Tumor Perforation Research Articles

Perforated gastrointestinal stromal tumor in the small intestine: A rare case of Torricelli-Bernoulli sign.

The Torricelli-Bernoulli sign is a computed tomography (CT) finding that occurs when ulceration/necrosis of a submucosal gastrointestinal tumor releases a stream of air bubbles into the intestinal lumen. A 75-year-old man developed acute abdominal pain at night and presented to a local doctor. Acute abdomen was diagnosed and he was referred to the Emergency Department at Tokai University Oiso Hospital. On CT scans, disseminated intestinal tumor-like lesions were seen in the right lower abdomen. The Torricelli-Bernoulli sign and free intraabdominal gas were observed, so perforation of an intestinal tumor was diagnosed and emergency surgery was performed. At operation, there was scanty opaque ascites in the right lower abdomen and an ileal tumor associated with nodules that suggested peritoneal dissemination. Partial resection of the ileum was performed and peritoneal lavage was conducted. The patient was discharged on postoperative day 11. Histopathological examination revealed a high risk gastrointestinal stromal tumor. The abdominal nodules were metastases, indicating that the tumor was Stage IV. The patient is currently on treatment with an oral tyrosine kinase inhibitor (imatinib).

Exploring minimally invasive options: Laparoscopic transabdominal levator transection for low rectal cancers.

Extralevator abdominoperineal excision (ELAPE) of the rectum offers wider circumferential margin and decreased rate of intraoperative tumour perforation. However, the need to change the position of the patient in between abdominal and perineal stages of the procedure and extended perineal resection result in increased morbidity and operative time. Evolving technique of laparoscopic transabdominal controlled division of levator ani muscles under direct vision could address these issues while providing all benefits of ELAPE for patients with low rectal cancers.

Perforation of the Small Bowel Due To Metastasis from Tongue Cancer—a Case Report

Squamous cell carcinoma has a variety of modes of metastasis. Small-bowel metastasis from squamous cell carcinoma is extremely rare, and tongue cancer metastasizing to the small bowel has been previously reported in only one case in 2011 in Japan. We report a 60-year-old male diagnosed case of cancer tongue stage IV presented as intestinal perforation after the first cycle of palliative chemotherapy. An intraoperative frozen section from one of the mesenteric nodes was used to confirm M1 disease as the cause of perforation in mesenteric nodes as well as in the bowel wall. The perforated ileum was resected and ileostomy was done. We assume rapid infusion of 5-FU as a cause of rapid tumor necrosis and perforation. While handling stage IV oral SCC, this thing should be kept in mind.

Management of Esophageal Perforation: 28-Year Experience in a Major Referral Center

Esophageal perforation constitutes a surgical emergency. Despite its gravity, no single strategy has been described as sufficient to deal with most situations to date. The aim of this study was to assess the etiology, management, and outcome of esophageal perforation over a 28-year period, to characterize optimal treatment options in this severe disease. A retrospective clinical review of all patients treated for esophageal perforation at Ramón y Cajal Hospital between January 1987 and December 2015 was performed (n = 57). Iatrogenic injury was the most frequent cause of esophageal perforation (n = 32). Abdominal esophagus was the main location (23 patients; 40.4%). Eight patients (14%) were managed with antibiotics and parenteral nutrition. In seven patients (12.3%), an endoscopic stent was implanted. Surgical therapy was performed in 38 patients (66.7%). Morbidity and 90-day mortality rates were 61.4 and 28 per cent, respectively. Five patients were reoperated (8.8%). Median hospital stay was 23.5 days. The mortality rate was higher among patients with spontaneous and tumoral perforation (54.5 and 100%; P = 0.009), delayed diagnosis (>24 hours; P = 0.0001), and abdominal/thoracic location (37.5%; P = 0.05). No statistical differences were found between surgical and conservative/endoscopic management (31% vs 20%; P = 0.205) although hospital staying was longer in surgical group (36.30 days vs 15.63 days; P = 0.029). Esophageal perforation was associated with high morbidity and mortality rates. Global outcomes depend on etiology, site of perforation, and delay in diagnosis. An individualized approach for each patient should be chosen to prevent septic complications of this potentially fatal disease.

