Colorectal Cancer Liver Mets: Multiple Bilateral Lesions

( Hauke Lang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Hepatic resection is the treatment of choice for CRLM. Depending on patient selection 5 year-survival rates of up to 50- 60% can be achieved. However, at the time of diagnosis, only a minority of about 15-30% of patients are candidates for upfront hepatic surgery. Most often, multifocal intrahepatic tumor spread in both liver lobes, extensive tumor burden or diffuse extrahepatic metastases result in either technical or functional irresectability or make a resection questionable from an oncologic point of view. In recent years, therapeutic options for CRLM have steadily improved and several strategies have been developed to increase resectability. The two most important steps were the development of effective downsizing chemotherapy regimens and the introduction of preoperative liver volume modulation techniques, mainly the invention of portal vein embolization (PVE) or ligation (PVL). Furthermore, two-stage hepatectomy (TSH) enables complete resection of bilateral multinodular hepatic metastases not amenable to resection in a single procedure, not even after effective downsizing chemotherapy. However, despite all these progresses, treatment of bilateral metastases in the setting of an estimated small future liver remnant (FLR) remained a big challenge. To cope with this problem, conventional TSH was further modified by combining tumor clearance of the FLR with simultaneous contralateral portal vein ligation or subsequent portal vein embolization (PVE) to stimulate growth of the FLR. The hypertrophy rates observed after this approach usually range between 20% - 40% but can reach almost 60-70% in highly specialized centers. Reported survival data after two stage hepatectomy with and without PVE/PVL vary tremendously depending on patient selection criteria. The best results are comparable to outcome data after surgery for primarily resectable CRLM, with a 5-year-survival of about 30% or, in selected cases, even higher. However, the two main risks inherent to this strategy are an ineffective liver hypertrophy and a probable stimulation of growth of both, the FLR and the tumor. This has been shown in several studies where up to 25-38% of patients did not proceed to step 2, mainly due to a tumor progression and less often due to an insufficient volume gain. ALPPS can overcome this problem by inducing a more effective hypertrophy in a shorter time period, thus allowing an almost 100% resectability rate. However, initial enthusiasm was hampered by high rates of morbidity and mortality and also early and frequent recurrence rates. Technical refinements and an improved patient selection led to a stepwise reduction of the perioperative complication rate of ALPPS. In the second large publication from the ALPPS Registry a mortality rate of now only about 5% for CRLM was found which is similar to the reported mortality after major conventional hepatectomy. One alternative to TSH or ALPPS may be one stage hepatectomy (OSH). In this concept, major anatomical resections are avoided if possible, and metastases are mainly removed by atypical resections. The charm of this approach is - next to avoiding the morbidity of a second or (in case of PVE) a third operation/intervention - minimizing parenchymal loss but at the expense of a high risk of tumor positive resection margins. Although in recent years the potential benefit of an R1-resection has been pointed out - in particular in multifocal CRLM with good response to chemotherapy - R0-resection is still the standard goal of surgery for CRLM. In OSH for multifocal CRLM, however, R1-resection is widely accepted, the more as also the detachment of metastases from major vascular structures (R1 vascular margin) has been shown to be almost equivalent to R0 resection. In conclusion, treatment of bilateral CRLM is still a challenge. Due to advances in medical and surgical therapy, treatment options have widened. Downsizing chemotherapy and liver volume modulation techniques enable to do liver resections even in initially extensive tumor burden and critical small FLR. Whenever applicable, OSH hepatectomy or conventional TSH should be the preferred method, while ALPPS should be reserved for those cases where there is no other possibility for resection.

Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Registry: What Have We Learned?

Hauke Lang,Janine Baumgart,Jens Mittler 거트앤리버 소화기연관학회협의회 2020 Gut and Liver Vol.14 No.6

In 2007, the first associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure was performed in Regensburg, Germany. ALPPS is a variation of twostage hepatectomy to induce rapid liver hypertrophy allowing the removal of large tumors otherwise considered irresectable due to a too small future liver remnant. In 2012, the international ALPPS registry was created, and it now contains more than 1,000 cases. During the past years, improved patient selection and refinements in operative techniques, in particular, less invasive approaches such as Partial ALPPS, Tourniquet ALPPS, Ablation-assisted ALPPS, Hybrid ALPPS or Laparoscopic or Robotic approaches, have resulted in significant improvements in safety. The most frequent indication for ALPPS is colorectal liver metastases. In the first randomized controlled study, ALPPS provided a higher resectability rate than conventional two-stage hepatectomy, with similar complication rates. Long-term outcome data are still missing. The initial results of ALPPS for hepatocellular carcinoma and for perihilar cholangiocarcinoma were devastating, but with progress in surgical technic and better patient selection, ALPPS could serve as a treatment alternative in carefully selected cases, even for these tumors. ALPPS has enlarged the armamentarium of hepato-pancreato-biliary surgeons, but there is still discussion regarding how to use this novel technique, which may allow resection of tumors that are otherwise deemed irresectable.

