Locoregional therapies have emerged as key components in the therapeutic arsenal against gastrointestinal cancers, offering minimally invasive options with curative potential. Beyond their direct cytotoxic effects, these interventions can remodel the tumour microenvironment by inducing immunogenic cell death and initiating local and systemic immune responses, including abscopal effects. This review aims to examine how these immunomodulatory properties may support locoregional therapies as an ideal platform for intratumoural immunotherapy, positioning their combination at the core of the evolving field of interventional immuno-oncology. Recent studies demonstrate that locoregional therapies can induce immune responses through modulation of the tumour microenvironment, creating conditions that may be exploited by intratumoural immunotherapy. This review provides a comprehensive overview of current locoregional modalities, including thermal and non-thermal ablative techniques, transarterial therapies, and minimally invasive radiation methods, detailing their mechanisms of action, clinical applications, and immune-related effects. Special attention is given to emerging evidence supporting the combination of these approaches with intratumoural delivery of immunomodulatory agents, to enhance anticancer immune responses. The convergence of locoregional intervention and targeted immunomodulation represents an emerging therapeutic concept in the treatment of gastrointestinal cancers, offering the prospect of personalised, tumour-directed immune activation. This approach holds the potential to extend the benefits of immunotherapy beyond genetically defined subgroups to a broader patient population.
Radiofrequency ablation (RFA) of cancer induces an anti-tumor immunity, which is insufficient to prevent recurrences. In mice, RFA–intratumoral immunotherapy by granulocyte–macrophage colony-stimulating factor (GM-CSF) and Bacillus Calmette-Guerin resulted in complete metastases regression. Infectious risk in human needs replacement of live vaccines. Intratumoral purified protein derivatives (PPD) have never been tested in digestive cancers, and the safety of intratumoral immunotherapy after RFA has not yet been validated in human models. We investigated the therapeutic efficacy of combined radiofrequency ablation (RFA) and intratumoral immunotherapy (ITI) using an immune-muco-adherent thermogel (IMT) in a mouse model of metastatic colorectal cancer (CRC) and the safety of this approach in a pig model. Intratumoral stability of the immunogel was assessed using magnetic resonance imaging (MRI) and bioluminescent imaging. Seventy-four CT26 tumor-bearing female BALB/c mice were treated with RFA either alone or in combination with intratumoral IMT. Regression of distant metastasis and survival were monitored for 60 days. Six pigs that received liver radiofrequency and intralesional IMT injections were followed for 15 days. Experimental gel embolisms were treated using an intravascular approach. Pertinent rheology of IMT was confirmed in tumors, by the signal stability during 3 days in MRI and 7 days in bioluminescence imaging. In mice, the abscopal effect of RFA–intratumoral immunotherapy resulted in regression of distant lesions completed at day 16 vs. a volume of 350 ± 99.3 mm3 in the RFA group at day 25 and a 10-fold survival rate at 60 days. In pigs, injection of immunogel in the liver RFA area was safe after volume adjustment without clinical, hematological, and liver biology disorder. Flow cytometry showed an early increase in CD3 TCRγδ+T cells at D7 (p < 0.05) and a late decrease in CD29+-CD8 T cells at D15 (p < 0.05), reflecting the inflammation status changes. Systemic GM-CSF release was not detectable. Experimental caval and pulmonary thermogel embolisms were treated by percutaneous catheterism and cold serum infusion. RFA–intratumoral immunotherapy as efficient and safe mini-invasive interventional oncology is able to improve ablative treatment of colorectal liver metastases.
