Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis.

BACKGROUND: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. METHODS: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. RESULTS: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. CONCLUSION: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.

Mortality after liver surgery in Germany.

BACKGROUND: Mortality rates after liver surgery are not well documented in Germany. More than 1000 hospitals offer liver resection, but there is no central regulation of infrastructure requirements or outcome quality. METHODS: Hospital mortality rates after liver resection were analysed using the standardized hospital discharge data (Diagnosis-Related Groups, ICD-10 and German operations and procedure key codes) provided by the Research Data Centre of the Federal Statistical Office and Statistical Offices of the Länder in Wiesbaden, Germany. RESULTS: A total of 110 332 liver procedures carried out between 2010 and 2015 were identified. The overall hospital mortality rate for all resections was 5·8 per cent. The mortality rate among 17 574 major hepatic procedures was 10·4 per cent. Patients who had surgery for colorectal liver metastases (CRLMs) had the lowest mortality rate among those with malignancy (5·5 per cent), followed by patients with gallbladder cancer (7·1 per cent), hepatocellular carcinoma (9·3 per cent) and intrahepatic cholangiocarcinoma (11·0 per cent). Patients with extrahepatic cholangiocarcinoma had the highest mortality rate (14·6 per cent). The mortality rate for extended hepatectomy was 16·2 per cent and the need for a biliodigestive anastomosis increased this to 25·5 per cent. Failure to rescue after complications led to mortality rates of more than 30 per cent in some subgroups. There was a significant volume-outcome relationship for CRLM surgery in very high-volume centres (mean 26-60 major resections for CRLMs per year). The mortality rate was 4·6 per cent in very high-volume centres compared with 7·5 per cent in very low-volume hospitals (odds ratio 0·60, 95 per cent c.i. 0·42 to 0·77; P < 0·001). CONCLUSION: This analysis of outcome data after liver resection in Germany suggests that hospital mortality remains high. There should be more focused research to understand, improve or justify factors leading to this result, and consideration of centralization of liver surgery.

ANTECEDENTES: En Alemania, los datos de mortalidad después de la cirugía no están bien documentados. En más de 1.000 hospitales se realizan resecciones hepáticas, pero no existe una regulación central de los prerrequisitos estructurales necesarios y de la calidad de los resultados. MÉTODOS: Las tasas de mortalidad hospitalaria relacionadas con las resecciones hepáticas se analizaron utilizando los datos estandarizados del alta hospitalaria (Diagnóstico de grupos relacionados, DRG), la clasificación internacional de enfermedades 10 (ICD10) y la clave de procedimientos y operaciones (códigos OPS) proporcionados por el RDC de la Oficina Federal de Estadística y Oficinas de Estadística de Länder en Wiesbaden, Alemania. RESULTADOS: Se identificaron un total de 110.332 procedimientos hepáticos (de 2010 a 2015). La tasa global de mortalidad hospitalaria para todas las resecciones fue del 5,8%. Las resecciones hepáticas mayores (n = 15.333) presentaron una mortalidad del 10,4%. Los pacientes con metástasis hepáticas colorrectales (colorectal liver metastases, CRLM) tuvieron la mortalidad más baja de entre los pacientes con neoplasias malignas (5,5%), seguidos de los pacientes con cáncer de vesícula biliar (7,1%), colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCC) (11,0%) y carcinoma hepatocelular (hepatocellular carcinoma, HCC) (9,3%). Los pacientes con colangiocarcinoma extrahepático (extrahepatic cholangiocarcinoma, eCC) presentaron la mortalidad más alta (14,6%). Las hepatectomías extendidas (16,2%) y la necesidad de una anastomosis biliodigestiva (biliodigestive anastomosis, BDA) aumentaron la mortalidad a un 25,5%. La falta de solución de algunas complicaciones llevó a tasas de mortalidad de más del 30% en algunos subgrupos. Hubo una relación significativa volumen-resultado para las CRLM en centros de alto volumen (25,3 a 59,7 resecciones mayores/año; razón de oportunidades, odds ratio, OR 0,60, i.c. del 95%: 0,42-0,77; P < 0,001), lo que resultó en una disminución en las tasas de mortalidad de 7,5/6,4/7,5/6,5% a 4,6%. CONCLUSIÓN: El análisis de los resultados después de la resección hepática en Alemania muestra una alta mortalidad hospitalaria inesperada. Este análisis indica la necesidad de efectuar una investigación más específica para comprender, mejorar o justificar los factores que determinan estos hallazgos.

