Laparoscopic observations of adhesions between peritoneal dialysis catheters and intraperitoneal organs: A retrospective, observational study.

Laparoscopy provides extensive data for the decannulation of a peritoneal dialysis catheter and is being increasingly used to diagnose encapsulating peritoneal sclerosis. However, there are few reports on the methods of decannulation of peritoneal dialysis catheters. In this study, we examined the laparoscopic findings and postoperative complications of patients undergoing peritoneal dialysis catheter removal. A total of 119 laparoscopic decannulations of peritoneal dialysis catheters were performed between 2003 and 2018 at the Juntendo University Hospital and Juntendo University Nerima Hospital. Laparoscopy was performed during peritoneal dialysis catheter removal by a gastrointestinal surgeon. Patient characteristics such as age, sex, duration of peritoneal dialysis, history of peritonitis and age at the time of peritoneal dialysis termination were assessed. Of these 119 cases, 19 (16.0%) showed adhesion between the peritoneal dialysis catheter and intraperitoneal organs. There were 13 (10.9%) cases involving a tangled omentum, 4 (3.4%) cases involving the small intestine and 2 (1.7%) cases of adhesions extending from the bowels to the abdominal wall. No postoperative complications were associated with the laparoscopic surgery. In these cases, blind decannulation of the peritoneal dialysis catheter may result in injury to the gastrointestinal tract in patients with adhesions. Therefore, we need to pay attention to adhesions between peritoneal dialysis catheters and intraperitoneal organs, and laparoscopy could be a valuable tool in detecting such adhesions and ensuring patient safety.

Impact of anemia treatment for left ventricular hypertrophy using long-acting erythropoietin-stimulating agents from the pre-dialysis to maintenance dialysis period in patients with chronic kidney disease, retrospective longitudinal cohort study.

BACKGROUND: Anemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs. METHODS: Physical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods. RESULTS: A lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with ß ≥ 0.4 in the absolute value was maintained. CONCLUSION: L-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Relationship among Left Ventricular Hypertrophy, Cardiovascular Events, and Preferred Blood Pressure Measurement Timing in Hemodialysis Patients.

This study aimed to identify the ideal timing and setting for measuring blood pressure (BP) and determine whether the left ventricular mass index (LVMI) is an independent risk factor associated with increased cardiovascular events in hemodialysis (HD) patients. BP and LVMI were measured at baseline and at 6 and 12 months after HD initiation. BP was monitored and recorded at nine different time points, including before and after HD over a one-week period (HDBP). The mean BP measurement was calculated as the weekly averaged BP (WABP). LVMI was significantly correlated with home BP, in-office BP, HDBP, and WABP. Receiver operating characteristic analysis indicated that the cutoff LVMI value for cardiovascular events was 156 g/m2. LVMI and diabetes mellitus were significant influencing factors for cardiovascular events (hazards ratio (95% confidence interval): diabetes mellitus, 2.84 (1.17,7.45); LVMI > 156 g/m2, 2.86 (1.22,6.99)). Pre-HDBP, post-HDBP, and WABP were independently associated with higher LVMI in the follow-up periods. Hemoglobin and human atrial natriuretic peptide (hANP) levels were associated with LVMI beyond 12 months after HD initiation. Treatment of hypertension, overhydration based on hANP, and anemia may reduce the progression of LVMI and help identify HD patients at high risk for cardiovascular events.

Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ-induced diabetic mice.

Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age. A more marked ACR increase was observed in STZ/KO group than STZ/WT group, although ACR did increase with weeks of age in both diabetic groups. The kidney sections from diabetic mice revealed a glomerular hypertrophy with mesangial expansion, but there was no appreciable difference in glomerular findings under a light microscope between STZ/WT and STZ/KO mice. However, an electron microscopy analysis revealed that regardless of the presence or absence of diabetes, both KO (KO and STZ/KO) groups had a higher rate of foot process effacement compared with both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm protein, podocin, was reduced with the induction of diabetes, and the levels in the STZ/KO group experienced a further reduction compared with the STZ/WT group. The number of WT1-positive cells in the STZ/KO group was more significantly decreased than that in the other three groups. In contrast, the numbers of cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group were more increased than those in the STZ/WT group. Thus, this study provides evidence that podocyte-specific deletion of Rac1 results in morphological alteration in podocytes, and that the induction of apoptosis or decreased expression of the slit diaphragm proteins by hyperglycemic stimuli are associated with the progression of diabetic nephropathy.

Circulating TNF receptors 1 and 2 are associated with the severity of renal interstitial fibrosis in IgA nephropathy.

