Recurrent Liver Research Articles

Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.

Among genetic disorders of vesicular trafficking, there are three causing recurrent acute liver failure (RALF): NBAS, RINT1, and SCYL1-associated disease. These three disorders are characterized by liver crises triggered by febrile infections and account for a relevant proportion of RALF causes. While the frequency and severity of liver crises in NBAS and RINT1-associated disease decrease with age, patients with SCYL1 variants present with a progressive, cholestatic course. In all three diseases, there is a multisystemic, partially overlapping phenotype with variable expression, including liver, skeletal, and nervous systems, all organ systems with high secretory activity. There are no specific biomarkers for these diseases, and whole exome sequencing should be performed in patients with RALF of unknown etiology. NBAS, SCYL1, and RINT1 are involved in antegrade and retrograde vesicular trafficking. Pathomechanisms remain unclarified, but there is evidence of a decrease in concentration and stability of the protein primarily affected by the respective gene defect and its interaction partners, potentially causing impairment of vesicular transport. The impairment of protein secretion by compromised antegrade transport provides a possible explanation for different organ manifestations such as bone alteration due to lack of collagens or diabetes mellitus when insulin secretion is affected. Dysfunction of retrograde transport impairs membrane recycling and autophagy. The impairment of vesicular trafficking results in increased endoplasmic reticulum stress, which, in hepatocytes, can progress to hepatocytolysis. While there is no curative therapy, an early and consequent implementation of an emergency protocol seems crucial for optimal therapeutic management.

Intrahepatic cholangiocarcinoma: Recurrence patterns, genomics and survival.

570 Background: Recurrence is common after resection of intrahepatic cholangiocarcinoma (IHC) but how recurrence patterns impact survival remains unclear. This study investigated the clinicopathologic and genomic factors associated with site of first recurrence and their impact on outcome after curative intent resection. Methods: Patients who underwent curative intent hepatectomy for IHC at two medical centers (MSKCC and EMC) with complete follow up and tumor genomic data were included. Documented sites of first disease recurrence were classified as liver only (LO), extrahepatic (EH) only or simultaneous liver and extrahepatic (SIM). Time to recurrence (TTR) and recurrence-free (RFS) were calculated from time of resection while OS was calculated from time of recurrence. Primary tumors underwent targeted next generation sequencing. Clinical, histopathologic and genomic factors associated with site(s) of recurrence, RFS and OS were assessed. Results: A total of 318 patients (n=296 MSK, n=22 EMC) treated between 1993 and 2021 met inclusion criteria and were analyzed; 232 patients (73%) developed recurrence. TTR was 11 (9.8, 12) months; OS and RFS was 26 (20, 33) and 14 (13, 18) months, respectively, among patients that recurred. Sites of first recurrence were LO 93 (40%), EH 80 (34%) and SIM 59 (26%). Median OS was similar in the LO (33 [26,42] months) and EH groups (33 [23,46] months) but much lower in SIM (12 [9.8,18] months) (p < 0.001). Moderate/poor tumor differentiation (p = 0.004), LVI (p = 0.004), N1 disease (p = 0.003), and PNI (p = 0.012) were associated with SIM; only positive resection margin predicted LO (p = 0.007). No individual genomic or pathway alterations predicted site of initial recurrence; however, for all patients, TP53 mut (HR 2.01, 1.4-2.9; p < 0.001), CDKN2A del (HR 1.96, 1.29-2.98; p = 0.003), CDKN2B del (HR 3.2, 2.03-5.05; p < 0.001) and KRAS mut (HR 2.49, 1.56-3.96; p < 0.001) were associated with worse survival. On multivariable analysis, SIM (HR 2.23, 1.49-3.34; p < 0.001), clinical stage III (HR 1.94, 1.26-2.99; p = 0.011), and alterations in TP53 (HR 2.07, 1.4-3.07; p < 0.001), CDKN2B (HR 4.1, 2.53-6.63; p < 0.001) and KRAS (HR 2.72, 1.68-4.43; p < 0.001) were independent predictors of worse OS. Of note, 13 LO patients were treated with regional chemotherapy after recurrence, with an associated median OS of 49 (33, NR) months compared to 28 (20, 39) months in the 80 patients treated with systemic therapy alone. Conclusions: Recurrence after resection of IHC was common, and the liver was the single most common site (66%). Clinicopathologic and genomic variables had limited ability to predict site of first recurrence. While LO and EH were associated with similar OS, simultaneous recurrences were dramatically worse. The data support adjuvant strategies targeting liver recurrence to improve outcome after resection of IHC.

