Bladder-Sparing Extended Resection of Locally Advanced Rectal Cancer Involving the Prostate and Seminal Vesicles

Purpose Total pelvic exenteration (TPE) is the standard procedure for locally advanced rectal cancer involving the prostate and seminal vesicles. We evaluated the feasibility of bladder-sparing surgery as an alternative to TPE. Methods Eleven patients with advanced primary or recurrent rectal cancer involving the prostate or seminal vesicles, or both, underwent bladder-sparing extended colorectal resection with radical prostatectomy. The procedures performed were abdominoperineal resection (APR) with prostatectomy (n = 6), colorectal resection using intersphincteric resection combined with prostatectomy (n = 4), and abdominoperineal tumor resection with prostatectomy (n = 1). Local control and urinary and anal function were evaluated postoperatively. Results Cysto-urethral anastomosis (CUA) was performed in seven patients and catheter-cystostomy was performed in four patients. Coloanal or colo-anal canal anastomosis was also performed in four patients. There was no mortality, and the morbidity rate was 38%. All patients underwent complete resection with negative surgical margins. After a median follow-up period of 26 months there was no sign of local recurrence, and ten patients were alive without disease, although distant metastases were found in three patients. Five patients had satisfactory voiding function after CUA, and three had satisfactory evacuation after intersphincteric resection (ISR). Conclusion These bladder-sparing procedures allow conservative surgery to be performed in selected patients with advanced rectal cancer involving the prostate or seminal vesicles, without compromising local control.     

A case of retroperitoneal dedifferentiated liposarcoma initially diagnosed as malignant fibrous histiocytoma: a case report

We report a case of retroperitoneal tumor which turned out to be liposarcoma by the histological evaluation of its recurrent tumor, although the initial tumor was diagnosed as malignant fibrous histiocytoma (MFH). A retroperitoneal tumor in a 62-year-old man was removed and pathologically diagnosed as MFH. Five years after the initial surgery, computed tomography (CT) demonstrated a recurrent tumor near the spleen. The tumor was resected together with the spleen, tail of pancreas, and connective tissue due to adhesion and diagnosed as well-differentiated liposarcoma with sclerosing component. Generally dedifferentiated liposarcoma is difficult to distinguish from MFH and the presence of a well-differentiated liposarcoma component in the adjacent adipose tissue leads to the diagnosis of dedifferentiated liposarcoma. The clinical course of the present case indicated that the initial tumor was dedifferentiated liposarcoma and the recurrent tumor developed from the surrounding well-differentiated liposarcoma.     

Successful perioperative blood purification therapy in patients with maintenance hemodialysis therapy who underwent living donor liver transplantation

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.     

Clinical significance of pulmonary metastases in stage D2 prostate cancer patients

Several prognostic factors such as the extent of bone metastases (EOD) in advanced prostate cancer (PCa) have been reported. Metastasis of the lung is rarely a significant clinical factor in the management of prostate cancer. The present study evaluates the clinical significance of lung metastases. We retrospectively reviewed the PCa database to identify patients with pulmonary metastases at initial diagnosis. The medical records of the patients were examined with respect to age, histologic grade, EOD score, marker response to endocrine therapy and clinical outcome. We then compared several potential clinical factors between patients with and without pulmonary metastases. Next, we retrospectively reviewed autopsy records of 60 Japanese patients who died of hormone-refractory metastatic PCa with particular focus upon metastatic profiles. A comparative study of stage D(2) patients with (n=20) and without (n=77) pulmonary metastases found no significant differences in EOD score, performance status, marker response and survival. Only tumor grade was better in the group with, than without pulmonary metastases (P=0.0120, chi-square analysis). In the series of autopsies, we found pulmonary metastases in 38 cases (63%), following metastases of the bone (57 cases, 95%) and lymph nodes (52 cases, 87%). A retrospective analysis of survival showed that patients with bone or lymph node metastases had a positive relative risk. In contrast, lung metastasis could be a positive prognostic indicator, although the findings were not statistically significant. These data suggest that the presence of pulmonary metastasis has no ominous impact on clinical course and disease outcome even in patients with disseminated prostate cancer.     

