Safety of Elderly Living Kidney Donors: 2 Cases of Donors Older Than 80 Years: A Case Report.

Much controversy exists over the performance of elderly living donor kidney transplantation. We report the safety of 2 cases of elderly living kidney donations in our hospital. CASE 1: An 82-year-old man was a living kidney donor for his 56-year-old son. The donor suffered from hypertension, but has successfully managed his blood pressure with only one medication. His serum creatinine was 0.7 mg/dL and inulin clearance was 122.5 mL/min, which met the usual criteria for living kidney donors. This was his son's secondary kidney transplantation, and no other donors existed. CASE 2: An 80-year-old woman was a living kidney donor for her 45-year-old son. Her serum creatinine was 0.61 mg/dL and inulin clearance was 71.7 mL/min, which met the marginal kidney donor criteria. In both cases, we determined that the donor kidney function was acceptable. Though we explained the risks of the transplantation thoroughly, the patients' strong will to offer a kidney to their family member did not change. We decided to carry out the transplantation. At the time of publication, nearly 2 years have passed since the transplantation, but both donors and recipients are doing well. In the future, it seems more likely that the number of elderly living donor kidney transplantation will rise. On one hand, there is no absolute contraindication for elderly donors, while on the other hand, the criteria for a living kidney donor must be strictly examined. Furthermore, careful observation of both donors and recipients after transplantation is required.

Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study.

The present study investigates the human leucocyte antigen (HLA) allele and haplotype frequencies in Japanese population. We carried out the frequency analysis in 5824 families living across Japanese archipelago. The studied population has mainly been typed for the purpose of transplant, especially the hematopoietic stem cell transplantation (HSCT). We determined HLA class I (A, B, and C) and HLA class II (DRB1) using Luminex technology. The haplotypes were directly counted by segregation. A total of 44 HLA-A, 29 HLA-C, 75 HLA-B, and 42 HLA-DRB1 alleles were identified. In the HLA haplotypes of A-C-B-DRB1 and C-B, the pattern of linkage disequilibrium peculiar to Japanese population has been confirmed. Moreover, the haplotype frequencies based on family study was compared with the frequencies estimated by maximum likelihood estimation (MLE), and the equivalent results were obtained. The allele and haplotype frequencies obtained in this study could be useful for anthropology, transplantation therapy, and disease association studies.

Prognostic nomogram for nonresectable pancreatic cancer treated with gemcitabine-based chemotherapy.

BACKGROUND: A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported. METHODS: Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots. RESULTS: In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction. CONCLUSIONS: The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.

A case of primary squamous cell carcinoma of the endometrium associated with extensive "ichthyosis uteri".

BACKGROUND: Ichthyosis uteri is an uncommon entity in which the entire endometrium is replaced by stratified squamous epithelium. Though the condition often is considered as benign, dysplastic changes have been reported. CASE: We describe herein an exceedingly rare case of primary squamous cell carcinoma of the endometrium (PSCCE) associated with extensive ichthyosis uteri with chronic pyometra, who presented with blood-stained vaginal discharge of six-seven months duration. Although repeated endometrial biopsies revealed only strips of stratified squamous epithelium showing moderate to severe dysplastic changes, the tumor markers and magnetic resonance imaging strongly suggested advanced uterine body malignancy. Exploratory laparotomy was performed, and histologic findings of the superficial layer were consistent with ichthyosis uteri; in contrast the lesion of invasive squamous cell carcinoma was located in the deeper layer and lymph nodes. No dysplastic changes of the cervix were noted. CONCLUSIONS: It is suggested that PSCCE could be associated with pre-existing ichthyosis uteri and deeper biopsies should be performed for the accurate preoperative diagnosis of cases with chronic pyometra.

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study.

BACKGROUND: This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer. METHODS: Patients were randomly assigned to 4-week treatment with gemcitabine alone (1000, mg m(-2) gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m(-2) gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m(-2) S-1 orally twice daily on days 1-15). The primary end point was progression-free survival (PFS). RESULTS: Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms. CONCLUSION: Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.

Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine.

BACKGROUND: The renin-angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth. METHODS: We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs). RESULTS: Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis. CONCLUSIONS: The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

Possible relationship between chronic inflammation and pyloric metaplasia in a patient with lobular endocervical glandular hyperplasia.

