severe psychiatric symptoms in an advanced cervical cancer patient without brain metastasis.

OBJECTIVE: Naldemedine, an oral peripheral µ-opioid receptor antagonist, was developed for the treatment of constipation, a side effect of opioid use. Naldemedine is not generally recognized as causing opioid withdrawal in which associated symptoms affecting the central nervous system. METHOD: From the series of cancer patients undergoing symptom management, we report a case treated with naldemedine for constipation in relation to the use of opioids for cancer pain and who displayed severe psychological symptoms associated with withdrawal immediately after the use of naldemedine. RESULTS: The patient was a 36-year-old woman diagnosed with cervical cancer Stage IIB, PS3. When the patient, who was using oxycodone hydrochloride hydrate (80 mg/day) for ileal pain, was started on naldemedine for constipation, she complained of sweating after just 5 min and hallucinations after 1 h. The patient also displayed physical/behavioral abnormalities such as diarrhea and hyperactivity, and psychological abnormalities such as aggression toward staff.Despite the psychiatric symptoms worsening over time, there were no abnormalities in terms of blood biochemical data, and no brain metastasis was observed on MRI. Based on the Clinical Opiate Withdrawal Scale, these symptoms were judged to indicate opioid withdrawal. Naldemedine was discontinued due to naldemedine-related opioid withdrawal syndrome and, thereafter, the psychiatric symptoms diminished, with no recurrence of similar symptoms observed to date. SIGNIFICANCE OF RESULTS: If mental and behavioral abnormalities occur in patients receiving naldemedine, it is necessary to consider the possibility of opioid withdrawal syndrome as a differential diagnosis.

Expression of estrogen and progesterone receptors in smooth muscle metaplasia of rectovaginal endometriosis.

To investigate expression of estrogen receptors (ER) and progesterone receptors (PR) in smooth muscle metaplasia (SMM) outside the endometriotic foci of rectovaginal endometriosis (RVE). One hundred and ninety-five specimens were obtained from the rectovaginal areas of the 63 patients who were underwent laparoscopic surgery for RVE. The patients were divided into 3 groups: a gonadotropin-releasing hormone (GnRH) agonist group, a non-GnRH group, including a proliferative phase group, and a secretory phase group. Expression of ER and PR in the rectovaginal tissues of RVE were determined using immunohistochemical methods. Smooth muscle metaplasia occurred in 172 specimens (88.2%), and ER and PR expression were found in the smooth muscle cells in the SMM areas outside the endometriotic foci of RVE. The expression of ER and PR in the GnRH agonist group were significantly lower than those in the non-GnRH agonist group. This is the first report demonstrating ER and PR in the smooth muscle cells in SMM outside the endometriotic foci of RVE. The ER and PR were expressed in the SMM areas, but these receptors were not recognized in fibrotic areas. We could identify the expression ratio of these receptors during each menstrual phase, with or without administered GnRH agonist.

Fibrosis and smooth muscle metaplasia in rectovaginal endometriosis.

Rectovaginal (RV) endometriosis presents with a nodular lesion composed of fibromuscular and endometriotic tissue, and the fibromuscular tissue is the major component in the severe stage. The purpose of our study was to examine the extending process of fibromuscular tissue in RV endometriosis. Histological examinations using immunostains, were performed in 90 RV tissue specimens from 37 women. Fibrosis was present in 89 specimens. In each specimen, the intensity of the fibrosis differed from area to area: in mildly fibrotic areas, the collagen fibers were present around the endometriotic tissue, and in severely fibrotic areas, the fibrosis widely extended into fat and connective tissus as well as within the endometriotic tissue. In the 60 specimens containing endometriotic tissue, the increase in the amount of endometriotic tissue significantly correlated to the increase in degree of fibrosis in the entire tissue. The presence of aggregated smooth muscles, unassociated with blood vessels, was defined as smooth muscle metaplasia (SMM), which was always present within the fibrotic areas, and was observed in 80 specimens. The degree of SMM in the entire tissue was significantly correlated with the degree of fibrosis. From these findings, the following was hypothesized. Initially, endometriotic tissue was present sporadically and fibrosis was present around the endometriotic tissue. Thereafter, proliferation of endometriotic tissue and an increase in fibrosis occur consecutively. The SMM was present within the fibrotic areas, and it became more severe, correlating with the increase in fibrosis. In conclusion, this is the first report describing the extending process of the fibromuscular tissue of RV endometriosis from a histological viewpoint, and we think that recognization of this process is useful for histological diagnosis and clinical management of RV endometriosis.

Peritoneal endometriosis in the broad ligament presenting as a large tumor.

Peritoneal endometriosis presenting as a tumor is very rare. A case of peritoneal endometriosis in the broad ligament presenting as a large tumor is reported. A 39-year-old woman had a solid and cystic tumor with many microcysts, measuring 17 x 13 x 3.5 cm, mainly located in the right posterior broad ligament. Histologically, the tumor consisted of many endometrial glands associated with various amounts of endometrial stroma. Neither the glands nor the stromal cells had cellular atypia. We diagnosed peritoneal endometriosis presenting as a tumor. Among the six cases (five previously reported cases and our case) of tumor-like endometriosis in the peritoneum, two cases (33%) had received tamoxifen therapy and four cases (67%) had cystic or solid and cystic tumor. Among them, the tumor size ranged from 3 to 17 cm in diameter, and our case was the largest. In conclusion, this case is rare, but it is important for pathologists to be aware of the phenomenon (that extensive peritoneal endometriosis produces a large tumor) in the histological diagnosis of a tumor in the peritoneum.

Uterine tumors resembling ovarian sex-cord tumors producing parathyroid hormone-related protein of the uterine cervix.

A case of uterine tumors resembling ovarian sex-cord tumors (UTROSCT) producing parathyroid hormone-related protein (PTH-rP) of the uterine cervix is reported. A 66-year-old woman underwent total hysterectomy with bilateral salpingo -oophorectomy due to the possibility of a malignant uterine tumor. A fairly well-circumscribed tumor, measuring 8 x 5 x 7 cm, was present in the myometrium of the cervix and extended into the endocervical mucosa. Histologically, the tumor showed predominantly sex-cord-like differentiation and the features of conventional endometrial low-grade stromal sarcoma were observed in part. Immunohistochemically, the tumor cells were negative for CD10. From these findings, we diagnosed the present case as Clement and Scully's group II UTROSCT arising from the uterine cervix. To our knowledge, this is the first report of the cervical occurrence of UTROSCT. Furthermore, in this tumor, production of PTH-rP was demonstrated by normalization of serum PTH-rP after the tumorectomy and immunoreactivity for PTH-rP in the tumor cells.