Fractalkine expression and the recruitment of CX3CR1+ cells in the prolonged mesangial proliferative glomerulonephritis

BACKGROUND: We established the reversible and the prolonged models of mesangial proliferative glomerulonephritis (GN) with anti-Thy 1 antibody 1-22-3. However, the essential factors leading to the prolonged glomerular alterations have not been identified. METHODS: The expressions of several chemokines and cytokines were compared in the reversible and the prolonged models. Expression of fractalkine and the number of the fractalkine receptor CX3CR1-positive cells in the glomeruli in the prolonged model were significantly higher than those in the reversible model. Then, the localization of fractalkine and the characteristics of CX3CR1+ cells were analyzed in glomeruli. To elucidate the significance of the fractalkine expression, we analyzed the expression in the model treated with angiotensin II receptor antagonist, candesartan. RESULTS: Immunostaining of fractalkine was detected on endothelial cells on the fifth day, and fractalkine staining also was detected in the mesangial area on day 14. Major parts of the CX3CR1+ cells in the glomeruli were macrophages, especially ED3+ cells. Candesartan treatment ameliorated the glomerular morphological findings at six weeks after disease induction. Although the treatment did not ameliorate the morphological finding at two weeks, decreased expression of fractalkine and CX3CR1+ were already detected at two weeks in rats treated with candesartan. CONCLUSIONS: Fractalkine expression and the recruitment of CX3CR1+ cells in glomeruli might play an important role in the development of the prolonged disease. These expressions could be predictors of the prolonged disease of the mesangial proliferative glomerulonephritis.     

Calcitonin gene-related peptide as a tumor marker for medullary thyroid carcinoma.

We have established a radioimmunoassay method for calcitonin gene-related peptide (CGRP) to monitor changes in plasma CGRP levels in patients with medullary thyroid carcinoma (MTC). Preoperative plasma CGRP levels (normal level less than 12.7 pg/ml) were as high as 128 pg/ml to 2,010 pg/ml in all five patients with MTC. Ten of 17 postoperative patients with MTC were positive for CGRP. A provocation test was performed in 12 patients with MTC. Plasma CGRP changes roughly paralleled serum calcitonin levels. In particular, in three patients with poorly-differentiated MTC which progressed aggressively, plasma CGRP levels were increased to 1.4 to 2.0 times levels before the test, i.e., lower than the 2.8- to 23.3-fold increase in nine patients with the well-differentiated MTC. These results suggest that CGRP may be a humoral marker of medullary carcinoma and be related to degree of malignancy.     

Malignant tumors in choledochal cysts.

Between 1960 and 1975, 17 patients with congenital cystic dilatation of the common bile duct (choledochal cyst) were treated and three were associated with malignant tumors in the cysts and one was with carcinoma of the gallbladder. Preoperative diagnosis of adenocarcinoma in the choledochal cyst was established in one patient by cytologic examination of the bile which was obtained during the procedure of endoscopic pancreaticocholangraphy (EPCG) and percutaneous transhepatic cholangiography (PTC). Definitive treatment of the choledochal cysts associated with malignant tumors in the biliary tract was accomplished by excision of the cysts with tumor and choledochojejunostomy in two patients, by cystoduodenostomy following external drainage in one and by cholecystectomy with resection of invaded transverse colon in one with cancer of the gallbladder. Successful excision of choledochal cysts in 11 patients including three cases associated with malignant tumors in the biliary tract during the last 15 year period is the basis of this report.     

Duodenum preservation in pancreatic head resection to maintain pancreatic exocrine function (determined by pancreatic function diagnostant test and cholecystokinin secretion)

Background/Purpose Organ-preserving surgery, such as pylorus-preserving pancreatoduodenectomy (PPPD), duodenum-preserving pancreatic head resection (DPPHR), or medial pancreatectomy (MP), is one of the recent advances in pancreatic surgery. There was a previous report that preservation of the duodenum maintained pancreatic function. However, concerning the resected pancreas, patients were divided into two groups; one group included pancreatic head resections such as Whipple, PPPD, and complete DPPHR, and the other group included MP that removed only the pancreatic neck and preserved the pancreatic head and distal pancreas. The present study was designed to clarify the significance of duodenum preservation, in comparison with duodenum removal, in patients with pancreatic head resection, in terms of pancreatic function, determined by a pancreatic function diagnostant (PFD) test and cholecystokinin (CCK) secretion.Methods The subjects were 61 patients (10 with Whipple, 41 with PPPD, and 10 with complete DPPHR). PFD tests and postprandial plasma CCK secretion were used for evaluation.Results There was a significant difference between pre- and postoperative PFD values in the patients who received Whipple or PPPD; however, there was no difference in those who had complete DPPHR. Concerning the postoperative PFD value, complete DPPHR was superior to Whipple and PPPD. Regarding postprandial CCK secretion, the pre- and postoperative values were significantly different in the patients with Whipple or PPPD, but there was no difference in those with complete DPPHR. Comparing the three kinds of operations, complete DPPHR was superior to the other two procedures in its maintenance of pancreatic function. There was the significant correlation between CCK and PFD in our patients in the Spearman Rank Correlation (P < 0.0029) and Fishers r to z (P < 0.0058).Conclusions When pre- and postoperative pancreatic exocrine function and postprandial CCK secretion were measured in patients with pancreatic head resection, it was found that preservation of the entire duodenum was an important factor for maintaining pancreatic function.     

