Analysis of factors associated with undescended testis in patients with congenital diaphragmatic hernia.

PURPOSE: This study aimed to investigate the incidence and clinical factors associated with undescended testes (UDT) in patients with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively reviewed the incidence of UDT in male neonates admitted to our institution and underwent surgery for CDH between January 2006 and December 2022. Patients were divided into two groups based on the presence or absence of UDT, and risk factors for UDT were compared between the two groups. RESULTS: Among the 66 male neonates with CDH, 16 (24.2%) developed UDT. Patients with UDT had a significantly smaller gestational age (p = 0.026), lower birth weight (p = 0.042), and lower Apgar score at 1 min (p = 0.016) than those without UDT. They had a significantly higher incidence of large diaphragmatic defects (p = 0.005), received more patch closures (p = 0.020), had a longer mechanical ventilation period (p = 0.034), and longer hospital stay (p = 0.028). Multiple logistic regression analysis revealed that large diaphragmatic defect was an independent risk factor for UDT (adjusted odds ratio of 3.87). CONCLUSION: CDH and UDT are strongly correlated. In patients with CDH, the incidence of UDT was related not only to patients' prematurity but also to the large diaphragmatic defect. Large diaphragmatic defect is an independent risk factor for UDT in patients with CDH.

Feasibility and safety of laparoscopic tumor resection in children with abdominal neuroblastomas.

PURPOSE: This study aimed to evaluate the feasibility and safety of laparoscopic resection of abdominal neuroblastoma by comparing operative and long-term oncologic outcomes between open and laparoscopic surgeries. METHODS: This single-center retrospective study included patients who underwent laparoscopic tumor resection, between January 2000 and June 2021, with a maximum tumor diameter of ≤ 60 mm and without image-defined risk factors (IDRFs) at surgery. Data from 35 abdominal neuroblastoma resections were reviewed and compared between the laparotomy and laparoscopic groups. RESULTS: Nineteen patients underwent laparotomy and 16 had laparoscopic tumor resection. All laparoscopic surgeries achieved complete resection without conversion to open surgery. Median blood loss was significantly lower in the laparoscopic group (0.6 mL/kg) than in the laparotomy group (8.4 mL/kg) (P < 0.0001). There were two locoregional recurrences in the laparoscopic group and two metastatic recurrences in the laparotomy group. Five-year overall survival was 93.8% in both groups. CONCLUSION: Laparoscopic resection of abdominal neuroblastomas in children is a feasible and safe procedure for tumors ≤ 60 mm in diameter with no IDRFs at surgery, with long-term outcomes equivalent to laparotomy.

Clinical Usefulness of Blenderized Food for Selenium Deficiency in Pediatric Patients with Severe Motor and Intellectual Disabilities.

INTRODUCTION: This study aimed to assess the preventive or therapeutic effects of blenderized food (BF) on selenium deficiency in pediatric patients with severe motor and intellectual disabilities (SMID). METHODS: The medical records of all 40 consecutive pediatric patients with SMID who underwent nutritional assessment were retrospectively reviewed and compared between two groups: the enteral formula (EF) group and the BF group fed with BF providing more than 10% of total caloric intake. Next, for the selenium-deficient patients who were newly started on blenderized tube feeds after the first nutritional assessment, improvement of selenium deficiency and change of dietary contents were assessed. RESULTS: The BF group patients had a significantly lower prevalence of selenium deficiency and higher serum selenium levels than the EF group patients. In all 7 selenium-deficient patients who started blenderized tube feeds after the first nutritional assessment, serum selenium levels were significantly increased at the second nutritional assessment, even though total selenium intake, selenium intake by EF, and total caloric intake did not differ significantly, and, in fact, caloric intake was significantly decreased by EF. CONCLUSION: Combined feeding of BFs can be useful for prevention and therapy of selenium deficiency in pediatric SMID patients.

Prevalence of urachal remnants in children according to age and their anatomic variants.

