Liver resection with thrombectomy for patients with hepatocellular carcinoma and tumour thrombus in the inferior vena cava or right atrium.

BACKGROUND: Hepatocellular carcinoma (HCC) with tumour thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is a rare advanced disease state with a poor prognosis. The aim of this study was to examine survival after surgical resection. METHODS: Patients with HCC and TT of either the IVC or RA, who underwent liver resection between February 1997 and July 2017, were included. Their short- and long-term outcomes and surgical details were analysed retrospectively. RESULTS: Thirty-seven patients were included; 16 patients had TT in the IVC below the diaphragm, eight had TT in the IVC above the diaphragm, and 13 had TT entering the RA. Twelve patients had advanced portal vein TT (portal vein invasion (Vp) greater than Vp3 and Vp4), ten had bilobar disease, and 12 had extrahepatic disease. There were no in-hospital deaths, although two patients died within 90 days. Median survival did not differ between patients who had resection with curative intent (18·7 months) and those with residual tumour in the lung only (20·7 months), but survival was poor for patients with residual tumour in the liver (8·3 months). CONCLUSION: Liver resection with thrombectomy for advanced HCC with TT in the IVC or RA is safe and feasible, leading to moderate survival.

ANTECEDENTES: El carcinoma hepatocelular con trombo tumoral (TT) en la vena cava inferior (inferior vena cava, IVC) o en la aurícula derecha (right atrium, RA) es un estado avanzado de la enfermedad raro, con un pronóstico desfavorable. En este estudio analizamos la supervivencia después de la resección quirúrgica. MÉTODOS: Se incluyeron pacientes con carcinoma hepatocelular con TT en la IVC o en la RA, que se sometieron a resección hepática entre febrero de 1997 y julio de 2017. Los resultados a corto y a largo plazo de estos pacientes y los detalles quirúrgicos se analizaron retrospectivamente. RESULTADOS: Se incluyeron 37 pacientes. Entre estos pacientes, se identificaron 16 pacientes con TT en la IVC infradiafragmática, 8 pacientes con TT en la IVC supradiafragmática y 13 pacientes con TT entrando en la AR. Doce pacientes asociaron TT avanzado en la vena porta más allá de vp 3 y 4, 10 pacientes tenían enfermedad bilobar y 12 pacientes tenían enfermedad extrahepática. A pesar de que la tasa de mortalidad hospitalaria fue cero, dos pacientes fallecieron a los 90 días. Aunque la mediana del tiempo de supervivencia no fue diferente entre el grupo al que se le realizó resección con intención curativa (18,7 meses) y aquellos con tumor residual solo en el pulmón (20,7 meses), la supervivencia fue extremadamente pobre para los pacientes con tumor residual en el hígado (8,3 meses). CONCLUSIÓN: La resección hepática con trombectomía para el carcinoma hepatocelular avanzado con trombo tumoral en la vena cava inferior o en la aurícula derecha es segura y factible, asociándose a una supervivencia moderada.

Association of sporadic and familial Barrett's esophagus with breast cancer.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.

Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients.

BACKGROUND: In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients. METHODS: We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer. RESULTS: Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p < 0.001, p = 0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs. CONCLUSIONS: B7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs.

Heating properties of a new hyperthermia system for deep tumors without contact.

In this paper, heating properties of the proposed hyperthermia system for non-invasive treatment of deep tumors are discussed. Our heating system is composed of a large size resonant cavity applicator. In this heating method, a human body is placed between the two inner electrodes. It is heated by electromagnetic fields stimulated in the cavity without contact between the surface of the human body and the applicator. First, we presented the experimental results of heating a cylindrical agar phantom and a cylindrical fat-agar phantom using the proposed system. From the thermal images of the heated phantoms, the center of the agar was locally heated to maximum temperature. Second, we presented the experimental results of heating a mini pig. In the heating experiment, temperature measurements were performed by using fiber-optical thermometers inserted in four locations inside the mini pig. From the results, the deepest region of the liver was heated to the highest temperature 43.3 °C.

A new heating method with dielectric bolus using resonant cavity applicator for brain tumors.

In this paper, we discuss a new method of controlling heating location in the proposed resonant cavity applicator. A dielectric bolus was used to non-invasively treat brain tumors. We have already confirmed that our heating system using resonant cavity is useful to non-invasively heat brain tumors. In order to heat tumors occurring at various locations, it is necessary to control the heating area with our heating system. First, we presented the proposed heating method and a phantom model to calculate temperature distributions. The results of temperature distributions were discussed. Second, a 3-D human head model constructed from 2-D MRI images was presented. The results of specific absorption rate distributions were discussed. From these results, it was found that the proposed heating method was useful to non-invasively treat brain tumors.