Trend Analysis by Risk Observation: How the German Statutory Accident Insurance Prepares for the Future in Occupational Safety and Health

Hauke Angelika,Flaspöler Eva,Klüser Ruth,Neitzner Ina,Reinert Dietmar 한국산업안전보건공단 산업안전보건연구원 2022 Safety and health at work Vol.13 No.4

Background: The risk observatory (RO) of the German Social Accident Insurance (DGUV) provides strategic support to the German Social Accident Insurance Institutions (GSAII) in proactive prevention. It does so by identifying future challenges and opportunities for occupational safety and health (OSH) resulting from new trends and developments that affect employees as well as children in elementary education, pupils, and students. Methods: The core of the RO is an online survey that relies on a pool of new trends and developments identified via internet and literature research. 865 prevention experts of the GSAII and the DGUV participated in the survey. They rated trends and developments regarding their sector-specific risks and opportunities for OSH in the 5 years to come. Results: Sector-specific and over-all results show that besides well-known OSH risks such as musculoskeletal stress and noise, developments relevant for OSH come to the fore that do not have their origin in work itself, but are strongly influenced by political, social, economic, environmental, or technical developments that accident insurance can only peripherally influence. Shortage of skilled staff was identified as a threat to OSH in almost all sectors. Conclusions: Prevention must find ways to address repercussions of such OSH risks. Cooperation and political awareness are therefore gaining in importance. Also, implementing a prevention culture in society and strengthening individuals’ health and safety literacy, e.g., by target-group-specific communication and sensitization, as well as early safety and health education, help to counteract those OSH risks.

Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Registry: What Have We Learned?

( Hauke Lang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

In 2007, now more than 10 years ago, Hans Jurgen Schlitt from Regensburg performed, moreorless by incident, the first ALPPS procedure, or, as it was initially and still is called in Germany “In-Situ Split”. The idea of the “In-Situ Split” soon spread all over Germany, but it was not all known outside of Germany. The concept was first presented at the E-AHPBA meeting in Capetown 2011, where it gained tremendous interest. In 2012, the initial experience of five German centers (Regensburg, Göttingen, Mainz, Tubingen, Giessen) in a total of 25 patients was published in the “Annals of Surgery”. In an editorial, the acronym ALPPS (“Associating Liver Partition and Portal vein ligation for Staged hepatectomy”) was proposed. Since then, HPB groups from all over the world started to work on this novel technique. As a result, the technique has been improved and refined, but also disadvantages and drawbacks have been identified. Nevertheless, ALPPS is currently the most fascinating and controversial technique in HPB surgery, since it enables extensive liver resections in otherwise unresectable cases. Originally, the ALPPS procedure was designed for right trisectionecomy, but the newly created “ALPPS registry” showed that it was also used for standard right hepatectomy in about 50% of cases. In 2015, an International Expert meeting was held in Hamburg in 2015 resulted in eight recommendations regarding preoperative diagnostics, operative technique and indication for ALPPS. One year later a consensus for the different technical variations was suggested to standardize terminology. During the 12th congress of the E-AHPBA in Mainz, Germany, the 10th anniversary of ALPPS was “celebrated” in expert meeting in order to discuss the status quo of this novel technique. The main findings and conclusions of this meeting, mainly drawn from data of the ALPPS registry which now gathers more than 1000 cases, were the following: Precise anatomical knowledge, in particular of the vasculo-bilary variants is paramount for the success in ALPPS. Preoperative imaging is mandatory to assess all individual anatomical details. More than anatomy, the two main diagnostic issues in ALPPS are the volumetric assessment of the future liver remnant and the timing of stage 2. Of note, volume increase is not necessarily associated with increased liver function. For this reason, imaging techniques such as 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) and single photon emission computed tomography (SPECT) have been used to estimate FLR function and to predict PHLF preoperatively. In addition, improvements have been achieved by patient selection and in particular by refining the surgical technique mainly aiming at reducing post stage 1 morbidity. Thus, the concept of only partial hepatic transection was created, named “partial ALPPS”. Other modifications, such as the combination of partial ALPPS and PVE, either simultaneously (“Mini ALPPS”) or subsequent, aimed to further limit interstage morbidity by avoiding surgical manipulation of the hepatic hilum. All these improvements led to a reduction of overall complications, and thus, in the second large publication from the ALPPS Registry a mortality rate of now only 5% for ALPPS in CRLM could be reported. Consistently, recent data from the only prospective randomized controlled trial confirmed significant higher resection rates in ALPPS with similar peri-operative morbidity and mortality rates compared to conventional two-stage hepatectomy including PVE. Currently, CRLM are supposed to be the best indication for ALPPS. Though recurrence rates appear higher than after conventional liver resections, ALPPS is offering a chance for cure for those patients who otherwise would never have any surgical option. However, long-term clinical and oncological outcome studies of ALPPS for CRLM are still lacking. Currently, CRLM are supposed to be the best indication for ALPPS. Though recurrence rates appear higher than after conventional liver resections, ALPPS is offering a chance for cure for those patients who otherwise would never have any surgical option. However, long-term clinical and oncological outcome studies of ALPPS for CRLM are still lacking. In contrast to CRLM, there is a major controversy regarding ALPPS in biliary tumors. The first report of the ALPPS registry included 11 patients with PHCC with a 90 day-mortality rate of 27%. In a recent matched case-controlled study, Olthof et al. compared ALPPS from the ALPPS registry versus PVE and right trisectionectomy for PHCC in two centers of excellence for HPB surgery. Postoperative mortality was twice as high in the ALPPS group (48% vs 24%). However, newly developed variants such as Mini-ALPPS which avoid surgical manipulation of the hepatic hilum may be attractive in particular for PHCC. Regarding treatment of HCC it is important to know that ALPPS is also effective in fibrosis and mild cirrhosis but the degree of FLR hypertrophy appears less than in non-cirrhotic livers. In summary, continuous efforts to improve patient selection and timing of stage 2 as well as refinements of the operative technique have allowed to perform ALPPS with morbidity and mortality rates comparable to standard major liver resections. Meanwhile, the “ALPPS” technique has been established as a new liver resection concept, but its place is still to be defined. ALPPS does definitely not replace other techniques such as portal vein embolization and standard two-stage hepatectomy but adds to the toolkit of liver resection in the hands of experienced hepatobiliary surgeons. Long-term oncological outcome results are needed to establish the place of ALPPS in the treatment of patients with initially non-resectable liver tumors.