The current study aimed to examine whether the levels of TNF receptors 1 and 2 (TNFR1 and TNFR2) in serum and urine were associated with other markers of kidney injury and renal histological findings, including TNFR expression, in IgA nephropathy (IgAN). The levels of the parameters of interest were measured by immunoassay in 106 biopsy-proven IgAN patients using samples obtained immediately before renal biopsy and in 34 healthy subjects. Renal histological findings were evaluated using immunohistochemistry. The levels of serum TNFRs were higher in IgAN patients than in healthy subjects. The levels of both TNFRs in serum or urine were strongly correlated with each other (r > 0.9). Serum TNFR levels were positively correlated with the urinary protein to creatinine ratio (UPCR) and four markers of tubular damage of interest (N-acetyl-ß-D-glucosaminidase [NAG], ß2 microglobulin [ß2m], liver-type fatty acid-binding protein [L-FABP], and kidney injury molecule-1 [KIM-1]) and negatively correlated with estimated glomerular filtration rate (eGFR). Patients in the highest tertile of serum TNFR levels showed more severe renal interstitial fibrosis than did those in the lowest or second tertiles. The tubulointerstitial TNFR2-, but not TNFR1-, positive area was significantly correlated with the serum levels of TNFRs and eGFR. Stepwise multiple regression analysis revealed that elevated serum TNFR1 or TNFR2 levels were a significant determinant of renal interstitial fibrosis after adjusting for eGFR, UPCR, and other markers of tubular damage. In conclusion, elevated serum TNFR levels were significantly associated with the severity of renal interstitial fibrosis in IgAN patients. However, the source of TNFRs in serum and urine remains unclear.

Role of the TNF pathway in the progression of diabetic nephropathy in KK-A(y) mice.

Chronic inflammation promotes the progression of diabetic nephropathy (DN). However, the role of TNF-α remains unclear. The objectives of the present study were to examine whether TNF-α inhibition with a soluble TNF receptor (TNFR)2 fusion protein, i.e., etanercept (ETN), improves the early stage of DN in the type 2 diabetic model of the KK-A(y) mouse and to also investigate which TNF pathway, TNFR1 or TNFR2, is predominantly involved in the progression of this disease. ETN was injected intraperitoneally into mice for 8 wk. Renal damage was evaluated by immunohistochemistry, Western blot analysis, and/or real-time PCR. In vitro, mouse tubular proximal cells were stimulated by TNF-α and/or high glucose (HG) and treated with ETN. ETN dramatically improved not only albuminuria but also glycemic control. Renal mRNA and/or protein levels of TNFR2, but not TNF-α and TNFR1, in ETN-treated KK-A(y) mice were significantly decreased compared with untreated KK-A(y) mice. mRNA levels of ICAM-1, VCAM-1, and monocyte chemoattractant protein-1 and the number of F4/80-positive cells were all decreased after treatment. Numbers of cleaved caspase-3- and TUNEL-positive cells in untreated mice were very few and were not different from ETN-treated mice. In vitro, stimulation with TNF-α or HG markedly increased both mRNA levels of TNFRs, unlike in the in vivo case. Furthermore, ETN partly recovered TNF-α-induced but not HG-induced TNFR mRNA levels. In conclusion, it appears that ETN may improve the progression of the early stage of DN predominantly through inhibition of the anti-inflammatory action of the TNF-α-TNFR2 pathway.

Differences in risk factors between patterns of recurrence in patients after curative resection for advanced gastric carcinoma.

BACKGROUND: Recurrence patterns in patients who have undergone curative gastrectomy for advanced gastric carcinoma can be classified as peritoneal, hematogenous, or lymphatic. The aim of this study was to clarify differences in risk factors between these different types of recurrence pattern. METHODS: Postoperative courses, including sites of recurrence and periods between surgery and recurrence, of patients who had undergone curative gastrectomy for advanced gastric carcinoma (more than pT2 invasion) were surveyed in detail. Clinicopathological factors were examined as potential independent risk factors for each recurrence pattern, based on recurrence-free survival, using multivariate analysis. RESULTS: Multivariate analysis identified depth of tumor invasion (pT4 vs. pT2/3; hazard ratio (HR), 7.05; P < 0.001), number of lymph node metastases (pN2/3 vs. pN0/1; HR, 4.02; P = 0.001), and histological differentiation (G3/4 vs. G1/2; HR, 2.22; P = 0.041) as independent risk factors for peritoneal metastasis. The number of lymph node metastases (HR, 26.21; P < 0.001) and venous vessel invasion (HR, 5.09; P = 0.001) were identified as independent risk factors for hematogenous metastasis. The number of lymph node metastases (HR, 6.00; P = 0.007) and depth of tumor invasion (HR, 4.70; P = 0.023) were identified as independent risk factors for lymphatic metastasis. CONCLUSIONS: This study clarified differences in risk factors between various patterns of recurrence. Careful examination of risk factors could help prevent oversight of recurrences and improve detection of recurrences during follow-up. The number of lymph node metastases represents an independent risk factor for all three patterns of recurrence; thus, patients with multiple lymph node metastases warrant particular attention.

