Velamentous cord insertion in monochorionic twin pregnancies: a step forward in screening for twin to twin transfusion syndrome and birthweight discordance?

OBJECTIVES: Two major complications of monochorionic diamniotic (MCDA) twin pregnancies are twin to twin transfusion syndrome (TTTS) and birthweight discordance. The current screening ultrasound test for these pathologies combines the detection of nuchal translucency discrepancy and abnormal ductus venosus in at least one twin, in the first trimester. We aim to determine whether combining the presence of velamentous cord insertion in at least one twin increases screening efficiency. METHODS: This was a retrospective cohort with a sample of 136 MCDA twin pregnancies followed at Centro Hospitalar Universitário São João, during a 16-year period. RESULTS: The combination of abnormal ductus venosus in at least one twin and nuchal translucency discrepancy is associated with the development of TTTS with an OR of 10.455, but not with birthweight discordance. The combination of these first trimester markers with velamentous cord insertion is not associated with the development of either outcome. CONCLUSIONS: The presence of velamentous cord insertion in MCDA pregnancies is not associated to TTTS development. Therefore, the addition of this marker to the first trimester screening would not effectively predict the development of birthweight discordance or TTTS. However, a positive currently used screening test increases the risk of developing TTTS by about ten times.

Identifying the role of neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio as prognostic markers in patients undergoing resection of pancreatic ductal adenocarcinoma.

BACKGROUNDS/AIMS: It is important to point out that the identification of inflammation is an essential component of the pathogenesis and the progression of cancer. In this study, we analysed the neutrophil-to-lymphocyte ratio (NLR) and the platelets-to-lymphocyte ratio (PLR), with an overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC), who were treated with a resection following or not following a procedure of neoadjuvant chemotherapy/chemoradiation. We intended to identify the significance of the role of NLR and PLR, as prognostic markers in patients undergoing surgery for PDAC. METHODS: There were 127 patients enrolled in the study. The NLR and PLR were calculated on the basis of the pre-treatment blood cell count. An NLR>4 and a PLR >120 were considered to be elevated as measured. OS was analysed in relation to the NLR and PLR values, by using both the Kaplan-Meier and multivariate Cox-regression methods. RESULTS: Both high the NLR and high PLR were associated with a decreased OS in the univariate analysis. In the multivariate analysis, the high NLR, but not the high PLR, was an independent predictor of a decreased OS. When we divided patients into three groups (group 1: normal both NLR and PLR, group 2: high NLR or high PLR, group 3: high both NLR and PLR), the three-years OS rates for these groups were 48%, 32%, 7% (p=0.001) respectively. CONCLUSIONS: It is noted that the pre-treatment NLR is an independent adverse prognostic factor, and considered to be superior to the PLR, in patients who undergo a resection for PDAC following or not neoadjuvant chemotherapy/chemoradiation.

Increased carcinoembryonic antigen (CEA) following neoadjuvant chemotherapy predicts poor prognosis in patients that undergo hepatectomy for liver-only colorectal metastases.

BACKGROUND: The importance of preoperative chemotherapy in a multimodality management of patients with colorectal liver metastases (CRLM) has been demonstrated. We analyse the carcinoembryonic antigen (CEA) changes following neoadjuvant chemotherapy in patients with CRLM who underwent liver resection. METHODS: The final cohort included 107 eligible patients. Increased CEA levels following neoadjuvant chemotherapy were defined as the increase of baseline CEA level at diagnosis of CRLM compared with the CEA level after completion of neoadjuvant chemotherapy. Disease-free survival (DFS), post-recurrence survival (PRS) and overall survival (OS) were calculated using both Kaplan-Meier and multivariate Cox-regression methods. RESULTS: CEA increase was associated with decreased PRS and OS (HR 2.69; 95 % CI, 1.28-5.63; p = 0.009, and HR 2.50; 95 % CI, 1.12-5.56; p = 0.025, respectively) in multivariate analysis, but there was no association between CEA changes and DFS. CEA increase was only associated with disease progression during preoperative chemotherapy (p = 0.014). Interestingly, this association was not absolute, as only 5 of the 11 patients with disease progression demonstrated CEA increase. Regarding the remaining 12 patients with CEA increase, according to RECIST criteria, eight patients demonstrated partial response and four patients stable disease. CONCLUSION: In this study, we demonstrated the CEA increase following neoadjuvant chemotherapy as an adverse prognostic factor for PRS, and OS but not for DFS in patients undergoing liver resection for liver-only colorectal metastases.