Abdominoperineal excision or extralevator abdominoperineal excision: which is the best oncological treatment?

Surgery of tumors of the lower third of the rectum is particularly difficult due to the complex anatomy of the pelvis, which can lead to an incomplete radical resection. Abdominoperineal excision (APE) is the operation of choice for tumors of the low rectum that infiltrate levatorani or sphincter muscles. Regardless, APE causes an important morbidity, a higher incidence of circumferential resection margin (CRM) infiltration, iatrogenic tumor perforation incidence and worsens the mesorectum quality due to the conicity induced during surgery while dissection between both distal mesorectum and levatorani planes is performed. An extralevator abdominoperineal excision (ELAPE), which involves a broader resection of the pelvic floor muscles, would theoretically reduce the risk of CRM infiltration and tumor perforation rate, independently from the position (prone vs . supine) or the approach (open vs . laparoscopic). This review is focused on the analysis of the scientific evidence published so far comparing both techniques, APE or ELAPE. In spite of some publications observe a possible benefit in terms of reduction in CRM involvement, iatrogenic perforations or local recurrence, there is not enough evidence to affirm the superiority of ELAPE compared to conventional APE in terms of oncological results. In general, similar rates of postoperative complications are described for both techniques. Further prospective, controlled and randomized studies are needed to conclude which of the two techniques is the best oncological treatment.

Extended outcomes of intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastases.

125 Background: Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a grave prognosis. Studies have shown increased drug concentration in the peritoneal cavity when chemotherapy is administered intraperitoneally (IP). We had previously published early results on IP paclitaxel plus XELOX for such patients and now present our longer term data. Methods: Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology, not previously-treated or received prior systemic therapy > 180 days ago and ECOG ≤2 are eligible. Patients were treated with 8 cycles of paclitaxel 40 mg/m2 IP on days 1 and 8, oxaliplatin 100 mg/m2 IV on day 1 and capecitabine 1000 mg/m2 b.i.d. PO for 2 weeks followed by 1 week of rest. The primary endpoint is 1-year overall survival rate and the secondary endpoints are safety, response rate and peritoneal cytological response. Patients who subsequently have no distant metastases, with stable or reduced peritoneal disease and 2 consecutive negative peritoneal cytology would be eligible for conversion gastrectomy. Results: 34 patients have been enrolled and received at least one cycle at the time of reporting. Median no. of cycles is 8 (range: 1–8) and median follow-up is 30.2 months. Median OS is 16.4 months (IQR: 10.1–27.2) and 1-year survival rate is 64.9% (95% CI: 45.5%–78.9%). Of 30 evaluable patients, 1 achieved CR (3.3%), 6 (20.0%) achieved PR, 16 (53.3%) achieved SD and 7 (23.3%) experienced PD. Peritoneal cytology turned negative in 17 of 32 (53.1%) patients. Severe (grade ≥ 3) AE were neutropenia ( N= 7), febrile neutropenia ( N= 3), diarrhoea ( N= 3), hand-foot syndrome ( N= 2), bacterial peritonitis ( N= 2) and hypokalaemia ( N= 4) and tumour perforation ( N= 1). One death occurred due to neutropenic sepsis. 8 patients had conversion gastrectomy with no additional morbidity, with a 1-year survival of 87.5% with a median OS of 18.8 months. Conclusions: XELOX + IP paclitaxel appears to be a well-tolerated and active regimen in gastric cancer with peritoneal metastases, and may offer survival benefits. Finally, conversion gastrectomy may be considered in patients with favourable response. Clinical trial information: NCT01739894.

