Histological reassessment of the role of bridging fibrosis in the angioarchitectural features associated with lobular distortion of the liver in chronic viral hepatitis.

AIM: To reassess the role of bridging fibrosis in the lobular distortion of the liver from an angioarchitectural aspect. METHODS: Two tissue samples obtained from surgically resected livers with chronic hepatitis and one obtained from an autopsy case with chronic hepatitis were used for the three-dimensional observation of angioarchitecture by histological reconstruction. RESULTS: Samples showed bridging fibrosis with various degrees of severity, without cirrhotic changes. Two different types of portal-portal bridging fibrosis were found. In our samples, the type that developed in the bifurcation region of the portal tracts was more common than the type observed between the distal portions originating from different parent portal tracts. The angioarchitecture tended to be generally maintained in these lesions. Concerning portal-central bridging fibrosis, two types were observed. One type developed in the lesion with partial paucity of the third-step portal branches in the portal tract at a relatively early stage of chronic hepatitis. The other type developed in an advanced lesion with a complete loss of the normal angioarchitecture of the parenchymal portion of the portal veins. The former was likely developed after large-scale necrosis, such as bridging necrosis, while the latter was presumed to be attributable to portal vein damage associated with long standing chronic inflammation. CONCLUSION: As has been previously noted regarding lobular angioarchitecture, portal-central bridging fibrosis clearly affects the lobular structure of the liver more than portal-portal bridging fibrosis. Therefore, portal vein damage may be a critical event in the eventual distortion of the lobular structure.

Giant Krukenberg tumor from a perforated gastric cancer that was successfully removed after multidisciplinary therapy: report of a case.

A 46-year-old female underwent total gastrectomy with a combined resection of the pancreatic tail, spleen, and lateral segment of the liver surgery after conservative medical management for a perforated advanced gastric cancer. The histological findings showed poorly differentiated adenocarcinoma, and the tumor was Stage IIIC. S-1 and "Kampo-Juzen-taiho-to" were administered as postoperative adjuvant chemo-immunotherapy. A Krukenberg tumor was identified 4 years later. The histological findings strongly suggested the presence of peritoneal dissemination, and S-1-based combined chemotherapies using key drugs such as CDDP, CPT-11, and taxane with the biochemical response modifier "Lentinan" was administered. However, the Krukenberg tumor rapidly increased in size after 4 years and she complained of abdominal distension. Therefore, it was removed with neither difficulties nor apparent recurrent disease, which was thought to be due to the S-1-based combined chemotherapy and the immunological agents are likely to have contributed to her long survival and good quality of life.

Pagetoid spread of urothelial carcinoma controlled without resection.

Introduction: Extramammary Paget's disease is an eczematous skin condition that affects the vulva and perineum. Extramammary Paget's disease secondary to urothelial carcinoma is a rare condition that is typically treated with invasive surgical resection of the lesion. Case presentation: An 80-year-old woman with a 7-year history of urothelial carcinoma presented with erythema of the labia majora. Immunostaining of skin biopsy specimens suggested extramammary Paget's disease secondary to urothelial carcinoma. The patient did not consent to resection of the lesion. Nine cycles of first-line platinum-based chemotherapy for metastatic urothelial carcinoma were administered. As tumor cells remained after systemic chemotherapy, pembrolizumab will be administered to the patient for treating residual extramammary Paget's disease. Conclusion: Platinum-based chemotherapy can control extramammary Paget's disease secondary to urothelial carcinoma.

[A case of Mycobacterium avium pleuritis and pneumothorax in a rheumatoid arthritis patient treated with a TNF-alpha antagonist].

A 70-year-old woman with rheumatoid arthritis received treatment with corticosteroids and methotrexate for 4 years, followed by an additional TNF-alpha antagonist (infliximab) for about 3 years. She presented with a several-week history of persistent cough, and CT images of the lung showed a thin-walled cavitary lesion abutting the pleural surface of the left upper lobe. While we investigated the cause of this lesion, we admitted her because of acute chest pain. Chest radiography demonstrated moderate left-sided pneumothorax with pleural effusion. After further investigation, we suspected that her pneumothorax and pleuritis had been caused by a ruptured cavitary lesion arising from a Mycobacterium avium infection. Despite multi-drug therapy, chest tube drainage and surgical pulmorrhaphy her pleural complications were intractable. This is a rare case of pneumothorax and pleuritis caused by Mycobacterium avium infection induced by a TNF-alpha antagonist. Physicians should be aware of nontuberculous mycobacterial infections in patients treated with TNF-alpha antagonists.

