COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

DURABLE RESPONSE IN A CASE OF METASTATIC ANAPLASTIC THYROID CANCER USING A COMBINATION OF TYROSINE KINASE INHIBITORS AND A CHECK POINT INHIBITOR.

Anaplastic thyroid cancer (ATC) is a highly uncommon (less than 2% of thyroid malignancies) and aggressive type of cancer, with aggressive behavior and, therefore, exhibiting poor prognosis. ATC tumors are automatically labeled as stage IV disease regardless of standard criteria such as tumor burden or metastasis. ATC tumors require a diversified treatment approach that includes surgical resection, followed by a complete an aggressive combination of radiation and chemotherapy and/or palliative care. Despite best efforts, 1-year overall survival of patients is 20% to 40% with nearly universal mortality rate. Consequently, novel approaches (targeted therapy, immunotherapy) have been studied, alone or in combination, to improve the dire prognosis of these patients. BRAF V600E mutation is the most common genetic mutation found in ATC. We report the case of a 57-year-old man diagnosed with stage IVc (undifferentiated) ATC with hepatic and osseous metastases. The molecular analysis of the tumor revealed a V600E BRAF-mutation. The patient was treated with Dabrafenib and Trametinib, and achieved remission 5 weeks after starting the treatment. Subsequently, he had a thyroidectomy, and pembrolizumab was added to the two tyrosine kinase inhibitors. 9 months later he is still in remission. This case illustrates the importance of obtaining molecular information in anaplastic thyroid cancer and the urgent need of studies investigating the combination of tyrosine kinase inhibitors and check-point inhibitors in patients with V600E BRAF- mutations.

LARGE CELL METASTATIC PANCREATIC NEUROENDOCRINE CARCINOMA TREATED WITH SOMATOSTATIN ANALOGUES - CASE REPORT AND LITERATURE REVIEW.

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.

Metastatic neuroendocrine pancreatic tumor - Case report.

Rationale.Pancreatic neuroendocrine tumors (NETs) are rare neoplasms that develop from the endocrine tissues of the pancreas. They have a better overall prognosis than pancreatic adenocarcinoma. However, all commonly used classification systems reflect a separation between more indolent, well-differentiated tumors and far more aggressive poorly differentiated types that behave clinically more like small-cell carcinoma of the lung. Objective.To present the case of a 62-year-old man with an aggressive pancreatic NET, with liver, splenic and bone metastases who underwent multidisciplinary treatment including several lines of chemotherapy, somatostatin analogs and radiotherapy. Methods and Results.The patient is a smoker and an occasional drinker, known with type two diabetes mellitus (DM), receiving insulin therapy. He was diagnosed by contrast-enhanced computed tomography (CT) in January 2015 with a locally invasive pancreatic body mass, intraabdominal adenopathies and liver nodules, suggestive of metastases. Histopathological diagnosis was obtained through liver biopsy: neuroendocrine tumor with a 10-15% Ki67 proliferation index. Palliative chemotherapy with oxaliplatin and capecitabine was started in March 2015. In June 2015, Sandostatin LAR was added. In March 2016, he had progressive disease. Subsequently, in September 2016, bone metastasis was found within the T10 vertebra. He underwent radiotherapy for multiple bone metastases in February 2017. Progressive disease was again found during a CT examination in May 2017. His performance status has gradually worsened since then and he died in July 2017. Discussion.As a group, well-differentiated gastroenteropancreatic NETs are generally indolent malignancies with prolonged natural history. Intermediate-grade NETs have a slightly worse prognosis than low-grade tumors. Abbreviations: NETs - neuroendocrine tumors, NEC - neuroendocrine carcinoma, CT - computed tomography, MRI - magnetic resonance imaging, DM - diabetes mellitus, WHO - World Health Organisation, HCV - hepatitis C virus, CEA - carcinoembryonic antigen, AFP - alpha-fetoprotein, 5-HIAA - 5-Hydroxyindoleacetic acid, IHC - immunohistochemistry, EUS - endoscopic ultrasonography, EUS FNA - endoscopic ultrasonography with fine needle aspiration, CgA - chromogranin A, PRRT - peptide receptor radioligand therapy.

