Tarik Delko

Absence of myeloperoxidase and CD8 positive cells in colorectal cancer infiltrates identifies patients with severe prognosis

Colorectal cancer (CRC) infiltration by cells expressing myeloperoxidase (MPO) or CD8 positive T lymphocytes has been shown to be independently associated with favorable prognosis. We explored the relationship occurring between CD8+ and MPO+ cell CRC infiltration, its impact on clinical-pathological features and its prognostic significance in a tissue microarray (TMA) including 1,162 CRC. We observed that CRC showing high MPO+ cell infiltration are characterized by a prognosis as favorable as that of cancers with high CD8+ T cell infiltration. However, MPO+ and CD8+ CRC infiltrating cells did not synergize in determining a more favorable outcome, as compared with cancers showing MPOhigh/CD8low or MPOlow/CD8high infiltrates. Most importantly, we identified a subgroup of CRC with MPOlow/CD8low tumor infiltration characterized by a particularly severe prognosis. Intriguingly, although MPO+ and CD8+ cells did not co-localize in CRC infiltrates, an increased expression of TIA-1 and granzyme-B was detectable in T cells infiltrating CRC with high MPO+ cell density.

OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

Background OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. Methods OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. Results OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40high/CD8high infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40low/CD8high, OX40high/CD8low or OX40low/CD8low infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40high/CD8high density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. Conclusions OX40high/CD8high density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers.

Internal hernia in late pregnancy after laparoscopic Roux-en-Y gastric bypass

A 27-year-old patient in late pregnancy presented to the department of obstetrics with crampy abdominal pain located in the right flank, 3 years after a laparoscopic Roux-en-Y gastric bypass. Clinical investigation showed tenderness on palpation in the upper abdomen without signs of peritonitis. The cardiotocogram and blood tests were normal. The ultrasound showed a hydronephrosis on the right side, and a pigtail catheter was inserted. The abdominal symptoms did not abate and the abdominal surgeon was consulted 36 hours after admission. Diagnostic laparoscopy was performed promptly because of high suspicion of internal hernia (IH). Laparoscopy showed IH at the mesojejunal intermesenteric defect with a herniated common channel and volvulus of the anastomosis. Conversion to open reduction and complete closure with non-absorbable interrupted sutures was performed. Small bowel resection was avoided. The patient was discharged 10 days after the operation and a healthy boy was born 4 weeks later.

Two similar cases of internal hernia after laparoscopic Roux-en-Y gastric bypass surgery

Internal hernia after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery can lead to acute small bowel obstruction or chronic recurrent abdominal pain. We present two cases of internal hernias after antecolic antegastric LRYGB. Both patients presented to the emergency room with acute diffuse abdominal pain. Other than that, a physical examination and routine laboratory workup did not reveal any pathological finding. An abdominal CT was performed in both cases. It showed mesenteric torsion as a sign of internal hernia in one case, but remained inconclusive in the other patient. Immediate diagnostic laparoscopy was performed in both cases. Intraoperatively, both patients revealed an internal hernia, where the common channel herniated through the mesojejunal space. The conversion to upper median minilaparotomy was necessary for hernia reduction in both cases. No bowel resection was required and both patients recovered fully.

A case of cecal volvulus mimicking Ogilvie Syndrome in a hospitalized patient with a pelvis fracture

Introduction Cecal volvulus and ogilvie syndrome are two entities which may display similar clinical presentation but require different treatment approaches. Presentation of case An 84-year old male patient admitted for conservative treatment of a pelvis fracture, complained of abdominal cramps and flatulence on the third hospitalization day. Abdominal radiographs arose suspicion of cecal volvulus. The diagnosis was ruled out on the CT scan but however was later confirmed by an exploratory laparotomy. Discussion The management of cecal volvulus requires prompt (emergency) surgical intervention while Ogilvie syndrome can be principally managed with conservative treatment. Our patients profile was typical for both entities. The absence of air throughout all colonic segments including the rectosigmoid on plain abdominal radiographs seems to be the most important sign in the exclusion of the Ogilvie syndrome diagnosis. Conclusion Cecal volvulus and Ogilvie syndrome display overlapping clinical features at their time of presentation and need to be carefully distinguished. By uncertainty, an exploratory laparotomy should always be performed, in view of the reported high mortality rate of cecal volvulus if surgery is delayed.

Acute thyroid swelling and elevated C reactive protein.

A 34-year-old lady presented with a painful swelling of the left thyroid lobe since 1 week and elevated C reactive protein (CRP) above 100 mg/L. An ultrasound examination revealed a thyroid cyst with partly solid component, suitable with a haemorrhage into a cyst. The serum thyroid stimulating hormone (TSH), as well as peripheral thyroid hormones, was in the normal range. The acute swelling could be well explained by a haemorrhage, but not an elevated CRP. Her medical history was uneventful apart from a tooth extraction 2 weeks ago due to an infection. Therefore, our hypothesis was a haemorrhage into a pre-existing thyroid cyst during bacteraemia caused by the tooth infection. Conservative treatment with the aim of delayed hemithyreoidectomy failed due to a second episode of haemorrhage. During surgical resection pus drained out of the cyst and the histological report afterwards confirmed our tentative diagnosis. The patient was discharged 2 days later.

Abstract 4715: OX40 expression improves the prognostic value of CD8 positive lymphocyte density in colorectal carcinoma

Background: The prognostic role of the immunological microenvironment in colorectal cancer (CRC) is well known. Among immune cell types, CD8 positive T lymphocyte infiltration is an established prognostic marker clearly associated with a favorable clinical course of the disease. In contrast, there is limited information about the prognostic role of OX40 positive immune cell infiltration in CRC. However, increasing evidence suggests that OX40 positive immune cell infiltration, as a single biomarker, has a positive prognostic effect in CRC patients. To the best of our knowledge, the impact of the combination of OX40 positive immune cells and CD8 positive T lymphocytes is unknown. Methods: A tissue microarray composed of 441 biopsies was evaluated for OX40 positive immune cells and CD8 positive T lymphocyte infiltration by immunohistochemistry. The intratumoral number of tumor infiltrating cells positive for OX40 and CD8 antigens was evaluated by 2 independent investigators achieving an optimal concordance rate of 90%. According to the frequency and staining intensity, we identified four subgroups of cell population: OX40low/CD8low, OX40high/CD8low, OX40low/CD8high and OX40high/CD8high. They were correlated with clinicopathological data, and a combined survival analysis was performed. Results: The mean age of the patients cohort was 69.9 ±10.7 years. A total of 230 (52%) biopsies were from female and 211 (48%) from male CRC patients. Both, OX40 and CD8 positive cell infiltration had a significant, prognostic impact on the clinical outcome of the disease as individual markers (p Conclusion: The combination OX40 and CD8 positive cell infiltration significantly enhances the overall survival compared to OX40 and CD8 positive cell infiltration alone. OX40high/CD8high positive cell infiltration is an independent, favorable, prognostic marker in CRC. Citation Format: Benjamin Weixler, Raoul A. Droeser, Roberto Sorge, Tarik Delko, Christian A. Nebiker, Giandomenica Iezzi, Giulio C. Spagnoli, Christoph Kettelhack, Urs W. von Holzen, Daniel Oertli, Luigi Terracciano, Luigi Tornillo, Giuseppe Sconocchia. OX40 expression improves the prognostic value of CD8 positive lymphocyte density in colorectal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4715. doi:10.1158/1538-7445.AM2014-4715