Laparoscopic pancreaticoduodenectomy for remnant pancreatic recurrence after laparoscopic distal pancreatectomy and hepatectomy for greater omentum leiomyosarcoma.

Laparoscopic pancreatic surgery is one of the most difficult procedures, and the adoption of laparoscopic pancreaticoduodenectomy has been limited. The application of laparoscopic surgery has extended to advance cancer, but there have been no reports of laparoscopic pancreaticoduodenectomy after laparoscopic liver resection and distal pancreatectomy. In the present case, a 67-year-old woman was diagnosed with remnant pancreatic recurrence of metastatic greater omentum leiomyosarcoma. She had previously undergone laparoscopic distal pancreatectomy and left lateral liver sectionectomy in 2016. We performed laparoscopic subtotal stomach-preserving pancreaticoduodenectomy in June 2017. The operation time was 274 minutes, and the estimated blood loss was 50 mL. There were no postoperative complications. In summary, laparoscopic pancreaticoduodenectomy is a safe and feasible procedure for a patient who had previously undergone pancreas and liver surgery.

Determination of Follicular Localization in Human Ovarian Cortex for Vitrification.

PURPOSE: To determine the optimal follicle localization for ovarian vitrification in adolescent and young adult (AYA)-aged (between 15 and 39 years of age) patients with cancer or primary ovarian insufficiency (POI). METHODS: In total, ovaries from 24 women were included in our study. These include women who received ovariectomy for fertility preservation before gonadotoxic treatments for cancer (n = 4), or for the treatment of POI by the in vitro activation method (n = 8), and other women and infants (0-3 years of age) whose ovaries were autopsied (n = 12). Before cryopreservation, a portion of the ovary sampled from cancer and POI patients was used for histological analysis. Depths of follicles from the surface of ovarian cortices were then measured by using digital imaging software. The locations of the follicles at different developmental stages in the ovarian cortex were noted. RESULTS: The mean depth at which the primordial and primary follicles were located was 271 µm in infants. This was deeper in women in their twenties, thirties, and forties (501, 462, and 493 µm, respectively). The majority of secondary follicles were located <1000 µm from the ovarian surface (mean depth, 639 µm). In regard to patients with POI, the mean depth of primordial and primary follicles was 566 µm, whereas 70% of secondary follicles were located >1000 µm deep. CONCLUSION(S): These findings suggest that <1 mm is a potential optimum thickness of normal ovarian tissue for vitrification and a requirement that thicker ovarian cortices include secondary follicles in POI patients.

A case of pulmonary lymphangioleiomyomatosis complicated with uterine and retroperitoneal tumors.

A 39-year-old female experienced dyspnea on exertion for eight months. Chest CT demonstrated findings of Lymphangioleiomyomatosis (LAM), including diffuse thin-walled cystic lesions. A surgical lung biopsy revealed human melanoma black-45-positive cell infiltration and aggregation, resulting in a diagnosis of sporadic LAM without tuberous sclerosis complex. Pelvic MRI showed two large tumors, one of which was in the myometrium and the other was in the retroperitoneal space. Because we were not able to exclude the presence of malignant tumors using MR imaging, the tumors were surgically resected. The histopathology demonstrated the resected tumors to be composed of LAM cells. The patient's symptoms worsened, and sirolimus was administered, which improved the dyspnea and pulmonary function. The adverse effect was mild liver damage. Following the initiation of treatment with sirolimus, transient elevation of the serum KL-6 level was detected without interstitial pneumonia. This LAM case complicated with large uterine and retroperitoneal tumors was successfully treated with surgical resection and sirolimus.

Expression of SGLT1 in Human Hearts and Impairment of Cardiac Glucose Uptake by Phlorizin during Ischemia-Reperfusion Injury in Mice.