PROGNOSTIC FACTORS IN PATIENTS WITH SURGICAL RESECTION OF PANCREATIC NEUROENDOCRINE TUMOURS.

CONTEXT: Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. OBJECTIVE: The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. SUBJECTS AND METHODS: The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. RESULTS: Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. CONCLUSIONS: Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%.

In vitro Research of the Concentration Dependence of Effect of Adrenaline on Platelets Aggregation.

PURPOSE: Paper intended to present experimental evidences that adrenaline has a direct effect of inducing platelets aggregation in the concentration range 1-8µM. MATERIAL/METHODS: Platelet rich plasma from patients of Colentina Clinical Hospital, following an informed consent. The platelet rich plasma (PRP) was prepared by centrifuging the anticoagulated sample at 200 G for 10 minutes. Aggregation was evaluated by optical aggregometry, classical method of Born, using Helena PACKS-4 Aggregometer. RESULTS: The curves transmission light-time followed the structure: a lag-time, a first phase aggregation, more or less linear, defined by a "Slope 1", a second wave of aggregation defined by "slope 2" and a "saturation" phase. Slope 1 increases with the concentration of adrenaline. The second slopes of the aggregation curves, maximum aggregation and areas under curves depended linear on adrenaline concentration. CONCLUSIONS: Adrenaline, in concentrations in the 1-8µM, induce aggregation of human platelets from platelet rich plasma. Linear regression models for slope and area were practically identical suggesting a rather unique than biphasic mechanism of action of adrenaline during the time course of aggregation.

Metachronous Ampulla of Vater Carcinoma after Curative-Intent Surgery for Klatskin Tumor.

Resection represents the single hope for long-term survival in a patient diagnosed with a hilar cholangiocarcinoma (Klatskin tumor). However, the largest part of these patients develops a recurrent disease. Second metachronous periampullary cancers after a curative-intent surgery for a Klatskin tumor represent an exceptional pathology, and the management of these patients was poorly documented. Hereby, it is presented a 32-year-old patient with bile duct resection, left hemi-hepatectomy and loco-regional lymph nodes dissection, for a type IIIB Bismuth-Corlette Klatskin tumor, which, furthermore, 6 years later, underwent a pancreaticoduodenectomy for a metachronous carcinoma of the ampulla of Vater. The management and outcomes were discussed in the reported case, along with a literature review of the previously published patients. In conclusion, a metachronous periampullary carcinoma after resection of a Klatskin tumor should be distinguished from a loco-regional recurrent disease. While most of the patients with recurrences are suitable to only chemotherapy and or radiotherapy, a second curative-intent surgery (i.e., pancreaticoduodenectomy) is feasible in the largest part of the patients with a metachronous cancer, with good long-term outcomes.

Outcome of liver transplantation for hepatocellular carcinoma -- a single center experience.

BACKGROUND & AIMS: Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The aim of our study was to evaluate our experience regarding the clinical and pathological staging of HCC in patients who underwent LT, as well as recurrence free and overall survival. METHODS: From January 2006 to December 2011, 38 patients with diagnosis of HCC, underwent LT in our Center. Demographic, clinical, imaging and pathologic information were recorded. A Cox proportional hazards survival analysis was performed in order to identify significant predictors of tumor recurrence and patient's death after LT. RESULTS: Eighteen patients (47.4%) in our study group were within Milan criteria. The mean follow-up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3- year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3-year overall survival rates were 83.5% and 63.6% respectively. No significant predictor for HCC recurrence was identified in our study group by survival analysis, taking into account 13 different variables. As independent predictors of patient'ss death after LT for HCC however, the presence of diabetes mellitus (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence after LT (p=0.03) were identified by multivariate Cox proportional hazards survival analysis. CONCLUSION: In our cohort HCC recurrence rate after LT was 13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence were significant predictors of poor overall survival after LT.

Case study of appendiceal carcinoid during pregnancy.

