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Hepatitis C viral (HCV) treatment has rapidly advanced with the use of direct-acting antivirals (DAA), and many patients achieve sustained virological response (SVR). Although the risk of liver tumors is greatly reduced, there are still patients who achieve SVR but will progress to hepatocellular carcinoma (HCC). HCV infection is also a known risk for cholangiocellular carcinoma (CLC), although it is considered a relative infrequent liver malignancy. We report a series of five cases of CLC in patients that achieved SVR after HCV treatment with DAA. There were three women and two males with a median age of 62 years (range 49 to 77 years). Four patients had liver cirrhosis at the time of their HCV treatment. The interval from achieving SVR until CLC diagnosis varied, ranging from 4 to 36 months (median=12). Three patients presented with advanced disease and had extrahepatic spread at the time of their diagnosis. One patient had a resectable tumor, with no recurrence 4 years later. In one case, the tumor was initially considered an atypical HCC and was treated by radiofrequency ablation. Three years later, she was diagnosed with a large tumor recurrence that was demonstrated to be a CLC on liver biopsy. The last two patients were older males with HCV compensated cirrhosis diagnosed with CLC more than two years after achieving SVR. Palliative chemotherapy was started in both. Only a handful of CLC cases have been reported in HCV patients after SVR. Clinicians should take into account the possible development of an aggressive CLC.

"Background: Cancer patients represent one of the most challenging group to care for during the Covid-19 pandemic. In this study, we aim to present the experience of our Oncology Department during the ongoing Covid-19 pandemic. Methods: The activity of our Oncology Department was retrospectively analyzed from 16th March to 15th December 2020 to investigate how the organizational changes related to Covid-19 pandemic influenced the oncological activity in comparison with the same period in 2019. We also assessed the cases of SARS-CoV-2 infections observed among patients and oncology health professionals from our department. Results: We report an important shift of the oncology activity at our department. The number of inpatients decreased by 50% while the number of treatments administered in the outpatient treatment unit decreased by 13%. We performed 4775 swabbing tests to detect SARS-CoV-2 infection in 1147 symptomatic and asymptomatic patients before receiving treatment or undergoing imaging examinations. SARS-CoV-2 infection was detected in 68 (5.9%) patients. Most of the patients were asymptomatic at the moment of the diagnosis (60%). Two patients were admitted to the intensive therapy unit; 12 had severe pneumonia and were hospitalized. All the other patients had a mild form of Covid-19 and were referred to home-based management, according to the local practice and clinical indications. Four patients died of Covid-19 related complications and 32 patients have already resumed their oncological treatment. Conclusion: Our experience demonstrates that timely adoption of protective measures and coordinated efforts of all medical staff can lead to effective protection of Journal of Medical and Radiation Oncology Journal homepage: www.jmedradonc.org Original research 36 patients with cancer and healthcare professionals, while minimally disrupting adequate cancer care. Methods: The activity of our Oncology Department was retrospectively analyzed from 16th March to 15th December 2020 to investigate how the organizational changes related to Covid-19 pandemic influenced the oncological activity in comparison with the same period in 2019. We also assessed the cases of SARS-CoV-2 infections observed among patients and oncology health professionals from our department. Results: We report an important shift of the oncology activity at our department. The number of inpatients decreased by 50% while the number of treatments administered in the outpatient treatment unit decreased by 13%. We performed 4775 swabbing tests to detect SARS-CoV-2 infection in 1147 symptomatic and asymptomatic patients before receiving treatment or undergoing imaging examinations. SARS-CoV-2 infection was detected in 68 (5.9%) patients. Most of the patients were asymptomatic at the moment of the diagnosis (60%). Two patients were admitted to the intensive therapy unit; 12 had severe pneumonia and were hospitalized. All the other patients had a mild form of Covid-19 and were referred to home-based management, according to the local practice and clinical indications. Four patients died of Covid-19 related complications and 32 patients have already resumed their oncological treatment. Conclusion: Our experience demonstrates that timely adoption of protective measures and coordinated efforts of all medical staff can lead to effective protection of Journal of Medical and Radiation Oncology Journal homepage: www.jmedradonc.org Original research 36 patients with cancer and healthcare professionals, while minimally disrupting adequate cancer care."