Background and Objectives: Previous reports showed an increased risk of infectious complications when liver radiofrequency ablation (RFA) is performed simultaneously to colorectal resection. The aim of this study was to compare early and long-term outcomes of simultaneous versus staged strategy. Methods: Data from colorectal cancer liver metastases consecutively treated by surgery of the primary tumor with an associated liver RFA procedure between January 1, 2010 and January 31, 2020. Patients were divided into two groups: RFA performed during colorectal surgery (simultaneous) or in a different moment (staged). Patients were manually matched (1:1) to minimize influence of known covariates. Results: Seventy-two patients were included. After matching, there was no difference between the two groups in morbidity or mortality. Hospital stay was 2 days shorter in the simultaneous group. Conclusions: Early or long-term outcomes were identical between the two strategies. The simultaneous strategy was associated with a shorter duration of hospitalization although not significant. Simultaneous colorectal resection and liver RFA is safe and must be included in surgeons' armamentarium.
Intratumoral injection of biocompatible gels is increasingly used for the sustained delivery of drugs and vaccines to enhance the anti-cancer immune response. Granulocyte-macrophage colony stimulating factor (GM-CSF) has become an attractive adjuvant thanks to its ability to boost the antitumor immune response by inducing proliferation, maturation and migration of the dendritic-cells (DCs) and the differentiation of lymphocytes. Killed Mycobacteria, such as Heat-killed Mycobacterium tuberculosis (HKMT) have been used in several studies as TLR-2 agonist to increase maturation of DCs. In this study, we designed a mucoadhesive thermosensitive formulation for the local delivery of GM-CSF and HKMT in order to enhance DCs activation and improve the local antitumor immune response. This formulation was selected based on its elastic and mucoadhesive properties obtained thanks to rheological studies. More importantly, intratumoral residence time of the labelled gel and protein were evidenced by means of MRI and non invasive in vivo optical imaging. Then, the efficacy of the combination of immunomodulators loaded thermogel was demonstated in vitro and in vivo. The selected thermogel exhibits rheological properties which confer a good elasticity and increased residence time of the immunostimulatory agents in the tumor, thus increasing the recruitment of DCs and T cytotoxic CD8+ lymphocytes.
Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. First, we demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. Remarkably, RFA and in situ immunomodulation with GM-CSF-BCG hydrogel induced complete cure of microscopic secondary lesions in mice, related to a strong specific immune response. Then, we demonstrated that the immune escape of large secondary lesions was reversed by addition of the systemic PD-1 blockade to the in situ immunomodulation. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of this new combination strategy. Increasing the in situ priming response of radiofrequency ablation provides effective adjuvants to induce an abscopal effect. In the case of large lesions, synergy between PD1 blockade inhibitor, ineffective alone or after single RFA, with in situ immunomodulation, could lead to reconsideration of the use of checkpoint inhibition in metastatic MSS CRC.
e15562 Background: After radiofrequency ablation (RFA), cancer cells death releasing tumor antigens and expression of danger signals activate a specific T-cell response however inadequate to avoid recurrence. We purpose to combine RFA with priming of a strong immune antitumor response as curative treatment of colorectal cancer (CRC). Methods: After RFA of colorectal liver metastases in patients, the tumour infiltration by lymphocyte (TILs) was characterized on later resected distant lesions. In mice, RFA was used to treat a CT26-luc tumor as primary lesion. Macroscopic or microscopic distant tumors were established as secondary lesions. Injection, in the treated area, of a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeted recruitment and maturation of dendritic cells. In mice with far large lesions, this strategy was combined with PD1 checkpoint inhibition. The efficiency was assessed on survival, morphologic and bioluminescent evolution of distant lesions, characterization of TILs and specific TNFα and IFN-y expression in spleen and lymph nodes Results: Proportion and characteristics of TILs were comparable in 17 patients who had preoperative RFA and in 53 paired patients who had a single hepatectomy for colorectal metastases. After RFA in mice the in situ injection of immunogel resulted in prolonged survival. Regression of distant lesions was related to the induction of a strong immune response and a great increase in TILs. This approach induced a complete cure of microscopic secondary lesions without another treatment. Immune escape of large secondary lesions was reversed by association of the RFA-immunogel with systemic PD1 checkpoint inhibition separately ineffective. Conclusions: The lack of an efficient distant immune response in RFA treated patients confirmed relevance of a new strategy. Combined to RFA the in situ priming of a strong immune response targeting microscopic disease is an effective abscopal adjuvant treatment. For distant large lesions the synergy between in situ immunomodulation and PD1 blockade, ineffective in microsatellite stable CRC or after single RFA, allows reconsidering the use of checkpoint inhibitors in CRC.