Gastrointestinal stromal tumors: a comprehensive review.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. Most GISTs present asymptomatically. They are best identified by computed tomography (CT) scan and most stain positive for CD117 (C-Kit), CD34, and/or DOG-1. There have been many risk stratification classifications systems which are calculated based on tumor size, mitotic rate, location, and perforation. The approaches to treating GISTs are to resect primary low-risk tumors, resect high-risk primary or metastatic tumors with imatinib 400 mg daily for 12 months, or if the tumor is unresectable, neoadjuvant imatinib 400 mg daily followed by surgical resection is recommended. Sunitinib is required for KIT exon 9, 13, and 14 mutations, while ponatinib is used for exon 17 mutations and regorafenib for highly refractory tumors. High-risk tumors should be monitored for recurrence with serial abdominal CT scans. Radiofrequency ablation has shown to be effective when surgery is not suitable. Newer therapies of ipilimumab, nivolumab, and endoscopic ultrasound alcohol ablation have shown promising results. This report addresses the epidemiology, clinical presentation, diagnostic imaging, histologic diagnosis, classification and risk stratification, staging and grading, surgical treatment, adjuvant treatment, and metastasis of GISTs.

Do high-risk features support the use of adjuvant chemotherapy in stage II colon cancer? A Turkish Oncology Group study.

A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western populations. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer. A total of 554 stage II colon cancer patients were retrospectively enrolled in the study. Three hundred fifty-three patients had received adjuvant chemotherapy (5-FU-LV, FOLFOX or FLOX) and 201 had received no adjuvant chemotherapy. T4 tumor stage, lymphovascular invasion, perineural invasion, bowel obstruction and/or perforation, <12 harvested lymph nodes, and poor differentiation were defined as high-risk factors. The median age of the patients was 62 years (range 26-88). The median disease-free survival (DFS) was 58.1 months (95% CI, 47.6 months to 68.5 months) in the non-treatment group and has not been reached in the treatment group (P <0.01). In univariate analysis, patient age >60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors. Adjuvant chemotherapy reduced the risk of recurrence with statistical significance (P <0.01). In multivariate analysis, patient age >60 years and T4 tumor stage were independent risk factors affecting DFS. In addition, adjuvant chemotherapy was an independent favorable prognostic factor for DFS (P <0.01). Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other populations. Further prospective studies in colon cancer are needed to understand the differences in biology and risk factors between races.

Critical and Challenging Issues in the Surgical Management of Low-Lying Rectal Cancer.

Despite innovative advancements, the management of distally located rectal cancer (RC) remains a formidable endeavor. The critical location of the tumor predisposes it to a circumferential resection margin that tends to involve the sphincters and surrounding organs, pelvic lymph node metastasis, and anastomotic complications. In this regard, colorectal surgeons should be aware of issues beyond the performance of total mesorectal excision (TME). For decades, abdominoperineal resection had been the standard of care for low-lying RC; however, its association with high rates of tumor recurrence, tumor perforation, and poorer survival has stimulated the development of novel surgical techniques and modifications, such as extralevator abdominoperineal excision. Similarly, difficult dissections and poor visualization, especially in obese patients with low-lying tumors, have led to the development of transanal TME or the “bottom-to-up” approach. Additionally, while neoadjuvant chemoradiotherapy has allowed for the execution of more sphincter-saving procedures without oncologic compromise, functional outcomes remain an issue. Nevertheless, neoadjuvant treatment can lead to significant tumor regression and complete pathological response, permitting the utilization of organ-preserving strategies. At present, an East and West dualism pervades the management of lateral lymph node metastasis, thereby calling for a more global and united approach. Moreover, with the increasing importance of quality of life, a tailored, individualized treatment approach is of utmost importance when taking into account oncologic and anticipated functional outcomes.

Histopathological report of colorectal carcinoma resections: A 5-year audit in Lagos.

