The management of oligometastatic disease in colorectal cancer: Present strategies and future perspectives.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.

Fluorescence-based sentinel lymph node mapping and lymphography evaluation: results from the IHU-IRCAD-EAES EURO-FIGS registry.

BACKGROUND: The identification of metastatic lymph nodes is one of the most important prognostic factors in gastrointestinal (GI) cancers. Near-infrared fluorescence (NIRF) imaging has been successfully used in GI tumors to detect the lymphatic pathway and the sentinel lymph node (SLN), facilitating fluorescence image-guided surgery (FIGS) with the purpose to achieve a correct nodal staging. The aim of this study was to analyze the current results of NIRF SLN navigation and lymphography through data collected in the EURO-FIGS registry. METHODS: Prospectively collected data regarding patients and ICG-guided lymphadenectomies were analyzed. Additional analyses were performed to identify predictors of metastatic SLN and determinants of fluorescence positivity and nodal metastases outside the boundaries of standard lymphadenectomies. RESULTS: Overall, 188 patients were included by 18 surgeons from 10 different centers. Colorectal cancer was the most reported pathology (77.7%), followed by gastric (19.1%) and esophageal tumors (3.2%). ICG was injected with higher doses (p < 0.001) via extraparietal side (63.3%), and with higher volumes (p < 0.001) via endoluminal side (36.7%). Overall, NIRF SLN navigation was positive in 75.5% of all cases and 95.5% of positive SLNs were retrieved, with a metastatic rate of 14.7%. NIRF identification of lymph nodes outside standard lymphatic stations occurred in 52.1% of all cases, 43.8% of which were positive for metastatic involvement. Positive NIRF SLN identification was an independent predictor of metastasis outside standard lymphatic stations (OR = 4.392, p = 0.029), while BMI independently predicted metastasis in retrieved SLNs (OR = 1.187, p = 0.013). Lower doses of ICG were protective against NIRF identification outside standard of care lymphadenectomy (OR = 0.596, p = 0.006), while higher volumes of ICG were predictive of metastatic involvement outside standard of care lymphadenectomy (OR = 1.597, p = 0.001). CONCLUSIONS: SLN mapping helps identifying potentially metastatic lymph nodes outside the boundaries of standard lymphadenectomies. The EURO-FIGS registry is a valuable tool to share and analyze European surgeons' practices.

Intracholecystic versus Intravenous Indocyanine Green (ICG) Injection for Biliary Anatomy Evaluation by Fluorescent Cholangiography during Laparoscopic Cholecystectomy: A Case-Control Study.

(1) Background: Fluorescence cholangiography has been proposed as a method for improving the visualization and identification of extrahepatic biliary anatomy in order to possibly reduce injuries and related complications. The most common method of indocyanine green (ICG) administration is the intravenous route, whereas evidence on direct ICG injection into the gallbladder is still quite limited. We aimed to compare the two different methods of ICG administration in terms of the visualization of extrahepatic biliary anatomy during laparoscopic cholecystectomy (LC), analyzing differences in the time of visualization, as well as the efficacy, advantages, and disadvantages of both modalities. (2) Methods: A total of 35 consecutive adult patients affected by acute or chronic gallbladder disease were enrolled in this prospective case−control study. Seventeen patients underwent LC with direct gallbladder ICG injection (IC-ICG) and eighteen subjects received intravenous ICG administration (IV-ICG). (3) Results: The groups were comparable with regard to their demographic and perioperative characteristics. The IV-ICG group had a significantly shorter overall operative time compared to the IC-ICG group (p = 0.017). IV-ICG was better at delineating the duodenum and the common hepatic duct compared to the IC-ICG method (p = 0.009 and p = 0.041, respectively). The cystic duct could be delineated pre-dissection in 76.5% and 66.7% of cases in the IC-ICG and IV-ICG group, respectively, and this increased to 88.2% and 83.3% after dissection. The common bile duct could be highlighted in 76.5% and 77.8% of cases in the IC-ICG and IV-ICG group, respectively. Liver fluorescence was present in one case in the IC-ICG group and in all cases after IV-ICG administration (5.8% versus 100%; p < 0.0001). (4) Conclusions: The present study demonstrates how ICG-fluorescence cholangiography can be helpful in identifying the extrahepatic biliary anatomy during dissection of Calot's triangle in both administration methods. In comparison with intravenous ICG injection, the intracholecystic ICG route could provide a better signal-to-background ratio by avoiding hepatic fluorescence, thus increasing the bile duct-to-liver contrast.

Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results.

BACKGROUND: Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). MATERIAL AND METHODS: On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. RESULTS: Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. CONCLUSIONS: The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations.

Fluorescence-based bowel anastomosis perfusion evaluation: results from the IHU-IRCAD-EAES EURO-FIGS registry.

BACKGROUND: Anastomotic leakage (AL) is one of the dreaded complications following surgery in the digestive tract. Near-infrared fluorescence (NIRF) imaging is a means to intraoperatively visualize anastomotic perfusion, facilitating fluorescence image-guided surgery (FIGS) with the purpose to reduce the incidence of AL. The aim of this study was to analyze the current practices and results of NIRF imaging of the anastomosis in digestive tract surgery through the EURO-FIGS registry. METHODS: Analysis of data prospectively collected by the registry members provided patient and procedural data along with the ICG dose, timing, and consequences of NIRF imaging. Among the included upper-GI, colorectal, and bariatric surgeries, subgroup analysis was performed to identify risk factors associated with complications. RESULTS: A total of 1240 patients were included in the study. The included patients, 74.8% of whom were operated on for cancer, originated from 8 European countries and 30 hospitals. A total of 54 surgeons performed the procedures. In 83.8% of cases, a pre-anastomotic ICG dose was administered, and in 60.1% of cases, a post-anastomotic ICG dose was administered. A significant difference (p < 0.001) was found in the ICG dose given in the four pathology groups registered (range: 0.013-0.89 mg/kg) and a significant (p < 0.001) negative correlation was found between the ICG dose and BMI. In 27.3% of the procedures, the choice of the anastomotic level was guided by means of NIRF imaging which means that in these cases NIRF imaging changed the level of anastomosis which was first decided based on visual findings in conventional white light imaging. In 98.7% of the procedures, the use of ICG partly or strongly provided a sense of confidence about the anastomosis. A total of 133 complications occurred, without any statistical significance in the incidence of complications in the anastomoses, whether they were ICG-guided or not. CONCLUSION: The EURO-FIGS registry provides an insight into the current clinical practice across Europe with respect to NIRF imaging of anastomotic perfusion during digestive tract surgery.

Transanal Endoscopic Microsurgery: Endoscopy Assisted Treatment of Colorectal Anastomotic Stenosis.

Transanal endoscopic microsurgery (TEM) is a type of natural orifice transluminal endoscopic surgery, developed for rectal tumors and used also to treat other rectal diseases. Anastomotic complications after colorectal surgery, including stenosis, represent a challenging problem. We present the case of a 36-year-old woman with a diagnosis of Hirschsprung disease that was submitted to a modified Duhamel operation. A postoperative barium enema showed a complete stricture of the anastomosis that was impossible to resolve by flexible endoscopic approach. Then an intraoperative endoscopic approach to facilitate the localization of preanastomotic colon (proximal colon from the anastomosis) was performed by a small colotomy and the colonic recanalization was obtained by the creation of a neo-anastomosis by TEM, under fluoroscopic-endoscopic control. The patient underwent a control barium enema showing regular retrograde transit of contrast medium without evidence of stenosis. In our experience, transanal approach by TEM-colonoscopy assisted is safe and feasible and represents a model of combined minimally invasive technique.

Atypical cellular neurothekeoma (ACN) of the elderly: case report and brief review of the literature.

Atypical cellular neurothekeoma (ACN) is an aggressive and rare variant of cellular neurothekeoma. Only few cases have been reported in the literature and the biological behavior seems to be uncertain. We describe the case of an ACN presenting on the scalp of an elderly man, emphasizing the cytologic features of malignancy. In addition, we provide a brief overview of the literature and discuss the differential diagnosis with other entities, and the possible diagnostic pitfalls.

Fluorescence-based cholangiography: preliminary results from the IHU-IRCAD-EAES EURO-FIGS registry.

