Multiple Liver Metastases Research Articles

Pancreatic cancer with multiple liver metastasis complicating multi-organ infarcts from marantic endocarditis and Trousseau's syndrome

A middle-aged previously healthy and fit man presented with left sided weakness, slurred speech, left sided sensory neglect, mild headache and fever. He denied having any cough, shortness of breath, chest pain, palpitations, abdominal pain or bowel-bladder symptoms. He has smoked 5–10 cigarettes

A Novel Case of Recurrent Mucinous Borderline Ovarian Tumor: Early Relapse and Fatal Outcome

Unlike ovarian carcinomas, borderline ovarian tumors (BOTs) are associated with a favorable prognosis: their recurrence rate is around 5–7%, and the survival rate is more than 97% when diagnosed early. There are only a few reports of recurrence and fatal outcomes. Herein, we report a novel case of recurrent mucinous BOT, with a literature review. A 63-year-old woman presented to a local doctor with abdominal fullness. She was diagnosed as having a polycystic tumor. The lesion was suspected to be a mucinous BOT (M-BOT) on magnetic resonance imaging. Upper and lower gastrointestinal endoscopy revealed no digestive cancerous lesions, and surgery was performed. Intra-operative diagnosis confirmed the diagnosis, and total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. The final pathological diagnosis was non-invasive M-BOT (stage I c1 (T1c1N0M0)). The result of immunohistochemical staining supported the diagnosis of primary ovarian mucinous tumor.Four months after surgery, relapse occurred. Blood tests revealed an elevated carbohydrate antigen 19-9 level, and computed tomography revealed multiple liver metastases, peritoneal dissemination, left ureter infiltration, and carcinomatous peritonitis. Although the patient underwent chemotherapy, she died. This case of a very short progression-free and overall survival in stage I M-BOT indicates that some M-BOTs could result in fatal clinical outcomes despite diagnosis at an early stage. Frequent follow-up appointments after surgery could help detect relapse and increase survival in such cases.

Analysis of Hepatic Artery Infusion (HAI) Chemotherapy Using Randomized Trials of Floxuridine (FUDR) for Colon Cancer Patients with Multiple Liver Metastases.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death, with most of the people who have the disease developing numerous liver metastases. Sixty percent of colon cancer patients have liver metastases. Only 25% of those with resectable hepatic metastases are alive, and recurrence occurs in nearly half of these cases. Regardless of the fact that left-sided cancer has a higher rate of liver metastases, past study reveals that left- and right-sided liver metastatic colon cancer patients have different survival rates. Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment option for patients with unresectable liver-only or liver-dominant colon liver metastases. Although HAI has only been performed in a few locations previously, this study used randomized trials of floxuridine (FUDR) to characterize patient selection and first perioperative results during the deployment of a new HAI program. In this research, we also looked at the technical aspects of placing implantable pumps and catheters for HAI chemotherapy, as well as the efficacy, morbidity, and outcomes of this therapy in colon cancer patients with numerous liver metastases. The parameters like toxicity, overall survival rate, response rate, and progression-free response for the suggested therapy are also analyzed. These findings have important implications for colon cancer adjuvant HAI chemotherapy.

Long-term survival of HER2 positive gastric cancer patient with multiple liver metastases who obtained pathological complete response after systemic chemotherapy: A case report.

Introduction and importanceAdvanced gastric cancer with liver metastasis is classified as stage IV disease and is generally treated with systemic chemotherapy. Despite recent advances in chemotherapy regimens, the prognosis for gastric cancer with liver metastasis is poor. Recent studies reported the effectiveness of upfront chemotherapy followed by conversion surgery for gastric cancer with liver metastasis. Here, we report a case of an advanced stage IV gastric cancer with liver metastasis treated with upfront systemic chemotherapy followed by conversion surgery, which resulted in pathological complete response and good prognosis.Case presentationA 79-year-old man diagnosed with human epidermal growth factor receptor type 2 (HER2)-positive gastric cancer with multiple liver metastases. He underwent systemic chemotherapy with capecitabine, cisplatin, and trastuzumab. After 14 courses of chemotherapy, the primary tumor and liver metastases shrank, suggesting a partial response. We performed distal gastrectomy with D2 dissection plus lateral hepatic segment resection. Pathological examination revealed no residual tumor cells in the primary or metastatic sites, which indicated a pathological complete response. The postoperative course was uneventful. The patient was discharged on postoperative day 8. Adjuvant S-1 chemotherapy was started on postoperative day 46 and given for 1 year. The patient has been alive and recurrence-free for approximately 5 years after surgery.ConclusionThis case shows the possibility of conversion surgery after systemic chemotherapy for stage IV advanced gastric cancer with liver metastasis.