Should ALPPS be Used for Liver Resection in Intermediate-Stage HCC?

BACKGROUND: Extended liver resections in patients with hepatocellular carcinoma (HCC) are problematic due to hepatitis, fibrosis, and cirrhosis. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has been promoted as a novel method to induce hypertrophy for patients with extensive colorectal liver metastases, but outcomes in HCC have not been well investigated. METHODS: All patients registered in the international ALPPS Registry ( www.alpps.org ) from 2010 to 2015 were studied. Hypertrophy of the future liver remnant, perioperative morbidity and mortality, age, overall survival, and other parameters were compared between patients with HCC and patients with colorectal liver metastases (CRLM). RESULTS: The study compared 35 patients with HCC and 225 patients with CRLM. The majority of patients undergoing ALPPS for HCC fall into the intermediate-stage category of the Barcelona clinic algorithm. In this study, hypertrophy was rapid and extensive for the HCC patients, albeit lower than for the CRLM patients (47 vs. 76 %; p < 0.002). Hypertrophy showed a linear negative correlation with the degrees of fibrosis. The 90-day mortality for ALPPS used to treat HCC was almost fivefold higher than for CRLM (31 vs. 7 %; p < 0.001). Multivariate analysis showed that patients older than 61 years had a significantly reduced overall survival (p < 0.004). CONCLUSION: The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

Unaltered graft survival and intragraft lymphocytes infiltration in the cardiac allograft of Cxcr3-/- mouse recipients.

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3(-/-) mice. Interestingly, in our hands, neither of the independently derived Cxcr3(-/-) lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-gamma production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3(-/-) recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.

Hand-assisted laparoscopic colorectal surgery (HALS) at a community hospital: a prospective analysis of 104 consecutive cases.

BACKGROUND: We report 104 consecutive cases of hand-assisted laparoscopic (HAL) colectomy over 5 years performed by a single surgeon. METHODS: Data were gathered prospectively and include patient demographic data, diagnosis, operating time, conversion rate, length of hospital stay, and complications. Virtually all patients presenting for elective resection with benign disease and metastatic cancer were treated using HAL techniques. RESULTS: The mean age was 61 years; 48% of patients had diverticulitis; 21%, colorectal cancer; 18%, benign polyps. In addition, 55% of patients underwent sigmoid or left colectomy; 27%; right hemicolectomy; 9%, low anterior resection, and two double resections were performed. Mean operating room time was 135 minutes; in 12% of the patients conversion to open surgery became necessary, in most cases requiring only a small extension of the HAL incision. Mean and median discharge was postoperative day 4 and postoperative day 3, respectively. There was 1 death (1%) and 21% of patients had complications, 12% of them major. CONCLUSIONS: Hand-assisted laparotomy colectomy is a safe and effective procedure. The data in terms of length of hospital stay and operative time compare favorably with published data for conventional laparoscopic (CL) colectomy. Although further study is necessary, it appears that HALS confers all of the advantages of CL for colectomy, with no obvious drawbacks.

[Adrenal adenomatoid tumor. A rare clinicopathological entity]. / Adenomatoider Tumor der Nebenniere. Eine seltene Differenzialdiagnose des Nebennierentumors.

Adenomatoid tumors are uncommon, benign tumors of the genital tract which have also been reported to occur extragenitally. Case reports on adenomatoid tumors of the adrenal gland exist. Most of these are incidentally discovered at autopsy or after the resection of incidentalomas. We report on the case of a young man with epigastic pain and with the finding of a 4 cm heterogeneous right adrenal mass on abdominal CT scan. After endocrine activity had been ruled out, an inactive, benign adrenal tumor was suspected and laparoscopic right adrenalectomy performed. The specimen was found to be an adenomatoid tumor. We discuss the differential diagnosis and the possible embryological origin of these tumors. The feature of 'local invasive ability' does not imply malignancy. All cases discovered surgically and at autopsy have been benign. Local resection seems to be the appropriate therapy.

