Background Endoscopic treatment options for postsurgical intrathoracic leaks include injection of fibrin glue, clip application, and stent placement. Endoscopic vacuum-assisted closure (E-VAC) may be ...an effective treatment option. Objective To demonstrate that E-VAC is an effective endoscopic treatment option for closure of major intrathoracic postsurgical leaks. Design and Setting A prospective, single-center study at an academic medical center. Patients Eight consecutive patients with major intrathoracic postsurgical leaks. Interventions Endoscopic placement of transnasal draining tubes, armed with a size-adjusted sponge at their distal end, in the necrotic anastomotic cavities, followed by continuous suction. Sponge and drainage were changed twice weekly. Patients were followed-up for 193 ± 137 days. Main Outcome Measurement Successful leak closure. Results Successful closure of leaks was achieved in 7 of 8 patients (88%) after a mean of 23 ± 8 days. A median of 7 endoscopic interventions was necessary. No major treatment-associated short-term or long-term (follow-up, 193 ± 137 days) complications were noted. Limitations Small sample size, single-center study, and lack of randomization. Conclusion E-VAC is an effective endoscopic treatment modality for major postsurgical intrathoracic leaks. (This study is registered at Clinicaltrials.gov , identifier NCT00876551 .)
Mucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To ...clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers;
p
< 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (
p
< 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (
p
< 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness.
Background DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating ...intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.
Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic ...characteristics is important for selection of patients and for development of adjuvant therapeutic strategies.
The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics.
Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence.
In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.
Sinusoidal obstruction syndrome (SOS) is a specific complication of hematopoietic stem cell transplantation (HSCT) that can lead to substantial morbidity and treatment-related mortality. Heparin is ...frequently used as prophylaxis of and defibrotide as therapy for mild to moderate SOS. In severe cases of SOS these therapies are often ineffective, and orthotopic liver trans-plantation (OLT) may be the only option. Reports in the literature about the outcome of liver transplantation for SOS are contradictory. We describe our second case of OLT after HSCT. The patient died of intracranial hemorrhage 2 weeks after liver transplantation with good initial organ function. In the first case at our center, however, the patient survived more then 8 years. The reported short- to medium-range survival rate for OLT following HSCT is approximately 50%. On the basis of the experience at our center and the findings in a review of the literature, we developed a rational approach to the selection for liver transplantation of patients with life-threatening liver dysfunction after marrow transplantation.
Background
Microsatellite instability (MSI) has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents a potential obstacle for the analysis of ...predicitive biomarkers. MSI has been reported in pancreatic cancer, but data on the possible extent of intratumoral heterogeneity are lacking.
Methods
To study MSI heterogeneity in pancreatic cancer, a tissue microarray (TMA) comprising 597 tumors was screened by immunohistochemistry with antibodies for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6.
Results
In six suspicious cases, large section immunohistochemistry and microsatellite analysis (Bethesda panel) resulted in the identification of 4 (0.8%) validated MSI cases out of 480 interpretable pancreatic ductal adenocarcinomas. MSI was absent in 55 adenocarcinomas of the ampulla of Vater and 7 acinar cell carcinomas. MMR deficiency always involved MSH6 loss, in three cases with additional loss of MSH2 expression. Three cancers were MSI-high and one case with isolated MSH6 loss was MSS in PCR analysis. The analysis of 44 cancer-containing tumor blocks revealed that the loss of MMR protein expression was always homogeneous in affected tumors. Automated digital image analysis of CD8 immunostaining demonstrated markedly higher CD8 + tumor infiltrating lymphocytes in tumors with (mean = 685, median = 626) than without (mean = 227; median = 124) MMR deficiency (
p
< 0.0001), suggesting a role of MSI for immune response.
Conclusions
Our data suggest that MSI occurs early in a small subset of ductal adenocarcinomas of the pancreas and that immunohistochemical MMR analysis on limited biopsy or cytology material may be sufficient to estimate MMR status of the entire cancer mass.
Addresses the question if antibody induction therapy with basiliximab compared to no induction therapy leads to better long term renal allograft function and/or patient survival after 10 years. ...Retrospectively analyzes patients enrolled in a multicentre phase III trial (CHIB 201) at Hanover Medical School, Germany in 1995/1996 and followed over a 10-year period. Compares the results of this study with published long-term data available for other IL-2R antagonists. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
AIM： To outline the surgical experience with donor liver splitting in split liver transplantation.METHODS： From March 1 to September 1 in 2004, 10 donor livers were split ex situ into a left lateral ...lobe （segments Ⅱ and Ⅲ） and a right extended lobe （segments Ⅰ, Ⅳ-Ⅷ） in Medical School of Hannover, and thereafter split liver transplantation was performed successfully in 29 cases. The average age, weight and ICU slaying period of the donors were 32.7 years （25-52 years）, 64.5 kg（45-75 kg） and 2.4 d （2-8 d） respectively.RESULTS： The average weight of the whole graft and the left lateral lobe was 2 322.6 g （956-2 665 g） and 282.8 g （298-373 g） respectively, and the average ratio of left lateral lobe to the whole graft was 0.225 （0.278-0.274）.The average graft to recipient weight ratio （GRWR） of the left lateral lobe and the right extended lobe reached 2.44% （2.22-5.42%） and 2.73% （2.32-2.30%） respectively.On average it took approximately 205 min （85-235 rain）to split the donor liver. Five donor organs showed anatomic variation including the left hepatic vein variation in two cases, the left hepatic artery variation in two cases and the bile duct variation in one case.CONCLUSION： Split liver transplantation has become a mature surgical technique to expand the donor pool with promising results. In the process of graft splitting, close attention needs to be paid to potential anatomic variations,especially to variations of the left hepatic vein, the left hepatic artery, and the bile duct.
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