Predictive preoperative clinical score for patients with liver-only oligometastatic colorectal cancer

BackgroundResection of liver metastases from colorectal cancer (CRC) in the oligometastatic stage improves survival and is a potentially curative treatment. Thus, predictive scores that reliably identify those patients who especially benefit from surgery are essential.Patients and methodsIn this multicenter analysis, 512 patients had undergone surgery for liver metastases from CRC. We investigated distinct cancer-specific risk factors that are routinely available in clinical practice and developed a predictive preoperative score using a training cohort (TC), which was thereafter tested in a validation cohort (VC).ResultsInflammatory response to the tumor, a right-sided primary tumor, multiple liver metastases, and node-positive primary tumor were significant adverse variables for overall survival (OS). Patients were stratified in five groups according to the cumulative score given by the presence of these risk factors. Median OS for patients without risk factors was 133.8 months [95% confidence interval (CI) 81.2-not reached (nr)] in the TC and was not reached in the VC. OS decreased significantly for each subsequent group with increasing number of risk factors. Median OS was significantly shorter (P < 0.0001) for patients presenting all four risk factors: 14.3 months (95% CI 10.5 months-nr) in the TC and 16.6 months (95% CI 14.6 months-nr) in the VC.ConclusionsIncluding easily obtainable variables, this preoperative score identifies oligometastatic CRC patients with prolonged survival rates that may be cured, and harbors potential to be implemented in daily clinical practice.

Usefulness of partial splenic embolization for left-sided portal hypertension in a patient with a pancreatic neuroendocrine neoplasm: a case report and review of the literature

Left-side portal hypertension (LSPH) is caused by isolated obstruction of the splenic vein and is associated with esophagogastric varices that extend from the lower esophagus to the greater curvature of the gastric body. Here, we report on a 74-year-old man with a pancreatic neuroendocrine neoplasm (NEN) in the pancreatic tail with multiple liver metastases. We decided that partial splenic embolization (PSE) was the best course of treatment to prevent rupture of the gastric varices, which were classified as markedly enlarged, nodular, or tumor-shaped and showed erosion of the mucosa. After PSE, the patient had no major complications and was discharged. At 3 and 6 months after the procedure, esophagogastroduodenoscopy and enhanced computerized tomography showed that the gastric varices had improved. This case demonstrates the usefulness of PSE for LSPH in patients with unresected pancreatic NEN.

Successful conversion surgery for stage IV gastric cancer with liver metastases after second-line chemotherapy with ramucirumab and paclitaxel: a case report

BackgroundIn recent years, conversion surgery after chemotherapy has been considered a promising strategy for improving the prognosis of patients with stage IV gastric cancer. However, there are few reports on conversion gastrectomy after second-line chemotherapy. Here, we report a case of long-term survival of a patient with liver metastases from gastric cancer who underwent conversion surgery after second-line chemotherapy with ramucirumab and paclitaxel.Case presentationA 77-year-old man complaining of weight loss was diagnosed with human epidermal growth factor receptor 2-positive gastric cancer with multiple liver metastases. Although the patient initially received trastuzumab-based chemotherapy, it was discontinued, because he experienced trastuzumab-induced infusion reactions. Thereafter, he was treated with six courses of S-1 plus cisplatin and six courses of ramucirumab plus paclitaxel as the first- and second-line regimens, respectively. The primary tumor and liver metastases remarkably shrank, and the reduction rate of the measurable metastatic liver lesions was 81.1%. According to the Response Evaluation Criteria in Solid Tumors, the patient responded partially. Therefore, he underwent total gastrectomy with D2 lymphadenectomy and partial hepatectomy of segments 3 and 4. Pathological examination revealed tumor invasion into the muscularis propria, a grade 1a histological response, and no lymph node metastases. No viable cancer cells were identified in the specimens resected from liver segments 3 and 4. Accordingly, the patient was pathologically diagnosed with stage IB (ypT2N0M0). Postoperatively, the patient received adjuvant chemotherapy with S-1 for 6 months, and he survived without recurrence for 42 months after conversion surgery.ConclusionsConversion surgery might be clinically useful for improving survival in certain patients with gastric cancer, including those who previously received second-line chemotherapy.