Neuroendocrine lung tumors are rare neoplasms, with an increasing incidence in the last thirty years. Metastatic disease is rarely curable. We present the case of a 65-year-old male patient with atypical functional carcinoid of the lung and synchronous liver metastases beginning with carcinoid syndrome treated with somatostatin analogues, chemotherapy and peptide receptor radionuclide therapy, with a good clinical response and remission of the carcinoid syndrome.

Background Although guidelines recommend systemic therapy even in patients with limited extrahepatic metastases from hepatocellular carcinoma (HCC), a few recent studies suggested a potential benefit for resection of extrahepatic metastases. However, the benefit of adrenal resection (AR) for adrenal-only metastases (AOM) from HCC was not proved yet. This is the first study to compare long-term outcomes of AR to those of sorafenib in patients with AOM from HCC. Methods The patients with adrenal metastases (AM) from HCC were identified from the electronic records of the institution between January 2002 and December 2018. Those who presented AM and other sites of extrahepatic disease were excluded. Furthermore, the patients with AOM who received other therapies than AR or sorafenib were excluded. Results A total of 34 patients with AM from HCC were treated. Out of these, 22 patients had AOM, 6 receiving other treatment than AR or sorafenib. Eventually, 8 patients with AOM underwent AR (AR group), while 8 patients were treated with sorafenib (SOR group). The baseline characteristics of the two groups were not significantly different in terms of age, sex, number and size of the primary tumor, timing of AM diagnosis, Child-Pugh and ECOG status. After a median follow-up of 15.5 months, in the AR group, the 1-, 3-, and 5-year overall survival rates (85.7%, 42.9%, and 0%, respectively) were significantly higher than those achieved in the SOR group (62.5%, 0% and 0% at 1-, 3- and 5-year, respectively) (P = 0.009). The median progression-free survival after AR (14 months) was significantly longer than that after sorafenib therapy (6 months, P = 0.002). Conclusions In patients with AOM from HCC, AR was associated with significantly higher overall and progression-free survival rates than systemic therapy with sorafenib. These results could represent a starting-point for future phase II/III clinical trials.

Background and Aims: The correlations between primary tumor location (right colon cancer – RCC, left colon cancer – LCC and rectal cancer – RC) and the incidence of metastatic sites are scarce and divergent. The current study is the first which compares the pattern of metastatic distribution (M1a: metastasis to one organ/site, excluding peritoneum; M1b: two or more metastatic sites; M1c: peritoneal metastases) between RCC, LCC and RC, respectively. Methods: All patients operated for colorectal cancer (CRC) between January 2006 and December 2015 were analyzed to assess the primary tumor location, the presence and site of synchronous metastases. Univariate analysis determined the statistical significance of association between each CRC location and the metastatic pattern. Multinomial logistical regression model compared the prevalence of each metastatic pattern for each CRC location. Results: Out of 5,107 patients, 1,318 (25.80%) had metastases on the moment of CRC diagnosis. There were no statistically significant association between the metastatic pattern and the patients’ gender (M1a, p=0.321; M1b, p=0.539; M1c, p=0.417, Chi-square) or patients’ age (p=0.616 Mann–Whitney U-test). RC had a significant higher relative risk for M1a (RR of 1.437, p=0.014) and a lower relative risk for M1c (RR of 0.564, p=0.001), compared to LCC. On the contrary, compared with LCC, the RCC showed a significant lower relative risk for M1a (RR of 0.673, p=0.006) and a higher relative risk for M1c (RR of 1.834, p=0.0001). Conclusion. There is a strong correlation between the primary location of CRC and the pattern of the metastatic spread, with potential prognostic implications.

