Multiple Liver Tumors Research Articles

Etiological Pattern & Clinical Presentation of Dysphagia

Background & objective: : Dysphagia can cause significant morbidity and mortality, especially in older and paediatric populations. The study was undertaken to determine the demographic and clinico-pathological profile of the patients diagnosed with oesophageal dysphagia in a tertiary care hospital of Bangladesh. Methods: This cross-sectional study was conducted at the Department of Medicine & Gastroenterology in Sir Salimullah Medical College & Mitford Hospital over a period of 6 months, from March to August 2015. A total of 100 adult (aged ≥ 18 years) patients (respondents) of dysphagia of both sexes were included in the study. However, patients who dropped out before investigations being completed, or unconscious patients (as endoscopy cannot be done in unconscious patients) were excluded from the study. Result: The age distribution shows that patients were predominantly older (60%), male and rural resident. In terms of occupation, retired persons comprised the main bulk (38%). About half (49%) of the patients were middle-class and smoker. Presence of both solid and liquid food dysphagia was more or less common (44%), followed by solid food dysphagia alone (36%) and liquid food dysphagia alone (20%). A substantial proportion (78%) of patients presented with heart-burn as well. Probing the clue to dysphagia, some 7% of the patients gave history of ingesting chemical substances (either accidentally or as an attempt to suicide), 15% had history of taking steroid and 12% taking NSAIDs. History of radiation injury and history of ingesting foreign substances were rare. Over 60% of the respondents had co-morbid conditions like diabetes mellitus (28%), hypertension (23%), candidiasis (6%), lymphoma (3%). Clinical examination revealed 30% of the respondents nutritionally compromised (20% underweight and 10% overweight or obese). Nearly two-thirds (63%) were anaemiac with glossitis and koilonychia being present in 47 and 17% of the patients respectively. About one-third (32%) exhibited cervical lymphadenopathy. Of the 100 respondents, only 4 respondents were found with cardiomegaly, 4 with COPD, 2 with mediastinal widening. Endoscopy of upper GI tract showed 29% with ulceroproliferative lesion, 22% with multiple white patches in the whole length of oesophagus, 18% with stricture & narrowing of the oesophagus, 13% with malignant stricture & narrowing, 10% with proliferative lesion at mid oesophagus with narrowing of lumen and 8% malignant-looking ulcer with elevated margin in the lower oesophagus. Ba-swallow X-ray of oesophagus revealed 47 with filling defect in the lower oesophagus, 5 narrowing in the middle part of oesophagus and only 4 dilatations in the mid oesophagus. Twenty respondents had positive findings on USG of whole abdomen; of them, 10 had multiple solid tumors in liver. Others had hepatoma, mass in the epigastrium, cystitis, intraabdominal lymphadenopathy and splenomegaly. Based on symptoms, signs and laboratory findings, 42% were diagnosed as oesophagial carcinoma, 16% as drug-induced oesophageal ulcer and 11% as diabetes mellitus with oesophageal candidiasis. Conclusion: The most common cause of oesphageal dysphagia is carcinoma of oesophagus followed by drug-induced oesophageal ulcer and diabetes mellitus with oesophageal candidiasis. To reduce morbidity and mortality of various etiologies leading to dysphagia, prompt and early diagnosis is essential. Ibrahim Card Med J 2022; 12 (1): 40-45

Study of ultrasound-guided percutaneous microwave ablation combined with portal vein embolization for rapid future liver remnant increase of planned hepatectomy.