Background: Radiofrequency ablation (RFA) is a valid treatment for liver metastases from colorectal cancer (CRLM) smaller than 25 mm and unsuitable for surgical resection. Tumor size is predictive for local tumor progression (LTP). The aim of this study was to evaluate whether RFA is indicated for lesions >25 mm at presentation but <25 mm after chemotherapy. Method: Patients who underwent RFA for CRLM after chemotherapy (January 2004-December 2012) were reviewed. Metastases were classified according to their size. Group 1: <= 25 mm before and after chemotherapy. Group 2A: >25 mm before but <= 25 mm after chemotherapy. Group 2B: >25 mm before and after chemotherapy. Results: 133 CRLM were ablated in 83 patients (median follow-up 56 months). At 1-year, the LTP rate was higher in group 2A than in group 1 (32% vs. 16%, p <= 0.001). The highest rate of 1-year LTP was 64% in group 2B. Time to LTP (TLTP) was shorter in group 2A than in group 1 (HR: 2.89; 95% CI [1.04-8.01]; p = 0.004). Following multivariate analysis, the group type was the only predictive factor for TLTP (p < 0.001). Conclusions: RFA is not the optimal treatment for CRLM > 25 mm at presentation.
Background: The American College of surgical risk calculator (SRC) score has never been validated specifically for surgery in emergency. The objective was to evaluate the reliability of this calculator in patients with malignant colon obstruction. Materials and methods: We retrospectively have analyzed the morbidity and mortality observed in operated patients. Risk factors for postoperative morbidity and mortality were analyzed by logistic regression model. We have compared the morbidity and mortality estimated by the SRC score with that observed using the Brier Score (BS). A BS of 0 indicated perfect prediction, whereas a BS of 1 indicated the poorest prediction. Results: Sixty-nine patients aged 75 y (41-93) have been operated on emergency from November 2001 to August 2015. The tumor was localized in the sigmoid in 33 cases (48%), in the splenic flexure in nine cases (13%), and in the right colon in 17 cases (25%). The surgical procedures were as follows: right colectomy with anastomosis (29%), diverting proximal iliac colostomy (23%), and subtotal colectomy with anastomosis (19%). The SRC score indicated a good predictivity formortality (9.8% predicted versus 8.7% observed, BS = 0.058), formorbidity (33.4% versus 40.6%, BS = 0.209), and for serious morbidity (25.5% versus 17.4%, BS = 0.131). In multivariate analysis, SRC was an independent risk factor for mortality (P = 0.030 odds ratio [OR] = 1.07 [1.01-1.15]) and morbidity (P = 0.001 OR = 1.16 [1.08-1.27]). Conclusions: SRC score is a reliable tool for assessing the morbidity and mortality of obstructive colon cancer and could help with adapting the surgical gesture to the risks predicted. (C) 2017 Elsevier Inc. All rights reserved.
102 Background: Radiofrequency ablation (RFA) efficiency of liver tumors is compromised by high rates of relapse. Death of cancer cells by hyperthermia induced tumor antigen releasing, expression of danger signals that activate a specific T-cell response. This effect is ineffective to avoid recurrence. We propose to combine RFA with priming of a strong immune antitumor response as curative treatment of an aggressive colorectal cancer (CRC) in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor as primary lesion. In two distinct clinical situations, macroscopic or microscopic distant tumors were established as secondary lesions. The immune response was modulated by the injection, in the treated area, of a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting recruitment and maturation of dendritic cells. In mice with far large lesions, this strategy was combined with PD1checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of tumoral lymphocyte infiltration TNF-α and IFN-y expression in peripheral T lymphocytes. Results: The in situ immunogel injection after RFA resulted in prolonged survival of mice. Regression of distant lesions was related to the induction of a strong systemic antitumor immune response and a great improvement of tumor infiltration by CD3+ T lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without another treatment. Immune escape of large secondary lesions was reversed by association of the RFA-immunogel vaccination with a systemic immune checkpoint inhibition, separately ineffective. Conclusions: Validation of this strategy, combining RFA of macroscopic lesions and activation of a strong immune response controlling the residual disease, could result in the design of a clinical assay including this approach within a standard treatment of colorectal liver metastases. The synergy between in situ immunomodulation as priming process and checkpoint blockade, ineffective alone in metastatic microsatellite stable CRC or after single RFA, allows reconsidering the use of checkpoint inhibitors in CRC.