SAR analysis of a re-entrant resonant cavity applicator for brain tumor hyperthermia treatment with a 3-D anatomical human head model.

A re-entrant resonant cavity applicator system for non-invasive brain tumor hyperthermia treatments was presented. We have already confirmed the effectiveness of the heating properties of this heating system with cylindrical agar phantoms and with computer simulations.

Heating properties of coaxial needle applicator made of SMA for hyperthermia treatments.

This paper describes heating properties of the developed coaxial needle applicator made of a shape memory alloy (SMA) for brain tumor hyperthermia treatments to avoid undesirable hotspots. We estimated the temperature distribution inside an agar phantom by the finite element method (FEM) and heated the agar phantom with the developed needle applicator.

Heating properties of the re-entrant type cavity applicator for brain tumor with several resonant frequencies.

We have proposed the re-entrant resonant cavity applicator system for non-invasive brain tumor hyperthermia treatment. In this method, a human head is placed in the gap of the inner electrodes. A brain tumor is heated with the electromagnetic field stimulated in the cavity without contact between the human head and the applicator. We have already presented the effectiveness of the heating properties of this system with cylinder-type agar phantoms and by computer simulations. This paper discusses the heating properties of the developed system with the human head-type agar phantom for brain tumor hyperthermia treatment. First, in order to heat deep brain tumors, we tried to heat the human head-type agar phantom by using several electromagnetic field patterns of the resonant frequency. We found that the temperature distributions can be controlled inside the agar phantom by changing the resonant frequencies. Second, to heat local and deep areas of the agar phantom, we tried to achieve heating using the two different resonant frequencies. We found distinct heating properties by changing the electromagnetic field patterns of resonant frequencies. From these results, it was found that our developed heating system can be applied to hyperthermia treatments of deep-seated brain tumors. Further, by changing resonant frequency, treatment can very correspond to the size and the position of a tumor.

Heating properties of the needle type applicator made of shape memory alloy by 3-D anatomical human head model.

Since the human brain is protected by the skull, it is not easy to non-invasively heat deep brain tumors with electromagnetic energy for hyperthermia treatments. Generally, needle type applicators were used in clinical practice to heat brain tumors. To expand the heating area of needle type applicators, we have developed a new type of needle made of a shape memory alloy (SMA). In this paper, heating properties of the proposed SMA needle type applicator were discussed. Here, in order to apply the SMA needle type applicator clinically. First, we constructed an anatomical 3-D FEM model from MRI and X-ray CT images using 3D-CAD software. Second, we estimated electric and temperature distributions to confirm the SMA needle type applicator using the FEM soft were JMAG-Studio. From these results, it was confirmed that the proposed method can expand the heating area and control the heating of various sizes of brain tumors.

Improvement of the matching speed of AIMS for development of an automatic totally tuning system for hyperthermia treatment using a resonant cavity applicator.

In this paper, we discuss the improvement of the speed of AIMS (Automatic Impedance Matching System) to automatically make impedance matching for a re-entrant resonant cavity applicator for non-invasive deep brain tumors hyperthermia treatments. We have already discussed the effectiveness of the heating method using the AIMS, with experiments of heating agar phantoms. However, the operating time of AIMS was about 30 minutes. To develop the ATT System (Automatic Totally Tuning System) including the automatic frequency tuning system, we must improve this problem. Because, when using the ATTS, the AIMS is used repeatedly to find the resonant frequency. In order to improve the speed of impedance matching, we developed the new automatic impedance matching system program (AIMS2). In AIMS, the stepping motors were connected to the impedance matching unit's dials. These dials were turned to reduce the reflected power. AIMS consists of two phases: all range searching and detailed searching. We focused on the three factors affecting the operating speed and improved them. The first factor is the interval put between the turning of the motors and AD converter. The second factor is how the steps of the motor when operating all range searching. The third factor is the starting position of the motor when detail searching. We developed the simple ATT System (ATT-beta) based on the AIMS2. To evaluate the developed AIMS2 and ATT- beta, experiments with an agar phantom were performed. From these results, we found that the operating time of the AIMS2 is about 4 minutes, which was approximately 12% of AIMS. From ATT-beta results, it was shown that it is possible to tune frequency and automatically match impedance with the program based on the AIMS2.

Heating properties of non-invasive hyperthermia treatment for abdominal deep tumors by 3-D FEM.