NC-6004 is a nanoparticle developed using micellar technology that can improve release of cisplatin, a standard treatment for many cancer types, and achieve selective distribution to tumors. Here, in the Phase II portion of this study, the activity, safety, tolerability, and effects on quality of life of NC-6004 in combination with gemcitabine was examined in 34 squamous non-small cell lung carcinoma (NSCLC) patients, 50 biliary tract cancer patients, and 13 bladder cancer patients. All patients received 135 mg/m2 NC-6004 on day one and 1,250 mg/m2 gemcitabine on days one and eight. The median progression-free survival was 3.9 months in NSCLC patients, 4.3 months in biliary tract cancer patients, and 6.8 months in bladder cancer patients fit for cisplatin treatment. The most frequently reported Grade 3 Treatment Emergent Adverse Events across all cohorts were nausea, anemia and neutropenia, and hyponatremia. Quality of life measures for patients who received the combined therapy were generally consistent with expectations for patients undergoing chemotherapy. Overall, combined NC-6004 and gemcitabine treatment resulted in long-lasting antitumor activity and had a favorable safety profile, suggesting that it should be investigated further as a therapy for various types of cancer.

International audience; Simple Summary There have been huge improvements in both vaccination and the management of COVID-19 in patients with cancer. In addition, different variants may be associated with different presentations. Therefore, we examined whether indicators of the severity of COVID-19 in patients with cancer who present to hospital varied during different waves of the pandemic and we showed that these indicators remained predictive. We validated that the COVID-19 Risk in Oncology Evaluation Tool (CORONET), which predicts the severity of COVID-19 in cancer patients presenting to hospital, performed well in all waves. In addition, we examined patient outcomes and the factors that influence them and found that there was increased vaccination uptake and steroid use for patients requiring oxygen in later waves, which may be associated with improvements in outcome. Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

We performed a meta-analysis of published data to investigate the diagnostic value of artificial intelligence for pancreatic cancer. Systematic research was conducted in the following databases: PubMed, Embase, and Web of Science to identify relevant studies up to October 2021. We extracted or calculated the number of true positives, false positives true negatives, and false negatives from the selected publications. In total, 10 studies, featuring 1871 patients, met our inclusion criteria. The risk of bias in the included studies was assessed using the QUADAS-2 tool. R and RevMan 5.4.1 software were used for calculations and statistical analysis. The studies included in the meta-analysis did not show an overall heterogeneity (I2 = 0%), and no significant differences were found from the subgroup analysis. The pooled diagnostic sensitivity and specificity were 0.92 (95% CI, 0.89–0.95) and 0.9 (95% CI, 0.83–0.94), respectively. The area under the summary receiver operating characteristics curve was 0.95, and the diagnostic odds ratio was 128.9 (95% CI, 71.2–233.8), indicating very good diagnostic accuracy for the detection of pancreatic cancer. Based on these promising preliminary results and further testing on a larger dataset, artificial intelligence-assisted endoscopic ultrasound could become an important tool for the computer-aided diagnosis of pancreatic cancer.

Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a high number of intra tumor infiltrating lymphocytes (TILs). Therefore, immunomodulation is considered to have an important role in cancer treatment, and immune checkpoint inhibitors may be useful for restoring T cell-mediated antitumor immunity. However, the data presented in the literature until now are not sufficient to allow for the identification and selection of patients who really respond to immunotherapy among those with ovarian cancer. Although there are some studies with favorable results, more prospective trials are needed in this sense. This review focuses on the current and future perspectives of PD-1/L1 blockade in ovarian cancer and analyzes the most important immune checkpoint inhibitors used, with the aim of achieving optimal clinical outcomes. Future studies and trials are needed to maximize the efficacy of immune checkpoint blockade therapy in ovarian cancer, as well as in all cancers, in general.

Due to the permanent discordance between the number of available liver grafts and the number of cases on the waiting lists, attention was focused on developing different solutions in order to increase the number of grafts. Once the technique of living donor has been proposed, the number of grafts increased but the gap between the number of available grafts and the cases on the waiting list is still significant. Therefore attention was focused on finding out other solutions such as splitting the graft or performing a domino liver transplant. The procedure of domino transplant consists of harvesting a graft from a young patient with metabolic disorders in which a healthy graft will be used and implants it to a marginal receiver. The method seems to associate minimal risks for the marginal donor to develop the metabolic disorder especially if the donor suffers from familial amyloid polyneuropathy; however, ethical issues in such cases are obvious. The aim of this paper is to analyse both the benefits of domino liver transplant and the ethical issues of the procedure.