e14540 Background: Results of radiofrequency ablation (RFA), increasingly used to treat liver tumors, are compromised by local and systemic relapse. Hyperthermia related cancer cells death, release of tumor antigens and expression of danger signals activate a tumor-specific T-cells response. This effect remains ineffective to avoid recurrence. Therefore we propose to combine RFA with an activation of a solid immune antitumor response as curative treatment of a colorectal (CRC) metastatic disease in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor. In two distinct clinical situations, distant macroscopic or microscopic tumors were established as metastases before or at the time of RFA. Immune response was modulated by an injection in situof a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting dendritic cells. In the group of mice with large far lesions this strategy was combined with immune checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of lymphocyte infiltration in tumors and systemic immunity through specific TNF- α and IFN-y expression in spleen and draining lymph nodes. Results: The in situ immunogel injection after RFA resulted in a prolonged survival of mice. Regression of distant lesions was related to a strong systemic antitumor immune response and a great improvement of tumor infiltration by specific cytotoxic lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without any treatment. Immune escape of large secondary lesions was reversed by association of RFA-immunogel vaccination with a systemic check point blockade, separately ineffective. Conclusions: Validation of this strategy, combining RFA of liver metastases and activation of a strong immune response controlling the residual disease, could result in a clinical assay including this approach within the standard treatment of CRC. Furthermorethe powerful synergy between RFA-in situ immunomodulation as a starter treatment and checkpoint blockade ineffective alone in CRC or after single RFA, allows reconsidering the use of immune checkpoint inhibitors in metastatic microsatellite stable CRC.
This prospective study aimed to compare outcomes after laparoscopic peritoneal lavage (LPL) and sigmoid resection with primary colorectal anastomosis (RPA).
Le traitement chirurgical optimal des péritonites purulentes (Hinchey III) par perforation diverticulaire (PPPD) reste débattu. Le but de cette étude était de comparer les résultats postopératoires du lavage-drainage laparoscopique (LDL) à ceux de la résectionanastomose colorectale protégée (RAP) pour PPPD. De 2010 à 2015, tous les malades opérés pour PPPD ont été inclus. Le choix entre LDL et RAP était laissé à l'appréciation du chirurgien. 24 malades ont eu une RAP et 15 un LDL. La proportion de malades ASA>2 était supérieure dans le groupe RAP (12/24 vs 1/15, p<0.01). La morbidité et la mortalité postopératoire n'étaient pas différentes après RAP et après LDL (42 % vs 67 %, N S ; 8.3 % vs 6.7 %, NS). Les taux de complications chirurgicales et de réopérations étaient plus élevés après LDL qu'après RAP (53 % vs 17 %, p=0.03 ; 47 % vs 4 %, p<0.01). Les 7 malades réopérés après LDL ont eu Hartmann (4), RAP (2), relavage (1). Tous les malades ayant eu une stomie non décédés ont eu un rétablissement de continuité (RDC) après un délai de 92 jours après LDL et de 72 jours après RAP (p=0.07). La morbidité globale de la prise en charge RDC inclus était de 73 % dans le groupe LDL et 52 % dans le groupe RAP (NS). En cas de PPPD, près de la moitié des malades ayant un LDL sont réopérés pour avoir une stomie. La RAP est une alternative fiable, elle limite le risque de réintervention pour complication grave sans augmenter le risque de stomie définitive. Les auteurs n'ont pas transmis de conflits d'intérêts.
