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BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes.METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias.RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively.CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable.

Adequate tissue oxygenation and perfusion remain fundamental to safe bowel resection surgery. Near infrared (NIR) imaging using indocyanine green has proven itself superior to clinical evaluation alone in assessing bowel perfusion, but requires expensive equipment not readily available in many centers. We studied the IntraOx device (Vioptix Inc, Newark, CA USA), a handheld, tissue oxygen saturation assessment tool, to assess whether tissue bed oxygen saturation (StO2) is comparable to NIR assessment of bowel viability. Patients undergoing elective colon resection for benign and malignant disease were included. After choosing a clinical margin (CM) and dividing the mesentery, StO2 was measured at 5-cm intervals along the colon. A tissue oxygen saturation margin (TOM) was assigned where StO2 dropped off by at least 10 percentage points. NIR perfusion was then assessed to determine NIR margin (NIRM). Intraoperative and postoperative data were collected. 32 consecutive patients undergoing colectomies were analyzed. IntraOx sensitivity was 90.6%, specificity was 94.3%. The mean StO2 difference across the NIRM was 23.1%. In all but one case, the TOM matched the NIRM. In 3 cases, the TOM and NIRM concurred, but were a mean of 3.3 cm proximal to the CM and altered the surgical plan. At 4-week follow-up, no significant complications were reported. The IntraOx device consistently identified a margin of significant saturation “drop-off” which correlated with the findings on NIR perfusion and clinical assessment. These early data indicate that StO2 measurement may be equivalent to NIR assessment of bowel perfusion. In addition, the IntraOx device may be a more cost-effective solution for surgeons looking for adjunctive evaluation of bowel viability. More study is warranted in a larger group of patients to confirm these preliminary findings and to judge the impact of StO2 assessment on reducing anastomotic leaks.

Introduction: PGRN is a growth factor involved in the regulation of cell proliferation, differentiation and pathological processes. OPN is an integrin binding phosphorylated glycoprotein involved in cell-mediated immunity, inflammation, cell survival, and tumor progression. MMP 2 is an extracellular matrix (ECM) remodeling enzyme that breaks down the ECM and also facilitates cancer growth. OPN promotes ERK pathway and VEGF mediated tumor angiogenesis and progression. PGRN stimulates VEGF expression in breast cancer cells in vitro. This study’s goals were to assess: 1) preoperative (preOp) plasma PGRN, OPN and MMP 2 levels in CRC and benign pathology (BP) patients (pts.), 2) tumor mRNA expression, and 3) the diagnostic potential of these proteins. Method: CRC and BP bowel resection pts enrolled in an IRB approved tissue bank for whom preOp plasma was available were studied. Basic demographic, clinical, operative, and pathology data were evaluated. Plasma PGRN, OPN and MMP2 levels (ng/ml) were measured in duplicate via ELISA (results: median + 95%CI). Also, protein expression levels in tumors and paired normal tissue were determined for a subset of pts by QRT-PCR. CRC and BP plasma levels were compared by the Mann-Whitney test (significant Result: Plasma from 102 BP (adenoma 32%, diverticulitis 53%, other 15%) and 172 CRC (70% colon, 30% rectal) pts. were analyzed. The CRC Stage (STG) distribution was: STG-1, 25%; STG-2, 32%, STG-3, 31%, STG- 4, 12%. Median PreOp proteins levels in CRC patients for all 3 proteins were significantly higher than BP levels (PGRN; 54.71, CI: 51.82,57.12 vs. 43.32, CI: 40.10,46.89; OPN; 82.38, CI: 77.1,89.38 vs. 63.86, CI: 54.95,69.03; MMP2; 205.3 CI:198.2,217.15 vs. 165.3 CI: 156.83,179.06; P Conclusion: Median PGRN, OPN and MMP2 plasma levels in CRC pts were significantly higher (26%, 29% & 24% respectively) than BP levels; the OPN and MMP2 increases may be related to tumor expression. Increased plasma PGRN and MMP2 may be the result of tumor angiogenesis and inflammation-induced tissue remodeling. OPN levels were increased in stage 4 pts. The 3 protein combination had improved AUC & specificity vs single protein results. Further study is needed. Citation Format: Chandana S. K. Herath Mudiyanselage, Xiaohong Yan, Neil Mitra, Hansani N. Angammana, Hiromichi Miyagaki, Yanni Yanni, Vesna Cekic, Joseph Martz, Richard L. Whelan. Plasma and tumor expression levels of progranulin osteopontin & matrix metalloproteinase 2 in colorectal cancer patients and assessment of plasma levels for diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3295.