Lymphoepithelial cyst of the pancreas.

Cystic lesions of the pancreas can be divided into true cysts, pseudocysts, and cystic neoplasms. Lymphoepithelial cysts (LECs) are a type of true cyst that can mimic pseudocysts and cystic neoplasms. LECs are rare lesions; fewer than 90 cases have been reported in the English language literature. The case of a 60-year-old man with an LEC of the pancreas is reported. He was admitted with upper abdominal discomfort. Computed tomography showed a 64 × 39 mm cystic mass in the retroperitoneum behind the duodenum and inferior caval vein. Magnetic resonance imaging revealed a right-sided mass on T1-weighted imaging, with a clear boundary between the mass and its surroundings, except for the pancreas. The mass had an inhomogeneous intensity on T2-weighted imaging. Within the mass, small floating nodules with low intensity were seen. Endoscopic ultrasound showed many high-echoic nodules and smaller grains scattered everywhere in the mass. Fine needle aspiration and cytologic examination were performed. Characteristic chylaceous fluid was obtained in which anucleate squamous cells were found. There were also a few atypical large cells with irregularly shaped marked nucleoli and degenerative cytoplasm. Cytologic diagnosis was suspicious for malignancy. The lesion was diagnosed as a retroperitoneal cyst, probably of pancreatic origin. Since a neoplastic lesion could not be ruled out, surgery was performed. The lesion was palpable on the dorsal side of the second portion of the duodenum. The mass was completely resected. Macroscopically, the lesion was a multilocular cyst with a thin septal wall. The cyst was filled with cottage cheese-like substance. Microscopically, the cyst wall was composed of stratified squamous epithelium and dense subepithelial lymphatic tissue with developed lymph follicles. The epithelial cells had no atypia. The histopathologic diagnosis was LEC of the pancreas. The patient's postoperative course was good.

Inadvertent Ingestion of a Press-Through Package Causing Perforation of the Small Intestine within an Incisional Hernia and Panperitonitis.

A 90-year-old woman was admitted to the emergency department of our hospital with abdominal pain and a fever of up to 39°C. She had a history of hysterectomy about 30 years previously, and redness and swelling were seen at the abdominal median scar. Serum biochemistry showed minor elevation of C-reactive protein and creatine phosphokinase. Abdominal computed tomography (CT) showed an edematous intestinal tract image over the median abdominal wall. Incarcerated incisional hernia and intestinal necrosis were suspected. Therefore, emergency surgery was performed. On laparotomy, abundant purulent ascitic fluid was found. The small intestine was incarcerated about 100 cm orally from the terminal ileum, and a 2-mm perforation was present in the incarcerated small intestine. In addition, some white areas measuring 1 mm were found in the small intestinal wall. A press-through package (PTP) of a tablet was confirmed in the intestinal tract near the perforated area. We removed the PTP through the perforation and performed direct suture. Postoperatively, we retrospectively reviewed the CT image and found a high-density shadow which seemed to represent the PTP.

Long-term survival of resected advanced gastric cancer with hepatic and pancreatic invasion.

A 64-year-old man was transferred to our division with a suspicion of gastric cancer. Computed tomography showed widespread irregular thickening of the stomach walls close to the liver and pancreas. Gastrointestinal fiberscopy showed a type 5 tumor in the upper to lower stomach, histologically diagnosed as tubular adenocarcinoma. Gastric cancer with hepatic and pancreatic invasion was diagnosed. Distant metastasis was not proven and complete resection was planned. At laparotomy, the tumor showed general expanding growth and invasion through the lateral segment of the liver and pancreas. Total gastrectomy and combined resection of the distal pancreas, spleen and left segment of the liver were performed. Hepatic and pancreatic invasion and lymph node metastasis were microscopically proven. Pancreatic fistula occurred postoperatively. On postoperative days 40, he was discharged. He received two cycles of adjuvant tegafur/gimeracil/oteracil chemotherapy. He has had no sign of recurrence for 7 years and 8 months.

Intrapulmonary cellular schwannoma.