3528 Background: Radiofrequency ablation (RFA) can be a valid treatment for liver metastases from colorectal cancer (CRLM) and is mostly dedicated to metastases unsuitable for surgical resection. Tumor size at the time of the RFA procedure is the main predictive factor for in situ recurrence (ISR) at the ablated zone. However, regardless to tumor size during procedure, the diameter of liver metastases at presentation, before chemotherapy infusion, may be predictive for ISR, although it has never been assessed. The aim of this study was to determine the risk for ISR after RFA for liver metastasis larger than 25mm initially but that have been downsized by preoperative chemotherapy. Methods: We retrospectively reviewed all RFA performed in patients treated for CRLM who had previously received at least one cycle of systemic chemotherapy from January 2004 to December 2012. Each tumor site treated by RFA was studied independently. Metastases were divided into 2 groups according to its size. Group1: ≤ 25mm before and after chemotherapy. Group 2: > 25 mm before chemotherapy; 2A: ≤ 25mm after chemotherapy 2B: > 25 mm after chemotherapy. Results: 133 CRLM were ablated in 83 patients after systemic chemotherapy (median follow-up 21 months). Among those patients, 57 underwent RFA combined with hepatectomy. The rate of 1-year ISR was significantly higher in group 2A than in group 1 (31.8% vs. 15.5% respectively, p = 0.0006). The highest rate of 1-year IRS was 63.6% in group 2B which was significantly higher than in group 1 (p < 0.001) and 2A (p = 0.04). Time to in situ recurrence (TTISR) was significantly shorter in group 2A than in group 1 (HR: 2.89; 95%CI [1.04-8.01], p = 0.004). The shortest TTISR was observed in group 2B. In multivariate analysis, RFA group was the only significant indicator for ISR after RFA (p < 0.001). Conclusions: Initially oversized CRLM do remain beyond the optimal indications for RFA despite downsizing and should be consider as contraindication to RFA procedure. The rate of ISR remains in this situation doubled to that of upfront small liver metastasis reaching 32%.
Background: Few data are available on management of very elderly colon cancer patients, especially concerning the parameters of therapeutic decisions and the role of geriatricians.Methods: We retrospectively reviewed the charts of patients over 80 years of age who underwent surgery for a localised colon cancer in a French academic hospital.Results: A total of 176 patients underwent surgery (postoperative morbidity and mortality rates: 25% and 6.7%). Adjuvant chemotherapy was discussed at a multidisciplinary team meeting for 91% of stage III patients, but only 13.5% of them were treated. Twenty-five patients relapsed: 19 were discussed at the multidisciplinary meeting and 16 were treated (5 had a metastasectomy). Despite their increase with time, geriatric assessments were infrequent, 17% (33% after 2006), and had no impact on postoperative morbi-mortality. Median overall survival and recurrence-free survival were 65.3 months and 65.1 months, respectively. Age, emergency surgery, and Charlson comorbidity index were independent prognostic factors.Conclusion: Selected elderly colon cancer patients have significant access to surgery. However, postoperative morbi-mortality rates remain high and adjuvant chemotherapy rarely prescribed. Perioperative geriatric assessment, especially before surgery, should be routinely proposed to these patients to evaluate its impact on postoperative morbi-mortality and prescription of adjuvant treatment. (C) 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Background Lymphoid infiltration is a prognostic marker in solid tumors, such as colorectal, breast and lung carcinomas. However, lymphoid infiltration is heterogeneous and the reproducibility of quantification based on single counts within a tumor is very low. We aimed to develop a reproducible method for evaluating lymphoid infiltration in tumors. Methods Virtual slides were obtained from tissue sections from the localized colorectal carcinomas of 117 patients, stained for CD3 and CD45R0. We assessed the variation of lymphoid cell density by automatic counts in 1 mm-wide, 5 μm-long segments of the invasive front, along an axis 4 mm in length running perpendicular to the invasive front of the tumor. Results We plotted curves of the variation of lymphocyte density across the tumor front. Three distinct patterns emerged from this linear quantification of lymphocyte (LQLI). In pattern 1, there was a high density of lymphocytes