http://www.umassmed.edu/globalassets/immunology-and-microbiology/documents/papers-for-bbs821-2015/nov-24-reviewfor-general-info.pdf

Role of the Microbiota in Immunity and Inflammation

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement neighbor-joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest-neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N^2) space and O(N^2 L) time, but FastTree requires just O( NLa + N sqrt(N) ) memory and O( N sqrt(N) log(N) L a ) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 hours and 2.4 gigabytes of memory. Just computing pairwise Jukes-Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 hours and 50 gigabytes of memory. In simulations, FastTree was slightly more accurate than neighbor joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.

/pdf/fast-tree-computing-large-minimum-evolution-trees-with-4grq0gwfpy.pdf

Fast Tree: Computing Large Minimum-Evolution Trees with Profiles instead of a Distance Matrix

The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1600266

The Human Intestinal Microbiome in Health and Disease

Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(07)70410-2.pdf

Gastroenteropancreatic neuroendocrine tumours.

For more than two decades, an increased interest in understanding relationship between obesity and cancer is observed in the medical literature. However, epidemiological data remain heterogeneous depending on cancer site, age, gender, type of tissue adipose (visceral, subcutaneous) and ethnicity: obesity is linked with a greater risk of colo-rectal cancer (CRC) for men of all ages and for premenopausal women. Mechanisms involved are not fully investigated: no specific genetic marker linking obesity and cancer is identified, and except for few metabolic markers, pathways in this field remain speculative. Effects of hormones are more investigated. Insulin is the best established biochemical mediator between obesity and CRC and insulin resistance is important in the pathogenesis of CRC. Leptin, a very well known hormone that regulates food intake and energy balance is reported as tumorigenic mediator to explain why polyps are over expressed in obese individuals, however it may influence also anti tumoral immune response. Regular exercise is identified to reduce the risk of developing CRC. We should consider exercise, obesity and anti tumor immune response when designing colon cancer screening protocols.

Obesity and Cancer: yin/yan Effects of Nutrition~!2009-04-30~!2009-09-09~!2010-07-13~!

e14584 Background: The safety profile and efficacy of the Folfirinox regimen as first-line chemotherapy in metastatic pancreatic cancer (MPC) was previously reported in a phase II study (Conroy, J ...

5-FU/leucovorin (5FU/LV) combined with irinotecan (CPT-11) and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma.

[Anomalies of fundic argyrophil cell proliferation (enterochromaffin-like cells) in Zollinger-Ellison syndrome].

Introduction Neurological symptoms associated with neuroendocrine tumours (NETs) may be related to metastatic disease or paraneoplastic syndromes (PNSs); these last are often associated with autoantibodies targeting various onconeural antigens. To better characterise neurological PNSs related to NETs, we report the largest case-series study to date. Methods We retrospectively reviewed the charts of all patients diagnosed with NETs of the gastrointestinal tract who presented with neurological symptoms at either of two tertiary academic hospitals (Henri Mondor and Beaujon, France) between 1994 and 2016. All patients underwent extensive neurological tests including clinical, laboratory, and radiological investigations. The clinical response to immunomodulating agents was recorded. Results In the 13 identified patients, the most common presentations were peripheral neuropathy (46.2%) and encephalopathy (26.6%). Of the 6 (53.3%) patients whose serum anti-neuronal antibodies were assayed, 5 had high titres. Short-term oral corticosteroid and immunosuppressant drug therapy was given to 4 of these patients, of whom 3 had a clinical response and one no response. Repeated high-dose intravenous immunoglobulin therapy induced a complete clinical response in one patient. Encephalopathy resolved fully after hepatectomy or intrahepatic chemoembolization for liver metastases in another two patients. Discussion The neurological symptoms associated with NETs may be due in part to autoimmune PNS. Based on experience at our two centres, we estimate that autoimmune PNS occurs in about 1% of patients with NETs. Early symptom recognition allows the initiation of effective treatments including corticosteroids, immunosuppressive drugs, and/or intravenous immunoglobulins.

Contribution of Immune-Mediated Paraneoplastic Syndromes to Neurological Manifestations of Neuroendocrine Tumours: A Retrospective Study.

Purpose Robotic surgery has been progressively implemented for colorectal procedures but is still limited for multiquadrant abdominal resections. The present study aims to describe our experience in robotic multiquadrant colorectal surgeries and provide a systematic review and meta-analysis of the literature investigating the outcomes of robotic total proctocolectomy (TPC), total colectomy (TC), subtotal colectomy (STC), or completion proctectomy (CP) compared to laparoscopy. Methods At our institution 16 consecutive patients underwent a 2- or 3-stage totally robotic total proctocolectomy (TPC) with ileal pouch-anal anastomosis. A systematic review of the literature was performed to select studies on robotic and laparoscopic multiquadrant colorectal procedures. Meta-analyses were used to compare the two approaches. Results In our case series, 14/16 patients underwent a 2-stage robotic TPC for ulcerative colitis with a mean operative time of 271.42 (SD:37.95) minutes. No conversion occurred. Two patients developed postoperative complications. The mean hospital stay was 8.28 (SD:1.47) days with no readmissions. Mortality was nil. All patients underwent loop-ileostomy closure, and functional outcomes were satisfactory. The literature appraisal was based on 23 retrospective studies, including 736 robotic and 9,904 laparoscopic multiquadrant surgeries. In the robotic group, 36 patients underwent STC, 371 TC, 166 TPC, and 163 CP. Pooled data analysis showed that robotic TC and STC had a lower conversion rate (OR = 0.17;95% CI, 0.04–0.82; p = 0.03) than laparoscopic TC and STC. The robotic approach was associated with longer operative time for TC and STC (MD = 104.64;95% CI, 18.42–190.87; p = 0.02) and TPC and CP (MD = 38.8;95% CI, 18.7–59.06; p = 0.0002), with no differences for postoperative complications and hospital stay. Reports on urological outcomes, sexual dysfunction, and quality of life were missing. Conclusions Our experience and the literature suggest that robotic multiquadrant colorectal surgery is safe and effective, with low morbidity and mortality rates. Nevertheless, the overall level of evidence is low, and functional outcomes of robotic approach remain largely unknown. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier: CRD42022303016.

Iradj Sobhani

Papers

Obesity and Cancer: yin/yan Effects of Nutrition~!2009-04-30~!2009-09-09~!2010-07-13~!

5-FU/leucovorin (5FU/LV) combined with irinotecan (CPT-11) and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma.

[Anomalies of fundic argyrophil cell proliferation (enterochromaffin-like cells) in Zollinger-Ellison syndrome].

Contribution of Immune-Mediated Paraneoplastic Syndromes to Neurological Manifestations of Neuroendocrine Tumours: A Retrospective Study.

Robotic multiquadrant colorectal procedures: A single-center experience and a systematic review of the literature