Liver toxicity following reirradiation and multiple-target SBRT for primary hepatocellular carcinoma.

514 Background: Stereotactic body radiation therapy (SBRT) is increasingly used to treat hepatocellular carcinoma (HCC), but its safety in the treatment of multiple synchronous or recurrent lesions is underreported. We aim to better characterize SBRT-related hepatic toxicity in this population. Methods: We conducted a retrospective analysis of patients with primary HCC who underwent SBRT for 2 or more synchronous or recurrent liver lesions. We collected patient characteristics and dosimetric data (mean liver dose, cumulative effective volume [Veff], cumulative volume of liver receiving 15Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). We employed a linear mixed-effects model to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions and 14 had recurrent lesions treated with separate SBRT courses. Eight local failures occurred at a median of 8 months (range: 4 – 25 months) after SBRT. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35mL, range: 0.5 – 388mL). There was no association between cumulative Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients an increase of Child-Pugh (CP) score by ≥ 2 points, within 3 to 6 months after SBRT. Neither increase in CP nor ALBI were associated with cumulative Veff, V15Gy, and PTV. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusions: LiverSBRT for multiple lesions in a single or in separate courses results in worsening of CP scores or ALBI in a small percentage of patients, suggesting a low risk of RILD. Prospective studies with a larger cohort are needed to better characterize safety in this population.

Predictors for early recurrence beyond up-to-7 or distant metastasis after hepatocellular carcinoma resection: proposal for borderline resectable HCC.

The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5years and early recurrence (within 1year) is now recognized as having a poor prognosis and has limited treatment options. We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes. Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis. In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.

Redo surgery for recurrent colorectal liver metastasis: does the robot extend the boundaries of minimally invasive surgery?

Redo surgery for recurrent colorectal liver metastasis: does the robot extend the boundaries of minimally invasive surgery?

Recurrent bacterial abscess of the left liver lobe caused by a foreign body (fish bone)

The authors present minimally invasive surgical treatment of recurrent liver abscess caused by migration of fish bone from the upper gastrointestinal tract. Two-stage treatment implied small-caliber transparietal drainage of abscess with evacuation of purulent detritus at the first stage. At the second stage, primary percutaneous approach was transformed into access of sufficient diameter for flexible or rigid optics for visually controlled bone extraction. Foreign body removal through the drainage tube with endoscopic capture under visual control is preferable regarding safety compared to removal under ultrasound and/or X-ray control. Indeed, endoscopic approach is valuable for optimal positioning of the object and prevention of damage to liver parenchyma during extraction.

CT-based radiomics analysis to predict local progression of recurrent colorectal liver metastases after microwave ablation

The objective of this study is to establish and validate a radiomics nomogram for prediction of local tumor progression (LTP) after microwave ablation (MWA) for recurrent colorectal liver metastases (CRLM) after hepatic resection. We included 318 consecutive recurrent CRLM patients (216 of training while 102 of validation cohort) with contrast-enhanced computerized tomography images treated with MWA between January 2014 and October 2018. Support vector machine-generated radiomics signature was incorporated together with clinical information to establish a radiomics nomogram. Our constructed radiomics signature including 15 features (first-order intensity statistics features, shape and size-based features, gray level size zone/dependence matrix features) performed well in assessing LTP for both cohorts. With regard to its predictive performance, its C-index was 0.912, compared to the clinical or radiomics models only (c-statistic 0.89 and 0.75, respectively) in the training cohort. In the validation cohort, the radiomics nomogram had better performance (area under the curve = 0.89) compared to the radiomics and clinical models (0.85 and 0.69). According to decision curve analysis, our as-constructed radiomics nomogram showed high clinical utility. As revealed by survival analysis, LTP showed worse progression-free survival (3-year progression-free survival 42.6% vs 78.4%, P < .01). High-risk patients identified using this radiomics signature exhibited worse LTP compared with low-risk patients (3-year LTP 80.2% vs 48.6%, P < .01). A radiomics-based nomogram of pre-ablation computerized tomography imaging may be the precious biomarker model for predicting LTP and personalized risk stratification for recurrent CRLM after hepatic resection treated by MWA.