To evaluate the efficacy of ultrasound-guided percutaneous microwave ablation (PMA) combined with portal vein embolization (PVE) for planned hepatectomy. We retrospectively reviewed data of 18 patients with multiple right liver tumors or hilar tumor of liver invades the surrounding tissue and insufficient future liver remnant (FLR) for hepatectomy from July 2015 to March 2017. Ultrasound-guided PMA was performed by using PMCT cold circulation microwave treatment apparatus. PVE was performed after PMA. The increase of FLR was evaluated by computed tomography (CT) 6-22 days after PVE. The proportion of FLR, increase in the amplitude of FLR, procedure-related complications, perioperative morbidity and mortality, and overall survival (OS) rates, the median survival time were analyzed. The median volume of FLR before PMA and PVE was 369.7ml (range: 239.4-493.1ml). After a median waiting period of 11.5 days (range: 6-22 days), the median volume of FLR was increased to 523.4ml (range: 355.4-833.3ml). The changes in FLR before and after PMA and PVE were statistically significant (p<0.001). No serious perioperative complications or mortality were found. After a median follow-up time of 51.0 months (range: 2-54 months), the 6-month, 1-year, 2-year, 3-year and 4-year survival rates were 88.9%, 72.2%, 44.4%, 33.3%, 22.2%, respectively, and the median survival time was 15.0 ± 7.1 months. PMA combined with PVE increases FLR rapidly, avoids touching malignant tumors, and produces fewer procedure-related complications. It appears safe and efficacious for planned hepatectomy.

A calcitonin-producing pancreatic neuroendocrine neoplasm treated with distal pancreatectomy a lengthy time after a left trisectionectomy for liver metastases: a case report.

Calcitonin-producing pancreatic neuroendocrine neoplasms (PanNENs) are extremely rare. There have been no reports of a patient in whom liver metastases were the presenting finding, and a calcitonin-producing PanNEN was subsequently detected after a lengthy period. A 53-year-old man had diarrhea for several years. Computed tomography (CT) revealed multiple liver tumors. We performed a left trisectionectomy with a bile duct resection. The histologic examination showed neuroendocrine tumors G1. Immunohistochemistry was positive for calcitonin and the serum calcitonin level was elevated. Neuroendocrine neoplasms of hepatic origin are extremely rare, so a systemic exploration was performed, but no tumor was detected. CT showed a 4-mm calcification in the pancreatic body, but no contrast-enhanced mass was noted. Although the liver tumors were resected, the diarrhea and high serum calcitonin level persisted. Serial examinations were performed for 6years, but no tumor was identified; however, 6.5years after the hepatectomy the serum calcitonin level increased. CT showed a 10-mm contrast-enhanced mass in the calcified area of the pancreatic body. A distal pancreatectomy was performed. The histologic examination showed a neuroendocrine tumor G1, which mimicked the liver tumors. Immunohistochemistry was positive for calcitonin. After the distal pancreatectomy, the serum calcitonin level decreased and diarrhea resolved. The calcitonin-producing neuroendocrine neoplasm was considered the pancreatic primary and the hepatic tumors were metastases. Calcitonin-producing PanNENs may be initially recognized as liver tumors and may become evident after a lengthy period, thus long-term observation is recommended. Aggressive surgeries may contribute to long-term survival.

Prognostic impact of neoadjuvant chemotherapy in patients with synchronous colorectal liver metastasis: A propensity score matching comparative study

BackgroundSynchronous colorectal liver metastasis (SCRLM) is at an advanced tumor stage and requires multidisciplinary treatments. Neoadjuvant chemotherapy (NAC) is thought to be an effective treatment modality, but its prognostic impact is still unclear. Materials and methodsPatients with resectable SCRLM presented to eight university hospitals between 2007 and 2017 were retrospectively reviewed. Propensity score matching (PSM) was performed to adjust baseline characteristics between patients who received NAC with those who underwent up-front hepatectomy. The prognostic impact of NAC was then evaluated. ResultsThe cohort comprised of 320 patients: 151 patients received NAC and the remaining 169 patients underwent up-front hepatectomy. After a 1:1 ratio of PSM, 102 patients per group were selected. Within the PSM cohort, 66% patients had multiple liver tumors, with 15% having five or more liver tumors. The median survival (95% confidence interval) periods for patients with and without NAC in the PSM cohort were 88.5 (68.4 – not reached) and 84.2 (52.1 – not reached) months, respectively (P = 0.51). On multivariate analysis, the postoperative events in these patients including operative complications and use of adjuvant chemotherapy after hepatectomy were prognostic factors with hazards (95% confidence interval) being 1.88 (1.18–2.98) and 0.65 (0.42–1.01), respectively. ConclusionThis PSM study was restricted to patients with SCRLM and relatively advanced tumor stagings. NAC did not show any significant prognostic impact. While operative complications had a significant prognostic impact, use of adjuvant chemotherapy after hepatectomy had only a marginal prognostic impact. Reconsideration of indications for NAC is needed.