INTRODUCTION: Near-infrared fluorescence cholangiography (NIRF-C) is a popular application of fluorescence image-guided surgery (FIGS). NIRF-C requires near-infrared optimized laparoscopes and the injection of a fluorophore, most frequently Indocyanine Green (ICG), to highlight the biliary anatomy. It is investigated as a tool to increase safety during cholecystectomy. The European registry on FIGS (EURO-FIGS: www.euro-figs.eu ) aims to obtain a snapshot of the current practices of FIGS across Europe. Data on NIRF-C are presented. METHODS: EURO-FIGS is a secured online database which collects anonymized data on surgical procedures performed using FIGS. Data collected for NIRF-C include gender, age, Body Mass Index (BMI), pathology, NIR device, ICG dose, ICG timing of administration before intraoperative visualization, visualization (Y/N) of biliary structures such as the cystic duct (CD), the common bile duct (CBD), the CD-CBD junction, the common hepatic duct (CHD), Visualization scores, adverse reactions to ICG, operative time, and surgical complications. RESULTS: Fifteen surgeons (12 European surgical centers) uploaded 314 cases of NIRF-C during cholecystectomy (cholelithiasis n = 249, cholecystitis n = 58, polyps n = 7), using 4 different NIR devices. ICG doses (mg/kg) varied largely (mean 0.28 ± 0.17, median 0.3, range: 0.02-0.62). Similarly, injection-to-visualization timing (minutes) varied largely (mean 217 ± 357; median 57), ranging from 1 min (direct intragallbladder injection in 2 cases) to 3120 min (n = 2 cases). Visualization scores before dissection were significantly correlated, at univariate analysis, with ICG timing (all structures), ICG dose (CD-CBD), device (CD and CD-CBD), surgeon (CD and CD-CBD), and pathology (CD and CD-CBD). BMI was not correlated. At multivariate analysis, pathology and timing remained significant factors affecting the visualization scores of all three structures, whereas ICG dose remained correlated with HD visualization only. CONCLUSIONS: The EURO-FIGS registry has confirmed a wide disparity in ICG dose and timing in NIRF-C. EURO-FIGS can represent a valuable tool to promote and monitor FIGS-related educational and consensus activities in Europe.

[Fluorescence-guided detection of lymph node metastases of gastrointestinal tumors]. / Fluoreszenzgesteuerte Detektion von Lymphknotenmetastasen bei gastrointestinalen Tumoren.

A correct lymph node (LN) staging is essential in oncological surgery. Indocyanine green (ICG) near-infrared fluorescence (NIRF) guided sentinel lymph node (SLN) navigation is a relatively novel technique. The aim of this review is to analyze the impact of ICG-NIRF on identification of LN metastases of gastrointestinal tumors. The Scopus and PubMed/MEDLINE literature databases were searched and 20 studies were included. The ICG-NIRF navigation of LN has been shown to enable and improve LN detection in gastrointestinal tumors; however, the mean detection, sensitivity, accuracy and false negative rates show substantial variation. This could be due to both the heterogeneous techniques applied and to the low retention of ICG by lymph nodes. Fluorescence imaging to identify LN drainage is a promising tool to improve oncological outcomes. Nonetheless, the technique requires further development in terms of hardware, software and fluorophores, which are currently being investigated.

Quality of life in patients with loco-regional rectal cancer after ELRR by TEM versus VLS TME after nChRT: long-term results.

BACKGROUND: Endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) may be an alternative treatment option to Laparoscopic total mesorectal excision (LTME), in selected patients with N0 rectal cancer. Post-operative quality of life (QoL) evaluation is an important parameter of outcomes related to high percentage of functional sequelae. We reported, in a previous paper, the short and medium term results of QoL in patients who underwent ELRR or LTME. The aim is to evaluate the 3 year QoL in patients with iT2-T3 N0/+ rectal cancer who underwent ELRR by TEM or LTME after neoadjuvant radio-chemotherapy (nChRT) in a retrospective analysis of prospectively collected data. METHODS: We enrolled in this study, 39 patients with iT2-T3 rectal cancer who underwent ELRR (n = 19) or LTME (n = 20), according to predefined criteria. QoL was evaluated by EORTC QLQ-C30 and QLQ-CR38 questionnaires at admission, after n-RCT and 1, 6, 12, and 36 months after surgery. RESULTS: No statistically significant differences in QoL evaluation were observed between the two groups, both at admission and after n-RCT. In short term (1-6 months) period, significantly better results were observed in ELRR group by QLQ-C30 in global health status (p = 0.03), physical functioning (p = 0.026), role functioning (p = 0.04), emotional functioning (p = 0.04), cognitive functioning, fatigue (p < 0.05), dyspnoea (p < 0.001), insomnia (p < 0.05), appetite loss (p < 0.05), constipation (≤ 0.05), and by QLQ-CR38 in: body image (p = 0.03) and defecation (p = 0.025). At 1 year, the two groups were homogenous as assessed by QLQ-C30, whereas the QLQCR38 still showed better results of ELRR versus LTME in body image (p = 0.006), defecation problems (p = 0.01), and weight loss (p = 0.005). At 3 years, no statistically significant differences were observed between the two groups. CONCLUSIONS: In selected patients with rectal cancer, who underwent ELRR by TEM or LTME, QoL tests at 3 years do not show any statistical differences on examined items.