Local Therapy Improves Survival for Early Recurrence After Resection of Colorectal Liver Metastases.

Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate whether local therapy benefits patients with early recurrence following hepatectomy for CLM. Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001-12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival [RFS] < 6months), intermediate (RFS 6-12months), and later (RFS > 12months). Local therapy was defined as ablation, resection, or radiation. Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32months, intermediate 72 vs. 39months, later 132 vs. 65months, all p < 0.001). Following recurrence, treatment with local therapy (hazard ratio [HR] = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all p ≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all p ≤ 0.04). While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.

Manganese-based microcrystals equipped with Ythdf1-targeted biomimetic nanovaccines for reinforced dendritic cell spatiotemporal orchestration

Undesired dendritic cell (DC) spatiotemporal orchestration and innate immune stimulation severely dampens anti-tumor efficacy of cancer vaccines. Here, we develop a manganese-based (Mn2+) metal-organic framework (MOF) microcrystal equipped with Ythdf1-targeted biomimetic nanovaccines to create an in situ proinflammatory immune niche for augmented DC spatiotemporal orchestration. The bimetallic MOF microcrystal serves as a self-adjuvanting delivery platform that cannot only gradually release tumor-associated antigens and Mn2+, but also create an in situ immune niche for DC spatiotemporal orchestration including recruitment (particularly for DC1s, cross-presenting antigens to CD8+ T cells), activation, and lymph node migration. Benefitting from the Mn2+-mediated cGAS-STING activation together with Ythdf1 downregulation-induced antigen cross-presentation reinforcement, the vaccines elicit robust prophylactic efficacy for delaying B16-OVA and MC38 tumor occurrence, and show potent therapeutic efficacy for suppressing postoperative MC38 tumor recurrence and metachronous liver metastasis. Our study provides a versatile and powerful approach for fabricating personalized scaffold cancer vaccines.

ОСОБЕННОСТИ ДИАГНОСТИКИ И ХИРУРГИЧЕСКОГО ЛЕЧЕНИЯ РЕЦИДИВ-НОГО ЭХИНОКОККОЗА ПЕЧЕНИ

The article presents the results of the use of immunological and instrumental diagnostic methods, as well as surgical treatment in 92 patients with recurrent liver echinococcosis. Postop-erative complications were detected in 15 (16.1%) patients, postoperative lethality was observed in 1 (1.07%) cases. As a result of the analysis of the study of immunological tests, it was shown that immunochemiluminescence (ICL) and enzyme immunoassay (ELISA) is a highly informa-tive test for the diagnosis of recurrent echinococcosis. The effectiveness of surgical treatment of recurrent echinococcosis is directly dependent on the choice of access, indications for various methods of operations, methods of disinfection and complete elimination of the residual cavity of the fibrous capsule

MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial

Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

The Recurrent Liver MAN2A1-FER Oncoprotein Lacks Kinase Activity: Implications for the Use of Tyrosine Kinase Inhibitors

The Recurrent Liver MAN2A1-FER Oncoprotein Lacks Kinase Activity: Implications for the Use of Tyrosine Kinase Inhibitors

Modern glucose-lowering drugs in liver transplant recipients: improvement in weight, glycemic control, and potentially allograft steatosis.