Ex vivo liver surgery techniques have been proposed almost two decades ago in order to extend the indications and feasibility of liver resections for large, but not absolutely unresectable liver lesions. However, the procedure remains a demanding one, being associated with high risks of postoperative complications; therefore it should be performed only in specialized centers. This is a literature review of the largest studies conducted on the theme of ex vivo liver resection for tumoral pathology.

Ovarian cancer remains one of the most aggressive biological malignancies which is characterised by a high capacity of relapse even in cases in which a curative intent treatment is performed. In such cases the therapeutic options are rather limited, especially in platinum resistant lesions. The aim of this paper is to analyse the reported results after performing intraperitoneal heated chemotherapy in such cases.

Duodenal carcinoma remains a very rare pathology, the most efficient therapeutic strategy remaining intensively debatable. However, it seems that the most appropriate therapeutic approach for each case can be established depending on the dimensions and stage of the tumor and according to the tumoral localization. Although initially it has been proposed that in all cases in which resection is feasible a duodenopancreatectomy should be performed, nowadays the therapeutic strategy has been submitted to permanent changes, more conservative approaches such as endoscopic full thickness resection or pancreas preserving duodenal resection being proposed with encouraging results. This is a literature review of the largest studies which investigated the feasibility of duodenal resections for duodenal malignant tumors.

Background/aim Although pelvic exenteration is an aggressive surgical procedure, it remains almost the only curative solution for patients diagnosed with large pelvic malignancies. Patients and methods We present a series of 100 patients submitted to pelvic exenteration with curative intent. Results The origin of the primary tumor was most commonly represented by cervical cancer, followed by, endometrial cancer, rectal cancer, ovarian cancer and vulvo-vaginal cancer. An R0 resection was confirmed in 68 cases, while the remaining 32 cases presented lateral positive resection margins or perineal positive margins. The postoperative morbidity rate was 37% while the mortality rate was 3%. As for the-long term outcomes, the median overall survival time was 38.7 months, being most significantly influenced by the origin of the primary tumor. Conclusion Although pelvic exenteration is still associated with an increased morbidity, an important improvement in the long-term survival can be achieved, especially if radical resection is feasible.

Background/aim Pancreatic cancer remains asymptomatic for a long period of time, being frequently diagnosed when vascular invasion is already present. Such cases are widely known as borderline lesions. The aim of this study was to identify the effectiveness of vascular resection in this subgroup of patients. Patients and methods Fifteen such cases were submitted to surgery with curative intent. Results Eight cases were diagnosed with borderline resectable lesions with portal vein invasion and were submitted to per primam resection and seven cases were initially diagnosed with arterial invasion and had been initially submitted to neoadjuvant chemotherapy followed by resection. In all cases portal vein resection was needed while in other four cases association of superior mesenteric artery resection was performed. Postoperatively, five patients developed complications requiring reoperation, three of whom died at the end of the first postoperative month. The histopathological studies confirmed the completeness of resection in all cases. Conclusion Vascular resections in pancreatic cancer resections remain demanding procedures, and are reserved for cases in which a radical resection is feasible.

Hepatocellular carcinoma (HCC) is a significant health problem. Globally is the second most common cause of cancer-associated death and the fifth most frequent neoplasm. The main risk factors for the onset of HCC are well recognized, including the presence of cirrhosis, chronic hepatitis C and hepatitis B infections and heavy alcohol consumption. In an early stage disease, there are potentially curative therapies, such as surgical resection, transplantation and loco-regional procedures. However, at the time of diagnosis, a large number of patients present an advanced stage disease, according to the Barcelona Clinic Liver Cancer (BCLC) classification. Background. Sorafenib chemotherapy is the first-line therapy for patients with hepatocellular carcinoma (HCC) in an advanced stage. The aim of this study was to evaluate prognostic factors of survival in HCC patients treated with sorafenib, in real-life clinical practice. Methods. We perform an retrospective, non-randomized study and we analyzed 162 patients with HCC who were treated with sorafenib 800 mg/day in Oncology Department of Fundeni Clinical Institute between 2009 and 2016. Results. Mortality in our patients group was more than 80%, with survival rate about 22 months and a median survival rate 13 months. The patients with liver cirrhosis has a severe evolution compared with those who has hepatitis. We found a good survival rate for HCV infected patients compared with HVB or VHB +VHD etiology. BCLC and Child-Pugh classification have an important role in overall survival.