A 75-year-old asymptomatic woman was admitted to our hospital after an abnormal shadow was found on a chest roentgenogram. Chest computed tomography showed a round mass in the right lower lobe. Magnetic resonance imaging showed the mass with high signal intensity on T2-weighted images and intermediate signal intensity on T1-weighted images. Fluorine-18-fluorodeoxyglucose-positron emission tomography showed high fluorine-18-fluorodeoxyglucose accumulation in the mass. A lobectomy was performed thoracoscopically. The pathologic diagnosis was cellular schwannoma. Immunohistochemical staining demonstrated the presence of S-100 protein, and the Ki67 labeling index was 12%. We present this case of intrapulmonary cellular schwannoma, which is extremely rare.

Multiple endocrine neoplasia type 1-associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas.

A novel combination of tumors was found in a 68 year-old female with Multiple Endocrine Neoplasia type-1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense-cored neurosecretory granules, larger zymogen-like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.

Scoring system for differential diagnosis of malignant mesothelioma and reactive mesothelial cells on cytology specimens.

Cytology is the only useful tool in the detection of malignant mesothelioma (MM) at an early stage. No other methods, such as immunocytochemistry or electron microscopy, are available to distinguish MM from reactive mesothelial cells (RMC). Some objective analysis of cytology specimens is necessary. On the basis of our case review and cytological features described in previous articles, we developed a scoring system for malignant mesothelioma (SSMM) of effusion cytology to distinguish MM cells from RMC. Mesothelioma cells in effusions from 22 patients (20 pleural and 2 peritoneal mesotheliomas) were compared with RMC from 20 patients without obvious tumor cells and 50 effusions containing metastatic carcinoma cells. The SSMM is based on characteristic features of mesothelial and malignant cells. The total achievable score is 10 points: one point each is given for variety of cell size, cyanophilic cytoplasm with villosity/windows/bleb, sheet-like arrangement, mirror-ball-like cell clusters, nuclear atypia, and cannibalism, respectively. Further two points each are ascribed for acidophilic large nucleoli and multinucleated cells with more than eight nuclei. The total score for each of the 22 mesotheliomas was more than 5 points. On the other hand, all RMC and the 50 metastatic carcinoma cases scored less than 3 points, aside from two cases that were treated with OK432. No single characteristic feature was observed to be consistent within the 22 mesotheliomas analyzed. Ancillary use of immunocytochemistry, such as podoplanin (D2-40) and calretinin, supported the diagnostic accuracy of the SSMM. SSMM is useful for the differential diagnosis of MM.

A retroperitoneal sympathetic paraganglioma invading the duodenum and mimicking a submucosal tumor.

We report a case of an autopsy of unusual retroperitoneal sympathetic paraganglioma (SPG) that directly invaded the duodenum and showed expansive growth mimicking a submucosal tumor. The tumor was clinically suspected to be a gastrointestinal stromal tumor (GIST) of the duodenum because of its location and extension to the retroperitoneum without catecholamine-associated symptoms. However, a small biopsy specimen of the tumor showed diffuse proliferation of large basophilic cells that were negative for C-kit and CD34, ruling out GIST and indicating an epithelial malignancy. An autopsy revealed that the tumor was mainly in the retroperitoneum, measuring 7.5 x 9.5 cm, weighing 600 g and extending into the duodenum, adjacent to the pancreas but free of the adrenal glands. On cut section, the tumor involved the entire wall of the duodenum. There were no metastases in any organs. For differential diagnosis, endocrine tumors of the duodenum or pancreas and extra-adrenal SPG were considered. The tumor cells were immunohistochemically strongly positive for chromogranin A and were surrounded by cells positive for S100 protein. The Ki67-labeling index was under 1%. The four catecholamine-synthesizing enzymes were detected in the tumor cells. We report this case of SPG with emphasis on differential diagnosis and the significance of its local invasion.

Two cases of inverted hyperplastic polyps of the colon and association with adenoma.

Here we report two cases of inverted hyperplastic polyps of the colon. The first patient showed three inverted hyperplastic polyps in the ascending colon, one of which was associated with adenoma. We immunostained this adenoma-associated polyp using anti-beta-catenin antibody and found accumulation of beta-catenin in the cytoplasm of the adenomatous lesion but not in the inverted hyperplastic polyp. This suggested an adenomatous polyposis coli (APC) mutation in the adenomatous region but not in the inverted hyperplastic polyp. The inverted hyperplastic polyp in the second patient was located at the caecum and was studied using magnifying colonoscopy. The polyp appeared to be flat and elevated with a depressed pit in the centre. After spraying with methylene blue dye, the pit pattern of the lesion was observed and small asteroid pits on the polyp were found, consistent with a hyperplastic gland pattern. From these results, we diagnosed inverted hyperplastic polyp of the colon by colonoscopy.