Recurrent allograft steatosis occurs in one-third of transplanted livers. Antidiabetic agents like glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type-2 (SGLT2) inhibitors are effective in the management of obesity and hepatic steatosis in the general population; however, there is limited evidence supporting their use in allograft steatosis. We aimed to evaluate their effects on steatosis, body weight, and glycemic control in liver transplant recipients at our institution. In this single-center retrospective cohort study of liver transplant recipients currently on a GLP1RA or SGLT2 inhibitor (transplanted 2015-2022), we compared clinical and radiological data before medication use and at follow-up. Differences were compared using Wilcoxon signed-rank test. Thirty-seven liver transplant recipients were taking the agents. Diabetes was the most common indication (n = 33) followed by obesity (n = 4). Median follow up was 427 days (301,798). Among those with documented steatosis (n = 21), steatosis improved in 5, worsened in 4, remained unchanged in 1, and change could not be evaluated in 11 due to lack of comparable pre and post imaging. Average weight loss was 3.2 kg (p < 0.001) and BMI decreased by 1.2 kg/m2 (p < 0.001). Hemoglobin A1c decreased by 0.6 mmol/mol (p = 0.0014), insulin requirement reduced by 7 units/day (p = 0.02), and there was no change in additional antidiabetic medications. GLP1RA and SGLT-2 inhibitors are tolerated in transplant patients and result in weight loss and better glycemic control. They are promising agents to treat recurrent or de-novo liver allograft steatosis, but further research is needed to evaluate long-term outcomes in liver transplant recipients.

Effect of different surgical approaches on the survival and safety of Siewert type II esophagogastric junction adenocarcinoma: a systematic review and meta-analysis

BackgroundWhether a transthoracic (TT) procedure by a thoracic surgeon or a transabdominal (TA) by a gastrointestinal surgeon is best for Siewert type II esophagogastric junction adenocarcinoma (EGJA) remains unknown. Survival and perioperative outcomes were compared between the two groups in this meta-analysis to clarify this argument.MethodsWe searched 7 databases for eligible studies comparing TT and TA procedures for Siewert type II EGJA. The final analyzed endpoints included intraoperative and hospitalization outcomes, recurrence, complication, and survival.ResultsSeventeen studies involving 10,756 patients met the inclusion criteria. The TA group had higher rates of overall survival (OS) (HR: 1.31 [1.20 ~ 1.44], p < 0.00001) and disease-free survival (DFS) (HR: 1.49 [1.24 ~ 1.79], p < 0.0001). The survival advantage of OSR and DFSR increased with time. Subgroup analysis of OS and DFS suggested that TA remained the preferred approach among all subgroups. More total/positive lymph nodes were retrieved, and fewer lymph node recurrences were found in the TA group. The analysis of perioperative outcomes revealed that the TA procedure was longer, had more intraoperative blood loss, and prolonged hospital stay. Similar R0 resection rates, as well as total recurrence, local recurrence, liver recurrence, peritoneal recurrence, lung recurrence, anastomosis recurrence and multiple recurrence rates, were found between the two groups. The safety analysis showed that the TT procedure led to more total complications, anastomotic leakages, cases of pneumonia, and cases of pleural effusion.ConclusionsThe TA procedure appeared to be a suitable choice for patients with Siewert type II EGJA because of its association with longer survival, fewer recurrences, and better safety.

Two cases of colorectal liver metastasis with residual liver recurrence after a long recurrence-free survival period

BackgroundThe rate of residual liver recurrence after the resection of colorectal liver metastases is high, and most cases recur within 5 years of the initial hepatectomy. Here, we report two cases of residual liver recurrence after radical resection of colorectal liver metastases after a long recurrence-free survival period.Case presentationCase 1 involved a 62-year-old woman treated for ascending colon cancer in April 2011 who underwent right hepatectomy for synchronous colorectal liver metastasis in April 2012. However, in September 2021, computed tomography revealed residual recurrence in the lateral segment of the liver, and a lateral segmentectomy of the liver was performed. In Case 2, a 52-year-old man treated for cecal cancer in July 2002 underwent lateral segmentectomy of the liver for metachronous colorectal liver metastasis in October 2006. Subsequently, there was no recurrence; however, computed tomography showed residual liver recurrence in the right lobe of the liver in October 2021, and an expanded posterior hepatic segmentectomy was performed.Histopathological findings in both cases were consistent with colorectal liver metastases.ConclusionsWe encountered two cases in which residual liver recurrence was observed after a long period of recurrence-free survival. Although rare, there have been a few cases of late recurrence of liver metastases after radical resection of cancer liver metastases.