Background: Patients with cancer are at increased risk of severe COVID-19, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 in cancer patients predicting severe disease and build a decision-support online tool; COVID-19 Risk in Oncology Evaluation Tool (CORONET). Methods: Patients with active cancer (stage I-IV) and laboratory confirmed COVID-19 presenting to hospitals worldwide were included. Discharge (within 24hrs), admission (≥24hrs inpatient), oxygen requirement (O2) and death were combined in a 0-3 point severity scale. Association of features with outcome were investigated using Lasso regression and Random Forest (RF) combined with SHapley Additive exPlanations (SHAP). RF was further validated in 4 cohorts, split by geography. The CORONET model was then examined in the entire cohort to build an online CORONET decision-support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Findings: The dataset comprised 920 patients; median age 70 (range 5-99), 56% males, 44% females, 81% solid vs. 19% haematological cancers. In derivation, RF demonstrated superior performance over Lasso with lower mean squared error (0.801 vs. 0.807) and was selected for development. During validation, RF achieved mean AUROC 0.77, 0.80 and 0.75 for prediction of admission, O 2 and death, respectively. Using the entire cohort, CORONET cut-offs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died. SHAP explanations revealed National-Early-Warning-Score-2, C-reactive protein and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. Interpretation: CORONET, a decision-support tool validated in healthcare systems worldwide can aid admission decisions and predict COVID-19 severity in patients with cancer. Funding Information: R. Lee and T. Robinson and J. Weaver are supported by the National Institute for Health Research as Clinical Lecturers. T. Bhogal is supported by the National Institute for Health Research as an academic clinical fellow. U. Khan is an MRC Clinical Training Fellow based at the University of Liverpool supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (Award Ref. MR/N025989/1). The Liverpool Experimental Cancer Medicine Centre for providing infrastructure support (Grant Reference: C18616/A25153) and The Clatterbridge Cancer charity (North West Cancer Research). C. Dive is funded by CRUK Core funding to Manchester Institute (C5757/A27412) and is supported by the CRUK Manchester Centre Award (C5759/A25254), and by the NIHR Manchester Biomedical Research Centre. C. Zhou is funded by the CRUK Manchester Centre Award (C5759/A25254), J. Stevenson and P. Fitzpatrick are funded by the CRUK Accelerator Award (29374). This research was funded in part, by the Wellcome Trust [205228/Z/16/Z]. LT is also supported by the National Institute for Health Research Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. LT is based at University of Liverpool. MS is supported by a grant from the Ministry of Science and Higher Education of the Russian Federation for the state support for the creation and development of World Class Research Centers "Digital biodesign and personalized healthcare” N.075-15-2020-926. Declaration of Interests: R Lee research funding (institution) BMS and speaker fees Astrazeneca. A. Croitoru Consulting or Advisory Role: Lilly, Merck, Roche, Bayer, Novartis, Ipsen, Research Funding me and my hospital: Gilead Sciences, Pfizer, Canfite, NanoCarrier, Bristol-Myers Squibb, Merck, Amgen, Servier, Five Prime Therapeutics, Travel Accommodations: Pfizer, Genekor, and oz, Merck, Pfizer, Servier, Roche. O. Michielin reports personal fees from Bristol-Myers Squibb, personal fees from MSD, personal fees from Novartis, personal fees from Roche, personal fees from Amgen, personal fees from NeraCare GmbH, outside the submitted work. E. Romano institutional research grants from Amgen, Astra Zeneca, Bristol-Myers Squibb. G. Pentheroudakis advisory board for Amgen, Astra Zeneca, Bristol-Myers Squibb, Lilly, Merck, MSD, Roche, Abbvie, institutional research grants from Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Debbio, Enorasis, Genekor, Ipsen, Janssen, Lilly, Merck, MSD, Pfizer, Roche, Sanofi, Servier. Solange Peters reports consultation/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody, talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda, receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. M Rowe honoraria from Astellas Pharma, speaker fees MSD and Servier. C. Wilson consultancy and speaker fees Pfizer, Amgen, Novartis, A Armstrong conference fee Merck, spouse shares in Astrazeneca. T Robinson financial support to attend educational workshops from Amgen and Daiichi-Sankyo. C Dive, outside of this scope of work, has received research funding from AstraZeneca, Astex Pharmaceuticals, Bioven, Amgen, Carrick Therapeutics, Merck AG, Taiho Oncology, Clearbridge Biomedics, Angle PLC, Menarini Diagnostics, GSK, Bayer, Boehringer Ingelheim, Roche, BMS, Novartis, Celgene, Thermofisher. C Dive is on advisory boards for, and has received consultancy fees/honoraria from, AstraZeneca, Biocartis and Merck KGaA. No other authors have nothing to declare. Ethics Approval Statement: Approval (reference 20/WA/0269) was granted from the UK Research Ethics Committee for the study. Information regarding governance/regulatory approvals for each international cohort are available in the Supp. Methods.