Two cases of gallbladder metastasis from renal cell carcinoma and review of literature.

BACKGROUND: Renal cell carcinoma accounts for 90% of renal neoplasms and metastatic disease is common. One third of newly diagnosed cases will have synchronous metastases at diagnosis and further 25-50 % will develop metachronous disease. CASE PRESENTATION: This study presents two new cases of gallbladder metastasis from renal cell carcinoma (RCC) from our institution and reviews the published literature. The final cohort included 52 evaluable patients. M/F ratio was 2:1 and median age was 62.5 years. Most patients were diagnosed incidentally after follow-up or staging imaging for RCC. Of the patients with available histology, all except one were clear cell type (n = 39) and 92% were polypoid. Thirty-six patients demonstrated metachronous gallbladder metastasis with median disease-free interval (DFI) from nephrectomy of 4 years. The most frequent site of metastasis was the contralateral kidney (46.7%) followed by the pancreas and lung. The median disease-free interval (DFS) after cholecystectomy was 37 months. Three- and five-year OS rates were 74 and 62%, respectively. Age younger than 45 years (p = 0.008) and DFI <24 months (p = 0.049) were associated with decreased OS. CONCLUSIONS: RCC metastasis to the gallbladder is associated with an unusual pattern of concomitant metastasis. Symptoms are not common. Simple cholecystectomy is associated with increased OS and nil local or port site recurrence. Young age and short DFI are associated with decreased OS.

Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST) mimicking hereditary GIST syndromes.

INTRODUCTION: Gastrointestinal stromal tumours (GISTs) are thought to derive from or differentiate towards the interstitial cells of Cajal (ICC) as most demonstrate a similar immunoprofile: CD117+, CD34+ and DOG1+. ICC hyperplasia refers to KIT-expressing microscopic spindle cell proliferations involving the myenteric plexus. CASE REPORT: 74 year-old male presented with a 5-year history of heartburn and dysphagia. Imaging revealed a 4cm GIST in the gastric fundus. Pathology of the resected specimen revealed diffuse segmental ICC hyperplasia harbouring two macroscopic GISTs and a 'tumorlet'. A mutation in c-KIT exon 11 was detected in both the solid and the diffuse components. DISCUSSION: ICC hyperplasia can occur either as a sporadic focal lesion or in a syndromic setting, known to predispose to multiple GIST tumours at different sites. The majority of cases of sporadic ICC hyperplasia previously reported were of localised type. The hereditary form is mostly caused by germline mutations in c-KIT and PDGFRA or in patients with NF-1 andpresents as a diffuse hyperplasia, usually with a confluent, nodular or multifocal growth pattern. CONCLUSION: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

Effective Downsizing of a Large Oesophageal Gastrointestinal Stromal Tumour with Neoadjuvant Imatinib Enabling an Uncomplicated and without Tumour Rupture Laparoscopic-Assisted Ivor-Lewis Oesophagectomy.

Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free.

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​.

The mechanisms and quantification of the selective permeability in transport across biological barriers: the example of kyotorphin.

This paper addresses the mechanisms behind selective endothelial permeability and their regulations. The singular properties of each of the seven blood-tissues barriers. Then, it further revisits the physical, quantitative meaning of permeability, and the way it should be measured based on sound physical chemistry reasoning and methodologies. Despite the relevance of permeability studies one often comes across inaccurate determinations, mostly from oversimplified data analyses. To worsen matters, the exact meaning of permeability is being lost along with this loss of accuracy. The importance of proper permeability calculation is illustrated with a family of derivatives of kyotorphin, an analgesic dipeptide.