Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

PURPOSE: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy. METHODS: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses. RESULTS: Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown. CONCLUSION: This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.

Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria.

BACKGROUND: Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. METHODS: Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39-91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). RESULTS: PFS after 24 months was 71% (95% CI: 56-87), and overall survival (OS) was 74% (95% CI: 60-88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39-86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66-98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). CONCLUSION: Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

Liver resection and transplantation in Caroli disease and syndrome.

INTRODUCTION: Caroli disease (CD) is a congenital dilatation of the intrahepatic bile ducts. In combination with liver fibrosis or cirrhosis, it is called Caroli syndrome (CS). Infectious complications and intrahepatic cholangiocarcinoma are secondary problems. The aim of this study was to analyse the clinical pattern and outcome in patients with CD/CS who underwent liver surgery. METHODS: Between January 2004 and December 2016, 21 patients with CD/CS were treated with liver resection or transplantation (LTX) and post-operative data of patients with CD/CS were retrospectively analysed in a database. RESULTS: Two patients underwent LTX, and 19 patients underwent liver resection due to CD/CS. During follow-up, one patient developed lung cancer nine years after LTX. Patients resected due to CD/CS were predominantly females (74%) with an overall low incidence of co-morbidities. The median post-operative Clavien-Dindo score was 1 (range: 0-3). There was no death during a median follow-up period of over five years. In four patients, cholangiocarcinoma was confirmed. Tumor recurrence was seen in three patients, and was treated with chemotherapy or repeated liver resection. CONCLUSIONS: LTX and liver resections due to CD/CS are rare and associated with an acceptable post-operative morbidity and low mortality. Surgical treatment should be performed as early as possible to avoid recurrent episodes of cholangitis or carcinogenesis.

The thalamic reticular nucleus in schizophrenia and bipolar disorder: role of parvalbumin-expressing neuron networks and oxidative stress.

Growing evidence points to a disruption of cortico-thalamo-cortical circuits in schizophrenia (SZ) and bipolar disorder (BD). Clues for a specific involvement of the thalamic reticular nucleus (TRN) come from its unique neuronal characteristics and neural connectivity, allowing it to shape the thalamo-cortical information flow. A direct involvement of the TRN in SZ and BD has not been tested thus far. We used a combination of human postmortem and rodent studies to test the hypothesis that neurons expressing parvalbumin (PV neurons), a main TRN neuronal population, and associated Wisteria floribunda agglutinin-labeled perineuronal nets (WFA/PNNs) are altered in SZ and BD, and that these changes may occur early in the course of the disease as a consequence of oxidative stress. In both disease groups, marked decreases of PV neurons (immunoreactive for PV) and WFA/PNNs were observed in the TRN, with no effects of duration of illness or age at onset. Similarly, in transgenic mice with redox dysregulation, numbers of PV neurons and WFA/PNN+PV neurons were decreased in transgenic compared with wild-type mice; these changes were present at postnatal day (P) 20 for PV neurons and P40 for WFA/PNN+PV neurons, accompanied by alterations of their firing properties. These results show profound abnormalities of PV neurons in the TRN of subjects with SZ and BD, and offer support for the hypothesis that oxidative stress may play a key role in impacting TRN PV neurons at early stages of these disorders. We put forth that these TRN abnormalities may contribute to disruptions of sleep spindles, focused attention and emotion processing in these disorders.