Syndrome of inappropriate antidiuretic hormone secretion following adjuvant CDDP and 5-FU administration in a patient with esophageal carcinoma

A case of hyponatremia following the first course of systemic adjuvant chemotherapy with cisplatin (CDDP) and 5-FU in a previously treated patient with esophageal cancer is reported. A 61-year-old man was admitted to our hospital for adjuvant chemotherapy after transthoracic esophagectomy and 3-field lymphadenectomy for esophageal cancer. Six days following chemotherapy, his serum sodium concentration was found to be 118 mEq/L, without edema or dehydration. This hyponatremic state was diagnosed as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by CDDP, based on the hypo-osmolality of his serum and urine, and an inappropriate level of plasma vasopressin.     

Long-term disease-free survival following multimodal treatment in a patient with curatively unresectable advanced gastric cancer with metachronous liver metastasis

A case was a 57-year-old man. Despite a diagnosis of cStage IV gastric cancer (cN2, cH0, cM0, cT3 (SE), cP1), we preferentially performed a non-curative surgery to avoid stenosis or bleeding by tumor invasion. Since no evidence of peritoneal metastasis was found at surgery, distal gastrectomy with D2 lymph node dissection was performed, and lymph nodes anterior to the pancreatic head were sampled. The pathological diagnosis was pT3 (SE), pN2, sH0, pM1 (LYM), pStage IV. After the surgery, S-1 was administered. One year and 9 months later, a solitary metastasis was found in S6 of the liver, and the patient underwent radiofrequency ablation (RFA) followed by adjuvant S-1. Currently, 5 years and 10 months after the surgery, the patient is under follow-up, and remains alive with recurrence-free. We speculate that in the presence of N or M (LYM) factors for stage IV gastric cancer, surgery with lymphadenectomy, which does not prevent the completion of adjuvant chemotherapy, followed by multimodal treatments such as continued chemotherapy and RFA, led to the long-term survival.     

Value of religious care for relief of psycho‐existential suffering in Japanese terminally ill cancer patients: the perspective of bereaved family members

Objective: This study aimed to clarify the experience of bereaved family members of cancer patients regarding the usefulness of religious care (perceived usefulness). The value of this care to palliate psycho‐existential suffering in future patients was also examined (predicted usefulness). Methods: A questionnaire was sent to 592 bereaved family members of cancer patients who were admitted to certified palliative care units in Japan. Responses were obtained from 378 families, indicating whether the patient received religious care, the perceived usefulness of the care, and its predicted usefulness for palliation of psycho‐existential suffering. Results: About 25% (N=83) indicated that the patient had received religious care, whereas 75% (N=255) had not received it. Families of patients who had received religious care evaluated pastoral care workers (86%), religious services (82%), and religious music (80%) as ‘very useful’ or ‘useful’. Families predicted usefulness of religious care for future patients: attending a religious service (very useful or useful, 56%; not useful or harmful, 44%), a religious atmosphere (48%, 52%), meeting with a pastoral care worker (50%, 50%), and religious care by physicians (26%, 74%), and nurses (27%, 73%). Families with a religion were significantly more likely to rate religious care as useful for future patients. Conclusions: Families of patients who received religious care generally evaluated this care to be very useful or useful. For future patients, some families felt that religious care would be useful, but some did not. In Japan, religious care is more likely to provide benefits to patients who have a religion. Copyright © 2009 John Wiley & Sons, Ltd.     

Anti‐cancer stem cell activity of a hedgehog inhibitor GANT61 in estrogen receptor‐positive breast cancer cells

Estradiol (E2) increases not only the cell growth but also the cancer stem cell (CSC) proportion in estrogen receptor (ER)‐positive breast cancer cells. It has been suggested that the non‐canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER‐positive breast cancer cells. We studied anti‐CSC activity of a non‐canonical Hh inhibitor GANT61 in ER‐positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER‐positive breast cancer cell lines. CSC proportion was measured using either the mammosphere assay or CD44/CD24 assay. Expression levels of pivotal molecules in the Hh pathway were measured. Combined effects of GANT61 with antiestrogens on the anti‐cell growth and anti‐CSC activities were investigated. E2 significantly increased the cell growth and CSC proportion in all ER‐positive cell lines. E2 increased the expression levels of glioma‐associated oncogene (GLI) 1 and/or GLI2. GANT61 decreased the cell growth in association with a G1‐S cell cycle retardation and increased apoptosis. GANT61 decreased the E2‐induced CSC proportion measured by the mammosphere assay in all cell lines. Antiestrogens also decreased the E2‐induced cell growth and CSC proportion. Combined treatments of GANT61 with antiestrogens additively enhanced anti‐cell growth and/or anti‐CSC activities in some ER‐positive cell lines. In conclusion, the non‐canonical Hh inhibitor GANT61 inhibited not only the cell growth but also the CSC proportion increased by E2 in ER‐positive breast cancer cells. GANT61 enhanced anti‐cell growth and/or anti‐CSC activities of antiestrogens in ER‐positive cell lines.     

Synchronous double primary lung cancers with different response to pemetrexed

We describe the case of a 74-year-old male patient with synchronous double primary lung cancers: adenocarcinoma in the right lower lobe and squamous cell carcinoma in the left upper lobe (LUL). These tumors were difficult to differentiate radiographically from a single metastatic primary cancer, but their eventual diagnoses were triggered by their responses to chemotherapy, which included pemetrexed. After two courses of chemotherapy with pemetrexed and carboplatin, the right lower lobe mass had partially resolved; however, the LUL mass had increased. When S-1 was used as fourth-line chemotherapy, the size of the LUL mass decreased. Pemetrexed is a potentially useful drug for treating nonsquamous cell carcinoma, but may not be appropriate in cases with a coexisting squamous cell carcinoma. Our experience with this interesting case leads us to propose that S-1 monotherapy may provide a treatment option in pemetrexed-refractory cases.     

Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection

Background

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer.

Methods

A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses.

Results

PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators.

Conclusions

PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.

     

Pharmacological inhibition of the Hedgehog pathway prevents human rhabdomyosarcoma cell growth

The Hedgehog pathway functions as an organizer in embryonic development. Recent studies have shown that mutation of the PTCH1 gene involved in the Hedgehog pathway affects rhabdomyosarcoma development. However, the expression of Hedgehog pathway molecules in human rhabdomyosarcoma cells has not been well clarified. In addition, the effect of pharmacological inhibition of the Hedgehog pathway is not known. We investigated the expression of the genes involved in the Hedgehog pathway using human rhabdomyosarcoma cell lines and biopsy specimens. Further, we evaluated the effect of pharmacological inhibition of the Hedgehog pathway using cyclopamine or GANT61 by WST assay, cell proliferation assay and cell death detection assay. Real-time PCR revealed that human rhabdomyosarcoma cell lines and biopsy specimens overexpressed the following genes: Sonic hedgehog, Indian hedgehog, Desert hedgehog, PTCH1, SMO, GLI1, GLI2 and ULK3. Immunohistochemistry revealed that rhabdomyosarcoma cell lines and biopsy specimens expressed SMO and GLI2. Inhibition of SMO by cyclopamine slowed the growth of human rhabdomyosarcoma cell lines. Similarly, inhibition of GLI by GANT61 slowed the growth of human rhabdomyosarcoma cell lines. Inhibition of cell proliferation and apoptotic cell death together prevented the growth of rhabdomyosarcoma cells by cyclopamine and GANT61 treatment. Our findings suggest that pharmacological inhibition of the Hedgehog pathway may be a useful approach for treating rhabdomyosarcoma patients.