Salvage parenchymal liver transection for patients with insufficient volume increase after portal vein occlusion -- an extension of the ALPPS approach.

BACKGROUND: Portal vein ligation (PVL) or embolization (PVE) are standard approaches to induce liver hypertrophy of the future liver remnant (FLR) prior to hepatectomy in primarily non-resectable liver tumors. However, this approach fails in about one third of patients. Recently, the new "ALPPS" approach has been described that combines PVL with parenchymal transection to induce rapid liver hypertrophy. This series explores whether isolated parenchymal transection boosts liver hypertrophy in scenarios of failed PVL/PVE. METHODS: A multicenter database with 170 patients undergoing portal vein manipulation to increase the size of the FLR was screened for patients undergoing isolated parenchymal transection as a salvage procedure. Three patients who underwent PVL/PVE with subsequent insufficient volume gain and subsequently underwent parenchymal liver transection as a salvage procedure were identified. Patient characteristics, volume increase, postoperative complications and outcomes were analyzed. RESULTS: The first patient underwent liver transection 16 weeks after failed PVL with a standardized FLR (sFLR) of 30%, which increased to 47% in 7 days. The second patient showed a sFLR of 25% 28 weeks after PVL and subsequent PVE of segment IV, which increased to 41% in 7 days after transection. The third patient underwent liver partition 8 weeks after PVE with a sFLR of 19%, which increased to 37% in six days. All patients underwent a R0 resection. CONCLUSION: Failed PVE or PVL appears to represent a good indication for the isolated parenchymal liver transection according to the newly developed ALPPS approach.

The clinical importance of flow cytometry crossmatch in the context of CDC crossmatch results.

BACKGROUND: The complement-dependent microcytotoxicity crossmatch (CDCXM) is a standard method for evaluating the presence of preformed antibodies before transplantation. The flow cytometry crossmatch (FCXM) is more sensitive, but there is controversy regarding translation of its increased sensitivity to clinically relevant graft outcomes. METHODS: We analyzed Organ Procurement and Transplant Network registry data for living and deceased donor kidney transplants performed in 1995 to 2009 after both CDCXM and FCXM testing. Transplants with negative CDCXM (CDCXM(-)) and with T-cell positive (T(+)), T-cell negative/B-cell positive (T(-)B(+)), or T- and B-cell negative (T(-)B(-)) FCXM results were included. Graft survival according to crossmatch results was compared by survival analysis. RESULTS: Among patients transplanted with negative CDCXM (CDCXM(-)), deceased and living donor graft recipients with T(+) FXCM experienced significant absolute reductions in 5-year graft survival of 11.5% and 8.8% compared to those with T(-) FCXM (P < .0001). Compared to patients with FCXM(-)/CDCXM(-) deceased and living donor recipients with T(-)B(+) FCXM/CDCXM(-) had absolute reductions in 5-year graft survival of 9.6% and 7.6%, respectively (P < .0001). Upon multivariate adjustment with Cox regression, T(+) FCXM/CDCXM(-) deceased donor transplantation was associated with 51% higher adjusted relative risk of 1-year graft loss than FCXM(-)/CDCXM(-). Relative risks were more marked at 1 year for the T(+) groups but stronger in the 1- to 5-year interval for the T(-)B(+) groups. CONCLUSION: Positive FCXM has important prognostic implications even when CDCXM is negative. Thus, positive FCXM should not routinely be dismissed as "overly sensitive" when CDCXM is negative.

[Duodenosigmoidal fistula in a patient with Crohn's disease]. / Duodenosigmoidale Fistel bei Morbus Crohn.