Receptor activator of NF-κB ligand-dependent expression of caveolin-1 in osteoclast precursors, and high dependency of osteoclastogenesis on exogenous lipoprotein

Although extensive studies have done much to clarify the molecular mechanisms of osteoclastogenesis during the last ten years, there may still be unknown molecules associated with osteoclast differentiation. Thus, we used fluorescent differential display to screen for genes whose expression is induced by receptor activator of NF-κB ligand (RANKL), a crucial molecule for osteoclast formation. We identified caveolin-1 (Cav-1) as a RANKL-induced gene. Cav-1 is a major structural protein of caveolae and lipid rafts, cholesterol-enriched microdomains in the plasma membrane (PM). The RANKL-induced Cav-1 was immediately conveyed to lipid rafts. Conversely, expression of flotillin-1 (Flot-1), another scaffolding protein of lipid rafts, was reduced during osteoclastogenesis, indicating conversion of Flot-1-predominant rafts into Cav-1-enriched rafts. However, in vitro osteoclastogenesis of precursor cells from Cav-1-null mice was comparable to that of wild-type mice, while Cav-2 expression in the knockout osteoclasts was maintained. Conversely, Cav-2 gene silencing in Cav-1-null osteoclast precursors using siRNA for Cav-2 increased osteoclast formation, suggesting that the Cav-1/Cav-2 complex may act as a negative regulator for osteoclastogenesis. On the other hand, destruction of lipid rafts by removal of cholesterol from the PM by methyl-ß-cyclodextrin (MCD) treatment caused disordered signal transductions for osteoclastogenesis, such as hyperactivation of Erk1/2 and insensitivity of Akt to RANKL stimulus. The abnormal signaling was reproduced by deleting exogenous lipoproteins from the culture medium, which also resulted in reduced osteoclast formation. In addition, the deletion caused delayed expression of nuclear factor of activated T cells c1 (NFATc1), and depressed its activation in the cytosol and inhibited its translocation into nuclei. Simultaneously, the deletion reduced the level of FcRγ, a trigger protein for initiating the calcium signaling needed to activate NFATc1, and decreased Cav-1 in lipid rafts. These findings indicate that the molecular mechanisms of osteoclastogenesis are highly dependent on extracellular lipoprotein and the integrity of lipid rafts, and suggest possible involvement of cholesterol.     

Nosocomial BK Polyomavirus Infection Causing Hemorrhagic Cystitis Among Patients With Hematological Malignancies After Hematopoietic Stem Cell Transplantation

BK polyomavirus (BKPyV) is recognized as a pathogen that causes diseases such as hemorrhagic cystitis and nephritis after allogeneic hematopoietic stem cell transplantation (HSCT) or renal transplantation. BKPyV‐associated disease is thought to occur through reactivation under immunosuppression. However, the possibility of its nosocomial transmission and the clinical significance of such transmission have not been elucidated. During a 6‐month period, nine adult patients (median age: 47 years) who had hematological disorders and who were treated with HSCT (n = 7) or chemotherapy (n = 2) in a single hematology department developed hemorrhagic cystitis due to BKPyV infection. The polymerase chain reaction products of BKPyV DNA obtained from each patient were sequenced. Of the nine patients, six had subtype I, 2 had subtype IV, and 1 had subtype II or III. In the alignment of sequences, four and two of the six subtype I strains were completely homologous (100%). These results strongly suggest that BKPyV has the potential to cause nosocomial infection within a medical facility, especially among recipients of HSCT. Further studies are clearly warranted to elucidate the route(s) of BKPyV transmission in order to establish optimal infection control.