HPB P06 The clinical and molecular landscape of early onset pancreatic cancer

Abstract Background The incidence of Pancreatic ductal adenocarcinoma (PC) is rising in the western world. There is a particularly concerning trend in the rapid increase in incidence of early onset PC (EOPC). The reason for this, and the implications of EOPC is not well understood. The aim of this study was to investigate the clinical outcomes of patients with EOPC and the molecular heterogeneity between EOPC and late onset disease. Methods Clinical, pathological and survival outcome data was obtained from 2 large independent prospective cohorts curated by the Australian Pancreatic Genome Initiative (APGI) and the West of Scotland pancreatic unit (Glasgow Royal Infirmary). Patients were categorised into 2 age groups, &amp;lt; 50 and &amp;gt;50 years at time of diagnosis. Clinicopathological and outcome data were compared between groups. Molecular data was obtained from the APGI’s contribution to the International Cancer Genome Consortium, this included transcriptomic, genomic and immunohistochemical data. Molecular subtypes, gene expression signatures, mutational signatures, and tumour microenvironment data was compared between groups. Results N=851 patients were identified and n=71 (8%) were &amp;lt; 50 years old. EOPC was associated with earlier recurrence (10.9 vs 14.2 months, P=0.011) and higher incidence of liver recurrence (50% vs 37%, P=0.031). There were no differences in validated clinicopathological variables. Despite an increased proportion of patients with EOPC receiving adjuvant chemotherapy (P=0.020), recurrence was earlier in those that completed &amp;gt; 3 cycles (12.6 vs 16.0 months, P=0.022). There is enrichment of the poor prognostic squamous (basal) subtype (42% vs 28%) in EOPC. There were no differences in the incidence of germline mutations to account for the early onset of disease. Conclusions EOPC appears to be increasing in incidence and is associated with earlier recurrence and more aggressive disease pattern. This appears to be associated with resistance to adjuvant chemotherapy and more aggressive, adverse molecular pathology. The onset of early disease cannot be explained by inherited genomic aberrations. Ongoing mutation signature, gene expression and microenvironmental data analysis will be presented upon acceptance of this abstract.

Recurrent Colorectal Liver Metastases: Upfront Local Treatment versus Neoadjuvant Systemic Therapy Followed by Local Treatment (COLLISION RELAPSE): Study Protocol of a Phase III Prospective Randomized Controlled Trial

PurposeThe objective of the COLLISION RELAPSE trial is to prove or disprove superiority of neoadjuvant systemic therapy followed by repeat local treatment (either thermal ablation and/or surgical resection), compared to repeat local treatment alone, in patients with at least one recurrent locally treatable CRLM within one year and no extrahepatic disease.MethodsA total of 360 patients will be included in this phase III, multicentre randomized controlled trial. The primary endpoint is overall survival. Secondary endpoints are distant progression-free survival, local tumour progression-free survival analysed per patient and per tumour, systemic therapy-related toxicity, procedural morbidity and mortality, length of hospital stay, pain assessment and quality of life, cost-effectiveness ratio and quality-adjusted life years.DiscussionIf the addition of neoadjuvant systemic therapy to repeat local treatment of CRLM proves to be superior compared to repeat local treatment alone, this may lead to a prolonged life expectancy and increased disease-free survival at the cost of possible systemic therapy-related side effects.Level of EvidenceLevel 1, phase III randomized controlled trial.Trial RegistrationNCT05861505. May 17, 2023.Graphical

Early onset Caroli’s disease with associated renal cystic disease presented with recurrent fever and epigastric pain: a case report