分斷된 獨逸과 其他의 分斷帝國 : 比較考察의 試圖

Gustav Fochler Hauke 영남대학교 통일문제연구소 1970 統一問題硏究 Vol.1 No.-

Safety of Stress Cardiac Magnetic Resonance in Patients With Moderate to Severe Aortic Valve Stenosis

Janek Salatzki,Andreas Ochs,Nadja Kirchgäßner,Jannick Heins,Sebastian Seitz,Hauke Hund,Derliz Mereles,Matthias G. Friedrich,Hugo A. Katus,Norbert Frey,Florian André,Marco M. Ochs 한국심초음파학회 2023 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.31 No.1

BACKGROUND: Dobutamine and adenosine stress cardiac magnetic resonance (CMR) imaging is relatively contraindicated in patients with moderate to severe aortic valve stenosis (AS). We aimed to determine the safety of dobutamine and adenosine stress CMR in patients with moderate to severe AS. METHODS: In this retrospective study patients with AS who underwent either dobutamine or adenosine stress CMR for exclusion of obstructive coronary artery disease were enrolled. We recorded clinical data, CMR and echocardiography findings, and complications as well as minor symptoms. Patients with AS were compared to matched individuals without AS. RESULTS: A total of 187 patients with AS were identified and compared to age-, gender- and body mass index-matched 187 patients without AS. No severe complications were reported in the study nor the control group. The reported frequency of non-severe complications and minor symptoms were similar between the study and the control groups. Nineteen patients with AS experienced non-severe complications or minor symptoms during dobutamine stress CMR compared to eighteen patients without AS (p = 0.855). One patient with AS and two patients without AS undergoing adenosine stress CMR experienced minor symptoms (p = 0.562). Four examinations were aborted because of chest pain, paroxysmal atrial fibrillation and third-degree atrioventricular block. Inducible ischaemia, prior coronary artery bypass grafting, prior stroke and age were associated with a higher incidence of complications and minor symptoms. CONCLUSIONS: Moderate to severe AS was not associated with complications during CMR stress test. The incidence of non-severe complications and minor symptoms was greater with dobutamine.