Somatostatinomas are rare neuroendocrine tumors (NET) that arise in the gastrointestinal (GI) tract. Because of their insidious growth, they are usually asymptomatic until late stages, presenting as malignant disease. We report the case of a 50-year-old woman who presented with epigastric abdominal pain, diarrhea and significant weight loss in the last two years. On clinical examination the patient met the criteria for neurofibromatosis type 1 (NF1). Abdominal CT and MRI revealed an infiltrative duodenal mass, with pancreatic invasion, locoregional enlarged lymph nodes and disseminated hepatic nodules. Microscopy and immunohistochemistry uncovered a neuroendocrine tumor, staining positive for chromogranin A (CgA), synaptophysin and somatostatin, with a Ki67 = 1%. Somatostatin receptors (SSTRs) type 2 were negative and SSTRs type 5 were positive in less than 50% of tumoral cells. Our patient was classified as a T3N1M1 stage IV metastatic duodenal grade 1 somatostatinoma and treatment with somatostatin analogues and chemotherapy with capecitabine and temozolomide was started, with so far abdominal imaging follow-up showing stable disease. When a patient is diagnosed with a rare NET, such as a somatostatinoma, it is of utmost importance to determine if it is a sporadic tumor or just a feature of a genetic disorder.

Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes&mdash, freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)&mdash, was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p &lt, 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification.

Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS).Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance.Between April 2017 and April 2021, five patients with median age of 68 years (range: 66-78), four male and one female, underwent psALPPS for colorectal liver metastases (N=2), intrahepatic cholangiocarcinoma (N=2), and hepatocellular carcinoma (N=1). Standardized FLR (sFLR) for segments 2-3 before stage 1 surgery would have been a median of 11.6%. PsALPPS could double the sFLR at stage 1 resulting in an increase of ps-sFLR from a median of 22.7% (at stage 1) to 34.0% (at stage 2) after a median interstage interval of 15 days. All patients tolerated surgery well and no major complications were recorded.Applying the principles of parenchyma sparing surgery to ALPPS offers the advantage to maximize FLR and simultaneously reduce ischemic injury of segment 4 compared to conventional ALPPS. In this way, psALPPS may markedly increase resectability while reducing morbidity.https://www.revistachirurgia.ro/pdfs/?EntryID=922974art=2021-parenchyma-sparing-ALPPS-ultrasound-guided-partition.pdf

We report the case of a 55-year-old-male with a large cell metastatic pancreatic neuroendocrine carcinoma treated for 14 months with lanreotide autogel having a stable disease (SD) and not responding to chemotherapy. The somatostatin analogues (SSA) were introduced after an episode of diarrhea and controlled the disease. Progression-free survival (PFS) as determined by Computerized Tomography (CT) scans was obtained for 14 months. After more than a year, the patient's health state deteriorated along with progressive disease. The capecitabine-temozolomide regimen was challenged, but after three cycles, a rapid clinical decline was noted. Conclusion This unexpected event (diarrhea) in the course of the disease could represent the beginning of carcinoid syndrome. While the lanreotide autogel helped the episode of diarrhea pass, it also helped gain control over the disease itself.