The development of enteral fistulas - internal and external - is common in Crohn's disease with a frequency of about 45 % in large series of patients. Most internal fistulas arise in the small bowel, but internal large bowel fistulas occur in about one fourth of all patients with fistulas in Crohn's disease. Colonic gastroduodenal fistulas do occur, but are very rare. Of the 35 cases of colonic-duodenal fistulas that we found in the literature, most have been described to involve either a previous ileocolostomy site or the ascending or transverse colon. There are only three cases displaying sigmoidoduodenal fistulas. To these we add a fourth case with this report. A 42-year-old woman presented with upper abdominal pain, loss of appetite and regurgitations with a foul smell as well as abdominal gas complaints. A duodenosigmoidal fistula was diagnosed by local application of contrast and the fistula tract was excised in typical fashion by resection of the colonic fistula and primary closure of the duodenum. The patient experienced a good recovery with relief of symptoms.

Expression of chemokines and their receptors in nephrotoxic serum nephritis.

BACKGROUND: Chemokines play a major role in leukocyte infiltration in inflammatory kidney diseases. The specificity of the chemokine action is determined by the restricted expression of the corresponding receptors on leukocytes. We therefore simultaneously studied the expression of CC-chemokine and CC-chemokine receptor 1-5 (CCR 1-5) mRNA in an accelerated model of nephrotoxic nephritis in CD-1 mice. METHODS: Kidneys were harvested at day 0, 2 and 7. Induction of nephritis was confirmed by assessment of albuminuria by ELISA and by histological evaluation. RNA was prepared from cortex and isolated glomeruli. RNase protection assays were performed to study the expression of chemokines, RNase protection assays as well as quantitative RT-PCR assays to study the expression of chemokine receptors. RESULTS: In the cortex of nephritic kidneys mRNA for MCP-1 was increased 5-fold on day 2 and increased 4-fold on day 7 as compared to controls. mRNA for RANTES was increased 5-fold on day 7 and mRNA for IP-10 6-fold on day 7. The increase of mRNA for the chemokine receptors CCR1 and 5 was between 2-fold and 3-fold determined by RNase protection assay and for CCR1, 2 and 5 between 2- and 4-fold as determined by RT-PCR. In isolated glomeruli we found by RT-PCR an increase of CCR1, CCR2 and CCR5 of between 3 and 12-fold. CONCLUSION: These results show that chemokines and their specific chemokine receptors are increased in parallel in this model of glomerulonephritis, consistent with the potential role of the chemokine system in leukocyte recruitment to the immune injured kidney.

Chemokine and chemokine receptor expression in a novel human mesangial cell line.

Chemokines are thought to play a pivotal role in mediating the selective migration of leukocytes into sites of tissue injury. The local production of chemokines by mesangial cells (MC) has been linked to inflammatory processes within the glomerulus. To study the chemokine biology of human MC, an immortalized human MC line was generated and then chemokine and chemokine receptor expression was examined in response to various proinflammatory stimuli. The results show that human MC have a specific and limited repertoire of chemokine expression. The stimulus-specific regulation of the chemokines monocyte chemoattractant protein- (MCP- 1), regulated upon activation, normal T cell expressed and secreted (RANTES), interleukin-8 (IL-8), and IP-10 was demonstrated using RNase protection assays. Transcripts for the chemokines MIP-1alpha, MIP-1beta, I-309, or lymphotactin could not be detected. The expression of CC chemokine receptors was investigated by reverse transcription-PCR and RNase protection assays. MC stimulated with interferon-gamma (IFN-gamma) expressed mRNA for the chemokine receptor CCR1. The expression could be further increased by activating the cells with a combination of tumor necrosis factor-a (TNF-alpha), IL-1beta, and IFN-gamma. Under these conditions, no mRNA for CCR2, CCR3, CCR4, CCR5, or CCR8 was detected. A comparison of the immortalized human mesangial cells with primary cells showed identical expression patterns of chemokine receptors. To demonstrate functional activity of chemokine receptors expressed by human MC, chemotaxis assays were performed. MC stimulated with a combination of TNF-alpha, IL-1beta, and IFN-gamma, but not unstimulated MC, migrated toward a RANTES gradient. Eotaxin did not enhance the migratory activity of human MC. In summary, a novel human mesangial cell line was established and the pattern of chemokine expression was examined. For the first time, the inducible expression of functionally active CCR1 by human MC was shown.