Five-fold Gastrointestinal Electrical Stimulation With Electromyography-based Activity Analysis: Towards Multilocular Theranostic Intestinal Implants

Jonas F Schiemer,Axel Heimann,Karin H Somerlik-Fuchs,Roman Ruff,Klaus-Peter Hoffmann,Jan Baumgart,Manfred Berres,Hauke Lang,Werner Kneist 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.3

Background/AimsMotility disorders are common and may affect the entire gastrointestinal (GI) tract but current treatment is limited. Multilocularsensing of GI electrical activity and variable electrical stimulation (ES) is a promising option. The aim of our study is to investigate theeffects of adjustable ES on poststimulatory spike activities in 5 GI segments. MethodsSix acute porcine experiments were performed with direct ES by 4 ES parameter sets (30 seconds, 25 mA, 500 microseconds or1000 microseconds, 30 Hz or 130 Hz) applied through subserosal electrodes in the stomach, duodenum, ileum, jejunum, and colon. Multi-channel electromyography of baseline and post-stimulatory GI electrical activity were recorded for 3 minutes with hook needleand hook-wire electrodes. Spike activities were algorithmically calculated, visualized in a heat map, and tested for significance byPoisson analysis. ResultsPost-stimulatory spike activities were markedly increased in the stomach (7 of 24 test results), duodenum (8 of 24), jejunum (23 of24), ileum (18 of 24), and colon (5 of 24). ES parameter analysis revealed that 80.0% of the GI parts (all but duodenum) required apulse width of 1000 microseconds, and 60.0% (all but jejunum and colon) required 130 Hz frequency for maximum spike activity. Fivereaction patterns were distinguished, with 30.0% earlier responses (type I), 42.5% later or mixed type responses (type II, III, and X),and 27.5% non-significant responses (type 0). ConclusionsMultilocular ES with variable ES parameters is feasible and may significantly modulate GI electrical activity. Automatedelectromyography analysis revealed complex reaction patterns in the 5 examined GI segments.

Optimized single-layer MoS₂ field-effect transistors by non-covalent functionalisation

Kim, HyunJeong,Kim, WungYeon,O'Brien, Maria,McEvoy, Niall,Yim, Chanyoung,Marcia, Mario,Hauke, Frank,Hirsch, Andreas,Kim, Gyu-Tae,Duesberg, Georg S. The Royal Society of Chemistry 2018 Nanoscale Vol.10 No.37

<P>Field-effect transistors (FETs) with non-covalently functionalised molybdenum disulfide (MoS2) channels grown by chemical vapour deposition (CVD) on SiO2 are reported. The dangling-bond-free surface of MoS2 was functionalised with a perylene bisimide derivative to allow for the deposition of Al2O3 dielectric. This allowed the fabrication of top-gated, fully encapsulated MoS2 FETs. Furthermore, by the definition of vertical contacts on MoS2, devices, in which the channel area was never exposed to polymers, were fabricated. The MoS2 FETs showed some of the highest mobilities for transistors fabricated on SiO2 with Al2O3 as the top-gate dielectric reported so far. Thus, gate-stack engineering using innovative chemistry is a promising approach for the fabrication of reliable electronic devices based on 2D materials.</P>

Kinetics of the Cassella's acid by the Azocouping Reaction

Youn, Joo-Hack,Song, Won-hauk,Lee, Sang-Kyu,Park, Eun-Sun 선문대학교 1998 공과대학논문집 Vol.1 No.1

본 논문은 예술적 표현에 작용하는 심리학적 기제를 설명하는 영향력 있는 세가지 접근방법, 즉 정신분석학적 접근, 실험미학적 접근 그리고 형태심리학적 접근방법에 대하여 비판적 시각에서 살펴보고 이들 접근방법의 가능성과 한계를 탐색해보고자 한다. 특히 복잡한 예술의 현상을 설명하는 가장 적절한 접근방법으로 평가될 수 있는, 그러나 심리학의 분야에서는 그동안 등한시되어 왔던 형태심리학의 표현지각이론이 예술현상에 대한 이해에 얼마나 유용하게 적용될 수 있는지 구체적으로 고찰해보고자 한다. In this paper from the kinetic data, It has been found that activation energies of azocoupling reaction are 10.7, 9.9, 12.6, 11.2, 11.8, 5.8, 6.4, 9.2, 8.0, 7.3 and 8.7 ㎉/mole for Cassella‘s acid, and also that those of azocoupling reaction of 2-naphthol are 10.3, 9.1, 12.0, 10.8, 11.4, 5.3, 5.2, 5.6, 8.4, 7.5, 6.5 and 6.1 ㎉/mole, respertively. The azocoupling reaction Increased In sequence of methoxy, methyl, halogen, sulfonic acid and nitro substituted diazonlum benzene compounds. Rho-sigma Ilneallty of Yukawa-Tsuno's modified Hammett relationship has been observed and the reaction constants for Cassella's acid and 2-naphthol are evaluated as 3.98 and 3.1 at 10℃, respectively.

Single incision gastrectomy compared to multiport laparoscopic gastrectomy in early gastric cancer: Propensity score matched analysis.

Felix BERLTH,Yun-Sukh SUH,Chun-Chao ZHU,Shin-Hoo PARK,Seung-Ho KONG,Hauk-Joon LEE,Han-Kwang YANG 대한외과학회 2017 대한외과학회 학술대회 초록집 Vol.2017 No.11