within the tumor. In pattern 2, lymphocyte density peaked close to the invasive margin. In pattern 3, lymphocytes were diffusely distributed, at low density. It was possible to classify all the tumors studied, and interobserver reproducibility was excellent (kappa =0.9). By contrast, single counts of CD3 + cells on tissue microarrays were highly variable for a given LQLI pattern, confirming the heterogeneity of lymphoid infiltration within individual tumors. In univariate analysis, all pathologic features (stage, metastatic lymph node ratio (LNR), vascular embolism, perineural invasion), CD3 + cell density, LQLI patterns for CD3 + and CD45R0 + cells) were found to have a significant effect on disease-free survival (DFS). In multivariate analysis, only the LQLI pattern for CD3 + cells (HR: 6.02; 95% CI: 2.74-13.18) and metastatic lymph node ratio (HR: 6.14; 95% CI: 2.32-16.2) were associated with DFS. Conclusion LQLI is an automated, reproducible method for the assessment of lymphoid infiltration. However, validation of its prognostic value in larger series is required before its introduction into routine practice for prognostic evaluation in patients with colorectal carcinomas. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9861460717895880
Background Cancer gene therapy by retroviral vectors is mainly limited by the level of transduction. Retroviral gene transfer requires target cell division. Cell synchronization, obtained by drugs inducing a reversible inhibition of DNA synthesis, could therefore be proposed to precondition target cells to retroviral gene transfer. We tested whether drug-mediated cell synchronization could enhance the transfer efficiency of a retroviral-mediated gene encoding herpes simplex virus thymidine kinase (HSV- tk ) in two colon cancer cell lines, DHDK12 and HT29. Methods Synchronization was induced by methotrexate (MTX), aracytin (ara-C) or aphidicolin. Gene transfer efficiency was assessed by the level of HSV-TK expression. Transduced cells were driven by ganciclovir (GCV) towards apoptosis that was assessed using annexin V labeling by quantitative flow cytometry. Results DHDK12 and HT29 cells were synchronized in S phase with MTX but not ara-C or aphidicolin. In synchronized DHDK12 and HT29 cells, the HSV-TK transduction rates were 2 and 1.5-fold higher than those obtained in control cells, respectively. Furthermore, the rate of apoptosis was increased two-fold in MTX-treated DHDK12 cells after treatment with GCV. Conclusions Our findings indicate that MTX-mediated synchronization of target cells allowed a significant improvement of retroviral HSV- tk gene transfer, resulting in an increased cell apoptosis in response to GCV. Pharmacological control of cell cycle may thus be a useful strategy to optimize the efficiency of retroviral-mediated cancer gene therapy.
The optimal strategy for identifying patients with Lynch syndrome among patients with newly diagnosed colorectal cancer (CRC) is still debated. Several predictive models (e.g., MMRpredict, PREMM1,2 and MMRpro) combining personal and familial data have recently been developed to quantify the risk that a given patient with CRC carries a Lynch syndrome-causing mutation. Their clinical applicability to patients with CRC from the general population requires evaluation. We studied a consecutive series of 214 patients with newly diagnosed CRC characterized for tumor microsatellite instability (MSI), somatic BRAF mutation, MLH1 promoter methylation and mismatch repair (MMR) gene germline mutation status. The performances of the models for identifying MMR mutation carriers (8/214, 3.7%) were evaluated and compared to the revised Bethesda guidelines and a molecular strategy based on MSI testing in all patients followed by the exclusion of MSI-positive sporadic cases from mutational testing by screening for BRAF mutation and MLH1 promoter methylation. The sensitivities of the three models, at the lowest thresholds proposed, were identical (75%), with similar numbers of probands eligible for further MSI testing (almost half the patients). In our dataset, the prediction models gave no better discrimination than the revised Bethesda guidelines. Both approaches failed to identify two of the eight mutation carriers (the same two patients, aged 67 and 81 years, both with no family history). Thus, like the revised Bethesda guidelines, predictive models did not identify all patients with Lynch syndrome in our series of consecutive CRC. Our results support systematic screening for MMR deficiency in all new CRC cases.