PURPOSE: The aim of this study was to elucidate the prevalence of urachal remnants in children in relation to patient age as well as to identify their anatomic variants, using a laparoscopic view. METHODS: The medical records of 394 pediatric patients who underwent laparoscopic inguinal hernia repair were reviewed. Patients were divided into four groups based on their age at surgery. Using laparoscopic visualization, the presence and anatomic variants of urachal remnants were analyzed. RESULTS: A urachal remnant was confirmed in 140 children (35.5%). Although the prevalence was significantly higher in the group of children aged < 1 year (63.2%) than in any other group, no significant difference in the prevalence was observed between the groups aged ≥ 1 year. In 42 cases (10.7%), the urachal remnant merged into the lateral umbilical ligament. CONCLUSIONS: Our results suggest a recommendation of nonoperative management of asymptomatic urachal remnants, especially in patients less than 1 year of age due to its probable spontaneous resolution. Knowledge of the anatomic variants could improve the accuracy of diagnosis of urachal remnants and the comprehension of its structure and localization for the achievement of accurate and complete excision.

Postoperative decrease in plasma acyl ghrelin levels after pediatric living donor liver transplantation in association with hepatic damage due to ischemia and reperfusion injury.

PURPOSE: Ghrelin was recently reported to promote recovery from hepatic injury. We hypothesized that it could also be associated with clinical recovery of the transplanted liver from ischemia and reperfusion injury. Our aims were to investigate perioperative ghrelin changes following pediatric living donor liver transplantation (LDLT) and to analyze the association of these changes with postoperative hepatic function. METHODS: We measured plasma acyl ghrelin (AG) concentrations before surgery, at the end of surgery and on postoperative days (PODs) 1, 3 and 7 in 12 children who underwent LDLTs, and, as controls, pre- and post-operatively and on POD1 in 7 children who underwent benign abdominal mass resection. The correlations between the participants' ghrelin profiles and hepatic function-related data were evaluated. RESULTS: AG levels significantly declined to 15.6% of preoperative levels after LDLT and almost returned to baseline on POD3. Post-operative AG levels were significantly reduced to a greater extent following LDLT than benign abdominal mass resection. AG levels on POD1 inversely correlated with aspartate aminotransferase levels and cold/total ischemia time (P < 0.05). CONCLUSION: These results suggest that reduced AG levels on POD1 may reflect the degree of damage to the transplanted liver due to ischemia and reperfusion injury.

Chemotherapy can promote liver metastasis by enhancing metastatic niche formation in mice.

BACKGROUND: Some chemotherapeutic agents have been reported to promote lung metastasis. However, there have been no reports regarding chemotherapy-induced liver metastasis. We hypothesized that chemotherapy might also enhance liver metastasis. The present study aimed to create a chemotherapy-enhanced liver metastasis mouse model and investigate its mechanism. MATERIALS AND METHODS: Mice were pretreated with cisplatin, vincristine, or saline by intraperitoneal injection. Next, B16F10 mouse melanoma cells and BE(2)-C human neuroblastoma cells were injected into the spleens of C57BL/6 and BALB/c nu/nu mice, respectively, to induce experimental liver metastasis, and the number of liver nodules was determined. We also analyzed the effect of chemotherapy on changes of the liver tissue regarding representative metastasis-promoting factors using real-time quantitative polymerase chain reaction and immunohistochemical and histological analysis. RESULTS: Cisplatin increased the number of nodules by 4.7-fold in the B16F10 liver metastasis model. Vincristine increased the number of nodules by 3.8-fold in the BE(2)-C liver metastasis model. Cisplatin increased mRNA levels of matrix-metalloproteinase (MMP)-2 and periostin, while vincristine increased MMP-9 and S100A8/9 levels in liver tissues. Cisplatin induced fibrosis, whereas vincristine induced neutrophil recruitment in liver tissues according to histological and immunohistochemical analysis. CONCLUSIONS: We concluded that cisplatin or vincristine could enhance liver metastasis of mouse melanoma cells or human neuroblastoma cells, respectively. In addition, the mRNA expression of MMP-2 and periostin, or MMP-9 and S100A8/9 is increased by cisplatin or vincristine pretreatment, possibly resulting in fibrosis or neutrophil recruitment, respectively. These niche factors might be associated with increased liver metastasis.

CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote cell spreading.