Treatment of Retinoblastoma 1-Intact Hepatocellular Carcinoma With Cyclin-Dependent Kinase 4/6 Inhibitor Combination Therapy.

Synthetic cyclin-dependent kinase (CDK) 4/6 inhibitors exert antitumor effects by forcing RB1 in unphosphorylated status, causing not only cell cycle arrest but also cellular senescence, apoptosis, and increased immunogenicity. These agents currently have an indication in advanced breast cancers and are in clinical trials for many other solid tumors. HCC is one of promising targets of CDK4/6 inhibitors. RB family dysfunction is often associated with the initiation of HCC; however, this is revivable, as RB family members are not frequently mutated or deleted in this malignancy. Loss of all Rb family members in transformation related protein 53 (Trp53)-/- mouse liver resulted in liver tumor reminiscent of human HCC, and re-expression of RB1 sensitized these tumors to a CDK4/6 inhibitor, palbociclib. Introduction of an unphosphorylatable form of RB1 (RB7LP) into multiple liver tumor cell lines induced effects similar to palbociclib. By screening for compounds that enhance the efficacy of RB7LP, we identified an I kappa B kinase (IKK)β inhibitor Bay 11-7082. Consistently, RB7LP expression and treatment with palbociclib enhanced IKKα/β phosphorylation and NF-κB activation. Combination therapy using palbociclib with Bay 11-7082 was significantly more effective in hepatoblastoma and HCC treatment than single administration. Moreover, blockade of IKK-NF-κB or AKT pathway enhanced effects of palbociclib on RB1-intact KRAS Kirsten rat sarcoma viral oncogene homolog mutated lung and colon cancers. In conclusion, CDK4/6 inhibitors have a potential to treat a wide variety of RB1-intact cancers including HCC when combined with an appropriate kinase inhibitor.

Neonatal streptozotocin treatment rapidly causes different subtype of hepatocellular carcinoma without persistent hyperglycemia in 4CS mice fed on a normal diet

Although diabetes mellitus (DM) is a well-known risk factor for hepatocellular carcinoma (HCC), the underlying mechanisms have not yet to be defined. We previously reported that DIAR mice fed with standard murine diet developed type 1 diabetes and HCC at age of 16 weeks old with a neonatal streptozotocin treatment (n-STZ). Because DIAR mice did not manifest obesity nor develop steatohepatitis, hyperglycemia with streptozotocin trigger or streptozotocin alone might turn on the hepato-carcinogenesis. An insulin-recruitment to DIAR-nSTZ mice showed an increased frequency of HCC during the first 12 weeks of age, although the diabetic indications notably improved. To elucidate the role of hyperglycemia in hepato-carcinogenesis, we performed a head-to-head comparative study by using 4CS mice and DIAR mice with n-STZ treatment. Newborn 4CS mice and DIAR mice were divided into STZ treated group and control group. The blood glucose levels of DIAR-nSTZ mice increased at age of eight weeks, while that of 4CS-nSTZ mice were maintained in the normal range. At eight weeks old, three out of five DIAR-nSTZ mice (60%) and one out of ten 4CS-nSTZ mice (10%) developed multiple liver tumors. At age of 12 weeks old, all eight of DIAR-nSTZ mice (100%) and two of 10 4CS-nSTZ mice (20%) developed multiple liver tumors. At 16 weeks old, all animals of DIAR-nSTZ and 4CS-nSTZ mice occurred liver tumors. DIAR-nSTZ showed hyperglycemia and HCC, and 4CS-nSTZ developed HCC without hyperglycemia. These results were interpreted that the onset of HCC maybe not related to the presence or absence of hyperglycemia but nSTZ treatment. On the other hand, since the carcinogenesis of 4CS-nSTZ is delayed compared to DIAR-nSTZ, hyperglycemia may play a role in the progression of carcinogenesis. Histologically, the liver tumor appeared irregularly trabecular arrangements of hepatocytes with various degrees of nuclear atypia. By immunohistochemical analyses, all liver tumors showed positive staining of glutamine synthetase (GS), an established human HCC marker. The expression pattern of GS was divided into a strong diffuse pattern and weak patchy pattern, respectively. The liver tumor showing the weak GS-patchy pattern expressed biliary/stem markers, EpCAM, and SALL4, partially. Because 4CS-nSTZ mice did not show any metabolic complications such as gaining body weight or high blood glucose level, it is a unique animal model with a simple condition to investigate hepatic carcinogenesis by excluding other factors.