Prognostic Factors in Patients with Breast Cancer Liver Metastases Undergoing Liver Resection: Systematic Review and Meta-Analysis.

Simple SummaryRobust predictive and prognostic tools are needed in the management of breast cancer liver metastases (BCLMs). Until now, surgery has not been the gold standard of treatment of patients with BCLMs. The present manuscript highlights several predictive factors related to the primary tumor and the BCLM that may help to identify candidates for surgery with favorable outcomes in a large cohort of patients.Background: The role of surgical resection of liver metastases in patients with breast cancer liver metastasis (BCLM) remains controversial. A systematic review and meta-analysis of prognostic factors related to survival after BCLM resection was performed. Methods: An electronic search of relevant publications was performed. Pooled outcome measures were expressed as hazard ratios (HRs), including 95% confidence interval values (95% CIs), and calculated through a random-effects model. Heterogeneity was tested through the I2 index. Results: Thirty-five publications reported analyses on prognostic factors and survival. A total of 2782 patients who underwent liver resection for BCLM were included. Positive axillary lymph nodes at breast cancer diagnosis were an unfavorable survival factor (HR 1.74, 95% CI 1.25 to 2.41, I2 = 0%). Cumulative predictive factor HRs (multiple liver metastases, size of the metastases, short interval between primary tumor and onset of liver disease) related to the BCLM pattern were 1.32 (95% CI 1.17 to 1.48, I2 = 71%) and 1.51 (95% CI 1.15 to 1.98, I2 = 76%) for surgical and pathological features (resection margin and presence of extrahepatic disease), respectively. Conclusion: Resection of BCLM may provide a survival benefit for selected patients. For better long-term results, surgical selection should consider both primary tumor and BCLM features such as negative axillary lymph nodes at breast resection, a single hepatic lesion, a time longer than 24 months between breast and hepatic diagnosis, and a realizable R0 liver resection. However, the high heterogeneity among studies suggests the need for an RCT to validate the present findings.

Yin Yang 1 regulates ITGAV and ITGB1, contributing to improved prognosis of colorectal cancer.

Yin Yang 1 (YY1) is a multifunctional transcription factor with critical roles in carcinogenesis and metastasis. However, its biological role and clinical impact in colorectal cancer (CRC) remain unclear. In the present study, the function and underlying molecular mechanisms of YY1 in CRC progression were investigated. The immunohistochemistry (IHC) of 143 CRC tissues revealed a significant correlation of low YY1 expression with aggressive clinicopathological features, increased metastasis and recurrence and poor patient survival. Multivariate analysis identified low YY1 expression as an independent poor prognostic factor. Subsequently, the IHC of 66 paired CRC primary tumor and liver metastasis tissues revealed that low YY1 expression in the primary CRC was significantly associated with multiple liver metastases, major hepatectomy, extrahepatic metastasis and poor prognosis. In vitro experiments revealed that YY1 knockdown promoted the migration and invasion of CRC cells. To examine the downstream genes of YY1, a cDNA microarray assay was conducted and the differentially expressed genes between the YY1-knockdown and control cells were compared. Integrin alpha V (ITGAV) and integrin beta 1 (ITGB1) were identified as upregulated hub genes using gene enrichment analysis and protein-protein interaction analyses. Western blotting and IHC confirmed YY1 expression to be negatively correlated with ITGAV and ITGB1 expression. In summary, it was revealed that YY1, as a tumor-suppressor in CRC, contributes to the survival of patients with CRC. Low YY1 expression was associated with the poor prognosis of the patients with primary CRC and liver metastases. YY1 suppressed the expression of ITGAV and ITGB1, and this transcriptional regulation may lead to the suppression of CRC cell migration and invasion.