This paper discusses the heating properties of a new type of hyperthermia system composed of a re-entrant type resonant cavity applicator for deep tumors of the abdominal region. In this method, a human body is placed in the gap of two inner electrodes and is non-invasively heated with electromagnetic fields stimulated in the cavity. Here, we calculated temperature distributions of a simple human abdominal phantom model that we constructed to examine the heating properties of the developed hyperthermia system. First, the proposed heating method and a simple abdominal model to calculate the temperature distribution are presented. Second, the computer simulation results of temperature distribution by 3-D FEM are presented. From these results, it was found that the proposed simple human abdominal phantom model composed of muscle, fat and lung was useful to test the heating properties of our heating method. Our heating method was also effective to non-invasively heat abdominal deep tumors.

Heating properties of re-entrant resonant cavity applicator for brain tumor with simple head model.

We have already confirmed the effectiveness of the re-entrant resonant cavity applicator system with non-invasive experiments of heating cylindrical agar phantoms and computer simulations. This paper discusses the heating properties of the developed heating system with a human head model made of agar for brain tumor hyperthermia treatment. First, we present the results of heating a uniform agar head model with the developed heating system. In the experiments, the temperature rise at the center of the agar was about 8 degrees C, it was found that the center of the agar is heated to maximum temperature non-invasively. Second, we present the results of heating a non-uniform agar head model having an oral cavity and a nasal cavity. We found that the center of the agar can be heated to maximum temperature as well as uniform agar head model. From these results, it is confirmed that the possibility of effective hyperthermia for various types of deep-seated brain tumors.

Development of automatic impedance matching system for hyperthermia treatment using resonant cavity applicator.

In this paper, we discuss a new system to make impedance matching automatically for a re-entrant resonant cavity applicator for brain tumor hyperthermia treatment non-invasively. We have already discussed about the effectiveness of the heating method using manual type impedance matching controller, with experiments of heating an agar phantom and computer simulations. However, it becomes difficult to perform an accurate impedance matching as resonant frequency becomes high. Here, in order to make a more accurate impedance matching, we developed the automatic impedance matching system (AIMS). We noticed that the reflected power was generated when the impedance matching was not complete. In this system, therefore, to reduce the reflected power fed back, the stepping motor to turn the dial of variable capacitors is controlled by developed software. To evaluate the developed AIMS, the experiments of heating the agar phantom were performed. From these results, we found that the temperature rise of the agar phantom by using AIMS was about 180% of using manual type controller under the same heating condition. It was found that the proposed system was very effective for hyperthermia treatment using resonant cavity applicator even when the resonant frequency was high.

Finite element analysis of the re-entrant type resonant cavity applicator for brain tumor hyperthermia.

In this paper, we have proposed a new heating method in which high frequency electric fields in a re-entrant type resonant cavity are used for the heating of deeply seated tumors. In this method, a human head is placed between the gap of the inner re-entrant cylinders, and is heated with electromagnetic fields stimulated in the cavity without contact between the surface of the human head and the applicator. Here, we proposed a new method to control the heating area. In this method, the resonant frequency inside the cavity was changed, then we use the TM010-like mode and the TM012-like mode from various types of the resonant frequency. First, the computer simulation results of electric and magnetic field patterns are presented. Second, a comparison of the heating properties of TM010-like mode and TM012-like mode are discussed. The heating area of the center of agar phantom is more concentrated by using TM012-like mode than that of using TM010-like mode. From these results, it is confirmed that the proposed method can be controlled to heat the various sizes of deep tumors.

Heating properties of re-entrant resonant applicator for brain tumor by electromagnetic heating modes.

This paper discusses a new method to control the heating area of a re-entrant resonant cavity applicator for brain tumor hyperthermia treatment non-invasively. We have already discussed about the effectiveness of a developed system with experiments of heating an agar phantom and computer simulations. Here, in order to heat a deep brain tumor, we propose the heating method of using several electromagnetic heating modes which are transverse magnetic (TM) modes. In this method, TM010-like and TM012-like modes obtained by selecting resonant frequencies can be used to heat the deep brain tumors. To control the heating area of the modes the agar phantom is used in the heating experiments by the developed system. From these results, we found that the heating area of the agar phantom by using TM012-like mode is about 50% of the heating area of TM010-like mode. It is found that the proposed heating system can be applicable to the hyperthermia treatment of brain tumors corresponding to the size and the position where it occurred.

Covered expandable metallic stent placement for hemostasis of colonic bleeding caused by invasion of gallbladder carcinoma.