Atrial natriuretic peptide (ANP) is a cardiac hormone released by the atrium in response to stretching forces. Via its receptor, guanylyl cyclase-A (GC-A), ANP maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated, in part, by endothelial cells. Both in vivo and in vitro, ANP enhances endothelial barrier function by reducing RhoA activity and reorganizing the actin cytoskeleton. We established mouse endothelial cells that stably express GC-A and used them to analyze the molecular mechanisms responsible for actin reorganization. Stimulation by ANP resulted in phosphorylation of myosin light chain (MLC) and promotion of cell spreading. p21-activated kinase 4 (PAK4) and cerebral cavernous malformations 2 (CCM2), a scaffold protein involved in a cerebrovascular disease, were required for the phosphorylation of MLC and promotion of cell spreading by ANP. Finally, in addition to the GC domain, the kinase homology domain of GC-A was also required for ANP/GC-A signaling. Our results indicate that CCM2 and PAK4 are important downstream mediators of ANP/GC-A signaling involved in cell spreading, an important initial step in the enhancement of endothelial barrier function.

Image-based surgical risk factors for Wilms tumor.

PURPOSE: The standard treatment for Wilms tumor (WT) is primary resection. However, in cases with unresectable tumor or tumor spillage, which are considered to have high surgical risks, more intensive chemotherapy and radiotherapy are required. In the present study, we retrospectively analyzed preoperative image parameters to identify factors associated with surgical risks. METHODS: Twenty-nine patients with WT were enrolled in this study. Data on various preoperative image parameters, such as tumor size, tumor volume, displacement of great vessels, and contralateral extension of the tumor were collected, and their relationship with surgical factors, including operative time, hemorrhage, tumor spillage, and unresectability were analyzed. RESULTS: Patients with unresectable tumor or with tumor spillage (surgical high-risk group) more frequently demonstrated displacement of great vessels and contralateral tumor extension. Operative time and blood loss were also significantly related to tumor size, area, volume, displacement of great vessels and contralateral extension. CONCLUSION: Besides tumor size, displacement of great vessels and contralateral extension were significantly associated with surgical risks. These factors are easily determined using CT images and are, therefore, useful to decide whether preoperative chemotherapy should be started instead of primary tumor resection for large localized WTs.

Role of surgery in delayed local treatment for INSS 4 neuroblastoma.

BACKGROUND: The aim of the present study was to compare the efficacy, complications and outcomes of the following two surgical strategies for delayed local treatment for International Neuroblastoma Staging System (INSS) 4 neuroblastoma (NB): complete resection (CR; period A); and gross total resection/subtotal resection (GTR/STR) with local irradiation (period B). METHODS: We retrospectively analyzed 17 patients with INSS 4 NB who received delayed local treatment (period A, n = 11; period B, n = 6). RESULTS: Eleven patients in period A received CR. Two patients underwent GTR and four patients underwent STR in period B. The amount of blood loss in period A was significantly greater than that in period B. Postoperative complications were observed in eight patients in period A (73%), but in only one patient in period B (17%; P < 0.01). Recurrence was observed in five patients in period A and in one patient in period B (45.4% vs 16.6%; P = n.s.). Distant metastasis at recurrence was observed in four patients in period A and in one patient in period B. CONCLUSIONS: Gross total resection/subtotal resection with local irradiation may be a safe and effective delayed local treatment for INSS 4 NB.

C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice.

