Malignant cell growth is fueled by interactions between tumor cells and the stromal cells composing the tumor microenvironment. The human liver is a major site of tumors and metastases, but molecular ...identities and intercellular interactions of different cell types have not been resolved in these pathologies. Here, we apply single cell RNA‐sequencing and spatial analysis of malignant and adjacent non‐malignant liver tissues from five patients with cholangiocarcinoma or liver metastases. We find that stromal cells exhibit recurring, patient‐independent expression programs, and reconstruct a ligand–receptor map that highlights recurring tumor–stroma interactions. By combining transcriptomics of laser‐capture microdissected regions, we reconstruct a zonation atlas of hepatocytes in the non‐malignant sites and characterize the spatial distribution of each cell type across the tumor microenvironment. Our analysis provides a resource for understanding human liver malignancies and may expose potential points of interventions.
SYNOPSIS
Single cell transcriptomics and spatial methods are used to generate a cell atlas of the human liver tumor microenvironment, exposing recurring tumor‐stroma interactions and zonation patterns in the healthy and malignant tissue.
A single cell atlas of the malignant and adjacent non‐malignant human liver is presented.
Recurring stromal cell gene expression signatures are found in liver metastases and cholangiocarcinomas.
Tumor and stromal cells communicate through a conserved ligand‐receptor interaction network.
Spatial transcriptomics reveal zonated expression patterns in the malignant and non‐malignant liver.
Single cell transcriptomics and spatial methods are used to generate a cell atlas of the human liver tumor microenvironment, exposing recurring tumor‐stroma interactions and zonation patterns in the healthy and malignant tissue.
As a result of increased life expectancy and a growing incidence of liver disease in the older population, demand for liver transplantation during later stages of life will continue to increase. ...Older patients (aged >70 years) can benefit from deceased donor liver transplantation (DDLT) with similar graft and patient survival as younger DDLT recipients 1.
Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. ...Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. Although the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). However, LT is not curative and only bone marrow transplantation (BMT) can correct the underlying enzymatic defect. Because liver disease results from accumulation of protoporphyrin in the liver, LT without hematopoietic stem cell transplantation leaves the new liver at risk for similar EPP‐related damage. A handful of pediatric patients undergoing sequential LT and stem cell transplantation have been described in the literature; however, to date none has been described in detail in adults. We report a case of an adult male with EPP and liver failure who successfully underwent a sequential liver and hematopoietic stem cell transplantation (HSCT).
This case report describes sequential liver and hematopoietic stem cell transplantation in an adult with liver failure and severe erythropoietic protoporphyria.
BACKGROUNDLiver transplantation (LT) is the treatment of choice for most end-stage liver diseases. This treatment increases survival rates and improves quality of life. Because of the shortage of ...organ donors, as opposed to waiting patients, the need to optimize the matching of donors to recipients for maximum utility is crucial.
AIMThe aim of this study was to examine a predictive model based on the combination of donor and recipient risk factors using the liver Donor Risk Index (DRI) and recipient Model of End-stage Liver Disease (MELD) to predict patients’ survival following LT.
PATIENTS AND METHODSThe charts of 289 adult primary LT patients, who had undergone transplantation in Israel between 2010 and 2015, were studied retrospectively using prospectively gathered data.
RESULTSTwo variables, DRI and MELD, were found to significantly affect post-transplant patient survival. DRI negatively affected survival in a continuous fashion, whereas MELD had a significantly negative effect only at MELD more than 30. Both female sex and the presence of hepatocellular carcinoma were associated with increased patient survival.
CONCLUSIONAccording to our findings, the model described here is a novel prediction tool for the success of orthotopic LT and can thus be considered in liver allocation.
Background. The prevalence of obesity is rising in the general population. Donor obesity (body mass index ≥30 kg/m 2 ) may potentially reduce the donor pool and impact outcomes in living donor liver ...transplantation (LDLT). Methods. We utilized the national transplant database to investigate the impact of donor obesity on donor and recipient outcomes. This was a retrospective cohort study of all LDLTs performed in the United States between January 2010 and June 2023. Outcomes of interest were analyzed by univariable and multivariable logistic regression. Patient and graft survival was evaluated using Kaplan-Meier and Cox proportional analysis. Results. Six hundred seventy-four donors with obesity and 3498 donors without obesity were analyzed. Donors with obesity had higher rates of readmission within 1 y of donation (15.9% versus 11.6%; P = 0.003). The risk of readmission was significantly different between 6 wk and 6 mo of donation (8.8% versus 5.9%; P = 0.036). Donor body mass index (odds ratio OR, 1.460; 95% confidence interval CI, 1.129-1.999; P = 0.004) and preoperative alkaline phosphatase levels (OR, 1.005; 95% CI, 1.000-1.011; P = 0.038) were independent predictors of donor readmission. High LDLT center volume was associated with reduced odds of donor readmission (OR, 0.509; 95% CI, 0.373-0.694; P < 0.001). Graft and recipient survival was comparable. Conclusions. Selection of living donors with obesity may be a potential avenue to increase the available donor pool without compromising recipient outcomes; however, they are at an increased risk for readmission between 6 wk and 6 mo of donation. The reason for readmission requires further study.