Recto-Urinary Fistula (RUF) treated by Transanal Endoscopic Microsurgery (TEM) Review of the literature and surgical technique.

AIM: Recto-Urinary Fistula (RUF) is a rare complication of pelvic surgery. Different approaches are reported in literature but a gold standard treatment has not yet been achieved. Transanal Endoscopic Microsurgery (TEM) is a miniinvasive approach with well known advantages as magnification, 3D view and lighting of the operative field. Aim of the present review is to report the current evidence in literature about technique and results of RUF treatment by TEM and to suggest some key points for its correct management. MATERIALS OF STUDY: After a medline in Pubmed and Scopus databases, seven papers were eligible for the present study. Data were reviewed on the basis of the cases reported, patient's characteristics, surgical techniques and results. RESULTS: Eighteen cases have been reported in the literature from 1996 to 2005. The healing success rate was 77.8%. Fecal and urinary diversion were performed before TEM-assisted procedure in the 83% and 94% of cases, respectively. Recurrence was observed in four patients (22%). DISCUSSION: A gold standard treatment of RUF should ensure the complete removal of scar tissue around the fistula, in order to perform a tension free suture on healthy margins with adequate vascularization. Preoperative stoma improves the healing of the fistula, reducing local inflammation and infections. CONCLUSIONS: There is not common view of this topic in literature and clarify which could be the best treatment is a key condition due to high failure rate of the surgical proposed techniques. Recurrences treatment has a lower cure rate if compared to primary lesions, nevertheless more studies are required to confirm this data. KEY WORDS: Recto-Urinary Fistula (RUF), Transanal Endoscopic Microsurgery (TEM), Transanal approach.

Quality of life in non-early rectal cancer treated by neoadjuvant radio-chemotherapy and endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) versus laparoscopic total mesorectal excision.

BACKGROUND: In selected patients with N0 rectal cancer, endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) may be an alternative treatment option to laparoscopic total mesorectal excision (LTME). Aim of this study is to evaluate the short- and medium-term quality of life (QoL) from a retrospective analysis of prospectively collected data in patients with iT2-iT3 N0-N+ rectal cancer, who underwent ELRR by TEM or LTME after neoadjuvant radio-chemotherapy (n-RCT). METHODS: Thirty patients with iT2-iT3 rectal cancer who underwent ELRR by TEM (n = 15) or LTME (n = 15) were enrolled in this study. The choice for one operation or the other was made on the basis of predefined criteria. QoL was evaluated by EORTC QLQ-C30 and QLQ-CR38 questionnaires at admission, after n-RCT and 1, 6, and 12 months after surgery. RESULTS: No statistically significant differences in QoL evaluation were observed between the two groups, both at admission and after n-RCT. At 1 month after surgery, significantly better results in the ELRR group were observed by QLQ-C30 in: Nausea/Vomiting (p = 0.05), Appetite Loss (p = 0.003), Constipation (p = 0.05), and by QLQ-CR38 in: Body Image (p = 0.05), Sexual Functioning (p = 0.03), Future Perspective (p = 0.05) and Weight Loss (p = 0.036). At 6 months after surgery, a statistically significant worse impact after LTME was observed by QLQ-C30 in: Global Health Status (p = 0.05), Emotional Functioning (p = 0.021), Dyspnea (p = 0.008), Insomnia (p = 0.012), Appetite Loss (p = 0.014) and by QLQ-CR38 in Body Image (p = 0.05) and Defecation Problems (p = 0.001). At 1 year, the two groups were homogenous as assessed by QLQ-C30, whereas the QLQ-CR38 still showed better results of ELRR versus LTME in Body Image (p = 0.006), Defecation Problems (p = 0.01), and Weight Loss (p = 0.005). CONCLUSIONS: Based on the present series, in selected patients, earlier restoration of patients' functions is observed after ELRR by TEM than after LTME.