Complete and accurate pathology reporting of colorectal carcinoma (CRC) resection specimen is critical to clinical management of individual patients. The study aims to audit colorectal cancer histopathology reporting in Lagos between 2011 and 2015 before the adoption of the Society for Gastroenterology and Hepatology in Nigeria pro forma in 2016. All resected CRC cases were identified from the Histopathology record of our Department and that of a private Laboratory in Lagos over a 5-year from 2011 to 2015. The dataset as contained in the pro forma was extracted from the reports and analysed using SPSS version 16 software. A total of 92 colorectal resections were received during the 5-year period consisting of 90 colonic and 2 rectal tumours. Data inclusiveness on tumour differentiation, extent of primary tumour, total lymph node and lymph node involvement were 96.7%, 91.3%, 83.7% and 92.4%, respectively. Tumour perforation, level of venous involvement and distant metastasis were reported in 73.9%, 21.7% and 96.7% respectively. The circumferential resection margin (CRM) in the 2 rectal tumours had 100% inclusiveness. Tumour node metastasis staging was complete in 87% of cases while Dukes staging was documented in 8.7% of the reports. None of the data items was 100% complete except the CRM for rectal carcinoma. Free text reporting results in incomplete data resulting in improper staging, especially the lymph node status. This highlights the need for pro forma reporting to ensure and maintain consistent reporting of important parameters required for proper staging and management of patients with colorectal cancer.

Do Types of Perforation Impact Outcomes in Perforated Stage II/III Colorectal Cancer Patients?

The purpose of this paper is to compare the oncologic outcomes between colorectal cancer (CRC) patients with tumor perforation and those with perforation proximal to the tumor. Medical charts of 39 patients who underwent emergency surgery for colonic perforation related to potentially curable CRC were reviewed. Eighteen patients developed tumor perforation (group A), whereas 21 patients developed perforation proximal to the tumor (group B). Twenty-four patients were pathologic stage II and 15 patients were stage III. There were no significant differences in the clinicopathologic and surgical data, including hospital mortality, between the groups; however, the incidence of diffuse peritonitis was higher in group B than that in group A (P &amp;lt; 0.01). The induction rates of adjuvant chemotherapy for survivors were identical between the 2 groups. Disease-free and overall survival periods did not significantly differ between the groups. Perforation type was not found to be associated with oncologic outcomes in patients with CRC-related perforation.

Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Pathology Standards and Datasets.

Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Pathology Standards and Datasets.

Signal Transduction and Activator of Transcription-3 (STAT3) in Patients with Colorectal Cancer: Associations with the Phenotypic Features of the Tumor and Host.

Purpose: In patients with colorectal cancer, a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL6/JAK/STAT3 pathway. The present study examines the relationship between tumor total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses, and survival in patients undergoing resection of stage I-III colorectal cancer.Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumor cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density, and Klintrup-Mäkinen grade) and systemic inflammatory responses and cancer-specific survival were examined.Results: A total of 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r = 0.363; P < 0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r = 0.130; P = 0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P = 0.012), CD8+ (P = 0.003), and FOXP3+ T lymphocytes (P = 0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P = 0.004).The combination of nuclear STAT3/pSTAT3 stratified 5-year survival from 81% to 62% (P = 0.012), however, was not associated with survival independent of venous invasion, tumor perforation, or tumor budding.Conclusions: In patients undergoing colorectal cancer resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Upregulation of tumor STAT3 may be an important mechanism whereby the tumor deregulates local and systemic inflammatory responses. Clin Cancer Res; 23(7); 1698-709. ©2016 AACR.