To the Editor: Stercoral perforation of the colon is rarely reported in the surgical literature. Infrequently, a stercoral disease or ulceration with perforation may represent the underlying etiology. Age, comorbidity, systemic disorders, reduced “functional reserve,” and poor tolerance to repeat surgical stresses are some of the medical factors that can lead to the high mortality rate (32–57%) related to this condition.1 In the present study, we reported on the surgical management of eight stercoral perforations and indicate the importance of preventive treatment. We retrospectively reviewed the medical records of eight patients operated on for peritonitis due to perforation of a fecaloma in two hospitals between 2004 and 2006. The demographic, operative, pathological, and outcome details were recorded to assess the conditions of colonic perforation due to fecaloma.2 The mean age of the eight patients (5 women and 3 men) was 81±5. Two patients came from a chronic nursing home or similar environment. All of the patients had a long history of chronic constipation preceding the stercoral perforation. Three patients were taking amitriptyline or others constipation sedatives, and two patients were in chronic renal failure. Three patients had neurological antecedents (1 psychotic, 1 depression, 1 dementia). Five patients had a lack of mobility. A diagnosis of acute abdomen was readily made with general peritonitis in five cases and local peritonitis in two. In four cases, a palpable impacted fecal mass was found on rectal examination. In one case, x-ray of the abdomen showed free air at; in another case, a pneumomediastinum was observed on the chest x-ray. In only five cases was observed pneumoperitoneum on a computed tomography scan. In all cases, the perforation occurred in the sigmoid. All patients were operated on through a median incision. Hartman's procedure, which involves resection of the diseased rectosigmoid colon at the level of the peritoneal reflection, with creation of proximal end colostomy and suture of the distal rectal stump, was the standard technique used. This surgical approach was applied in the case of five patients. Exteriorization of perforation without resection was carried out in two cases; in the last case, a resection of the colon with double colostomy was achieved. Three patients died (33%) in the early postoperative course. All patients with exteriorization of perforation died. Five patients were alive, but four patients had a colostomy. The profiles of morbidity and mortality are shown in Table 1. Observations reported in the present study underline the difficulty of determining precisely the true incidence of stercoral perforation. An explanation for the rarity of the disease is not apparent but almost certainly is underreported.1, 2 The first step of this pathology began by constipation that often pass unperceived, asymptomatic stercoral ulcer appeared in the second step (rarely they can lead to intestinal bleeding),3 and in the final step, perforation of the colon occurred. The mean age of the patients in this study explains the greater rate of mortality than in Mauer's report.2 Data reported in a French multicentric study showed that four independent preoperative risk factors of mortality exist: emergency surgery, loss of more than 10% of weight, neurological comorbidity, and age 70 and older.4 Moreover, six independent risk factors for morbidity were found: age 70 and older, neurological comorbidity, hypoalbuminemia, cardiorespiratory comorbidity, long duration of surgery, and peritoneal contamination.4 The study presented here is the anecdotal concept that stercoral ulceration and perforation are complications that develop in older individuals or in those with chronic pathologies (e.g., neurological and cardiorespiratory comorbidity). The perforation may have an atypical presentation (e.g., asthenic peritonitis) or result in few laboratory abnormalities (e.g., acute renal failure, hyperleukocytosis).5 Moreover, an empty rectal fecaloma does not exclude perforation by fecaloma, although the most appropriate approach would be a preventive policy with active treatment of terminal constipation and fecaloma. Chronic constipation with fecal impaction is a mundane problem. Clinical symptoms such as anorexia, nausea, vomiting, abdominal pain, paradoxical diarrhea, and incontinence are among the most common symptoms in