The carcinoid tumor of the appendix is one of the most common tumors of the appendix, but one of the rarest anatomic locations of carcinoids. The prognosis is very good, as most tumors are incidentally discovered during surgery for acute or sub-acute appendicitis. The diagnosis is exceptional when combined with pregnancy. We present such a case of a 27-year-old female patient. An emergency appendectomy was performed, and soon after, pregnancy was confirmed. The patient had a tumor smaller than 1 cm in diameter, at the tip of the appendix. The immunochemistry revealed the neuroendocrine profile by positive reaction for chromogranin A and synaptophysin, with a ki-67 profile at an undetectable level. After surgery, the neuroendocrine markers and the octreoscan were negative, consequently indicating a favorable prognosis. Further follow-up is necessary, even though not all the authors recommend it (considering the low index to the associated metastases, especially for small appendiceal tumors). A short review of the literature is presented, starting with this case report.

Simultaneous resection of the primary colorectal tumor and liver metastases--a safe and effective operation.

BACKGROUND: The aim of this retrospective study was to compare the results achieved by simultaneous resection (SR) vs. delayed resection (DR) in patients with synchronous colorectal liver metastases (SCRLM). METHODS: In "Dan Setlacec" Center of General Surgery and Liver Transplantation from Fundeni Clinical Institute, between 1995 and 2010, 117 patients underwent SR and 25 patients underwent DR. It was compared the outcome of the patients in the two groups. It was also assessed if certain subgroups of patients present a better outcome after DR than after SR. RESULTS: The location of the primary tumor, the number and diameter of liver metastases, and the proportion of major hepatectomies were similar in the two groups (p value > 0.05). For all patients, the morbidity, mortality, disease-free and overall surrvival rates were not statistically significant different between the two groups (p value > 0.05). In subgroups of patients with rectal tumors, with multiple liver metastases, and undergoing major hepatectomies, the morbidity, mortality and survival rates achieved by SR were similar to those achieved by DR. CONCLUSION: Simultaneous resection of SCRLM is similarly safe and efficient as the delayed resection, even in patients with rectal tumors, with multiple liver metastases, or undergoing major hepatectomies.

[Primary pancreatic cystic neoplasms--diagnosis and treatment]. / Neoplasmele chistice primare pancreatice--diagnostic si conduita terapeutica.

The paper's purpose is to analyze the diagnosis and treatment methods of primary pancreatic cystic neoplasms. Between 1996-2007, 10 patients (3 male and 7 female), ages between 30 and 71, were committed and surgically treated in the Surgical Unit of Colentina Clinical Hospital of primary pancreatic cystic neoplasms: 2 serous cystadenomas (SCAs) and 8 mucinous cystic neoplasms (MCNs) (in one case there were liver and peripancreatic lymph nodes metastases). Following clinical and paraclinical evaluation, patients with serous cystadenomas received distal pancreatectomy and splenectomy, and MCNs patients received cephalic duodenopancreatectomy (3 cases), distal pancreatectomy and splenectomy (3 cases), segmental corporeo-caudal pancreatectomy (1 case) and choledocoduodenostomy and gastrojejunostomy (1 case). In patients with serous cystadenomas the post-operatory mortality and morbidity were null, and the long-term prognostic excellent, both patients, after 26 months and 5 years respectively, being in good health, with no evidence of illness. In patients with mucinous cystic neoplasms the post-operatory mortality was null, the post-operatory morbidity was 37.5% and the global survival rate was 50% in 5 years and 66.66% in 3 years. Primary cystic neoplasms are lesions that can be surgically treated, with good results. Surgical resection is the ideal therapeutic solution, while palliative surgeries alternatives are done in exceptional situations.

Malignancy and overdiagnosis of malignancy in Peutz Jeghers polyposis.