Background
Current guidelines include the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to ...examine whether oxaliplatin confers survival benefit in this patient population.
Methods
Using the National Cancer Database (2006–2013) we identified 6,868 individuals with clinical stage II or III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. We used multivariate Cox regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage.
Results
We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (hazard ratio HR, 0.78; 95% confidence interval CI, 0.67–0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III disease (HR, 0.69; 95% CI, 0.57–0.83) and was not observed in patients who progressed from clinical stage II to pathological stage III disease. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0 or I disease, regardless of their clinical stage.
Conclusion
Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease.
Implications for Practice
Current guidelines include the use of oxaliplatin as part of adjuvant chemotherapy (AC) in patients with clinical stage II or III rectal adenocarcinoma (RAC). However, its efficacy is supported only by a single phase II trial. This study found an association with improved overall survival with the use of doublet AC in patients diagnosed with clinical stage III and subsequent pathological stage III, and not in patients with pathological stage 0 or I, regardless of their clinical stage. Therefore, omission of oxaliplatin can be considered in patients with either pathological complete response or pathological stage I RAC, thereby avoiding oxaliplatin‐induced neuropathy.
摘要
背景。目前的指南包括在临床 II 或 III 期直肠腺癌中使用奥沙利铂辅助化疗。然而，他的疗效仅由单臂 II 期试验支持。我们的目的是检验奥沙利铂是否对该患者群体的生存有益。
方法。通过国家癌症数据库(2006 ‐ 2013 年)，我们确定了 6 868 名经过新辅助放化疗、手术和辅助化疗治疗的临床 II 期或 III 期直肠腺癌患者。我们使用多变量 Cox 回归分析根据治疗强度和从临床到病理分期的改变来评估的生存期差异。
结果。我们证实了在病理 III 期直肠腺癌中使用双联辅助化疗与总生存率得到改善之间存在关联 风险比 (HR)，0.78；95% 置信区间 (CI)，0.67‐0.92。这种关联在临床 III 期和随后的病理 III 期疾病(HR，0.69；95% CI，0.57‐0.83)的患者中得到证实，且并未在从临床 II 期进展至病理 III 期疾病的患者中观察到。无论临床分期如何，双联辅助化疗与病理 0 期或 I 期患者的总体生存率改善均无关。
结论。在临床 III 期和随后的病理 III 期疾病患者中确认了直肠腺癌新辅助放化疗后进行奥沙利铂辅助化疗。在病理性完全缓解或病理性 I 期疾病中可考虑省掉奥沙利铂辅助化疗。
实践意义:目前的指南包括在临床 II 期或 III 期直肠腺癌 (RAC) 患者中使用奥沙利铂作为辅助化疗 (AC) 的一部分。然而，其功效仅由单臂 II 期试验支持。本研究发现，无论其临床分期如何，在被诊断为临床 III 期和随后的病理 III 期的患者中，而不是在病理 0 期或 I 期的患者中，使用双联 AC 与总生存率得到改善存在关联。因此，在病理性完全缓解或病理 I 期 RAC 的患者中可以考虑省掉奥沙利铂，从而避免奥沙利铂诱发的神经病变。
This article reports on results of a study that examined overall survival differences according to chemotherapy intensity (doublet vs. monotherapy) in patients with clinical stage II or III rectal adenocarcinoma who were treated with neoadjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy.