BACKGROUND: Lobular endocervical glandular hyperplasia (LEGH) is a rare entity of a pseudoneoplastic benign condition of the uterine cervix, and its histogenesis and pathological significance including a connection with carcinogenesis of the endocervical gland has not yet been fully recognized. CASE: We describe a rare case of localized LEGH, which developed adjacent to a cesarean section scar. A 53-year-old premenopausal woman presented with a recent onset of abdominal distention and menorrhagia. Magnetic resonance imaging revealed multiple uterine myomas including submucosal myoma and localized small cystic lesions in the proximal area of the anterior wall of the cervix. Total hysterectomy was performed. The cystic lesions were diagnosed as LEGH. Thread-like foreign bodies and inflammatory reaction were demonstrated around several hyperplastic lesions. Focal immunoreactivity for MIB-1 was detected only in the LEGH cells adjacent to the fibrosis and foreign body reaction. DISCUSSION: The histological findings, in relation to the previous cesarean section suggest that the ectopic pyloric hyperplasia in the present case could represent a heteroplastic or metaplastic process due to a multidirectional differentiation of cervical glands during chronic inflammation by foreign bodies.

Endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia showing rapid reaccumulation of hydrometra.

Mucinous endocervical adenocarcinoma is characterized by increased watery vaginal discharge, but the early diagnosis is sometimes difficult because biopsy specimen might only serve to sample a superficial part of the tumor. The patient presented with complaints of abdominal distention. No vaginal bleeding or watery discharge was observed. Hydrometra was suspected by imaging studies. Rapid reaccumulation of hydrometra was seen despite drainage. Papanicolaou smear of endocervix and endometrium followed by fractional curettage was performed, but failed to confirm the diagnosis. To investigate the unknown origin of hydrometra, an exploratory laparotomy with total hysterectomy and bilateral salpingo-oophorectomy was performed, followed by pelvic lymphadenectomy because biopsy specimens during operation suggested adenocarcinoma of the cervix. The final pathologic study of surgical specimens revealed mucinous adenocarcinoma, which was located on the proximal area of cervix. Adjacent to carcinoma tissue, lobular endocervical glandular hyperplasia (LEGH) was detected. Pyloric gland mucin (HIK1083), MUC6, and MUC5AC were diffusely immunopositive in the cytoplasm of LEGH cells and the immunoreactivity became weaker in adenocarcinoma cells with tumor progression and loss of differentiation. Based on histopathologic features of the present case, there seems to be a possible link between LEGH and conventional mucinous endocervical adenocarcinomas. The physician should keep in mind the possible existence of endocervical adenocarcinoma in a patient showing rapid reaccumulation of hydrometra, when uterine malignancies are clinically suspected and biopsy finding fails to confirm the diagnosis.

Self-expandable metallic stents for malignant biliary obstruction with an anomalous pancreaticobiliary junction.

BACKGROUND: Anomalous pancreaticobiliary junction (APBJ) is associated with pancreaticobiliary cancer. Limited data are available on endoscopic biliary drainage for unresectable malignant biliary obstruction with APBJ. This study evaluated the efficacy and safety of self-expandable metallic stents (EMSs) for the management of malignant biliary obstruction with APBJ. METHODS: Between 1993 and 2005, 324 patients with unresectable malignant biliary obstruction underwent insertion of an EMS. Six of these patients with concomitant APBJ constituted the subjects of this study. Early (30 days after EMS insertion) stent-related complications and stent patency were evaluated in these six patients. RESULTS: The cause of biliary obstruction was gallbladder cancer in four patients and pancreatic cancer in two patients. Uncovered EMSs were inserted across the common channel without performance of a biliary sphincterotomy. The diameter of the uncovered EMS used was based on the diameter of the common channel. For all six patients, endoscopic biliary drainage was successful, and their jaundice subsided steadily. None of the six patients experienced early complications, including acute pancreatitis. The mean stent-related complication-free period was 163 days. Stent occlusion caused by tumor ingrowth occurred in two patients. Acute cholangitis and cholecystitis were observed in one patient each. CONCLUSIONS: Uncovered EMSs are effective for palliation of unresectable malignant biliary obstruction in patients who have APBJ without increasing the risk of stent-related early complications.

Endoscopic transpapillary approach to the gallbladder for diagnosing gallbladder cancer.