OBJECTIVE: Sodium-glucose cotransporter 1 (SGLT1) is thought to be expressed in the heart as the dominant isoform of cardiac SGLT, although more information is required to delineate the subtypes of SGLTs in human hearts. Moreover, the functional role of SGLTs in the heart remains to be fully elucidated. We herein investigated whether SGLT1 is expressed in human hearts and whether SGLTs significantly contribute to cardiac energy metabolism during ischemia-reperfusion injury (IRI) via enhanced glucose utilization in mice. METHODS AND RESULTS: We determined that SGLT1 was highly expressed in both human autopsied hearts and murine perfused hearts, as assessed by immunostaining and immunoblotting with membrane fractionation. To test the functional significance of the substantial expression of SGLTs in the heart, we studied the effects of a non-selective SGLT inhibitor, phlorizin, on the baseline cardiac function and its response to ischemia-reperfusion using the murine Langendorff model. Although phlorizin perfusion did not affect baseline cardiac function, its administration during IRI significantly impaired the recovery in left ventricular contractions and rate pressure product, associated with an increased infarct size, as demonstrated by triphenyltetrazolium chloride staining and creatine phosphokinase activity released into the perfusate. The onset of ischemic contracture, which indicates the initiation of ATP depletion in myocardium, was earlier with phlorizin. Consistent with this finding, there was a significant decrease in the tissue ATP content associated with reductions in glucose uptake, as well as lactate output (indicating glycolytic flux), during ischemia-reperfusion in the phlorizin-perfused hearts. CONCLUSIONS: Cardiac SGLTs, possibly SGLT1 in particular, appear to provide an important protective mechanism against IRI by replenishing ATP stores in ischemic cardiac tissues via enhancing availability of glucose. The present findings provide new insight into the significant role of SGLTs in optimizing cardiac energy metabolism, at least during the acute phase of IRI.

Histopathologically proven autoimmune pancreatitis mimicking neuroendocrine tumor or pancreatic cancer.

Autoimmune pancreatitis (AIP) can be difficult to distinguish from pancreatic cancer. We report a case of histopathologically proven AIP mimicking neuroendocrine tumor (NET) or pancreatic cancer in a 53-year-old man. He was referred to our hospital for further evaluation of a pancreatic mass detected on ultrasonography at a medical check-up. Abdominal ultrasonography showed a 15-mm hypoechoic mass located in the pancreatic body. Computed tomography revealed a tumor without any contrast enhancement, and magnetic resonance imaging demonstrated the mass to be hyperintense on diffusion-weighted image. Endoscopic retrograde cholangiopancreatography revealed slight dilatation of a branch of the pancreatic duct without stricture of the main pancreatic duct. The common bile duct seemed intact. Under suspicion of a non-functioning NET or malignant neoplasm, laparotomy was performed. At laparotomy, an elastic firm and well-circumscribed mass was found suggestive of a non-functioning NET, thus enucleation was performed. Histopathologically, the lesion corresponded to AIP.

Radiographic and CT features of radiation-induced organizing pneumonia syndrome after breast-conserving therapy.

PURPOSE: To investigate radiographic and computed tomography features of radiation-induced organizing pneumonia syndrome after breast-conserving surgery. MATERIALS AND METHODS: The appearances and distribution of lung parenchymal abnormalities were retrospectively analyzed on chest radiographs (n = 12) and computed tomography scan images (n = 10) of 12 women (range 37-78 years, mean 55.8 years) with radiation-induced organizing pneumonia syndrome after breast-conserving surgery. RESULTS: The principal radiographic feature was an airspace filling pattern in all patients that involved the middle and lower lung zones in 10 of the 12 patients. Multi-focal lesions manifesting airspace consolidation surrounded by ground-glass opacities were the predominant CT finding in all 10 of these patients. The main lesion was predominantly located in the lung periphery in nine patients and contiguously extended to the central portion of the lung in seven patients. Frequent ancillary findings were airway dilation within the consolidation and lobar volume loss in nine and eight patients, respectively. All had solitary (6/10) or multifocal (4/10) distant lung opacities, mostly consistent with the finding of ground-glass opacities (9/10). Migration of the lung disease was observed in ten patients on subsequent radiographs. CONCLUSION: The cardinal radiologic feature of this syndrome is airspace consolidation surrounded by ground-glass opacification with airway dilation and volume loss, involving primarily the irradiated, subpleural area, along with distant opacities.