BACKGROUND: Pulmonary fibrosis has high rates of mortality and morbidity; however, no effective pharmacological therapy has been established. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, selectively binds to the transmembrane guanylyl cyclase (GC)-B receptor and exerts anti-inflammatory and anti-fibrotic effects in various organs through vascular endothelial cells and fibroblasts that have a cell-surface GC-B receptor. Given the pathophysiological importance of fibroblast activation in pulmonary fibrosis, we hypothesized that the anti-fibrotic and anti-inflammatory effects of exogenous CNP against bleomycin (BLM)-induced pulmonary fibrosis were exerted in part by the effect of CNP on pulmonary fibroblasts. METHODS: C57BL/6 mice were divided into two groups, CNP-treated (2.5 µg/kg/min) and vehicle, to evaluate BLM-induced (1 mg/kg) pulmonary fibrosis and inflammation. A periostin-CNP transgenic mouse model exhibiting CNP overexpression in fibroblasts was generated and examined for the anti-inflammatory and anti-fibrotic effects of CNP via fibroblasts in vivo. Additionally, we assessed CNP attenuation of TGF-ß-induced differentiation into myofibroblasts by using immortalized human lung fibroblasts stably expressing GC-B receptors. Furthermore, to investigate whether CNP acts on human lung fibroblasts in a clinical setting, we obtained primary-cultured fibroblasts from surgically resected lungs of patients with lung cancer and analyzed levels of GC-B mRNA transcription. RESULTS: CNP reduced mRNA levels of the profibrotic cytokines interleukin (IL)-1ß and IL-6, as well as collagen deposition and the fibrotic area in lungs of mice with bleomycin-induced pulmonary fibrosis. Furthermore, similar CNP effects were observed in transgenic mice exhibiting fibroblast-specific CNP overexpression. In cultured-lung fibroblasts, CNP treatment attenuated TGF-ß-induced phosphorylation of Smad2 and increased mRNA and protein expression of α-smooth muscle actin and SM22α, indicating that CNP suppresses fibroblast differentiation into myofibroblasts. Furthermore, human lung fibroblasts from patients with or without interstitial lung disease substantially expressed GC-B receptor mRNA. CONCLUSIONS: These data suggest that CNP ameliorates bleomycin-induced pulmonary fibrosis by suppressing TGF-ß signaling and myofibroblastic differentiation in lung fibroblasts. Therefore, we propose consideration of CNP for clinical application to pulmonary fibrosis treatment.

Primary renal neuroblastoma with metastasis and matrix metalloproteinase-14 expression.

We herein report the rare case of a 4-year-5-month-old boy who presented with primary renal neuroblastoma. The patient developed repeated lung and liver metastatic recurrences, but, following a combination of chemotherapy, radiation therapy and aggressive surgical resection, the patient is now in remission. To investigate the pathogenesis of lung metastasis, immunohistochemistry was performed for matrix metalloproteinase-9 and -14 (MMP-9 and MMP-14), molecular markers of invasion, metastasis and angiogenesis in neuroblastoma. In the present case, MMP-9 expression was not observed, but MMP-14 expression was detected in the primary lesion and was more highly expressed in the metastatic lesion compared with the primary one. Given the MMP-14 staining in other cases, expression of MMP-14 may be associated with the aggressiveness of the tumor. This suggests that selected clones with high MMP-14 expression in the primary tumor might metastasize and form MMP-14-rich lesions.

Patient satisfaction after sclerotherapy of venous malformations in children.

BACKGROUND: We have introduced and performed percutaneous sclerotherapy on pediatric patients, and information regarding the mid- and long-term results after percutaneous treatment of peripheral venous malformations is necessary to counsel patients and their parents about the outcome of the therapy. This study was designed to retrospectively evaluate the long-term satisfaction of pediatric patients following percutaneous sclerotherapy for venous malformations (VMs). METHODS: A total of 53 children younger than 16 years of age with VMs who underwent sclerotherapy were included in this study. Self-assessment questionnaires regarding the treatment effectiveness and patients' satisfaction were sent to 50 of 53 patients. Sclerotherapy was performed using 3% polidocanol, absolute ethanol, or 5% ethanolamine oleate (EO). RESULTS: The median numbers of sessions per patient was 2.0 (range, 1-12), and the median follow-up time was 1.8 years (range, 6months-8.3years). Forty-two patients (84%) returned the questionnaire. The most frequent symptom was swelling (95%, 40/42) before sclerotherapy. After treatment, patients felt less pain (82%, 23/28), functional limitation (78%, 14/18), swelling (70%, 28/40), and cosmetic disfigurement (59%, 13/22). None of the patients responded "worse" for any symptoms, and 30 patients (71%) reported being "very satisfied" or "satisfied" with the treatment. CONCLUSION: Percutaneous sclerotherapy of VMs was safe and effective for relieving symptoms in our pediatric patients, and many of them were satisfied with the outcomes.

A case of pediatric live-donor liver transplantation with a left lateral segment reduction by a linear stapler after reperfusion.