Background & Aims: To evaluate the predictive factors for recurrence of the disease and overall survival(OS) after achieving complete response (CR) in patients with hepatocellular carcinoma (HCC) treated withtransarterial chemoembolization (TACE).Methods: From January 2013 to December 2017, 168 treatment-naïve patients diagnosed with HCCunderwent TACE as a first-line therapy and the gathered data was retrospectively reviewed. We determined the predictive factors for complete response (CR), for recurrence after CR and for survival using the Cox proportional hazard model.Results: Median follow-up was 27.4 months (range 4-65 months). The mean patient age was 62.2±7.9 years. Eighty-three patients had an α-fetoprotein (AFP) level > 20ng/mL. The median maximal diameter of the tumors was 3.5 cm. Sixty-three patients (37.5%) achieved CR after TACE, and recurrence after CR was detected in 37 patients (58.7%). In multivariate analysis, tumor size (≤4.5 cm) and a single tumor were found to be predictive factors for CR, with hazard ratios (HRs) of 2.352 (p=0.022) and 3.964 (p 25 ng/mL and multiple tumors were demonstrated to have a significant relationship with recurrence after CR, with HRs of 1.650 (p=0.05) and 3.932 (p=0.038), respectively. Increased initial serum AFP > 22 ng/mL, tumorsize > 4.5 cm, outside Milan criteria, not receiving a liver transplant and presence of portal vein thrombosis (PVT) were correlated with poor survival.Conclusions: In patients treated with TACE as an initial therapy, tumor size (≤4.5 cm) and single tumor were predictive factors for CR. Multiple nodules and an elevated serum AFP > 25 ng/mL were predictive factors for recurrence after CR. Outside Milan criteria tumors, elevated AFP levels and the presence of PVT were significantly correlated with decreased survival.

Gastric cancer is one the most common maligancies and a considerable health problem throughout the world. Multimodal approach, encompassing both radical surgery and perioperative chemotherapy provides the best chance to cure resectable gastric cancer. Data originating from well-conducted randomized trials demonstrate that chemotherapy improves survival in patients with metastatic disease. During the last years, two targeted therapies have been approved in metastatic setting. Based on promising clinical trials results, it is expected for the near future that immunotherapy to be incorporated in the multimodal treatment of gastric cancer.

Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child&ndash, Pugh B, CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg, n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82, 95% confidence interval [CI] 0.49&ndash, 1.38, p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months, HR, 0.81, 95% CI: 0.45&ndash, 1.43, p = 0.46. PFS: 3.5 versus 1.9 months, HR, 0.89, 95% CI: 0.51&ndash, 1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom &ge, 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported, no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.

BACKGROUND AIMS The emergence of tyrosine kinase inhibitors, radically altered the management of GISTs and sparked controversy regarding the role of hepatic resection for metastatic tumors. This study aims to identify whether there is improvement in the overall survival of patients with gastrointestinal liver metastases, undergoing hepatic resection in the context of multimodal treatment strategy, as to those approached only by systemic therapy. Methods: Using a retrospective database, we identified 57 patients treated at our center over a 12-year period: Group A (n=31) underwent hepatic resection alongside systemic therapies, and B (n=26) only systemic therapies. In order to obtain a more robust sample, needed for the survival analysis, we performed a propensity score matching and a bootstrapping selection with Jackknife correction for errors; thus, we created an extended sample of 1000 virtual patients. Results: The overall survival measured in all patients was 47 months (95%CI:34-60); significantly higher for group A (56 months, 95%CI:37-75) compared to group B (38 months, 95%CI:19-56), (p=0.007, Log Rank test). Multivariate analysis identified one risk factor: the presence synchronous liver metastases upon diagnosis of primary. Conclusions: Liver resection following TKI therapy is the current mainstay of treatment strategy for potential cure and prolonged survival, in appropriately selected patients evaluated in an multidisciplinary tumor board.