patients in institutions and should be carefully taken into account.6 Although most impactions are in the rectal vault, the absence of palpable stool on rectal examination does not rule out a fecal impaction.7 Although enemas and suppositories alone may eliminate the impaction, the manual fragmentation and extraction of the fecal mass is almost always indicated first.6 Extraction of fecal mass may be made under local or general anesthesia.6 The evolution of a bad extraction may continue to ischemic colitis and perforation. Surgical treatment of a perforation of fecaloma must be done with resection and proximal colostomy. Exteriorization of perforation is not recommended, because sepsis of ischemic colon is not controlled. However, the best treatment would be prevention. Institutionalized, neurological, or elderly patients may be carefully observed and constipation taken into account and treated. After constipation and incontinence signs, a rectal examination may often be made to treat early fecaloma. Financial Disclosure: None. Author Contributions: Study concept and design: M. Ouaïssi, I. Sielezneff, S. Benoist, B. Sastre, B. Nordlinger. Acquisition of data: M. Ouaïssi, N. Pirrò, S. Benoist, E. Cretel. Analysis and interpretation of data: M. Ouaïssi, S. Benoist, I. Sielezneff, E. Cretel. Drafting of letter: M. Ouaïssi, E. Cretel, J. B. Chaix, F. Peschaud. Critical revision of the letter for important intellectual content: B. Sastre, B. Nordlinger, R. Malafosse, B. Consentino, C. Penna. Statistical analysis: M. Ouaïssi, S. Benoist. Study supervision: S. Benoist, B. Nordlinger, B. Sastre. Sponsor's Role: None. The authors wish to thank Dr. Ali Ouaissi, Head of Research at INSERM for his precious help and advice.
Although anesthesia and post-operative analgesia are associated with specific morbidity, regional anesthesia is not systematically given during groin hernia surgery. The goals of this work were to determine the anatomical bases of safe ilio-inguinal (II)-hypogastric anesthesia that can be prolonged into the post-operative period and to validate this technique on anatomical preparations and in clinical situations. We studied the courses of the ilio-hypogastric (IH) and II nerves in 33 halves of 20 embalmed adult cadavers. The intermediate portion of the IH and II nerves, located between the transverse and the internal oblique muscles, were found to be suitable for a simultaneous block with a single injection. We assessed the feasibility of injecting a percutaneous infiltration into this space by injecting a dye before dissection. In 75% of cases, we observed percutaneous coloring of the nerves, confirming that this site was suitable. To guide the infiltration, the points where the nerves passed through the transverse and the internal oblique muscles were located from the iliac crest and anterior and superior iliac spine, respectively. The nerve trunks were grouped for over 5 cm in a cell-fat layer running between these two deep muscles. It was possible to position a micro-catheter in this anatomical space to allow repeated injections. The results of this anatomical study were used to modify the technique so that it could be used to provide regional anesthesia in five patients operated on for hernia. Post-operative pain was very effectively controlled in four cases with no complications.
A variation in liver vascularization was discovered in a 50-year-old man. A single common hepatic artery was found to be responsible for vascularization of the entire liver. This artery was unusual in that it formed the first branch of the superior mesenteric artery, crossing the portal trunk shortly after its origin, and passed in front of the portal vein to reach the hilum of the liver, where it divided into a right and a left branch. This artery was a true common hepatic artery because a gastroduodenal artery emerged from it 2 cm after its origin. A common hepatic artery originating from the mesenteric artery and passing in front of the portal vein has never been described before. The patient had a second anatomical variation: the left gastric artery and the splenic artery arose directly from the aorta, without celiac trunk separation. This observation confirms the importance of carrying out a precise vascular assessment before all types of hepatic or pancreatic surgery, to identify possible variations in the number or trajectory of hepatic arteries.