The role of robotics in colon and rectal surgery has been established as an important and effective tool for the surgeon. Its inherent technologies have provided for increased visualization and ease of dissection in the minimally invasive approach to surgery. The value of the robot is apparent in the more challenging aspects of colon and rectal procedures, including the intracorporeal anastomosis for right colectomies and the low pelvic dissection for benign and malignant diseases.

Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials.We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection.We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years.This was a multicenter trial.Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge.Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy.Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention.This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34).The predetermined sample size to adequately reduce the risk of type II error was not achieved.Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560.ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).

Introduction: Cancer-Testis antigens (CTA’s) are normally expressed in germline tissue, however, aberrant expression occurs in some cancers. Restricted CTA expression in normal tissues make CTA’s potential vaccine targets. CTA’s have been associated with tumor cell proliferation and invasion. The CTA A-kinase anchor proteins 4 (AKAP 4) plays a role in cancer development and progression. The expression pattern of AKAP4 gene in CRC is not well characterized. This study’s aim was to assess AKAP4 expression in CRC and to assess this CTA’s potential as a vaccine target. Methods: CRC patients (pts) undergoing surgery who donated tissue to an IRB approved tissue/data bank comprise the study group. Demographic and pathologic data were assessed. Tissues were OCT embedded and stored at -800C. Total purified RNA was isolated from tissue samples and cDNA synthesized. AKAP4 expression was analyzed by quantitative PCR (QPCR) using EXPRESS qPCR universal Supermix and Taqman assay. Comparative quantitative analysis was performed based on the delta-delta Ct method with GAPDH as internal control. Tumor and testis AKAP4 expression levels were determined; tumors with levels 0.1% or more than the testis was considered positive. Immunohistochemistry (IHC) was performed on a subset of tumor and normal tissue. The impact of tumor location and cancer stage on AKAP4 expression was determined and assessed (Wilcoxon signed rank test). Results: 70 paired CRC and normal tissue specimens (35 M/36 F, age 67.8±14) were studied (86% colon,14% rectal; cancer stage: 1, 24%; 2,37%; 3, 31.%;stg 4, 7%). The percent of pts with a relative Malignant to Normal tissue AKAP4 expression ratio (MN) over 1 was 17%; the percent with both MN ratio over 1 and expression levels above 0.1% of testis levels was 16%. IHC demonstrated AKAP4 in a subset of CRC tumor samples. No significant difference was noted between colon vs rectal, or cancer stage groups. No expression was found in 21 normal samples. Discussion: In a tumor subset the relative expression of AKAP4 was above that of normal colon and more than 0.1% of testis expression. IHC study demonstrated the antigen in CRC tumors. A larger study is needed determine if AKAP4 expression correlates with T, N, or final tumor stage. AKAP4 holds some promise as a vaccine target. Citation Format: Chandana S. K. Herath Mudiyanselage, Neil Mitra, Otavia L. Caballero, Dasuni N. Gamage, Xiaohong Yan, Vesna Cekic, Joseph Martz, Richard L. Whelan. Assessment of the Cancer Testis antigen AKAP4, via tumor expression analysis and IHC, as a potential vaccine and immunotherapy target for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1414.