We present the case of a 37-year-old patient with a surgical history of a gastrointestinal stromal tumor with jejunal location, AFIP classification 6a, hospitalized in our center for synchronous liver metastases. The oncological assessment performed after 12 months from surgery for primary tumor, during which Imatinib was administered, reveals stable disease. CT scan showed a single very large centrally located liver metastasis, 14 cm in diameter, involving segments V and VIII IV, IV and VII, compressing the main portal bifurcation, right hepatic vein, umbilical (scizural) vein and left hepatic vein, invading the middle hepatic vein. We considered it feasible to apply the concept of R1 vascular resection, performing a limited, non-anatomical, ultrasound-guided central hepatectomy, allowing detachment of the tumor from the right hepatic vein and from the umbilical vein. Thus, we sacrificed only the ventral portal pedicles of segments V and VIII and partially preserved these segments to avoid the risk of post-resection liver failure.Currently, the patient is disease-free after 53 months, supporting the concept of ultrasound-guided R1 vascular resection, in the context of systemic therapy with tyrosine kinase inhibitors for metastases of stromal gastrointestinal tumors. (video article https://www.revistachirurgia.ro/pdfs/video/Liver-Resection-Metastases-Stromal-Tumors-2283.mp4).

video width="640" height="480" controls controlsList="nodownload" poster="https://www.revistachirurgia.ro/pdfs/video/Complete_segment_resection_hepatectomy_klatskin_tumor.jpg" style="margin-top: -20px;" source src="https://www.revistachirurgia.ro/pdfs/video/Complete_segment_resection_hepatectomy_klatskin_tumor.mp4" type="video/mp4" Your browser does not support the video tag. /video We present the case of a 37-year-old male patient with no significant history, hospitalized in our center for painless jaundice with sudden onset. CT contrast portal phase imaging revealed a tumor located at the main biliary confluence, in the proximity of the main portal bifurcation, with no venous or arterial vascular invasion, nor extrahepatic metastases. MRCP diagnosed a Bismuth- Corlette type Klatskin IIIb tumor. For complete assessment of biliary involvement and surgical planning, in addition to the Bismuth-Corlette classification, we took into consideration the presence of infiltration of the bile ducts for segment 1, documented at MRCP. Therefore, a left hepatectomy with en-bloc complete segment 1 resection, along with the main bile ducts and hilar lymphadenectomy, was considered best suited for achieving curative resection in this case. After an uneventful postoperative course, the patient was discharged in the 12th postoperative day. Currently, the patient is disease-free after 84 months. We consider that the long-term recurrence free survival was favored by the complete segment 1 resection. Therefore, for complete assessment of biliary involvement in Klatskin tumor, we recommend that in addition to Bismuth-Corlette classification, infiltration of the bile duct for segment 1 should always be evaluated. If present, the entire segment 1 should be removed for best oncological results.

Hematopoietic bone marrow toxicity is most often the limiting factor for chemotherapy doses. Increasing the intensity of chemotherapy doses (higher doses or more frequent administration) would improve antitumor effects, but the hematological toxicity does not allow these dose increases. This study evaluated the impact of chemotherapies on the parameters belonging to the red blood cell series in the hemogram and aimed to identify some particular evolution profiles. We selected 855 evaluations performed before the administration of chemotherapy belonging to the treatments initiated during the period December 2018-February 2020, containing 5-fluorouracil, cisplatin, docetaxel, epirubicin or pemetrexed. The data of the 644 evaluations related to the cycles 1-4 of chemotherapy were subject to this processing. The average relative loss of hemoglobin is -11% after the first three cycles of treatment, with statistically significant differences in hemoglobin levels in favor of men. There are risk factors associated with higher average losses, such as age 65 years (statistically significant), body mass index (BMI) >25, cisplatin treatment (insufficient number of cases to reach statistical significance).