Histological Heterogeneity of Primary Liver Cancers: Clinical Relevance, Diagnostic Pitfalls and the Pathologist's Role.

Simple SummaryPrimary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined (c)HCC-CCA. Both small duct types iCCA (a subtype pf iCCA) and cHCC-CCA are known to be tumors with histological heterogeneity. Understanding key tumor heterogeneity is crucial as it reflects tumor aggressiveness, patient outcome, treatment choice, and is predictive of treatment efficacy. In addition, PLCs often present with multiple liver tumors, which can be a combination of different types of PLCs or HCCs (intrahepatic metastasis or multicentric occurrence), and the pathological interpretation plays an important role in these cases. The aim of this review is to clarify the pathological features of HCC, iCCA, and cHCC-CCA, including their diagnostic pitfalls, molecular profiles, and the correlation between tumor subtypes and treatment choice.Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.

The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis–associated liver tumors in a novel murine model

BackgroundDiabetes and obesity contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). However, how diabetes and obesity accelerate liver tumorigenesis remains to be fully understood. Moreover, to verify the therapeutic potential of anti-diabetic drugs, there exists a strong need for appropriate animal models that recapitulate human pathophysiology of NASH and HCC. MethodsWe established a novel murine model of NASH-associated liver tumors using genetically obese melanocortin 4 receptor-deficient mice fed on Western diet in combination with a chemical procarcinogen, and verified the validity of our model in evaluating drug efficacy. FindingsOur model developed multiple liver tumors together with obesity, diabetes, and NASH within a relatively short period (approximately 3 months). In this model, sodium glucose cotransporter 2 inhibitor Tofogliflozin prevented the development of NASH-like liver phenotypes and the progression of liver tumors. Tofogliflozin attenuated p21 expression of hepatocytes in non-tumorous lesions in the liver. InterpretationTofogliflozin treatment attenuates cellular senescence of hepatocytes under obese and diabetic conditions. This study provides a unique animal model of NASH-associated liver tumors, which is applicable for assessing drug efficacy to prevent or treat NASH-associated HCC.

Feasibility and outcomes of multiple simultaneous laparoscopic liver resections.

Surgeons often remain reluctant to consider laparoscopic approach in multiple liver tumors. This study assessed feasibility and short-term results of patients who had more than 3 simultaneous laparoscopic liver resections (LLR). All consecutive patients who underwent LLR for primary or secondary malignancies between 2009 and 2019 were analyzed. After exclusion of major LLR, patients were divided into three groups: less than three (Group A), between three and five (Group B), and more than five resections (Group C) in the same procedure. Intraoperative details, postoperative outcomes, and textbook outcome (TO) were compared in the 3 groups. During study period, 463 patients underwent minor LLR. Among them, 412 (88.9%) had less than 3 resections, 38 (8.2%) between 3 and 5 resections, and 13 (2.8%) more than 5 resections. Despite a difficulty score according to IMM classification comparable in the 3 groups (with high difficulty grade 3 procedures of 16.5% vs. 15.7% vs. 23.1% in Group A, B, and C, respectively, p = 0.124), mean operative time was significantly longer in Group C (p = 0.039). Blood loss amount (p = 0.396) and conversion rate (p = 0.888) were similar in the 3 groups. Rate of R1 margins was not significantly different between groups (p = 0.078). Achievement of TO was not different between groups (p = 0.741). In multivariate analysis, non-achievement of TO was associated with difficulty according to IMM classification (OR = 2.29 (1.33-3.98)). Since intra- and post-operative outcomes and quality of resection are comparable, multiple liver resections should not preclude the laparoscopic approach.