Recidyvo rizikos veiksniai po radikalios kolorektalinio vėžio operacijos

Įvadas Lietuvoje kasmet diagnozuojama apie 1500 kolorektalinio vėžio atvejų ir sergamumas šia liga kiekvienais metais didėja. Radi­kalus chirurginis gydymo būdas taikomas siekiant pašalinti vėžį ir taip pailginti pacientų išgyvenamumą. Po operacijos profi­laktinių patikrų metu suvėžėjusias pilvaplėvės ląsteles yra sunku diagnozuoti dėl klinikinių simptomų stokos ir nepakankamo vaizdinių tyrimų jautrumo. Todėl pacientams, turintiems rizikos veiksnius recidyvui atsirasti, tikslinga taikyti diagnostinę rela­parotomiją, kurios metu būtų atliekama HIPEC procedūra.Ligoniai ir metodai Atliktas retrospektyvusis tyrimas VULSK Pilvo chirurgijos centre. Tirti 321 pacientai, kuriems 2011–2014 m. diagnozuotas kolo­rektalinis T3–T4 stadijos neišplitęs navikas ir taikytas radikalus chirurginis gydymas. Į tyrimą įtraukti 208 pacientai. Analizuoti operacijų protokolai bei histologiniai navikų aprašai.Rezultatai Analizuoti 208 pacientų duomenys. 34 (16,3 %) pacientams buvo nustatyti pirminio naviko recidyvai. Recidyvavo 15 (26,8 %) T4 histologinio tipo navikų ir 19 (12,5 %) T3 navikų (p=0,013). Recidyvavimas pagal išplitimą į regioninius limfmazgius buvo 10 (9,8 %) N0, 12 (18,2 %) N1 ir 12 (30 %) N2 grupėse (p=0,012). Iš žarnos spindį užkimšusių navikų recidyvavo 7 (46,7%) (p=0,003). Statistiškai reikšmingo ryšio tarp recidyvų dažnio ir pirminio naviko lokalizacijos, histologinio tipo ir pirminio navi­ko perforacijos nenustatėme. Penkerių metų išgyvenamumas nenustačius ligos recidyvo buvo 24,65 %, o recidyvavus – 0 %.Išvados Atlikus radikalią kolorektalinio naviko šalinimo operaciją, svarbu šiuos pacientus stebėtis dėl galimo ligos recidyvavimo. Paci­entams, turintiems didelę riziką recidyvui atsirasti, yra tikslinga svarstyti relaparotomijos su CRS ir HIPEC galimybę.

Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer: A Nationwide Database Study.

It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. The aim of this study was to assess the effect of unintended intraoperative tumor perforation on postoperative mortality and long-term survival. This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. Intraoperative tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative mortality of 17% compared to 7% in non-perforated tumors, p < 0.001. We showed that tumor fixation, emergency operations, and laparotomies were associated with an increased risk of intraoperative tumor perforation. This nationwide study demonstrates that intraoperative tumor perforation in colon cancer is associated with statistically significant reduced long-term survival and increased postoperative mortality.

Completeness of pathology reports in stage II colorectal cancer

Introduction: The completeness of the pathological examination of resected colon cancer specimens is important for further clinical management. We reviewed the pathological reports of 356 patients regarding the five factors (pT-stage, tumor differentiation grade, lymphovascular invasion, tumor perforation and lymph node metastasis status) that are used to identify high-risk stage II colon cancers, as well as their impact on overall survival (OS).Methods: All patients with stage II colon cancer who were included in the first five years of the MATCH study (1 July 2007 to 1 July 2012) were selected (n = 356). The hazard ratios of relevant risk factors were calculated using Cox Proportional Hazards analyses.Results: In as many as 69.1% of the pathology reports, the desired information on one or more risk factors was considered incomplete. In multivariable analysis, age (HR: 1.07, 95%CI 1.04–1.10, p < .001), moderately- (HR: 0.35, 95%CI 0.18–0.70, p = .003) and well (HR 0.11, 95%CI 0.01–0.89, p = .038) differentiated tumors were significantly associated with OS.Conclusions: Pathology reports should better describe the five high-risk factors, in order to enable proper patient selection for further treatment. Chemotherapy may be offered to stage II patients only in select instances, yet a definitive indication is still unavailable.

Pure Primary Ovarian Squamous Cell Carcinoma Perforating the Rectum

Rectal perforation is uncommon in ovarian cancer, even in advanced stages. Pure primary ovarian squamous cell carcinoma is a very rare subtype of ovarian cancer and has not been reported to cause rectal perforation. A 50-year-old woman presented with rectal bleeding. Rectosigmoidoscopy suggested perforation of a pelvic tumor into the rectum. Abdominopelvic magnetic resonance imaging revealed a 9 cm heterogeneous mass in the pouch of Douglas. We performed complete cytoreduction, including an en-bloc resection of the tumor and rectosigmoid colon. Histopathology showed squamous cell carcinoma of the left ovary penetrating the rectal wall. A common symptom of rectal bleeding was caused by a very rare entity of ovarian cancer penetrating the rectal wall, but thorough evaluation led to its accurate diagnosis and appropriate treatment.