In pediatric LDLT, graft reduction is sometimes required because of the graft size mismatch. Dividing the portal triad and hepatic veins with a linear stapler is a rapid and safe method of reduction. We herein present a case with a left lateral segment reduction achieved using a linear stapler after reperfusion in pediatric LDLT. The patient was a male who had previously undergone Kasai procedure for biliary atresia. We performed the LDLT with his father's lateral segment. According to the pre-operative volumetry, the GV/SLV ratio was 102.5%. As the patient's PV was narrow, sclerotic and thick, we decided to put an interposition with the IMV graft of the donor between the confluence and the graft PV. The graft PV was anastomosed to the IMV graft. The warm ischemic time was 34 min, and the cold ischemic time was 82 min. The ratio of the graft size to the recipient weight (G/R ratio) was 4.2%. After reperfusion, we found that the graft had poor perfusion and decided to reduce the graft size. We noted good perfusion in the residual area after the lateral edge was clamped with an intestinal clamp. The liver tissue was sufficiently fractured with an intestinal clamp and then was divided with a linear stapler. The final G/R ratio was 3.6%. The total length of the operation was 12 h and 20 min. The amount of blood lost was 430 mL. No surgical complications, including post-operative hemorrhage and bile leakage, were encountered. We believe that using the linear stapler decreased the duration of the operation and was an acceptable technique for reducing the graft after reperfusion.

Importance of nutrient balance in severe congenital diaphragmatic hernia: A retrospective case-control study.

BACKGROUND & AIMS: Growth retardation is a common morbidity in infants with severe congenital diaphragmatic hernia (CDH). This study aimed to investigate the appropriate amount of nutrition and nutrient balance in early infants with severe CDH. METHODS: This was a retrospective case-control study. Isolated CDH patients with more than half of the chest wall devoid of diaphragmatic tissue and treated between 2006 and 2022 were included. The patients were divided into positive (n = 16) or negative (n = 8) weight gain velocity groups in early infancy (from 1 to 3 months of age). Clinical variables and amount of nutrition were compared between the two groups. RESULTS: The earlier start of enteral nutrition (EN) and higher replacement rate of the naso-duodenal (ND) tube were observed more frequently in the positive group than in the negative group. Regarding daily intake by both EN and parenteral nutrition (PN), total caloric intake and caloric intake of proteins and lipids were significantly higher in the positive group than in the negative group at 1 month of age. At 2 months, total caloric intake and caloric intake of lipids were significantly higher in the positive group than in the negative group. At 3 months of age, only caloric intake of lipid was significantly higher in the positive group than in the negative group. CONCLUSIONS: The early replacement of the ND tube may contribute to the early start of EN, which may subsequently lead to appropriate nutrient supplementation including adequate lipid administration, resulting in early catch-up growth.

Factors reducing psychological satisfaction after the Nuss procedure in pediatric patients.

PURPOSE: We examined patient satisfaction with postoperative chest appearance after Nuss procedure and analyzed the factors for postoperative low satisfaction. METHODS: We retrospectively reviewed data of 133 patients who underwent the Nuss procedure from 2000 to 2016. Their medical records, X-rays, and computed tomography scans were evaluated. Haller index and concave rate were used as objective indices of the deformity. The questionnaires were used to evaluate satisfaction with the chest appearance by a linear scale including five markers (1: dissatisfaction, 5: satisfaction). The patients were divided into two groups: the low satisfaction (score = 1, 2) and the high satisfaction (score = 3-5). RESULTS: The median age during the Nuss procedure was 7.6 (interquartile range, 5.8-12.8) years. Out of 133, 65 patients replied, and the mean postoperative satisfaction score was 3.8 ± 0.2. Out of the 65 respondents, 16 patients (24.6%) were classified as low satisfaction group. Haller index and concave rate were significantly higher and the previous instances of chest operation history were more frequent in the low satisfaction group than in the high satisfaction group, although there was no significant intergroup difference in terms of the postoperative concave rate. CONCLUSIONS: Severe deformity and previous chest operation history were considered to be factors for low satisfaction.

A case of early onset adenocarcinoma associated with colorectal polyposis with an unknown germline mutation.