Persistent hepatocyte apoptosis promotes tumorigenesis from diethylnitrosamine-transformed hepatocytes through increased oxidative stress, independent of compensatory liver regeneration

Hepatocellular carcinoma highly occurs in chronic hepatitis livers, where hepatocyte apoptosis is frequently detected. Apoptosis is a mechanism that eliminates mutated cells. Hepatocyte apoptosis induces compensatory liver regeneration, which is believed to contribute to tumor formation. Hepatocyte-specific Mcl-1 knockout mice (Mcl-1Δhep mice) developed persistent hepatocyte apoptosis and compensatory liver regeneration with increased oxidative stress in adulthood but had not yet developed hepatocyte apoptosis at the age of 2 weeks. When diethylnitrosamine (DEN) was administered to 2-week-old Mcl-1Δhep mice, multiple liver tumors were formed at 4 months, while wild-type mice did not develop any tumors. These tumors contained the B-Raf V637E mutation, indicating that DEN-initiated tumorigenesis was promoted by persistent hepatocyte apoptosis. When N-acetyl-L-cysteine was given from 6 weeks of age, DEN-administered Mcl-1Δhep mice had reduced oxidative stress and suppressed tumorigenesis in the liver but showed no changes in hepatocyte apoptosis or proliferation. In conclusion, enhanced tumor formation from DEN-transformed hepatocytes by persistent hepatocyte apoptosis is mediated by increased oxidative stress, independent of compensatory liver regeneration. For patients with livers harboring transformed cells, the control of oxidative stress may suppress hepatocarcinogenesis based on chronic liver injury.

Initial experience with novel Embocure Plus microspheres for transarterial chemoembolization (TACE) of liver metastatic colorectal cancer tumours - a clinical and in vitro study.

PurposeTransarterial chemoembolization (TACE) is currently recommended for unresectable intrahepatic tumours with no vascular invasion or metastasis to other organs. It is based on drug-eluting microspheres pre-loaded with chemotherapeutics, which are injected selectively into vessels supplying the tumour, to embolize them inducing ischaemia, and elute the drug, to induce tumour response. We present our initial experience with novel irinotecan- loaded Embocure Plus microspheres in patients with metastatic colorectal cancer tumours in the liver, and their effect on HCT-116 cell cultures in vitro.Material and methodsThree consecutive male patients (median age 62 [50-76] years) with liver metastatic colorectal cancer tumours were selected. All patients had a pre-procedure contrast-enhanced computed tomography, confirming multiple metastatic liver tumours (mean tumour diameter = 42 mm; range: 14-77 mm) and periprocedural dyna-CT scans for rapid treatment results assessment. In vitro: Human colon HCT116 cancer cell line was cultured, irinotecan loaded Embocure Plus microspheres were added. Cultures were assessed after 24 hours and 72 hours of incubation in normoxia or hypoxia.ResultsAll embolizations were technically successful, and no complications were observed. Stabilization of the targeted metastatic liver tumours in all patients was noted. In vitro: Significant decrease of the growth of HTC 116 cell lines were observed in controls compared to cells treated with Embocure Plus loaded with irinotecan in normoxia and hypoxia after 48 and 72 hours. We observed a tendency for less inhibited cell proliferation in low-oxygen conditions.ConclusionsTACE therapy of liver metastatic tumours shows satisfactory results and a low complication rate. Embocure Plus microspheres are safe and technically feasible for superselective chemoembolization of metastatic colorectal cancer liver tumour. Dyna-CT can be used for assessment of treatment results during repeated TACE procedures.