Synchronous double primary malignancies of the pancreatic body and extrahepatic bile duct treated with pancreatoduodenectomy and splenic artery resection following neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel: a case report

BackgroundPrimary pancreatic cancer with synchronous primary tumors in other organs is a rare condition, and its treatment largely depends on the progression of pancreatic cancer. Here, we describe a rare case of double primary malignancies involving borderline resectable pancreatic body and extrahepatic bile duct cancers that were successfully resected after neoadjuvant chemotherapy (NAC), subsequently avoiding total pancreatectomy.Case presentationA 61-year-old Japanese male was referred to our hospital by his general practitioner after presenting with elevated liver enzymes during a routine check-up for type 2 diabetes mellitus. He was diagnosed with synchronous borderline resectable pancreatic cancer in the body of the pancreas and lower extrahepatic bile duct cancer with obstructive jaundice. Abdominal computed tomography (CT) confirmed a hypovascular mass in the pancreatic body with partial encasement of the common hepatic artery, left gastric artery, celiac artery, and splenic artery and invasion of the splenic vein. Endoscopic retrograde cholangiopancreatography and bile duct biopsy confirmed lower bile duct cancer. Following multidisciplinary discussion, endoscopic retrograde biliary drainage was performed, and neoadjuvant chemotherapy comprising gemcitabine plus nanoparticle albumin-bound paclitaxel (GEM + nab-PTX) was administered. After a total of seven cycles of chemotherapy, follow-up CT showed that the size of the pancreatic lesion reduced, following which the patient underwent pancreatoduodenectomy with splenic artery resection. The postoperative course was uneventful without any surgical complications or intensive hypoglycemic treatment. The pathological diagnosis was pancreatic ductal adenocarcinoma (ypT3N1aM0 ypStage IIB/UICC 8th) with synchronous extrahepatic cholangiocarcinoma (ypT2N1M0 ypStage IIB/UICC 8th). R0 pancreatic resection was performed with an Evans grade III response to neoadjuvant chemotherapy. The patient was followed up and had no tumor recurrence at 22 months after surgery with adjuvant S-1 chemotherapy, however, died after 32 months after surgery due to multiple liver metastasis and para-aortic lymph node metastasis despite salvage GEM + nab-PTX chemotherapy.ConclusionIn our case, neoadjuvant chemotherapy for borderline resectable pancreatic cancer and function-preserving pancreatoduodenectomy (R0 resection) for double primary malignancies achieved balanced patient survival and postoperative quality of life.

Abstract P1-06-04: Spatial, temporal and therapy dependent heterogeneity in transport phenotype of multiple liver metastases in murine breast cancer model