Pigmented perivascular epithelioid cell tumor of the kidney.

A case of pigmented perivascular epithelioid cell tumor of the kidney in a 57-year-old woman with a clinically indicated tuberous sclerosis is presented. The lesion was a 3.0-cm, well-demarcated, black-colored mass. The tumor was histologically characterized by an epithelioid arrangement of round to polygonal cells with round nuclei and clear cytoplasm containing abundant melanin. Tumor cells showed mild atypia and low mitotic activity. A spindle cell proliferation was focally observed. There were no adipose elements or thick-walled vascular vessels. The stroma demonstrated intervening, thin, fibrovascular septa. Immunohistochemically, the tumor cells were strongly positive for HMB-45 but negative for epithelial and muscle markers, vimentin, and S100 protein. The patient had no evidence of disease 3 months after surgery. Pathologists and clinicians should know about the existence of pigmented perivascular epithelioid cell tumor of the kidney. This type of tumor should be differentiated from clear cell renal cell carcinoma or malignant melanoma.

Extracorporeal bioartificial liver using the radial-flow bioreactor in treatment of fatal experimental hepatic encephalopathy.

An extracorporeal bioartificial liver (BAL) that could prevent death from hepatic encephalopathy in acute hepatic insufficiency was aimed to develop. A functional human hepatocellular carcinoma cell line (FLC-4) was cultured in a radial-flow bioreactor. The function of the BAL was tested in mini-pigs with acute hepatic failure induced by alpha-amanitin and lipopolysaccharide. When the BAL system was connected with cultured FLC-4 to three pigs with hepatic dysfunction, all demonstrated electroencephalographic improvement and survived. Relatively low plasma concentrations of S-100 beta protein, as a marker of astrocytic damage, from pigs with hepatic failure during BAL therapy were noted. BAL therapy can prevent irreversible brain damage from hepatic encephalopathy in experimental acute hepatic failure.

Gallstone pancreatitis: positive correlation between severe pancreatitis and passed stone.

BACKGROUND/PURPOSE: Little is known about whether the severity of pancreatitis depends upon persistent stone impaction or stone passage into the duodenum, and the role of endoscopic sphincterotomy (ES) has remained controversial. METHODS: This study reviewed our experience of 183 patients with gallstone pancreatitis, with special attention paid to the relationship between the severity of pancreatitis, the severity of coexisting biliary pathology, and the outcome. RESULTS: Sixteen patients (9%) had severe pancreatitis (SP) and the remaining 167 (91%) had mild pancreatitis (MP). All of the SP patients had pancreatic necrosis, and 6 of them developed multiple organ failure (MOF). No SP patients had stones impacted at the papilla of Vater or persistent stones and purulent bile in the bile duct (severe cholangitis). Most SP patients (94%) had stones in the gallbladder alone, suggesting stone passage into the duodenum. Of the 167 MP patients, on the other hand, 58 (35%) had severe cholangitis. Four patients (25%) with SP died of MOF. There were four deaths in the MP group (2%) and all in patients with coexisting severe cholangitis, 2 of whom were in septic shock at the time of admission. CONCLUSIONS: None of the SP patients had severe cholangitis. The positive correlation between SP and passed stone suggests that early ES should not be advocated for SP patients. MP patients with coexisting severe cholangitis are likely to benefit from ES.

Hepatoduodenal ligament invasion by gallbladder carcinoma: histologic patterns and surgical recommendation.

A consensus for the optimal management of hepatoduodenal ligament (HDL) invasion by gallbladder carcinoma has yet to be reached. We retrospectively correlated the patterns of HDL invasion with the surgical outcome. From 1985 to 2000, 59 patients underwent combined resection of the extrahepatic bile duct and gallbladder and contiguous organs if required. Pathologic staging (UICC) was stage II, 4; stage III, 14; stage IVa, 10; and stage IVb, 31. Hepatoduodenal ligament invasion was subdivided into lymph node involvement (LNI) and bile duct infiltration (BDI). Patterns of HDL invasion were compared with bile duct morphology, resectability, and outcome. Bile duct infiltration ( n = 32) caused stenosis of the bile duct in all cases, whereas LNI ( n = 40) caused stenosis in only 4 cases. Resection was complete after extended cholecystectomy ( n = 22) in 36%; 4b/5 segmentectomy ( n = 10) in 90%; major hepatectomy ( n = 2) in 50%; and hepatopancreatoduodenectomy ( n = 17) in 53% of cases. Surgery was curative in 75% of patients without BDI, and was < 30% with BDI. The most common factor preventing curative resection in BDI was perineural invasion around the HDL. Perineural invasion occurred in over 70% of cases at either the cut end of the bile duct or in the margin of dissection. The 3-year survival rates, excluding patients with R2 resection (residual cancer) and death in hospital, were LNI(-)BDI(-) ( n = 8), 65.6%; LNI(+)BDI(-) ( n = 17), 35.3%; LNI(-)BDI(+) ( n = 7), 14.3%; and LNI(+)BDI(+) ( n = 17), 5.9%. There were no 5-year survivors with BDI. In conclusion, perineural invasion in BDI is an important obstacle to complete resection. Hepatopancreatoduodenectomy is a feasible strategy only for LNI(+)BDI(-) disease.

Preparatory hepatic resection with right hepatic vein reconstruction for paracaval liver tumor.

A liver tumor in the paracaval portion was very difficult to resect because of its anatomical situation. We therefore employed a technique using right hepatic vein (RHV) resection and reconstruction following the resection of segments VII/VIII with the paracaval portion. The patient was a 70-year-old man who had a hepatocellular carcinoma in the paracaval portion, and the root of the RHV was compressed by the tumor. Computed tomography (CT) during arterioportography under temporary balloon occlusion of the RHV demonstrated hypoattenuation of the entire posterior segment, meaning that RHV reconstruction following the resection of segments VII/VIII with RHV resection would be necessary. We performed the above-mentioned operation without any trouble. On mobilizing segments VI/V to the caudal direction after dissecting the distal RHV, the paracaval Glissons were easily exposed and dissected anteriorly from the first order of the right Glissonean sheath. Our preliminary surgical technique, based on IVR-CT, could provide a better surgical field and result in decreased operating time and decreased blood loss in paracaval liver malignancy.

Cholangitis score: a scoring system to predict severe cholangitis in gallstone pancreatitis.

BACKGROUND/PURPOSES: Emergency biliary decompression and stone extraction are mandatory for patients with gallstone pancreatitis who have ampullary stone impaction or persistent stones and pus in the bile duct (severe cholangitis). The aim of this study was to devise a simple scoring system for the prediction of complicating severe cholangitis in gallstone pancreatitis. METHODS: Clinical signs, laboratory data, and ultrasonography (US) findings at the time of admission, and the bile duct pathology at the time of bile duct exploration, were reviewed in 66 patients with gallstone pancreatitis. Variables which discriminated 26 patients with bile duct stones from 40 without were defined as predictive factors of bile duct stones. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values of numerical variables. One point was allocated to each predictive factor, and the total score was defined as the cholangitis score (CS). Bile duct pathology identified at the time of bile duct exploration was graded into three categories: mild, moderate, and severe cholangitis. A threshold value of the CS, claimed to be predictive of severe cholangitis, was determined by using the ROC curve. RESULTS: The scoring system consisted of four predictive factors: (1) pyrexia (temperature > or =38 degrees C), (2) elevated serum bilirubin (> or =2.2 mg/dl), (3) dilated bile duct (> or =11 mm maximum diameter on US), and (4) bile duct stones detected on US. The scoring system predicted severe cholangitis with 92% sensitivity and 98% specificity in patients with scores of three or four points. CONCLUSIONS: Patients with gallstone pancreatitis who meet three or four of the above predictive factors at the time of admission are likely to have severe cholangitis, and should be rapidly treated by biliary decompression and stone extraction.