Organ-preserving surgery for locally advanced duodenal gastrointestinal stromal tumor after neoadjuvant treatment.

This report aims to investigate the feasibility and outcomes of neoadjuvant imatinib mesylate (IM) administration followed by organ-preserving surgery (OPS) for patients with locally advanced duodenal gastrointestinal stromal tumor (GIST). Between 2012 and 2015, 10 consecutive patients with locally advanced duodenal GISTs were treated in Peking University Cancer Hospital. Multidisciplinary assessment was implemented, and pancreaticoduodenectomy (PD) was initially indicated as the most probable surgical procedure for all 10 patients. To attempt to create opportunities of less-invasive OPS for patients, neoadjuvant IM was administered followed by radical resection. All data were prospectively collected, and the short- and long-term outcomes of the treatment strategy were analyzed. The median treatment duration of neoadjuvant IM administration was 5 mo (range 2-18 mo). Significant tumor shrinkage (from 9.2 to 5.9 cm on average) was observed in all patients, and partial response was achieved in eight patients (80.0%) according to the Response Evaluation Criteria in Solid Tumors 1.1. No tumor perforation occurred, and nine patients (90.0%) underwent successful OPS with four different operation types. Postoperative morbidity rate of OPS was 55.6% (5/9), and no mortality occurred. After a median follow-up of 36 mo, one patient developed multiple distant metastases, but no local recurrence was observed. For long-term follow-up, patients who underwent OPS did not show any degradation in quality of life, whereas the patient who underwent PD suffered weight loss of ~10 kg. In conclusion, in patients with locally advanced duodenal GISTs, neoadjuvant IM administration followed by OPS is a feasible treatment strategy which leads to favorable short- and long-term outcomes.

Transperineal extralevator abdominoperineal excision performed by double laparoscopic approach with no position change

Background: The aim of this study was to assess the feasibility of such an approach and to appraise short-term outcomes. Methods: The abdominal phase and perineal phase of the operation were both performed laparoscopically simultaneously. All patients were enrolled in an enhanced recovery programme. Results: The conversion rate to laparotomy was 0%. All patients had circumferential resection margins (CRM) >1 mm; no intraoperative tumour perforation (IOP) occurred. The median length of stay was 8 days. Conclusions: Double laparoscopic-assisted extralevator abdominoperineal excision (ELAPE) can be safely performed without compromising short-term outcomes.

Abstract A130: The association between markers of tumor cell metabolism, the tumor microenvironment, and outcomes in patients with colorectal cancer