BackgroundCaroli’s disease is characterized by non-obstructive dilatation of intrahepatic biliary radicals with formation of calculi followed by recurrent episodes of cholangitis. It is a rare congenital malformation and often remains silent, diagnosed accidentally. But if kept unattended, and without any early intervention, it may lead to fatal residual complications. Hence, its early recognition is of utmost importance to prevent recurrent cholangitis, hepatic abscess, liver cirrhosis and cholangiocarcinoma. Hence, we feel that this case must be reported so as to increase awareness among physicians regarding this entity.Case presentationWe hereby report a case of 10-year-old boy who reported with complaints of recurrent episodes of fever, breathing difficulty and multiple episodes of epigastric abdominal pain with apparently healthy siblings. His routine investigation, laboratory parameters were within normal limits. Ultrasonography abdomen showed liver with normal echo-texture with varying sized multiple thin walled cysts involving both the lobes, right more than left with saccular dilatation of 2nd and 3rd order intra-hepatic biliary radicals without calcification without any colour flow on Doppler evaluation. The common hepatic and common bile ducts were normal in calibre and lumen. Magnetic resonance imaging abdomen had similar findings and upper GI endoscopy was also normal. He was finally diagnosed to be a case of Caroli’s disease and was managed with broad spectrum antibiotics, ursodeoxycholic acid, multivitamins, and calcium supplements. He made an uneventful recovery thereafter. Parents were counselled about the risk of cholangitis and cholangiocarcinoma and was referred to tertiary care centre for genetic counselling and for future need of liver transplantation.ConclusionAge presentation of Caroli’s disease varies. Majority present during adolescence and early adulthood. This often poses a diagnostic challenge owing its rare entity and silent presentation. A strong index of suspicion and prompt diagnosis is warranted to prevent its fatal residual complications.

Efficacy of local treatment for isolated liver metastasis after pancreatectomy in pancreatic ductal adenocarcinoma: A propensity score-matched analysis.

Although attempts of local treatment for isolated liver recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) have increased, the efficacy remains unclear. Therefore, we aimed to evaluate the effect of local treatment for recurrent liver lesions after pancreatectomy on the survival of patients with PDAC. Patients who were diagnosed with isolated liver recurrence after pancreatectomy at a high-volume center were included. We classified these patients based on the treatment options after recurrence and performed propensity score matching to minimize confounding. Median with interquartile range survival after recurrence was significantly longer for patients who underwent local treatment for recurrent liver lesions plus chemotherapy (22.0 [17.0-29.0] months) than those treated with chemotherapy alone (13.0 [7.0-21.0] months, p = .027). In multivariate analysis, not only local treatment for recurrent liver lesions plus chemotherapy (hazard ratio [95% confidence interval], 0.55 [0.32-0.94]; p = .030) but also indicators for systemically controlled tumor such as late recurrence (0.57 [0.35-0.92]; p = .021), chemotherapy for ≥6 months (0.25 [0.15-0.42]; p < .001), and disease control by chemotherapy (0.36 [0.22-0.60]; p < .001) were identified as favorable prognostic factors. PDAC patients with stable recurrent liver lesions should be considered a candidate for local treatment.

Recurrent Non-islet Cell Tumor Hypoglycemia Secondary to Hepatocellular Carcinoma: Case Report and Literature Review.

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome caused by tumors other than insulinoma that is primarily due to excessive production of insulin-like growth factor-II (IGF-II). The prevalence of NICTH is likely underestimated because of a lack of clinical recognition. A 41-year-old male with massive malignant liver tumors presented with recurrent severe hypoglycemia, weight loss, and liver cirrhosis. NICTH related to IGF-II produced by hepatocellular carcinoma was diagnosed based on clinical symptoms, biochemical tests, and elevated IGF-II/IGF-I ratio. Initial treatment with intravenous glucose and parenteral nutrition showed limited efficacy. Glucocorticoids and recombinant human growth hormone led to progressive improvement in blood glucose levels. Due to extensive tumor burden and liver failure, surgical resection was not feasible, and the patient ultimately succumbed to refractory hypoglycemia and passed away in two weeks. Early recognition and diagnosis of NICTH are crucial in patients with recurrent hypoglycemia and large tumors. Surgical resection is the preferred treatment option, but supportive care and pharmacological interventions, such as glucocorticoids and growth hormone, can help manage refractory hypoglycemia. Further research is needed to explore novel treatment options, including anti-IGF-I and -IGF-II neutralizing antibodies.