Abstract Introduction: Inter- and intra-tumor heterogeneities in response of tumors to systemic anti-cancer therapy are the major source of therapeutic resistance. Cancer cells from bulk tumors and cancer cell lines are not clonal but are composed of subclones, creating heterogeneous tumor microenvironment. Furthermore, metastasis can evolve during the disease progression as well as in response to systemic therapies. These spatial and temporal heterogeneities in tumors can affect blood perfusion and vascular permeability which determine the transport of various masses and chemotherapeutic (we refer to as “transport phenotype”). Insufficient drug transport to the tumor in vivo can generate transport-based therapeutic resistance even for agents with proven efficacy against the target cells in vitro. Our goal is to understand spatial and temporal heterogeneity in the transport of mass/anti-cancer drugs to metastatic tumors to leverage novel strategies for improving therapeutic efficacy using mouse tumor models. The study of bulk tumors will provide a mixture of different functions from heterogeneous sets of various clones. We sought to establish single cell-derived clones from the parental murine breast cancer cell line to dissect and simplify tumor heterogeneity. Methods: Single cells were isolated via aliquoting 4T1-luc-tomato red cell suspension (polyclonal) in single-cell concentration into 96 well plate. To evaluate the phenotype of the clonal and parental cells, we performed clonogenic assay, proliferation and growth inhibition assay using pegylated liposomal doxorubicin (PLD), and angiogenic protein production assay using membrane array. Among the established clones, we selected 2 clones and parental cells for further experiments. Experimental liver metastases were created by injecting cell suspension into the spleen of BALB/c mice. Then, the window chamber was implanted above the liver of anesthetized mice and fluorescently labeled dextran tracers with different molecular weights were intravenously (iv) injected. To determine transport phenotype, circulation and diffusion of tracers inside/around individual metastasis were imaged and quantified through the window using Intravital Microscopy (IVM) at various time points. In another set of experiment, PLD was iv injected, and change in the transport phenotype was monitored. Results: While parental cells formed heterogeneous colonies, clonal cells created each cell line dependent uniform colonies in petri dish. Also, parental and selected two clonal cells exhibited different growth, response to PLD, and protein production in vitro. IVM imaging of individual liver metastasis over time using different cell lines revealed that relative fluorescent intensity of tracers transported inside/around tumor compared to that in the uninvolved tumor-free liver was more heterogeneous among parental cell derived tumors compared to clonal cells. Interestingly, these “transport phenotypes” evolved and increased their heterogeneity as tumors progressed regardless of cell type. Furthermore, transport phenotype was modulated from one to another after PLD therapy, creating possible mechanisms of transport based on drug resistance. Discussion: These data suggest that transport phenotype cannot be determined solely by genotype of tumors but modulated as a function of tumor growth and therapy response to become more heterogeneous. The intrinsic heterogeneity of transport phenotype and its acquired transformation suggests a more complicated scenario of tumor drug-resistance mechanism. The clinical implication of our findings is that the transport of therapeutics to the tumor and its efficacy may not be predicted by DNA-based assay and transport-based therapeutics resistance will eventually occur in every tumor type. Citation Format: Thao Nguyen, Yan ting Liu, Arturas Ziemys, Shen Haifa, Kenji Yokoi. Spatial, temporal and therapy dependent heterogeneity in transport phenotype of multiple liver metastases in murine breast cancer model [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-06-04.

Effect of tumour size ratio on liver recurrence-free survival of patients undergoing hepatic resection for colorectal liver metastases

BackgroundThe study aimed to assess the impact of size differences of multiple liver metastases on liver recurrence-free survival (RFS) in patients undergoing hepatic resection for colorectal liver metastases (CRLMs).MethodsOverall, 147 patients with CRLMs who underwent hepatic resection between January 2010 and December 2016 were retrospectively analysed. Tumour size ratio (TSR) was defined as the maximum diameter of the largest liver lesion over the maximum diameter of the smallest liver lesion. The univariate and multivariate analyses were performed to determine independent prognostic risk factors. The prognostic value of the TSR was further explored in each Tumour Burden Score (TBS) zone. Log-rank survival analyses were used to compare liver RFS in the new clinical score and the Fong clinical score.ResultsBased on the TSR, patients were classified into three groups: TSR < 2, 2 ≤ TSR < 4, and TSR ≥ 4. According to the multivariate analysis, TSR of 2–4 (hazard ratio [HR], 2.580; 95% confidence interval [CI] 1.543–4.312; P < 0.001) and TSR < 2 (HR, 4.435; 95% CI 2.499–7.872; P < 0.001) were associated with worse liver RFS. As TSR decreased, liver RFS worsened. TSR could further stratify patients in zones 1 and 2 into different risk groups according to the TBS criteria (zone 1: median liver RFS, 3.2 and 8.9 months for groups 1 and 2, respectively, P = 0.003; zone 2: median liver RFS, 3.5, 5.0, and 10.9 months for groups 1, 2, and 3, respectively, P < 0.05). The predictive ability of the new clinical score, which includes TSR, was superior to that of the Fong clinical score.ConclusionsTSR, as a prognostic tool, could accurately assess the effect of size differences across multiple liver metastases on liver RFS in patients undergoing hepatectomy for CRLMs.Trial registrationRetrospectively registered