Treatment of recto-vesical fistula by transanal endoscopic microsurgery approach.

INTRODUCTION: Rectovesical Fistula (RVF) is a rare major surgery complication. Despite different techniques have been proposed as yet there is still no standard treatment. Transanal Endoscopic Microsurgery provides a magnified three-dimensional vision and it is less invasive than the traditional surgical procedure used in RVF treatment. MATERIALS AND METHODS: A 62 years-old man, who developed a rectovesical fistula after laparoscopic radical prostatectomy, underwent TEM-assisted RVF repair by full-thickness excision and both bladder and rectal wall suture. The patients had a temporary ileostomy RESULTS: The patient could ambulate on day one, was fed on day three and was discharged on day 10 with the indwelling bladder catheter left in place. The ileostomy was taken down and the catheter removed three months later when colonoscopy and cystoscopy showed no rvf recurrence. DISCUSSION AND CONCLUSIONS: From 2004, only ten cases of TEM-assisted treatment of RVF are reported with three recurrences and good results even in patients who had already undergone previous surgical attempts. TEM is safe and effective. It provides a tension free suture line on healthy tissue with adequate hemostasis and it may be a good alternative in the treatment of rectovesical fistula. KEY WORDS: Endoscopic Surgery, Microsurgery, Recto-vesical Fistula, Transanal Endoscopic.

Rare extra-adrenal paraganglioma mimicking a painful Schwannoma: case report.

INTRODUCTION: Paragangliomas originate from chromaffin tissue primarily found in the Zuckerkandl body. A 53 years old man, was investigated with abdominal MRI for chronic backache, that had lasted for 2 years. CASE REPORT: MRI revealed an incidental mass in para-aortic region, at the adrenal lodge, with characteristics of a solid nodular mass, which did not seem to arise from the adrenal gland. An abdominal CT showed a mass localized prior to left adrenal gland; the radiologist reported this mass as a malignant peripheral nerve sheath tumor (Schwannoma). During his stay in hospital, tumoral markers chromogranin and neuron-specific enolase were dosed, with a concentration of 187.00 ng/mL and 7.7 ng/mL. Patient's back pain was treated first with ketorolac, without any resolution of the problem, then with ketorolac plus tramadol in elastomeric pump, again with no relief, and finally with a continuous infusion of morphine. Since the exact nature of the neoplasm was not known and a CT guided biopsy was not technically feasible to do, a laparoscopic excision of the mass, with transperitoneal anterior submesocolic approach, as well as for the left adrenalectomy, was planned. After surgery, the patient no longer needed morphine. The postoperative course was uneventful. RESULTS: Histopathological findings consisted of periadrenal paraganglioma. Extra-adrenal paragangliomas are rarely recognized during preoperative study. This is often due to its capacity of mimicking other type of tumors. CONCLUSIONS: Paragangliomas could be successfully resected by laparoscopy, they are difficult to distinguish from other tumor and they should be investigated even if preoperative findings argue for something else.

What is the role of nodal ratio as a prognostic factor for gastric cancer nowadays? Comparison with new TNM staging system and analysis according to the number of resected nodes.

Nodal ratio (NR) has been demonstrated to be an important prognostic factor in patients with gastric cancer. The aim of this study is to evaluate the prognostic role of nodal ratio comparing it with the new TNM (2010) classification. One hundred forty-two patients were submitted to potentially curative gastrectomy for cancer. Patients with low performance status underwent D1.5 lymphadenectomy, whereas the other patients underwent D2-D2.5 lymphadenectomy. Nodal staging was classified according to 2010 International Union Against Cancer/American Joint Committee on Cancer classification. Kaplan-Meier method was used to evaluate survival, stratified for nodal classes and nodal status. Total gastrectomy was performed in 39 per cent of cases and distal gastrectomy in 61 per cent. Mean number of resected nodes was 25.5. Whereas N status was strictly related to the number of resected nodes, the NR was independent from the extension of the lymphadenectomy. Overall five-year survival was 81 per cent for N0 patients, 72 per cent for N1, and 26 and 23 per cent for N2 and N3, respectively. Patients with NR0 had 81 per cent five-year survival, whereas NR1 67 per cent, NR2 51 per cent, and NR3 22 per cent. NR seems to be a simple method to predict the prognosis of patients with gastric cancer; unlike N status, it is independent from the number of resected nodes, and therefore it is particularly useful in case of inadequate lymphadenectomy.