Many obstacles may complicate renal transplant, the preferred treatment for end-stage renal disease. Anatomic anomalies are of special importance during surgery. Double inferior vena cava is a rare ...anomaly reported in 0.2% to 3% of the population and may complicate renal transplant in certain cases. We present a case of a 29-year-old man with end-stage renal disease who was scheduled for repeat kidney renal transplant from a living related donor. His transplant posed many challenges to the transplant team. These included (1) difficult access for dialysis, which required transhepatic insertion of a dialysis catheter, (2) anomalous inferior vena cava anatomy with a double inferior vena cava, (3) a blocked right inferior vena cava, and (4) a small blocked bridging vein connecting the right inferior vena cava to an additional left inferior vena cava. A stent was inserted into the bridging vein to allow venous drainage from the graft. During the transplant procedure, the donated kidney was transplanted into the left iliac fossa and anastomosed to the left external iliac vein. The surgery was successful, without major operative or postoperative complications. The patient was discharged with normal renal function and enjoys normal renal function 6 months after surgery. This case emphasizes the importance of pretransplant evaluation and preparation and the need for high index of suspicion for anatomic variants in donors and recipients.
The most common bariatric operation in Europe, laparoscopic adjustable gastric banding (LAGB), is reported to have a high incidence of long-term complications. Also, insufficient weight loss is ...reported. The optimal conversion technique is unknown. Our objective was to report our experience in the conversions of failed laparoscopic gastric banding procedures to 4 different bariatric procedures at a university hospital.
From March 2006 to December 2010, 630 bariatric operations were performed. Of these patients, 45 underwent conversion of failed LAGB (n = 38) and nonadjustable gastric banding (n = 7). Using a prospectively collected database, we analyzed these procedures.
The 45 patients underwent laparoscopic conversion of failed LAGB (n = 38) and nonadjustable gastric banding (n = 7) to 4 different procedures. Of the 45 patients, 18 underwent conversion to laparoscopic sleeve gastrectomy, 18 to laparoscopic Roux-en-Y gastric bypass, 7 to laparoscopic biliopancreatic diversion with duodenal switch, and 2 to laparoscopic biliopancreatic diversion. All conversions but 1 were completed laparoscopically. The mean operating time and hospital stay for laparoscopic sleeve gastrectomy, laparoscopic Roux-en-Y gastric bypass, laparoscopic biliopancreatic diversion with duodenal switch, and biliopancreatic diversion was 111 ± 28 minutes and 4.3 ± 1.4 days, 195 ± 59 minutes and 3.9 ± 1.5 days, 248 ± 113 minutes, and 5.9 ± 2.6 days, and 203 minutes and 6.5 days, respectively. No patient died. Perioperative complications occurred in 4 patients (9.8%). The mean body mass index decreased from 41.5 ± 8 kg/m(2) to 31.3 ± 6.8 kg/m(2) during a mean follow-up period of 13.7 ± 9.6 months. Although laparoscopic biliopancreatic diversion with and without duodenal switch had the greatest preoperative body mass index, they achieved the greatest excess weight loss.
Conversion of LAGB or nonadjustable gastric banding to laparoscopic sleeve gastrectomy, laparoscopic Roux-en-Y gastric bypass, and laparoscopic biliopancreatic diversion with or without duodenal switch is feasible and effective to treat the complications of LAGB and to further reduce the weight of morbidly obese patients.
The Silastic ring vertical gastroplasty (SRVG), a modification of Mason's vertical banded gastroplasty (VBG), was the restrictive procedure of choice for many bariatric surgeons. The reoperation rate ...for failure/complications reported in long-term studies is approximately 50%.
We report our experience in laparoscopic conversion of failed SRVG to Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD).
A single surgeon's experience at a university-affiliated hospital.
Between March 2006 and April 2014, 39 patients underwent conversion of SRVG to laparoscopic RYGB (n = 25) or BPD (n = 14). The outcomes were retrieved from a prospectively collected database and analyzed.
Most (89%) of the conversions were completed laparoscopically. The mean operative time was 195 and 200 min for RYGB and BPD, respectively. There was no mortality. Complications occurred in 11 patients (28%), 5 in RYGB (19%) and 6 in BPD (42%). At the 3-year follow-up, the mean body mass index decreased from 47±8 kg/m(2) to 26±4 kg/m(2) for BPD, and from 43 kg/m(2) to 34 kg/m(2) (P = .05) for RYGB. Weight (kg) decreased from 110 to 84 and to 92, and from 123 to 81 and 68, at 1 and 3 years for RYGB and BPD, respectively.
The weight loss for RYGB and BPD was equal at 1 year but tended to be better for BPD at 3 years postoperatively. Laparoscopic conversion of failed VBG to RYGB or BPD was feasible, but it was followed by prohibitively high complication rates in BPD patients. The risk:benefit ratio of these procedures in this series is questionable.
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