PURPOSE: Gallbladder cancer (GBC) has a poor prognosis that is related to delayed diagnosis. The present study evaluated the efficacy of the transcystic ductal approach in diagnosing GBC. METHODS: A catheter was introduced into the gallbladder endoscopically via the cystic duct to obtain bile for cytology. Subsequently, cytology specimens were collected using a brush, and intraductal ultrasonography (IDUS) was performed using a miniature probe in patients suspected of having GBC. RESULTS: Bile cytology was performed successfully in 23 of 25 patients (92%). The sensitivity, specificity and accuracy of cytology were 44.4%, 100% and 78.3%, respectively. Brush cytology and IDUS were successful in six of eight (75%) and nine of 15 (60%) patients, respectively. Brush cytology was positive in two of five patients with GBC. In all four patients with invasive cancer, IDUS showed an irregularity or disruption of the outermost hyperechoic layer. CONCLUSIONS: The endoscopic transpapillary approach to the gallbladder was useful for the diagnosis of GBC. Brush cytology and IDUS may improve diagnostic efficacy and provide more useful information.

Impressive remission of locally advanced malignant peritoneal mesothelioma treated with combination of radiotherapy and intraperitoneal paclitaxel.

BACKGROUND: The results of treatment of malignant peritoneal mesothelioma are quite unsatisfactory, especially in the later stages of the disease, regardless of the treatment modality employed. CASE: We report a case of locally advanced malignant peritoneal mesothelioma, in which the combination of radiotherapy and intraperitoneal paclitaxel was beneficial for long-term disease stabilization. A 71-year-old woman presented with abdominal pain. Abdominal ultrasound and magnetic resonance imaging confirmed the presence of a mass with both cystic and solid components with moderate ascites. Serum CA-125 concentration was 727 IU/ml. At exploratory laparotomy, a large mass originating from the pouch of Douglas was found. A total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed with partial excision of the mass and involved the peritoneum of the pouch of Douglas. The histologic study showed malignant peritoneal mesothelioma. One year and five months after surgery, significant progression of the residual tumor with increasing ascites was noted. Radiotherapy to the whole pelvis with 45 Gy in 25 fractions was given over five weeks together with intraperitoneal paclitaxel (60 mg/m2) instillation, which was repeated every three weeks. The patient received eight cycles of paclitaxel instillation over seven months. The compliance of the patient was excellent under therapy and her general condition improved significantly one and half year with a marked regression of the tumor masses after this treatment. CONCLUSION: The combination of radiotherapy and intraperitoneal paclitaxel seems suitable in palliative settings primarily aimed at improving the quality of life.

Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer.

Recent studies have identified vimentin, a type III intermediate filament, among genes differentially expressed in tumours with more invasive features, suggesting an association between vimentin and tumour progression. The aim of this study, was to investigate whether vimentin expression in colon cancer tissue is of clinical relevance. We performed immunostaining in 142 colorectal cancer (CRC) samples and quantified the amount of vimentin expression using computer-assisted image analysis. Vimentin expression in the tumour stroma of CRC was associated with shorter survival. Overall survival in the high vimentin expression group was 71.2% compared with 90.4% in the low-expression group (P=0.002), whereas disease-free survival for the high-expression group was 62.7% compared with 86.7% for the low-expression group (P=0.001). Furthermore, the prognostic power of vimentin for disease recurrence was maintained in both stage II and III CRC. Multivariate analysis suggested that vimentin was a better prognostic indicator for disease recurrence (risk ratio=3.5) than the widely used lymph node status (risk ratio=2.2). Vimentin expression in the tumour stroma may reflect a higher malignant potential of the tumour and may be a useful predictive marker for disease recurrence in CRC patients.

Expression of PPARdelta in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology.

Whether peroxisome proliferator-activated receptor (PPAR) delta is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPARdelta expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPARdelta in CRC. Immunohistochemical analysis indicated that PPARdelta expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARdelta protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPARdelta-positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPARdelta-positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPARdelta in CRC samples. Based on Western blot analysis and quantitative RT-PCR, high PPARdelta protein expression correlated with high PPARdelta mRNA levels. Peroxisome proliferator-activated receptor delta may have a supporting role in tumorigenesis, and the close association between PPARdelta expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue.