Photoacoustic Tomography of Human Hepatic Malignancies Using Intraoperative Indocyanine Green Fluorescence Imaging

Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous) was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10) under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases), photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical advances are needed to improve the visibility of photoacoustic signals emitted from deeply-located lesions.     

超声引导下Mammotome微创旋切术治疗乳腺良性肿块

目的:研究超声引导下Mammotome微创旋切术对乳腺良性肿块的治疗价值。方法:回顾性分析2014年9月至2016年9月在本院就诊的BI-RADS分级为2~3级的387例乳腺良性肿块患者,运用Mammotome对729处乳腺病灶行微创旋切术,分析术后病理、并发症、随访半年后的治疗结果。结果:387例患者的729处乳腺病灶均获一次性成功切除。病理示均为良性病灶,其中32个合并不典型增生。术后出现局部血肿共11例(2.8%),皮下瘀斑共16例(4.1%),所有患者均未发生感染及气胸等严重并发症。术后6个月18个在病灶原部位发现肿块;手术无残留率为97.5%。结论:应用超声引导下Mammotome微创旋切术治疗乳腺良性肿块临床可行。     

Fine needle aspiration cytology of mesenchymal hamartoma of the liver. A case report

BACKGROUND: Mesenchymal hamartoma (MH) of the liver constitutes the third or fourth most common tumor of the liver in childhood and occurs most commonly in the first two years of life. MHs of the liver are seldom aspirated, and reports on the role of fine needle aspiration (FNA) in the diagnosis of MH are scarce. Clinically, cytologically and even histologically, MH can be mistaken for a number of reactive and neoplastic hepatic lesions that may occur in children under 2 years of age. CASE: A 10-month-old Pakistani female presented with a history of a right-sided, nonpainful abdominal swelling. Abdominal computed tomography showed a large, partly solid and partly cystic, heterogeneous hepatic mass. FNA cytology showed clusters of both epithelial and mesenchymal/spindle-shaped cells with pieces of loose connective tissue. A cytologic differential diagnosis of mesenchymal hepatic hamartoma and hepatoblastoma of the possible mixed mesenchymal/epithelial subtype was rendered. The histopathologic diagnosis of the resected tumor mass was benign mesenchymal hamartoma of the liver. CONCLUSION: In children under 2 years of age who present with partly solid and partly cystic hepatic masses, the possibility of MH of the liver should be considered. FNA has a role in the diagnosis of MH. The cytopathologist should be aware of the patient's age, radiologic features and cytologic appearances of this rare, benign neoplasm. Histologic examination of tru-cut biopsies and immunohistochemical stains can help to exclude other pediatric neoplasms that may show cytologic features similar to or mimicking those of MH.     

Clinical considerations on 2 cases of hepatic fascioliasis. Importance of the imaging examinations]

Two cases of hepatic human fascioliasis, both with antecedents of eating watercress, hepatobiliary symptoms and high eosinophilia are described. In the first one (42 year-old male), at the beginning the abdominal ecotomographical and computed tomography images suggested an hepatic tumor, but afterwards, the finding of Fasciola hepatica ova in feces and the observation of numerous typical images of the fluke in the choledochus by means of an endoscopic cholangiography, plus lesions related to a L?ffler syndrome detected in a chest radiography, lead to the diagnosis of hepatic fascioliasis. The patient was treated with dehydroemetine. In the second case (52 year-old male), presented pain in the upper right abdominal quadrant; in an abdominal ecography three cystic lesions in the right liver lobe were found. Nor in the feces neither in the bile F. hepatica eggs were observed. Serological tests for fascioliasis and hydatidosis resulted positive. The endoscopic cholangiography was normal. With the presumptive diagnosis of fascioliasis the patient was treated with dehydroemetine. But as his disturbances remained during the following six months, and raising the possibility of a suppurated hydatid cyst or hepatic abscesses, he was submitted to surgery, finding F. hepatica eggs in the chocolate-like hematic liquid. In the wall and in a liver mass resected a grunuloma with eggs of the parasite was detected. The patient was treated again and cured with dehydroemetine. The existence of subcapsular hematomata and granulomas in hepatic fascioliasis, which can give raise to a diagnosis confusion due to their aspect in the ecotomography and computed tomography are commented. The cholangiographic aspect of the affection is discussed.     

Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes

Introduction

The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.

Methods

A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.

Results

Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

Conclusions

MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.     

Improving liver lesions classification on CT/MRI images based on Hounsfield Units attenuation and deep learning

The early sign detection of liver lesions plays an extremely important role in preventing, diagnosing, and treating liver diseases. In fact, radiologists mainly consider Hounsfield Units to locate liver lesions. However, most studies focus on the analysis of unenhanced computed tomography images without considering an attenuation difference between Hounsfield Units before and after contrast injection. Therefore, the purpose of this work is to develop an improved method for the automatic detection and classification of common liver lesions based on deep learning techniques and the variations of the Hounsfield Units density on computed tomography scans. We design and implement a multi-phase classification model developed on the Faster Region-based Convolutional Neural Networks (Faster R–CNN), Region-based Fully Convolutional Networks (R–FCN), and Single Shot Detector Networks (SSD) with the transfer learning approach. The model considers the variations of the Hounsfield Unit density on computed tomography scans in four phases before and after contrast injection (plain, arterial, venous, and delay). The experiments are conducted on three common types of liver lesions including liver cysts, hemangiomas, and hepatocellular carcinoma. Experimental results show that the proposed method accurately locates and classifies common liver lesions. The liver lesions detection with Hounsfield Units gives high accuracy of 100%. Meanwhile, the lesion classification achieves an accuracy of 95.1%. The promising results show the applicability of the proposed method for automatic liver lesions detection and classification. The proposed method improves the accuracy of liver lesions detection and classification compared with some preceding methods. It is useful for practical systems to assist doctors in the diagnosis of liver lesions. In our further research, an improvement can be made with big data analysis to build real-time processing systems and we expand this study to detect lesions from all parts of the human body, not just the liver.     

The evaluation of the possibility of using prodigiozan for isolating extracts that stimulate proliferative processes in the resected liver]

The experiments were performed on 126 white male rats. The inclusion of 3H-thymidine in nuclear DNA of the liver was studied on h 24 and 48 after 70% resection of the liver versus prodigiosan injection or combination of prodigiosan with 70% resection of the liver. Liver extracts stimulating proliferation (ESP) obtained under the above schedules were studied on the model of 30% liver resection. It is shown that prodigiosan (0.25 mg/kg) injected to intact rats and rats with 70% resected liver initiated ESP production promoting the inclusion of 3H-thymidine in nuclear DNA of the liver after 30% resection of the liver.     

The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from gastric or colorectal cancers

Twenty-four patients with liver metastases from gastric or colorectal cancer were treated with OK-432-combined adoptive immunotherapy (AIT). Lymphocytes isolated from regional lymph nodes or peripheral blood were cultured with medium containing T cell growth factor and sonicated tumor extract antigen (SE-Ag) for 9–13 days. The cultured lymphocytes were transferred mainly through the hepatic artery after the administration of OK-432, a streptococcal preparation. Sixteen of the 24 patients received a low dose of anti-cancer agents between the OK-432 injection and cell transfer. When cultured without SE-Ag, regional lymph node lymphocytes (RLNL) showed significantly (P<0.05) higher cytotoxic activity against autologous tumor cells and, on the contrary, lower cytotoxic activity against K562 than peripheral blood lymphocytes (PBL). When cultured with SE-Ag, cytotoxicity of RLNL against autologous tumor cells was nearly equivalent to that of PBL. The blastogenesis of fresh PBL to SE-Ag was significantly (P<0.05) augmented after the OK-432-combined AIT. Two patients showed complete response and 4 patients showed partial response among 19 patients who had evaluable lesions. Five patients whose liver metastases were resected were treated with OK-432-combined AIT as an adjuvant therapy. To date they are alive without recurrence in the liver.Abbreviations AIT adoptive immunotherapy - RLNL regional lymph node lymphocytes - SE-Ag sonicated tumor extract antigen     

Prevalence and risk factors of vertebral compression fractures in female SLE patients

Introduction

The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.

Methods

A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.

Results

Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

Conclusions

MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.     

Contrast-enhanced power doppler sonography in detection and differentiation of focal liver lesions

The aim of the study is to evaluate the contrast enhanced power doppler technique as a method to detect and differentiate vascular patterns of focal liver lesions. Fourty-nine patients with focal liver lesions were included in the study, twenty-nine of them with malignant liver lesions (9 HCC, 20 metastatic), twenty patients with benign lesions (12 haemangiomas, 5 focal nodular hyperplasia, 3 focal steatosis). In all patients classic B-mode and power doppler sonography was performed prior to administration of the contrast medium Levovist (300 mg/ml) and a power doppler examination subsequent to medium administration. Contrast administration led to lowering the number of "no-flow" lesions from 19 to 11. Postcontrast scan analysis revealed markedly enhanced flow in 15 cases in comparison to only 4 in pre-contrast examinations. The pre-contrast power doppler showed central flow in 7, and peripheral in 26 focal liver lesions. On the other hand, the postcontrast study revealed a central flow in 14, and peripheral in 34 focal liver lesions. Statistical significance between pre- and post-contrast power doppler detection of vascularization existed in malignant focal liver lesions and haemangiomas. The same pre- and post-contrast evaluation proved to be statistically non-significant in the focal nodular hyperplasia and focal steatosis groups. Administration of contrast medium enables a better visualization of intratumor blood vessels in focal liver lesions. This, in combination with the power doppler technique, brings such scans close to angiographic findings.     

Hepatic protoporphyrin metabolism in patients with advanced protoporphyric liver disease.

Protoporphyria is a genetic disorder in which liver damage is caused by the toxic effect of protoporphyrin accumulation in the liver. In this study protoporphyrin was measured in the resected livers of 7 patients who had liver transplantation and an additional patient from whom liver tissue was obtained post mortem. Comparison of liver, erythrocyte and serum protoporphyrin levels demonstrated a marked gradient between these compartments: erythrocyte, 5781 +/- 655 micrograms/dl; serum, 384 +/- 102 micrograms/dl; liver 377,238 +/- 55,568 micrograms/100 gm wet weight, (mean +/- SE). Protoporphyrin levels in bile of 3 patients were 55,559, and 1,153 micrograms/dl, indicating a gradient between liver and bile as well. Examination of the livers by polarization microscopy and electron microscopy demonstrated protoporphyrin pigment crystals. In one patient who had recurrent liver disease after transplantation, the protoporphyrin concentration in the graft at the time of death was similar to that in the resected liver. These data indicate that liver protoporphyrin levels in patients with advanced protoporphyric liver disease are much higher than levels in blood and bile, in part because protoporphyrin forms crystalline deposits in liver tissue. Thus, progressive hepatic accumulation of protoporphyrin occurs in the face of impaired biliary excretion. An intrinsic defect in hepatic excretion of protoporphyrin is probably not necessary for this condition to develop because liver disease can occur in the graft following transplantation.     

Histologic classification and differential diagnosis of mesothelioma.

Controversy surrounds the diagnosis, classification, and therefore the epidemiology of those tumors which have been designated as mesotheliomas. The group includes lesions which are as broadly different as benign fibrous lesions which some authors refer to as fibromas and anaplastic tumors which are extremely difficult to differentiate from peripheral lung cancers. The former are benign tumors which are usually readily resected and therefore cured. The latter are unresectable tumors which are invariably fatal and which may terminate with extensive metastatic disease. The reasons for including all of these lesions under the category of mesothelioma and the differential diagnosis of the various types is discussed.     

Liver tumors in wild flatfish: a histopathological, proteomic, and metabolomic study

Fish play host to viral, bacterial, and parasitic diseases in addition to non-infectious conditions such as cancer. The National Marine Monitoring Programme (NMMP) provides information to the U.K. Government on the health status of marine fish stocks. An aspect of this work relates to the presence of tumors and other pathologies in the liver of the offshore sentinel flatfish species, dab (Limanda limanda). Using internationally agreed quality assurance criteria, tumors and pre-tumors are diagnosed using histopathology. The current study has expanded upon this work by integrating these traditional diagnostic approaches with ones utilizing modern technologies for analysis of proteomic and metabolomic profiles of selected lesions. We have applied SELDI and FT-ICR technologies (for proteomic and metabolomic analyses, respectively) to tumor and non-tumor samples resected from the liver of dab. This combined approach has demonstrated how these technologies are able to identify protein and metabolite profiles that are specific to liver tumors. Using histopathology to classify "analysis groups" is key to the success of such an approach since it allows for elimination of spurious samples (e.g., those containing parasite infections) that may confuse interpretation of "omic" data. As such, the pathology laboratory plays a central role in collating information relating to particular specimens and in establishing sampling groups relative to specific diagnostic questions. In this study, we present pilot data, which illustrates that proteomics and metabolomics can be used to discriminate fish liver tumors and suggest future directions for work of this type.     

In vivo micro-CT imaging of liver lesions in small animal models

Three-dimensional micro computed tomography (microCT) offers the opportunity to capture images liver structures and lesions in mice with a high spatial resolution. Non-invasive microCT allows for accurate calculation of vessel tortuosity and density, as well as liver lesion volume and distribution. Longitudinal monitoring of liver lesions is also possible. However, distinguishing liver lesions from variations within a normal liver is impossible by microCT without the use of liver- or tumor-specific contrast-enhancing agents. The combination of microCT for morphologic imaging with functional imaging, such as positron emission tomography (PET) or single photon emission tomography (SPECT), offers the opportunity for better abdominal imaging and assessment of structure discrepancies visible by functional imaging.This paper describes methods of current microCT imaging options for imaging of liver lesions compared to other imaging techniques in small animals.     

Solitary angiomyolipoma of the liver. Report of a case initially examined by fine needle aspiration biopsy

Transabdominal fine needle aspiration biopsy of a solitary space-occupying lesion in the liver produced smears containing irregular bundles of smooth muscle cells with granular or fibrillary cytoplasm and slightly pleomorphic nuclei. In a few bundles, aggregates of mature fat cells were present, which is characteristic for an angiomyolipoma. Histologic examination of the resected mass showed it to be a solitary angiomyolipoma of the liver. The diagnosis was further confirmed by immunohistochemical and electron microscopic studies.     

Action of hepatic chalones on the proliferation of hepatocytes from intact and denervated livers

The paper is concerned with the action of chalones, tissue-specific inhibitors of cell proliferation, on DNA synthesis and mitotic activity of hepatocytes in the intact and denervated liver during regeneration. Experiments were made on Wistar rats. Liver denervation was performed by bilateral subdiaphragmal vagotomy. In control and vagotomized animals, two thirds of the liver was resected. The data obtained indicate that chalones noticeably reduce the number of DNA-synthesizing cells and mitoses in the regenerating liver of intact animals. During regeneration of the denervated liver, chalones do not produce any inhibitory action on the intensity of proliferation. Analysis of the data obtained allows a conclusion that preservation of adequate innervation of the organ is needed for realization of the action of hepatic chalones.     

The nature and extent of histopathologic injury in human avulsed arteries and veins and in experimentally avulsed monkey arteries

To determine the end point of histopathologic damage in avulsed arteries, the forearm arteries of five monkeys being sacrificed were avulsed longitudinally and samples of proximal and distal arteries prepared for light microscopy and transmission and scanning electron microscopy. A severe and consistent circumferential skip lesion was found on the luminal surface involving the intima and media. In 30 percent of vessels, histopathologic damage extended more than 3.0 cm from the rupture point. Similar circumferential tears occurred on the luminal surface of resected human avulsed arteries collected at the time of replantation surgery. No consistent lesions were noted in resected veins from human avulsed amputations. It is possible that in the human artery (as in the monkey) circumferential lesions frequently extend many centimeters from the rupture point and therefore beyond resection distances. Lesions present in the vessel after resection and microsurgical repair might be the site of thrombosis and subsequent occlusion.     

高频超声引导下导丝定位在不可触及乳腺包块切除术中的应用

目的:探讨高频超声引导下导丝定位在不可触及乳腺包块切除术中的应用价值。方法:回顾性分析90例临床不可触及但超声提示为乳腺包块的患者的临床资料,其中50例在高频超声引导乳腺病灶体表定位下行乳腺病灶切除术,40例在高频超声引导导丝定位下行乳腺病灶切除术。比较两组术前定位时间、手术时间、切除组织量/肿物组织量及术后并发症的发生情况、术后病理诊断及术后超声随访情况。结果:与体表定位组比较,导丝定位组定位时间显著延长(P0.05),手术时间明显缩短(P0.05),切除组织量/肿物组织量显著减小(P0.05)。体表定位组出现2例切口感染,5例血肿,两组不良反应的发生率相比差异无统计学意义(P0.05)。体表定位组良性48例(96.0%),恶性病灶2例(4.0%)。导丝定位组良性病灶36例(90.0%),恶性病灶4例(10.0%)。两组病理诊断为良/恶病灶的比例无统计学意义(P0.05)。术后超声随访6~12个月,病灶切除情况比较差异无统计学意义(P0.05)。结论:高频超声引导下导丝定位精确,可明显缩短手术时间,减少对正常乳腺组织的破坏,可作为行不可触及乳腺包块切除术的优先选择。     

Liver lesions seen at slaughter as an indicator of necrotic enteritis in broiler flocks

Historical data of necrotic enteritis incidence and carcass condemnations owing to liver lesions in south-eastern Norway during 1978-1998 revealed covariance in the occurrence of the two variables. In histological examination during the first half of 1998, 33 of 45 sampled carcasses condemned owing to liver lesions showed histopathological changes consistent with earlier described Clostridium perfringens-associated hepatitis. The results suggest that the occurrence of necrotic enteritis in broiler flocks may be monitored by using meat inspection data on liver lesions.     

Intermittent selective clamping improves rat liver regeneration by attenuating oxidative and endoplasmic reticulum stress

Intermittent clamping of the portal trial is an effective method to avoid excessive blood loss during hepatic resection, but this procedure may cause ischemic damage to liver. Intermittent selective clamping of the lobes to be resected may represent a good alternative as it exposes the remnant liver only to the reperfusion stress. We compared the effect of intermittent total or selective clamping on hepatocellular injury and liver regeneration. Entire hepatic lobes or only lobes to be resected were subjected twice to 10 min of ischemia followed by 5 min of reperfusion before hepatectomy. We provided evidence that the effect of intermittent clamping can be damaging or beneficial depending to its mode of application. Although transaminase levels were similar in all groups, intermittent total clamping impaired liver regeneration and increased apoptosis. In contrast, intermittent selective clamping improved liver protein secretion and hepatocyte proliferation when compared with standard hepatectomy. This beneficial effect was linked to better adenosine-5′-triphosphate (ATP) recovery, nitric oxide production, antioxidant activities and endoplasmic reticulum adaptation leading to limit mitochondrial damage and apoptosis. Interestingly, transient and early chaperone inductions resulted in a controlled activation of the unfolded protein response concomitantly to endothelial nitric oxide synthase, extracellular signal-regulated kinase-1/2 (ERK1/2) and p38 MAPK activation that favors liver regeneration. Endoplasmic reticulum stress is a central target through which intermittent selective clamping exerts its cytoprotective effect and improves liver regeneration. This procedure could be applied as a powerful protective modality in the field of living donor liver transplantation and liver surgery.