Abstract Introduction: Tumor cells favor glycolysis even in the presence of normal oxygen partial pressures. This phenomenon termed the Warburg effect may be facilitated by the tumor-supporting stroma. The present study investigated the association between proteins associated with tumor metabolism; monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumor microenvironment, and outcome in patients with colorectal cancer. Methods: Patients who underwent elective, potentially curative surgery, and who were included in a previously constructed tissue microarray (TMA), were identified from a prospectively collected and maintained database of colorectal cancer resections at a single surgical unit from 1997-2007. Patients who underwent emergency or palliative surgery, with pre-existing inflammatory or auto-immune co-morbidity, or who underwent neoadjuvant chemoradiotherapy were excluded. Immunohistochemical assessment of MCT 1, MCT 2, LDH 1, and LDH 5 expression was performed using the weighted histoscore method. All antibodies were validated by western blotting and blocking experiments. Routine H&amp;E staining and specific staining of tumor sections for CD3+, CD8+, CD45R0+, and FOXP3+ T cells was used to assess the tumor microenvironment including tumor stroma percentage (TSP). Patients were then stratified by a combination of TSP (≤50% or &amp;gt;50%) and expression of MCT 1, MCT 2, LDH 1, and LDH 5 (low or high) to give 4 groups for each protein in each intracellular location (membrane, cytoplasm and nucleus); low TSP and low protein expression, low TSP and high protein expression, high TSP and low protein expression, and high TSP and high protein expression. The relationship between a combination of TSP and markers of tumor metabolism, clinicopathological characteristics, local and systemic inflammatory responses, and cancer specific survival was examined using univariate and multivariate Cox regression Results: 190 patients were included of which the majority were male (106, 56%), over 65 (115, 61%), with colonic (120, 63%) and node negative disease (103, 54%). 52 patients (27%) received adjuvant therapy. Mismatch repair deficiency was identified in 23 patients (13%). The median follow up of survivors was 132 months (range 74-194) with 63 cancer associated deaths and 51 non-cancer deaths. At univariate analysis there was a significant association between cancer specific survival and TNM stage (HR 2.26, 95% CI 1.50-3.41, p&amp;lt;0.001), venous invasion (HR 2.53, 95% CI 1.62-3.95, p&amp;lt;0.001), margin involvement (HR 2.44, 95% CI 1.12-5.31, p = 0.025), peritoneal involvement (HR 2.11, 95% CI 1.34-3.30, p = 0.001), tumor perforation (HR 7.79, 95% CI 2.78-21.85, p&amp;lt;0.001), modified Glasgow Prognostic Score (mGSP) (HR 1.68, 95% CI 1.25-2.26, p = 0.001), neutrophil platelet score (NPS) (HR 1.91, 95% CI 1.23-2.98, p = 0.004), Klintrup-Makinen grade (HR 2.36, 95% CI 1.34-4.14, p = 0.003), and TSP (HR 2.01, 95% CI 1.23-3.29, p = 0.005). At univariate analysis there was a significant association between cancer specific survival and the combination of TSP and membrane expression of MCT 1 (HR 1.49, 95% CI 1.16-1.91, p = 0.002), TSP and cytoplasmic expression of MCT 1 (HR 1.44, 95% CI 1.13-1.83, p = 0.003), MCT 2 (HR 1.33, 95% CI 1.04-1.70, p = 0.021), LDH 1 (HR 1.53, 95% CI 1.18-1.98, p = 0.001), LDH 5 (HR 1.60, 95% CI 1.21-2.11, p = 0.001), TSP and nuclear expression of MCT 1 (HR 1.47, 95% CI 1.17-1.85, p = 0.003), MCT 2 (HR 1.49, 95% CI 1.16-1.90, p&amp;lt;0.001), LDH 1 (HR 1.36, 95% CI 1.07-1.74, p = 0.037), and LDH 5 (HR 1.57, 95% CI 1.20-2.05, p&amp;lt;0.001). At multivariate analysis the combination of TSP and nuclear MCT 2 expression (HR 1.61, 95% CI 1.13-2.31, p = 0.009), venous invasion (HR 3.51, 95% CI 1.55-7.95, p = 0.003), and tumor perforation (HR 25.31, 95% CI 2.75-233.11, p = 0.004), remained independently associated with cancer specific survival. The combination of TSP and nuclear MCT 2 expression was significantly associated with tumor differentiation (p = 0.017), budding (p&amp;lt;0.001), and CD3+ lymphocyte cancer cell nest density (p = 0.045). Conclusions: In patients undergoing surgery for colorectal cancer, the combination of tumor stroma percentage and nuclear MCT 2 expression is prognostically significant independent of stage at presentation. Furthermore the combination of tumor stroma percentage and nuclear MCT 2 expression was associated with tumor budding. Metabolic interactions between the stroma and tumor cell may be an important method by which invasion and metastases occur. Citation Format: Stephen T. McSorley, Jennifer Clark, Hester C. van Wyk, Paul G. Horgan, Donald C. McMillan, Joanne Edwards, James H. Park. The association between markers of tumor cell metabolism, the tumor microenvironment, and outcomes in patients with colorectal cancer [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A130.