Mesenchymal Hamartoma of the Liver and Spleen-A Rare Pseudotumour in Adults

Hepatic mesenchymal hamartoma is the third most common liver neoplasm of the pediatric age group, rarely diagnosed in adults, with under 50 cases having been reported so far. Mesenchymal hamartoma of the spleen is a very rare vascular lesion, documented in less than 200 cases since 1861 when it was first described by Karl von Rokitansky. 1.1. Aim: The aim of this paper is to discuss the differential diagnosis of these tumour-like lesions and the association between them, especially considering their rarity. 1.2. Methods: We present a case of multifocal mesenchymal hamartoma of the liver and spleen in a 51-year-old female patient. The hepatic tumour appears as a macro nodular lesion involving the interface between segments V and VIII [30x28mm], showing central scarring upon MRI imaging and suggesting the diagnosis of focal nodular hyperplasia. Moreover, a sub capsular splenic cystic mass was also revealed, involving the sub diaphragmatic surface of the organ [15x10mm]. 1.3. Results: The histological examination of the hepatic tumour revealed a myxoid stromal proliferation, composed of stellate and fibroblastoid cells, bile ducts with inconspicuous lumina, small vascular structures and chronic non-specific inflammatory infiltrate. On microscopic examination, the splenic lesion exhibited nodular collagenous fibrosis, radial septa and large hyalinized areas. 1.4. Conclusion: A key aspect in the effective treatment of patients diagnosed with mesenchymal hamartomas is surgery with negative margins. The peculiarity of this case consisted of the incidental finding of multiple liver tumours, the incidental finding of the splenic mass, and the rarity of this particular association in adults.

A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.

While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC. Patients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS). A total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22%vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non-LR patients. LR patients had decreased OS(2-year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years(HR, 3.61; 95% CI, 1.10-11.81), colorectal histology (HR, 3.84; 95% CI, 1.69-12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21-9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2-year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%). As CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

Laparoscopic repeat liver resection for hepatic epithelioid hemangioendothelioma

BackgroundOptimal treatment for patients with hepatic epithelioid hemangioendothelioma (HEHE) remains unclear. Laparoscopic repeat liver resection (LR) is a minimally invasive and potentially effective surgical option for multiple HEHEs.Case presentationA 42-year-old woman with no relevant history was admitted for multiple liver tumors. Six tumors were observed on T2-weighted magnetic resonance imaging (MRI) including one in S2, two in S3, two in S7, and one in S8. Pathological evaluation of percutaneous tumor biopsy tissue suggested a diagnosis of HEHE and laparoscopic LR was planned. The procedure began with partial resection of S7 and partial resection of S8 and left lateral sectionectomy were performed. Another tumor was found intraoperatively on the surface of S6, necessitating removal by partial resection. Pathological evaluation of the resected tumor tissue from all seven tumors concurred with that of the preoperative biopsy. The patient was discharged on postoperative day 6 without any complications. A follow-up MRI 15 months after the primary surgery revealed one tumor each in S4, S6, and S8. Laparoscopic repeat LR was performed. The patient was discharged on postoperative day 5 without any complications. All three recurrent tumors were pathologically confirmed as HEHEs.ConclusionsWe successfully treated primary and recurrent HEHEs with laparoscopic LR, which is a reasonable minimally invasive procedure considering the possibility of multiple courses of liver surgery in patients with HEHE.

Multimodal therapy with surgery and adjuvant nivolumab for late-onset multiple liver metastases of choroidal malignant melanoma: a case report