Peutz Jeghers (PJ) polyps are rare hamartomatous tumors of the gastrointestinal tract frequently associated with skin and mucosal pigmentation. Despite their benign nature there is a certain increased risk of progression to malignancy in some cases, justifying a sustained follow-up of the patients. We present 3 cases of Peutz Jeghers syndrome (PJS) diagnosed in our hospital on gastrointestinal specimens obtained by endoscopy and opened surgery. We analyzed different degrees of dysplastic changes, epithelial intussusception, association with other types of polypoid lesions and other various aspects possibly related with disease progression. Clinico-pathological correlations were made. Two of these cases were related (mother and daughter); both of them were operated in another hospital for small bowel tumors with a subsequent diagnosis of adenocarcinoma. The daughter (28 years old) was referred to our hospital for endoscopic follow-up; a small polyp of the transverse large bowel was excised by colonoscopy with a histopathologic diagnosis of PJ polyp; a careful histopathologic reevaluation of both specimens of enterectomy (slides and paraffin blocks) revealed an overdiagnosis of cancer due to the epithelial cystic dilatation and pseudoinvasion in both patients. The other case showed diagnostic changes of PJS and also various aspects of adenomatous polyps some of them with mild and moderate dysplastic changes. When a PJ polyp is diagnosed, the possibility of pseudoinvasion should be kept in mind, in order to avoid overdiagnosis of malignancy; also, due to the fact that the malignant transformation of a PJ polyp is still on debate (hamartoma-dysplasia-carcinoma sequence versus malignant transformation of an adenomatous aria of a hamartoma versus coincidental association of a digestive cancer due to genetic aberrations of PJS), all the other associated microscopic aspects of the lesion should be carefully analyzed.

[Transtumoral drilling--an efficient solution and in many cases the only one available in the surgical treatment of Klatskin tumors]. / Forajul transtumoral--solutie eficienta si de multe ori singura posibila în tratamentul chirurgical al tumorilor Klatskin.

PURPOSE: Reviewing the cases and evaluate the efficacity of the trans-tumoral drilling in the Klatskin tumours which were operated in Colentina Surgical Department. MATERIAL AND METHOD: This is a clinical retrospective study on 109 cases of Klatskin tumours operated between 1998-2004. in 80 cases of them we could practice a biliary drainage using a trans-tumoral drilling. SURGICAL INDICATION: Malignant tumours of the main biliary duct developed at the level and above the junction of the two hepatic ducts , extended to the liver in many cases. SURGICAL TECHNIQUE: Through the choledochostomy, we performed with a special instrument the trans-tumoral drilling with the setting of a biliary axial drainage (40 cases), external biliary drainage through a semirigid trans-choledochal tube (25 cases), Kehr tube (9 cases), U tube (3 cases), internal drainage with intra-choledochal stent (2 cases), lost tube (1 case). RESULTS: In all cases we observed the early decrease of the jaundice. In the cases in which we used internal drainage, we had to perform a replacement of the closed tubes in 1-2 months after the first operation. Instead, the external biliary drainage, less expensive and periodically washed to preserve his permeability, proved his high efficiency. The average survival time was 8,9 months (between 5-20 months). CONCLUSIONS: The external biliary drainage through trans-tumoral drilling remains in many cases the only one available therapeutical solution for the Klatskin tumours.

[Cancer of the head of pancreas--resection vs. palliative surgery]. / Cancerul de cap de pancreas--rezectie vs. paleatie.

Pancreatic cancer remains a disease with high mortality. The unspecific symptoms for a long time make the diagnostic difficult. Between 1995-2004, only 85 from 465 patients with this diagnosis, had pancreatic resection. To them, we performed Whipple pancreaticoduodenectomy (60), pylorus preserving pancreaticoduodenectomy (15), pancreatico-duodenectomy with preserving of duodenum (2), pancreaticoduodenectomy with associated resections (5), subtotal pancreatico-duodenectomy (30). The reconstruction after pancreatic resection was pancreatico-jejuno anastomosis (26) and pancreatico-gastro-anastomosis (59). Morbidity was about 34% and the mortality was about 9%.

[Therapeutic options in gallstone ileus]. / Optiuni terapeutice în ileusul biliar.

Gallstone ileus is a rare, serious condition, requiring emergency surgery, specific to elderly age. The present study deals with 16 cases operated in 25 years period, with median age about 64 years old. The patients had clinical evidence of intestinal obstruction, confirmed by radiological examination and ultrasonography. Emergency operations were performed. In 7 cases had been treated radically both the obstruction (entero-lithotomy) and the bilio-digestive fistula (cholecystectomy, duodenal closure, enteral closure, colon-suture) with good results (only one death). In 9 cases, it had been treated only the intestinal obstruction, with only 2 cases of persistent cholangitis. Generally, we have used biliary drainage with Kehr tube in the presence of biliary stones and cholangitis. The biliodigestive fistula may close in evolution or become a harmless secondary route for internal biliary drainage.

