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Microvascular invasion of hepatocellular carcinoma predicts microvascular invasion of its recurrence: potential implications for salvage liver transplantation?

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Hepatobiliary Surgery and Nutrition 2023年第2期12卷 183-191页

作者： Stefan Heinrich Jens Mittler Juliane Theurer Dirk ARidder Jens UMarquardt Arndt Weinmann Uwe Scheuermann Gerd Otto Peter RGalle Beate KStraub hauke lang General Visceral and Transplantation SurgeryUniversity Hospital of MainzMainzGermany Institute of Pathology University Hospital of MainzMainzGermany Department of Medicine I University Medical Center Schleswig-HolsteinCampus LübeckGermany Department of Medicine I University Hospital of MainzMainzGermany Visceral TransplantationThoracic and Vascular SurgeryUniversity Hospital LeipzigLeipzigGermany

Background:Microvascular invasion(MVI)can only be assessed on a full surgical *** aimed at evaluating,whether the histology of the primary tumor is predictive of MVI in a hepatocellular carcinoma(HCC)***:Patients,who underwent liver resection or orthotopic liver transplantation(OLT)for recurrent HCC from January 2001 until June 2018 were eligible for this retrospective *** specimens were evaluated for HCC subtype/morphology,vessels encapsulating tumor clusters(VETC)-pattern and *** parameters were analyzed using χ^(2)-test andϕ-values,with P values<0.05 being considered ***:Of 230 HCC recurrences,37(16.1%)underwent repeated liver resection(n=22)or OLT(n=15).Of these,67.6%initially exceeded the Milan *** correlated Milan criteria(P=0.005),tumor size(P=0.015)and VETC-pattern(P=0.034)in the primary *** recurrences shared many features of the primary HCC such as tumor grade(P=0.002),VETC-pattern(P=0.035),and MVI(P=0.046).In recurrences,however,only the concordance with the Milan criteria correlated with MVI(P=0.018).No patient without MVI in the primary HCC revealed MVI on early recurrence(<2 years)(P=0.035).Conclusions:HCC recurrences share many biological features of the primary ***,early recurrences of MVI-negative HCC never revealed *** finding offers novel concepts,e.g.,patient selection for salvage OLT.

关键词： Microvascular invasion(MVI) resection selection vessels encapsulating tumor clusters(VETC) angioinvasion salvage transplantation

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Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging

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Hepatobiliary & Pancreatic Diseases International 2021年第3期20卷 262-270页

作者： Fabian Bartsch Felix Hahn Lukas Müller Janine Baumgart Maria Hoppe-Lotichius Roman Kloeckner hauke lang Department of General Visceral and Transplant SurgeryUniversity Medical Center of the Johannes Gutenberg-University MainzLangenbeckst155131 MainzGermany Department of Diagnostic and Interventional Radiology University Medical Center of the Johannes Gutenberg-University MainzLangenbeckst155131 MainzGermany

Background: Intrahepatic cholangiocarcinoma(ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. Methods: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. Results: Out of 184 patients, 135(73.4%) underwent curative intended resection. Median overall survival(OS) was 22.2 months with a consecutive 1-, 3-and 5-year OS of 73%, 29%, and 17%. Median recurrencefree survival(RFS) was 9.3 months with a consecutive 1-, 3-and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction(POP) score was created showing significance for OS and RFS(all P<0.001). In multivariate analysis, POP score(HR=1.779;95% CI: 1.26 8-2.4 95;P=0.001), T stage(HR=1.255;95% CI: 1.040-1.514;P=0.018) and N stage(HR=1.334;95% CI: 1.081-1.645;P=0.007) were the independent predictors for OS. For RFS, POP score(HR=1.733;95% CI: 1.30 0-2.311;P<0.0 01) and M stage(HR=3.036;95% CI: 1.376-6.697;P=0.006) were the independent predictors. Conclusions: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

关键词： Intrahepatic cholangiocarcinoma Cholangiocarcinoma Liver surgery Preoperative imaging Survival

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High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

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World Journal of Gastroenterology 2009年第17期15卷 2089-2096页

作者： Carl Christoph Schimanski Kirsten Frerichs Fareed Rahman Martin Berger hauke lang Peter R Galle Markus Moehler Ines Gockel First Department of Internal Medicine Johannes Gutenberg University of Mainz 55131 Mainz Germany Unit of Toxicology and Chemotherapy GermanCancer Research Centre 69120 Heidelberg Germany Department of General and Abdominal Surgery Johannes Gutenberg University of Mainz 55131 Mainz Germany

AIM: To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis. METHODS: The impact of miR-196a on the restriction targets HoxA7, HoxB8, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction (RT-PCR) after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectal cancer samples, mucosa samples and diverse cancer cell lines was quantifi ed by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo. RESULTS: HoxA7, HoxB8, HoxC8 and HoxD8 were restricted by miR-196a in a dose-dependent and gene-specific manner. High levels of miR-196a activated the AKT signaling pathway as indicated by increased phosphorylation of AKT. In addition, high levels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towards platin derivatives but did not impact on proliferation or apoptosis. Furthermore, miR-196a increased the development of lung metastases in mice after tail vein injection. CONCLUSION: miR-196a exerts a pro-oncogenic influence in colorectal cancer.

关键词：大肠癌细胞逆转录聚合酶链反应 AKT信号通路 microRNA 表型致癌 SW480 转移模型

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Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

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World Journal of Gastroenterology 2013年第9期19卷 1424-1437页

作者： George Sgourakis Ines Gockel hauke lang Department of General and Abdominal Surgery Johannes Gutenberg University Hospital of Mainz 2nd Surgical Department and Surgical Oncology Unit of "Korgialenio-Benakio" Red Cross Hospital of Athens

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A

关键词： Superficial esophageal cancer Endoscopic resection Mucosal infiltration Submucosal involvement Recurrent tumor Controversies in treatment Squamous cell carcinoma Adenocarcinoma Lymphatic invasion Vascular invasion Submucosal layer Superficial submucosal layer Middle third submucosal layer Deep third submucosal layer Esophageal cancer Endoscopic gastrointestinal surgical procedures Endoscopic gastrointestinal surgery Lymph node dissection Dysplasia

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Multidisciplinary management of gastric and gastroesophageal cancers

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World Journal of Gastroenterology 2008年第24期14卷 3773-3780页

作者： Markus Moehler Orestis Lyros Ines Gockel Peter R Galle hauke lang First Department of Internal Medicine of Johannes Gutenberg University of Mainz Institute of Surgery of Johannes Gutenberg University of Mainz

Carcinomas of the stomach and gastroesophageal junction are among the fi ve top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer,surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer (UICC) stages in Western countries because of the high risk of recurrence and metachronous metastases. However,recent large phase-Ⅲ Studies improved the diagnostic and therapeutic options in gastric cancers,indicating a more multidisciplinary management of the disease. Multimodal strategies combining dif-ferent neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular,the perioperative (neoadjuvant,adjuvant) chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection,mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastro-esophageal cancer,and discusses future strategies toimprove locoregional failures.

关键词：胃癌化疗辅助剂胃食管癌

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