Aggressive behavior of anaplastic undifferentiated carcinoma arising from the hilar bile duct

BackgroundUndifferentiated carcinoma of the biliary tree is extremely rare, and biliary undifferentiated carcinoma mostly originates from the gallbladder. We herein present a case of anaplastic undifferentiated carcinoma of the hilar bile duct and reviewed the literature.Case presentationThe patient was an 81-year-old male with obstructive jaundice. Contrast-enhanced computed tomography (CT) showed a protruded tumor located at the hepatic hilum. Obstructive jaundice was relieved by endoscopic drainage. Endoscopic biopsy revealed carcinoma without glandular differentiation, and the patient was diagnosed with resectable hilar undifferentiated carcinoma. During the 5-week preoperative examination, the tumor increased in size from 23 to 45 mm. Left hemi-hepatectomy and extrahepatic bile duct resection were performed, and there were no postoperative complications. Histological findings demonstrated that the tumor was mainly composed of non-cohesive polygonal neoplasms with pleomorphic nuclei, and was diagnosed as anaplastic undifferentiated carcinoma of the common hepatic duct (T2a N0 M0 Stage II). One month after surgery, the patient was readmitted to our hospital with pyrexia due to cholangitis, and liver nodules suggestive of multiple liver metastases were detected by CT. Three months after surgery, the patient died of multiple liver metastases.ConclusionsThis is the first case report of undifferentiated cholangiocarcinoma with anaplastic features. Anaplastic undifferentiated carcinoma of the hilar bile duct showed preoperative rapid growth and early relapse despite a cancer-negative surgical margin.

Impact of COVID-19 on the oncological outcomes of colorectal cancer surgery in northern Italy in 2019 and 2020: multicentre comparative cohort study.

BackgroundThis study compared patients undergoing colorectal cancer surgery in 20 hospitals of northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes.MethodThis was a retrospective multicentre cohort analysis of patients undergoing colorectal cancer surgery in March to December 2019 versus March to December 2020. Independent predictors of disease stage (oncological stage, associated symptoms, clinical T4 stage, metastasis) and outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression.ResultsThe sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean age 69.6 years). The proportion of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were respectively: 80.8 versus 84.5 per cent; 6.2 versus 8.7 per cent; 10.2 versus 10.3 per cent; and 3.0 versus 4.4 per cent. The proportions of surgical complications, palliative surgery and death in 2019 and 2020 were, respectively: 34.4 versus 31.9 per cent; 5.0 versus 7.5 per cent; and 1.7 versus 2.4 per cent. Cancers in 2020 (versus 2019) were more likely to be symptomatic (odds ratio 1.36 (95 per cent c.i. 1.09 to 1.69)), clinical T4 stage (odds ratio 1.38 (95 per cent c.i. 1.03 to 1.85)) and have multiple liver metastases (odds ratio 2.21 (95 per cent c.i. 1.24 to 3.94)), but were not more likely to be associated with surgical complications (odds ratio 0.79 (95 per cent c.i. 0.68 to 0.93)).ConclusionColorectal cancer patients who had surgery between March and December 2020 had an increased risk of advanced disease in terms of associated symptoms, cancer location, clinical T4 stage and number of liver metastases.

Prognostic Factors in Patients with Breast Cancer Liver Metastases (BCLM) Undergoing Liver Resection: Systematic Review and Meta-Analysis