BackgroundChoroidal malignant melanoma is the most common primary malignant tumor of the eye in adults. Prognosis after recurrence of this disease has been dismal because of the absence of an effective therapy. However, resection of recurrent foci and a subsequent treatment with immune-checkpoint inhibitor may improve the prognosis after recurrence of this disease. This study presents a case of late-onset liver metastases of choroidal malignant melanoma, successfully treated with hepatectomy and postoperative adjuvant nivolumab.Case presentationA 53-year-old woman had undergone left ocular enucleation because of choroidal malignant melanoma 13 years prior to admission. She visited a nearby clinic with complaints of epigastric pain. She was referred to our hospital because a giant liver tumor was observed on abdominal ultrasonography. Enhanced computed tomography revealed multiple liver tumors in the right lobe, 49 mm in diameter with ring enhancement in subsegment (S) 5/6, and 14 and 8 mm without any enhancement in S7 and S5, respectively. On magnetic resonance imaging, the main tumor showed high intensity on T1-weighted with fat suppression, suggesting melanin deposition. Based on the diagnosis of multiple liver metastases of choroidal malignant melanoma, right hepatectomy and regional lymphadenectomy were performed. She was discharged without postoperative complications. Histological examination revealed that all tumors were metastatic malignant melanoma. She was treated with nivolumab postoperatively, and no recurrences were observed during 22 months of follow-up.ConclusionsAggressive surgery plus adjuvant nivolumab appears to be a promising treatment for choroidal malignant melanoma with late-onset liver metastases.

Hepatoblastoma with multiple tumors in a school-aged child.

Clinicians need to consider hepatoblastoma in the differential even in school‐aged children or adolescents presenting with multiple liver tumors.

Simultaneous Stereotactic Radiofrequency Ablation of Multiple (≥ 4) Liver Tumors: Feasibility, Safety, and Efficacy

PurposeTo assess feasibility, safety, and clinical outcome of simultaneous stereotactic radiofrequency (RF) ablation of multiple (≥ 4) primary and metastatic liver tumors. Materials and MethodsThis retrospective observational study included 92 patients (29 women, 62 men), 35 with ≥ 4 hepatocellular carcinomas (HCCs) and 57 with ≥ 4 metastatic liver tumors at initial stereotactic RF ablation between 2005 and 2018. The median size of 178 HCCs and 371 metastases was 2.2 cm (range, 1.0–8.5 cm) and 3.0 cm (range, 0.5–13 cm), respectively. At initial stereotactic RF ablation, 17 (48.6%) patients with HCC and 19 (33.3%) with metastases had 4 liver tumors, 11 (31.4%) and 19 (33.3%) had 5 tumors, and 7 (20%) and 19 (33.3%) had ≥ 6 tumors. ResultsMajor complications occurred in 2 of 35 ablations (5.4%) in patients with HCCs and in 7 of 63 (10%) with metastases. The primary technical efficacy rate (ie, successful initial ablation) was 100% (178/178) in HCCs and 98.8% (363/371) in metastases. Local recurrence was observed in 4 of 178 (2.2%) HCCs and in 17 of 371 (4.6%) metastases. Overall survival (OS) rates at 1, 3, and 5 years from the date of the first stereotactic RF ablation were 88.0%, 54.0%, and 30.4% for patients with HCCs with a median OS of 38.2 months and 86.1%, 53.1%, and 37.3% for patients with metastases with a median OS of 37.4 months. ConclusionsStereotactic RF ablation is a feasible, safe, and efficacious option in simultaneous management of multiple primary and metastatic liver tumors.

Strategies to optimize stereotactic radiosurgery plans for brain tumors with volumetric-modulated arc therapy.

PurposePrescription practice in SRS plans for brain tumors differs significantly for different modalities. In this retrospective study, the strategies to optimize SRS plans for brain tumors with volumetric arc therapy (VMAT) were presented.MethodsFifty clinically treated cases were stratified by the maximum target size into two groups (≥ 2 cm in 25 cases and <2 cm but ≥1 cm in 25 cases), which were optimized using traditional LINAC MLC‐based approaches with the average prescription isodose line (P‐IDL) of (91.4 ± 0.6)%. Four to five plans have been created for each case with variation of the P‐IDL from 65% to 90%. The optimization strategies to select an optimal P‐IDL, to use tuning structures within the target and beyond as well as to use NTO (normal tissue objectives), were applied to all new plans.ResultsThe optimal P‐IDL was found to be around 75%. After applying the new optimization strategies with an average P‐IDL of 74.8%, the mean modified gradient index (mGI) and V12 were reduced by 25% and 35%, respectively for both groups. The Paddick conformity index (PCI) was averagely improved by 8%. The average homogeneity index (HI) and focal index (FI) were increased by 22% and 50%, respectively. The mGI was inversely proportional to the PTV volumes. The shape of the dose distribution in target was also changed from concave to convex. The comparison of PCI with historical data from other institutes and modalities shows that the plans in this study have the best conformity near the target.ConclusionsWith the new optimization strategies for VMAT SRS plan of brain tumor more conformal plans in both high and intermediate dose region (~50% of the PD) were created, in which the dose in the core of the target was notably increased while V12 and mGI were significantly decreased, and PCI was improved. The mGI was inversely proportional to the PTV volumes. The optimal P‐IDL is around 75%. The average PCI is the best in this study compared with the published historical data. These strategies are applicable to treatment planning for multiple brain and liver tumors where sparing the tissue peripheral to the target is critical.