Introduction: Expression of Osteopontin (OPN) and Matrix Metalloproteinase 2 (MMP 2) are elevated in CRC. OPN is an integrin binding phosphorylated glycoprotein implicated in cell-mediated immunity, inflammation, tumor progression, and cell viability. OPN is secreted by macrophages and leukocytes. OPN activity is associated with the PI3K/AKT and ERK pathways and VEGF mediated tumor angiogenesis. MMP-2 degrades type IV collagen and facilitates tumor cell invasion and metastasis. MMP-2 also promotes tumor angiogenesis. This study’s first purpose was to compare preoperative (PreOp) plasma OPN and MMP2 levels in CRC and benign pathology (BP) patients (pts); the 2nd purpose was to assess the combination of these proteins for diagnosis. Method: PreOp plasma samples obtained from consenting CRC and BP pts undergoing surgery were used for this study. Prospectively gathered demographic, clinical and pathologic data were analyzed. Plasma levels of OPN and MMP2 (ng/ml) were measured via ELISA and reported as median + 95% CI. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of each protein alone and in combination. Expression levels of OPN and MMP2 were determined in tumor and normal tissue for a subset of pts by QRT-PCR. The Mann-Whitney test was used for analysis. Results: Plasma from 156 CRC (73% colon, 27% rectal) and 102 BP (polyp 32%, diverticulitis 56%, other 12%) pts was studied. CRC stage breakdown was: 1, 26%; 2, 33%, 3, 29%, 4, 12%. CRC median preop plasma levels were significantly higher vs. the BP group for both proteins [OPN; 82.4,CI:75.4, 89.5 vs 59.2, CI:53.8,63.3;MMP2; 203.6,CI:195.0,214.5 vs 160.2,CI:151.9,172.2; P Conclusion: Median CRC OPN and MMP2 levels were significantly higher (39% and 27%) than BP levels. OPN and MMP2 expression was confirmed in a subset of pts. This 2 protein combination improved the AUC and specificity for CRC diagnosis. Further study with more protein combinations is warranted. Citation Format: Chandana S. k. Herath Mudiyanselage, Hiromichi Miyagaki, Neil Mitra, Yanni Hedjar, Xiaohong Yan, Vesna Cekic, Joseph Martz, Jennifer Agnew, Richard L. Whelan. Osteopontin and matrix metalloproteinase 2 plasma levels are elevated in colorectal cancer (CRC) vs benign disease; The 2 protein combination improves specificity as regards CRC diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1415.

Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.

Two decades have passed since the late 1970s, which witnessed the introduction of total mesorectal excision (TME)-based operations for rectal cancers on both sides of the Atlantic. Since the introduction of TME, clinical experience has been reported widely in the form of single- and multisurgeon reports from wide geographic regions with multiple participants, and from specialty services with narrow focus and high levels of expertise. All of these published results conclude that in comparison with conventionally practiced blunt surgery for rectal cancer, TME-based (i.e., anatomically correct, sharply performed) operations are associated with significantly lower rates of pelvic (local) recurrences, a significantly higher rate of survival, and significantly lower long-term morbidity. The latter is accomplished through dramatically higher rates of sphincter preservation, and the preservation of both sexual and urinary functions. Overall, there is a remarkable similarity in the clinical results that have been reported from diverse centers. TME now forms the basis of large randomized clinical trials in which the role of adjuvant therapy is being reexamined. The current status of TME is reviewed, and the authors’ clinical results of a consecutive series of 544 TME-based operations performed through 1998 are updated. Semin. Surg. Oncol. 19:321–328, 2000. © 2000 Wiley-Liss, Inc.

In the design of operations for rectal cancers, the focus is often on circumventing the local extent of disease and leaving the pelvis free of cancer. The local extent of disease may range from minimal intramural invasion to the direct extension of a primary tumor to pelvic sidewall structures, e.g., the internal iliac vessels. In the absence of distant spread, understanding the planes of pelvic anatomy may allow the knowledgeable surgeon to cure patients who would otherwise be declared unresectable. We present the four planes (and one rare situation) available for sharp dissection which allow for the resection of all but a few cases of locally advanced disease. Semin. Surg. Oncol. 18:199–206, 2000. © 2000 Wiley-Liss, Inc.