A 72-year-old Japanese man was admitted to our hospital complaining of right upper-quadrant abdominal pain, blood in his stool, and symptoms of anemia. On physical examination a hard mass, about 6 cm in diameter, was palpable in the right upper quadrant of the abdomen. Computed tomography revealed a gallbladder carcinoma which had invaded the transverse colon, with liver metastasis. We diagnosed gallbladder carcinoma, stage IVB. Colonoscopy was performed for persistent blood in the stools. This revealed an elevated lesion which appeared to be an invasion of gallbladder carcinoma, with diffuse bleeding from the right-side of the transverse colon. It proved difficult to stop this bleeding by ordinary therapeutic endoscopy. In order to achieve hemostasis we therefore inserted a covered Ultraflex metallic stent to compress the tumor. After stent placement, blood was no longer seen in the patient's stools, he became able to eat soft food and was discharged. This treatment was uninvasive and effective. Covered stent placement appears to be a new and useful method in the management of bleeding from malignant gastrointestinal tumors.

Stimulation of hyaluronan synthesis by tumor necrosis factor-alpha is mediated by the p50/p65 NF-kappa B complex in MRC-5 myofibroblasts.

The lesions of fibrocontractive diseases result from an excessive myofibroproliferative response to numerous forms of inflammatory stimuli, which elicit the net deposition of extracellular matrix (ECM) in the interstitium of the affected tissue. Hyaluronan (HA), reported to be a key player supporting cellular migration and adherence, is a major component of ECM that undergoes dynamic regulation during inflammation. The molecular regulation of HA biosynthesis by inflammatory cytokines on myofibroblasts is not yet completely understood. Here we report the biochemical characteristics of the lung myofibroblast cell line MRC-5, and we demonstrate that the production of HA by this cell line is inducible by the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), at the message level of HA synthase (HAS). In TNF-alpha-stimulated MRC-5 cells, DNA-binding and competition experiments indicated that the predominant NF-kappa B binding activity detected with nuclear extract-stimulated cells is mediated by the p50/p65 complex. Using antisense oligonucleotides, we confirmed that the TNF-alpha-stimulation of HA synthesis by MRC-5 cells is dependent on the activation of the p50/p65 NF-kappa B complex. These findings indicate that TNF-alpha production within inflamed tissues may enhance the HA synthesis via the transcriptional induction of HAS on myofibroblasts, thereby providing a provisional matrix for supporting cellular migration and adhesion, and that the p50/p65 NF-kappa B complex that plays an important role in the regulation of HA production by TNF-alpha might be an appropriate target for therapeutic compounds to treat tissue fibrosis accompanied by inflammation.

Difference in hepatic tissue oxygenation between total vascular exclusion and inflow occlusion of the liver and the possible role of hepatic venous blood under liver ischemia.

The difference between total vascular exclusion (TVE) and inflow occlusion (IO) of the liver was assessed by the extent of DNA injury in rats and by hepatic tissue oxygen saturation (SahtO2) in pigs. Moreover, the role of hepatic venous blood under liver ischemia was discussed. Seventy percent of the rat livers were exposed to complete IO (hepatic artery + portal vein) or to TVE (IO + hepatic vein) for 30 or 60 min. DNA strand breaks following blood flow interception were measured using the in situ nick translation technique as an indicator of liver damage. IO/TVE were performed on pigs as well under portosystemic bypass, and the oxygen saturation of the hepatic venous blood (SahvO2) was altered by changing the fraction of inspiratory oxygen or by oxygenating the inferior caval blood using an extracorporeal membrane oxygenator. The changes in SahtO2 were measured sequentially using near-infrared spectroscopy. The results were as follows: (1) DNA injury occurred more severely under TVE than under IO of the rat liver at the end of ischemia, as well as 30 min after revascularization. (2) SahtO2 during TVE was significantly lower than that during IO. (3) The increase in SahvO2 by oxygenation of the inferior caval blood resulted in the elevation of SahtO2 under IO. In conclusion, TVE could cause greater damage to the liver than IO due to the lack of the hepatic venous blood. Hepatic venous blood might play an important role in hepatic tissue oxygenation in the case of hepatic blood flow interception.

Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines.

Interleukin-8 (IL-8) may play an important role in Helicobacter pylori infection-associated chronic active gastritis and peptic ulcer disease in human. We have recently reported that a gastric cancer cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori. Moreover, H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the production of IL-8 in several gastric cancer cell lines infected with H. pylori. In addition, rebamipide suppressed H. pylori-induced IL-8 gene expression at the transcriptional level as revealed by northern blotting analysis and luciferase activity in cells that were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44). Furthermore, rebamipide significantly suppressed the NF-kappaB activation by H. pylori infection. These results suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflammatory cytokine, IL-8.