Introduction: Surgical treatment of Breast Cancer Liver Metastasis (BCLM) is debated. We perform a systematic review and meta-analysis of prognostic factors on survival after hepatic resection for BCLM. Methods: An electronic search was performed using PubMed/MEDLINE and Cochrane library databases. Two independent reviewers screened the titles and abstracts. Qualitative and quantitative evaluation of included studies was performed. The pooled effect was calculated using the random-effects model. Results: Thirty-five publications reported analysis on the role of prognostic factors influencing survival after hepatic resection for BCLM and were included in the meta-analysis. Two thousand seven hundred eighty-two patients underwent liver resection for BCLM. The positivity of the axillary lymph nodes at breast cancer diagnosis and the negative Estrogen Receptor status were survival unfavorable factors (HR 1.74, CI 95% 1.25 to 2.41, I2=0% and HR 2.09, CI 95% 1.40 to 3.12, I2=0%). Cumulative HR for predictive factors (multiple liver metastases, size of the metastasis, short interval between primary tumour and onset of liver disease, resection margin and presence of extrahepatic disease) related to the BCLM pattern was 1.32 (CI 95% 1.17 to 1.48, I2=71%) and 1.51 (CI 95% 1.15 to 1.98, I2=76%) for surgical and pathological features. Conclusion: Surgical treatment of BCLM is an option with survival advantages for selected patients. For better long-term results, surgical selection should consider both primary tumour and BCLM features. N0 stage at breast diagnosis, metachronous disease limited to the liver, single BCLM, and highly achievable R0 liver resection may determine the ideal candidate to resection.

Severe and delayed-onset acneiform eruptions as an adverse reaction to regorafenib.

Regorafenib is an oral multikinase inhibitor targeting several tyrosine kinase receptors including BRAF and epidermal growth factor receptor (EGFR) and is approved as a third-line treatment for metastatic gastrointestinal stromal tumor (GIST). While acneiform eruptions have been observed in patients receiving other BRAF and EGFR inhibitors, the commonly reported adverse reactions to regorafenib are fatigue and palmar-plantar erythrodysesthesia. Herein, we report, to the best of our knowledge, the first case who presented with a severe acneiform eruption 24 months after beginning regorafenib for the treatment of GIST. A 61-year-old woman developed GIST with multiple liver metastases, and she was treated with imatinib and sunitinib. However, these therapies were discontinued, and regorafenib was administered. Twenty-four months after beginning regorafenib, she developed an acneiform eruption on her back. Histopathologic analysis of a skin biopsy from the back revealed neutrophilic suppurative folliculitis. Therefore, she postponed regorafenib administration for 2 months and was treated with topical application of clindamycin phosphate hydrate, which was effective. Consistent with reported evidence that the presence of acneiform eruption and the efficacy of EGFR inhibitors are positively associated, regorafenib had good anticancer activity in our patient. Ultimately, we found that although regorafenib- associated skin toxicities usually appear within 1 month of treatment, patients potentially can present with delayed-onset acneiform eruptions even 24 months later.

Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis.

Liver metastasis is a leading cause of cancer morbidity and mortality. Thus, there has been strong interest in the development of therapeutics that can effectively prevent liver metastasis. One potential strategy is to utilize molecules that have broad effects on the liver microenvironment, such as miR-122, a liver-specific miRNA that is a key regulator of diverse hepatic functions. Here we report the development of a nanoformulation miR-122 as a therapeutic agent for preventing liver metastasis. We engineered a galactose-targeted lipid calcium phosphate (Gal-LCP) nanoformulation of miR-122. This nanotherapeutic elicited no significant toxicity and delivered miR-122 into hepatocytes with specificity and high efficiency. Across multiple colorectal cancer liver metastasis models, treatment with Gal-LCP miR-122 treatment effectively prevented colorectal cancer liver metastasis and prolonged survival. Mechanistic studies revealed that delivery of miR-122 was associated with downregulation of key genes involved in metastatic and cancer inflammation pathways, including several proinflammatory factors, matrix metalloproteinases, and other extracellular matrix degradation enzymes. Moreover, Gal-LCP miR-122 treatment was associated with an increased CD8+/CD4+ T-cell ratio and decreased immunosuppressive cell infiltration, which makes the liver more conducive to antitumor immune response. Collectively, this work presents a strategy to improve cancer prevention and treatment with nanomedicine-based delivery of miRNA. SIGNIFICANCE: Highly specific and efficient delivery of miRNA to hepatocytes using nanomedicine has therapeutic potential for the prevention and treatment of colorectal cancer liver metastasis.