Retained foreign body is a recognized complication of abdominal, pelvic, and thoracic surgery and a cause of medical malpractice. Efforts to reduce its incidence include safe exposure and the use of fewer laparotomy pads. The EZ DASH is an absorbent 12-thickness laparotomy pad covering a malleable stainless steel mesh, providing both the needed retraction and a reduction in the use of individual pads. EZ DASH has been introduced into clinical use in 183 consecutive cases by specialty surgeons (colorectal, gynecology, and gynecologic oncology services) at multiple medical centers. The retractor may be shaped to the individual needs of an operating field, eg, the pelvis, and the small bowel secured behind the retractor, held in place by the tension of its mesh and the security of the abdominal wall. Positioning has been intuitive and secure, and the intraoperative use of sponges and of operating time have both been noticeably reduced. Among 183 cases, 91% of uses were felt to reduce OR time by ≤5 to ≥10 minutes. Ninety-three percent of EZ DASH cases used fewer individual laparotomy pads for small bowel retraction. Ninety-five percent of uses suggested a value added to the case by the operating surgeon with an expressed desire to use the product repeatedly. The EZ DASH is a simple method of obtaining small bowel retraction and laparotomy pad absorption with a reduction in the need for individual pads, providing excellent exposure for the operative field and reducing the risk of retained foreign body.

Background: The side effects of acute elevations in intraabdominal pressure (IAP) are related to a multifactorial etiology. Previous studies have reported that acute elevations in IAP produce an immediate increase in intracranial pressure (ICP). This study was designed to analyze the reasons for increased ICP during acute elevations of IAP and to determine the combined effects of IAP and changes in ventilation indices on ICP and hemodynamic indices. Study Design: Five pigs were studied. A subarachnoid screw was placed for ICP monitoring. The jugular vein, femoral vein, and femoral artery were cannulated. Mean arterial pressure (MAP), central venous pressure (CVP), ICP, and arterial pressure of carbon dioxide (PaCO 2 ) were monitored before and after carbon dioxide pneumoperitoneum was established at 0, 10, and 20 mmHg of IAP. Effects of hyperventilation and hypoventilation were recorded and compared with baseline ventilation. Cavography was performed to evaluate the morphology of the inferior vena cava (IVC) at different levels of IAP. Multiple regression and Student's t -test were used to examine the effects of IAP and ventilation on dependent variables. Results: The IVC showed a progressive narrowing at the level of the diaphragm as IAP was increased. There was a simultaneous increase in CVP, MAP, and ICP. The mean changes in ICP with hypoventilation were significantly larger than with hyperventilation. Conclusions: Acutely increased IAP displaces the diaphragm cranially, narrowing the IVC and increasing intrathoracic pressure. This increases CVP and increases ICP by venous stasis and increased pressure in the sagittal sinus with decreased resorption of cerebrospinal fluid. Hemodynamic changes are directly related to the rise in ICP. Hypoventilation and hypercarbia significantly increase ICP when compared with hyperventilation and hypocarbia. Hyperventilation does not significantly decrease ICP during acute elevations of IAP.

Highlights • We describe the first reported case of perianal pyoderma gangrenosum after anorectal surgery for benign disease. • We review the literature regarding postsurgical pyoderma gangrenosum. • Increased awareness of postsurgical pyoderma gangrenosum will aid in prompt diagnosis and proper medical management of this uncommon postoperative morbidity., Introduction Pyoderma gangrenosum (PG) is a rare, inflammatory skin pathology frequently associated with systemic inflammatory disease. While rare after surgery, recognition of this disease in the post-surgical setting is important as it can mimic wound infection. Presentation of case We herein present a dramatic presentation of perianal PG four days after routine excision and fulguration of anal condyloma acuminatum. The affected area did not improve with broad spectrum antibiotics or surgical debridement. A diagnosis of PG was made from clinical suspicion and pathology findings, and further confirmed with rapid improvement after starting steroids. Diagnosis of this disease in the postoperative period requires high suspicion when the characteristic ulcerative or bullae lesions are seen diffusely and show minimal improvement with antibiotic treatment or debridement. Discussion Our case highlights the importance of recognizing this disease in the post-operative period, to allow for early initiation of appropriate treatment and prevent unnecessary surgical debridement of a highly sensitive area. There have been 32 case reports of PG in the colorectal literature, mostly following stoma creation. There is one case report of idiopathic perianal pyoderma gangrenosum with no known prior trauma. To our knowledge there are no previously reported cases of perianal PG after routine elective anorectal surgery. Conclusion This is the first reported case of perianal pyoderma gangrenosum in the post-surgical setting. Increased awareness of pyoderma gangrenosum in the surgical literature will aid in prompt diagnosis and proper medical management of this uncommon postoperative morbidity.