BACKGROUND: Typically, in cases of adenomatous polyposis, colorectal cancer develops in the third or fourth decade of life. We report the case of a female patient with colorectal polyposis who developed adenocarcinoma at 8 years of age. CASE PRESENTATION: An 8-year-old girl was admitted with a 4-year history of occasional bloody stools. Colonoscopy revealed colon polyposis and histopathological assessment confirmed a well-differentiated adenocarcinoma in the adenomatous polyps, so laparoscopy-assisted proctocolectomy was performed in the lithotomy position by a simultaneous abdominal and anal approach. To completely resect the rectal mucosa, excision was commenced just distal to the dentate line. After the mucosal resection up to the peritoneal reflection level, an inverted muscular cuff was cut circumferentially, and the terminal ileum was pulled through the muscular cuff and anastomosed to the anal canal. Histopathology revealed multiple adenomatous polyps and scattered well-differentiated tubular adenocarcinomas (tub1) in the adenomatous polyps and the non-polypoid mucosal lesions. Because complete resection was achieved, additional adjuvant chemotherapy was not administered. Polymerase chain reaction (PCR)-direct sequencing of the entire coding region and the exon-intron junctions, and real-time PCR of DNA extracted from blood cells, revealed no mutations of either APC or MUTYH. No deletions, duplications, translocations or inversions of APC, MUTYH and GREM1 genes were found using multiplex ligation-dependent probe amplification (MLPA) and G-banding analysis. Multi-gene panels sequencing for polyposis syndromes or hereditary colorectal cancers, and trio-whole exome sequencing was conducted. However, no candidate pathogenic variants of genes were detected in de novo dominant or autosomal recessive model. Somatic mutation of APC was not detected in 4 polyps by loss of heterozygosity analysis at a single nucleotide polymorphism in intron 14. The patient has remained disease-free for 5 years. Currently, the patient is on loperamide and passes stool 5 times/day without any soiling. CONCLUSIONS: The genetic analysis suggests that she may have a germline mutation at unscreened region of these genes or in unidentified FAP gene. The patient will be carefully followed up for residual rectal carcinoma and for the development of other cancers.

CT and MRI Findings of Inflammatory Myofibroblastic Tumor in the Bladder.

Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is a rare soft tissue tumor characterized by spindle cell proliferation with inflammatory cell infiltration. We present a case of bladder IMT occurring in a 6-year-old boy. Pretreatment CT images depicted a polypoid and broad-based mass measuring 18 mm in the superior to the front wall of the bladder, and the mass showed isodensity on precontrast image and ring enhancement of the mass after the intravenous administration of contrast material. Pelvic MRI demonstrated the 18 × 17 × 16 mm broad-based mass, suggesting submucosal tumor in the dome of the bladder. The mass showed low-to-moderate signal intensity on T1-weighted images and slight high signal intensity on T2-weighted images and restricted diffusion with low signal intensity on ADC map and abnormal high signal intensity on DWI. Transurethral resection of the bladder tumor and partial cystectomy were undertaken, and the pathology revealed IMT of the bladder. We suggest its inclusion in the differential diagnosis of cases of a polypoid and broad-based mass on the superior wall or the front wall of the bladder with ring enhancement on contrast-enhanced CT and MRI.

Kampo medicines Rikkunshito and Hangeshashinto prevent cisplatin-induced intestinal mucosal injury in rats.

BACKGROUND/PURPOSE: We examined the effects and mechanisms of rikkunshito (RKT) and hangeshashinto (HST) on cisplatin-induced mucosal injuries in the rat small bowel. METHODS: Juvenile rats were divided into 6 groups: sham control, cisplatin injection without kampo medicines, and cisplatin injection with oral administration of low and high doses of RKT (1000 mg/kg and 2000 mg/kg) and HST (500 mg/kg and 1000 mg/kg). Fecal condition, intestinal morphological changes, enterocyte proliferation, and enterocyte apoptosis were assessed. RESULTS: Diarrhea and atrophy of ileal villi observed in the cisplatin group were significantly improved in all kampo groups. Injury scores of the jejunum were significantly lower with RKT (2000 mg/kg) and HST (500 and 1000 mg/kg) than with cisplatin, and those of the ileum were significantly lower with HST (500 and 1000 mg/kg) than with cisplatin. Enterocyte proliferation of the jejunum was significantly increased with RKT (2000 mg/kg) and HST (500 mg/kg) compared with cisplatin, and those of the ileum were significantly increased in all kampo groups compared with the cisplatin group. Jejunal and ileal apoptosis following cisplatin administration was significantly inhibited by HST. CONCLUSIONS: RKT and HST prevented cisplatin-induced intestinal mucosal injury with increasing proliferation of intestinal epithelial cells. HST also attenuated cisplatin-induced crypt cell apoptosis.