Laparoscopic Parenchymal Sparing Multiple Metastatectomy Combined with Left Lateral Segmentectomy for Long Term Hepatic Recurrence from Resected Solid Pseudopapillary Tumor of Pancreas

Introduction: Solid pseudopapillary neoplasm(SPN) of the pancreas are rare tumors that occurs in young women. SPN can metastasizes in 5–15% of all cases and the common site is the liver. The management of metastatic tumors of SPN is unclear. We report a case of Laparoscopic Parenchymal Sparing Multiple Metastatectomy Combined with Left Lateral Segmentectomy for long term Hepatic Recurrence from Resected Solid Pseudopapillary tumor of Pancreas. Case/methods: A 26-year-old lady underwent distal pancreatectomy with splenectomy on 30/3/2015 for solid pseudopapillary tumor of pancreas. Patient was on routine follow up and a PET CT done on 14/10/2020 showed Multiple Bilobar Liver Metastasis in Segments 2/3, 6, 7, 8. Patient underwent of Laparoscopic Parenchymal Sparing Multiple Metastatectomy Combined with Left Lateral Segmentectomy on 22/10/2020. Intra operatively, metastasis was noted at segment 6,7,8 sub capsular. Intraoperative USG showed deep seated segment 2 metastasis for which Laparoscopic left lateral Segmentectomy was done. Results: Postoperative period was uneventful. Histopathology confirmed the 4 metastasis with adequate margins. She was discharged on post-operative day 2. Post 10 months of surgery patient is having a disease-free survival. Conclusion: Long term hepatic recurrence in SPN is rare. Aggressive management of Liver Metastasis ensures a long term disease free survival. In our case we were able to manage the multiple liver metastasis using a combination of Laparoscopic Parenchymal sparing hepatic metastatectomy and Left Lateral Segmentectomy to achieve a R0 resection and this reinforces the role of laparoscopic liver surgery even in such rare tumors.

Gastric Mixed Adenoneuroendocrine Carcinoma with Revised Diagnosis after Retrospective Pathologic Review

Gastric mixed adenoneuroendocrine carcinoma (MANEC) is an entity defined by World Health Organization in 2010, which is composed of adenocarcinoma and neuroendocrine neoplasm. This is a very rare type of tumor in the stomach, which is estimated to be one to two per one million people per year on gastrointestinal track. In general, as MANEC often shows a poor prognosis, early diagnosis of the disease is important for achieving a favorable outcome. However, due to its rarity and histological heterogeneity, it is hard to suspect this disease initially, and sometimes this tumor is misdiagnosed as adenocarcinoma. The present case was a 76-year-old man who was initially diagnosed with gastric tubular adenocarcinoma without distant metastasis. Only 1 month after a curative surgery, multiple liver metastases were newly detected. Retrospective pathologic review resulted in a revised diagnosis as a gastric MANEC, and the patient underwent palliative systemic chemotherapy to achieve partial response.

Primary hepatic neuroendocrine tumour with multiple liver metastases: A case report with literature review.

Introduction and importanceTo describe an unusual case with a primary hepatic neuroendocrine tumour (PHNET) with multiple liver metastases.Case presentationWe reported a 65-year-old woman with PHNET with multiple liver metastases. She was highly suspected of having primary liver cancer with multiple intrahepatic metastases before liver biopsy, but was diagnosed with PHNET with multiple liver metastases after histopathology and immunohistochemistry (IHC) examinations. The patient successfully underwent three times of transcatheter arterial chemoembolization (TACE), and is currently living in a good state without related complications.Clinical discussionNeuroendocrine tumors (NETs), also known as carcinoids or argyrophilic tumors, are very rare malignant tumors. The liver is the main metastasis site of NETs, but primary hepatic neuroendocrine tumors (PHNETs) are extremely rare. Histopathology and immunohistochemistry (IHC) examinations are still the main methods used for diagnosing NETs. There are no treatment guidelines for PHNETs, and surgical resection is generally the preferred treatment. For PHNET patients who are not suitable for surgery, TACE has been proven to be an effective alternative treatment that can effectively reduce the tumour burden and relieve symptoms, but the current evidence is still limited.ConclusionThe clinical diagnosis of PHNET still faces great challenges, imaging examinations often lead to misdiagnosis, and its diagnosis mainly depends on histopathology and immunohistochemical examinations. For PHNET patients who are not suitable for surgery, TACE may be an effective alternative therapy.