[Neoadjuvant radiochemotherapy in the treatment of esophageal squamous carcinoma:Preliminary results in a series of 15 patients]. / Radiochimioterapia neoadjuvanta în tratamentul carcinomului epidermoid esofagian. Rezultate preliminare pe un lot de 15 pacienti.

The purpose of this study is to analyze the experience of the Center of General Surgery and Liver Transplantation from Fundeni Clinical Institute (Bucharest) regarding the results of neoadjuvant radiochemotherapy in the squamous carcinoma of the esophagus. During 01.01.2001-09.07.2003, 15 patients with squamous carcinoma of the esophagus were treated using neoadjuvant radiochemotherapy (RCT); 13 patients (86%) underwent esophageal resection (in 2 patients resection was not possible due to the mediastinal invasion). Complete histological response (the lack of malignant tissue on the esophagectomy specimens) was noted in 5 cases. The morbidity and mortality rates were 48%, respectively 6%. RCT increases the resectability in esophageal cancer and decreases the postoperative morbidity and mortality.

Primary epithelioid angiosarcoma of the adrenal gland.

Primary angiosarcomas of the adrenal gland are exceptionally rare vascular tumors. We report a case of a 63-year-old man with an epithelioid angiosarcoma of the left adrenal gland. Visualized on computed tomography as a nonhomogeneous round mass, the tumor measured 3 cm in diameter. Histology showed a vascular tumor composed of epithelioid cells with vesicular nuclei and prominent nucleoli that lined irregular vascular spaces and also formed solid areas and showed pleomorphism and rare mitotic activity. Immunohistochemical stain confirmed the diagnosis of epithelioid angiosarcoma. We report our findings and review previously described literature cases of this rare entity.

[Late results after the Mark Belsey IV antireflux procedure in achalasia]. / Rezultate tardive dupa procedeul Mark Belsey IV în achalazie.

Cardial achalasia (cardiospasm, megaesophagus) represents the failure or lack of relaxation capacity of the inferior esophageal sphincter; it is the second esophageal disease and is considered a premalignant lesion. Treatment of achalasia is surgical but palliative, considering the lack of an etiopathogenic therapy for this moment. We present a retrospective study done on 19 patients (10 males and 9 females, with a mean age of 49 years) operated in "Colentina" Surgical Clinic in the period of 1996-1999 for achalasia (presenting symptoms-dysphagia, regurgitation, weight loss) by extramucosal esocardiomyotomy practiced on a length of 5-10 cm, by thoracic approach, followed by the Mark Belsey IV antireflux procedure. Results were good, without reflux pathology or dysphagia in the postoperative evolution.

[Pancreatic insulinomas]. / Insulinoamele pancreatice.

In the period of 1980-1999 (20 years) were operated 18 patients (8 males and 10 females) in "Colentina" Surgical Clinic, the average age being of 45 years, with hystopathologically confirmed insulinomas. The topography of these lesions was in the head of the pancreas (4), in the isthmus (5), in the body and tail (9). The classical clinical and biochemical signs were presented in 13 cases, the rest of the patients presenting atypical signs of disease. These patients had benefit from the surgical treatment. The approach was bi-subcostal in 11 cases and by upper and lower midline incision in the rest of cases. We practiced enucleation in 5 cases, corporeal-caudal pancreatico-splenectomy in 10 cases and cephalic pancreatico-duodenectomy in 3 cases. The malignancy of the tumour was hystopathologically confirmed in 30% of the situations. The postoperative mortality was in 3 cases, by acute pancreatitis, MSOF and myocardial infarction. We consider that in case of these generally benign tumours the most efficient therapy is the surgical one.

[Sugiura's procedure--a treatment modality for esophageal varices]. / Operatia tip Sugiura--o modalitate de tratament chirurgical a varicelor esofagiene.

This study present the "N. Gh. Lupu" surgical experience with Sugiura technic for bleeding caused by oesophageal varicose. Is a 5 years retrospective study with 30 patients who are submitted of this operation. After the results analysis our opinion is to do this operation in stabilised patient, but she is possible even in emergency.