A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.

37 Background: While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery(CRS) and heated intraperitoneal chemotherapy(HIPEC), liver resection(LR) is increasingly performed concomitantly with CRS/HIPEC. As this practice continues to expand, identification of preoperative factors associated with poor outcomes is paramount. Methods: Patients from the US HIPEC Collaborative(2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival(OS). Results: 658 patients were included. Average age was 54 years and 45% were male; 83 (15%) underwent liver resection of colorectal (58%) or invasive appendiceal (42%) metastases. Liver resection patients had more complications (81 vs 60%; p = 0.001), greater number of complications (2.3 vs 1.5; p &lt; 0.001), and required more reoperations (22 vs 11%; p = 0.007) and readmissions (39 vs 25%; p = 0.014) than non-liver resection patients. Liver resection patients had decreased OS (2-year OS 62% vs 79%, p &lt; 0.001), which persisted on multivariable Cox regression when accounting for PCI and histology type. Preoperative factors associated with decreased OS on multivariable analysis in patients undergoing liver resection included age &lt; 60 years (HR:3.61), colorectal histology (HR:3.84), and multiple liver tumors (HR:3.45) (all p &lt; 0.05). When assigning one point for each factor, there was an incremental decrease in 2-yr survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%; p &lt; 0.001). Conclusions: As concurrent liver resection with CRS/HIPEC has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC with liver resection. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in overall survival.

Inflamatory fibroblast tumor and liver abscesses in the young patient

Introduction: Inflammatory fibroblast tumor is rare tumor that most often occurs in younger people, usually 30 years old or younger, but most commonly in children age 6-10 years. It usually affects gastrointestinal tract and the lungs but it can also occur in several places at the same time. Clinical manifestations vary depending of the affected system of the body so it is very difficult to determine diagnosis without surgical extirpation and patohistological analysis. Complete surgical resection is curative in most patients and recidivism is rare. Liver abscesses more common occur in females with risk factors and medical history of diabetes, previous liver disease and less likely in patients with granulomatous diseases. Liver abscesses mortality in developing countries is 2-12%, increasing due to open surgical drainage.Case report: We present a 35 years-old patient who was treated at the Clinic for Infectious Diseases University Hospital Mostar and University Hospital Sarajevo, Clinic for Infectious Diseases in August and September 2018 and Clinical Hospital Merkur, Zagreb Surgery Clinic in December 2018. Data was used from medical documentation. Young, immunocompetent patient who was addmited to a hospital following high fever, chills and poor general condition was diagnosed with multiple focal necrotic lesions, differential-diagnostically most likely liver and spleen abscesses with high suspicion of liver malignancy. Liver biopsy was performed and patohistological analysis confirmed the diagnosis of multiple liver abscesses in the IV and VI liver segment, and inflamatory fibroblast tumor in the IV liver segment. Eight weeks of conservative treatment resulted in a complete regression of liver abscesses and inflamatory fibroblast tumor was surgically extirpated at the Clinic Hospital Merkur, Surgery Clinic in the Zagreb in December 2018.Conclusion: An approach to a patient with a multiple liver abscesses and liver tumor requires sub-specialists experience and urgent multidisciplinary diagnostic and treatment approach to prevent further complications and deadly outcome.