Indocyanine green (ICG) is a fluorescent dye that has been widely employed in different fields: for confirming the patency of vascular reconstruction surgery, anastomosis of the gastrointestinal tract, brain aneurysms, identification of sentinel lymph node, and it also plays an important role in fluorescence imaging during hepatobiliary surgery, in both malignant and benign pathologies. ICG characteristics In the early 1970s, fluorescence imaging systems using ICG were introduced as an intra-operative method for retinal angiography. Since then, as mentioned before, its usage has been extended. When ICG is injected intravenously is selectively taken up by the liver, and then secreted into the bile. The catabolism and fluorescence properties of ICG permit a wide range of visualization methods in hepatobiliary surgery. ICG emits fluorescence when excited by infrared light. Light penetration depth is no larger than 10 mm (tissue optical window), which sometimes makes difficult to observe the fluorescence in obese patients or inflammatory situations. ICG binds to plasma proteins and lipoproteins to form aggregated dye molecules in physiological environments. Binding of ICG to plasma proteins does not alter protein structure, therefore intravenous administration of ICG is not toxic. The side effects reported with the use of ICG are seen in less than 1 out of 40,000 patients. ICG fluorescence imaging in hepatobiliary surgery. – Liver mapping: During resection, all the liver segments should be clearly defined. For this purpose, intra-operative contrast-enhanced ultrasound remains the gold standard. However, portal hypertension caused by liver cirrhosis might obstruct conventional liver mapping by ultrasonography. Fluorescence imaging is a safe and sensitive method for identifying liver segments during liver resection, even in the case of liver cirrhosis. – Partial liver transplantation: ICG has been employed to visualize flow turbulence in reconstructed vessels and to evaluate patency, kinking, and stenosis of vascular anastomoses following partial liver transplantation. – Intra-operative fluorescence cholangiography: ICG cholangiography is an alternative to conventional cholangiography. It does not involve radiation. With intravenous ICG administration, the cystic duct can be identified without dissection of Calot’s triangle. It can be administered directly into the gallbladder as well, to identify the biliary tree anatomy. ICG cholangiography during laparoscopic cholecystectomy. Laparoscopic cholecystectomy (LC) is one of the most common operations in the surgical field. Bile duct injury is rare, with an incidence of 0.3% to 0.7% but it can lead to serious consequences. Surgery for cholecystitis tends to be difficult, even for high-volume surgeons. An intraoperative cholangiography technique during laparoscopic cholecystectomy, involving the excretion of fluorescent ICG in the bile after intravenous injection has been used to determine the bile duct anatomy. ICG cholangiography during laparoscopic cholecystectomy. One of the most significant drawbacks of cholangiography following systemic ICG injection lies in the very high background signal due to the rapid accumulation of ICG in the liver, which can impair the visualization of the biliary structures. Injecting ICG directly into the gallbladder could be a valid strategy to improve the visualization of the cystic duct and the common bile duct without suffering from the disturbing background liver enhancement. ICG cholangiography during laparoscopic cholecystectomy. In case of severe inflammatory reaction (e.g cholecystitis), ICG cholangiography enabled a significantly better visualization of Hartmann’s pouch, of the common bile duct and of the common hepatic duct. However, in case of cystic duct occlusion because of stone impaction, the biliary tree could not be visualized by means of NIR imaging, after intragallbladder ICG injection, which makes it necessary to remove the stones. ICG cholangiography, either administered intravenously or directly into the gallbladder is a valuable tool to increase the safety of laparoscopic cholecystectomy.
Published
Feb 2021
5 THINGS YOU SHOULD KNOW ABOUT WATCH&WAIT STRATEGY FOR RECTAL CANCER 1.- What is the watch & wait strategy? 2.- Who are the adequate candidates to be enrolled in this strategy? 3.- Advantages and Disadvantages of the watch and wait strategy. 4.- Which is the appropriate follow-up once a patient is included in this program? 5.- Published results 1. What is the Watch&Wait strategy? The Watch&Wait strategy is a non-operative management for patients with rectal cancer who develop a clinical complete response after neoadjuvant therapy (chemoradiotherapy or radiotherapy alone). Angelita Habr-Gama and her team, from São Paulo in Brazil, published in 2004 their first long-term outcomes of a cohort of patients managed according to this strategy. It is currently being practiced in 15 countries all over the world, according to the International Watch & Wait Database. Despite of this, many aspects of the W&W approach are undefined or controversial, especially when it comes to oncological safety in patients who experience tumor regrowth. 2. Who are the adequate candidates to be enrolled in this strategy? As a general rule, all those patients who achieve a clinical complete response after neoadjuvant therapy can be managed with a watchful waiting strategy. CLINICAL COMPLETE RESPONSE is defined as following: · No evidence of tumor when assessed by digital rectal examination (DRE), endoscopy-biopsy and MRI. One issue becomes crucial in this process: the assessment of tumor response. Reassessment should be done in all patients after neoadjuvant therapy and it could be challenging due to numerous uncertainties including optimal timing for reassessment and clinical/radiological tools for such purpose. Anyway, all the patients should meet all the criteria mentioned about (clinical and radiological). Also, there are different categories of patients who are suitable for the W&W strategy: · Patients not fit for radical resection: patients whose comorbidities or performance status preclude any attempt at radical operation. Some of them achieve clinical complete response but surgery will never be an option. We have to remember that the essence of active surveillance is in patients who are able to avoid surgery but to whom the procedure will be considered when necessary. · Patients who wish to avoid abdominoperineal excision (APE) at any cost: At present, it is not possible to advise a patient who is facing an APE what the likelihood is that preoperative CRT will succeed in achieving a complete response and thus the likely success of a W&W approach. 3. Advantages and Disadvantages of the Watch&Wait strategy. ADVANTAGES: · Avoidance of the perioperative mortality of 1–2% associated with total mesorectal excision. · Avoidance of long-term morbidity, such as urinary and sexual dysfunction. · Reduce the rate of temporary or permanent colostomy. DISADVANTAGES: · It’s difficult to assess clinical complete response, as it doesn’t correlate exactly with the complete pathological response. · Lack of evidence regarding the appropriate timing for reassessment and strict monitoring is required. · Treatment of local regrowth is a major concern. 4. Which is the appropriate follow-up once a patient is included in this program? Once we know that a patient is suitable for W&W strategy, the follow-up should be done as following: · Digital rectal examination, proctoscopy, CEA every 1 or 2 months + MRI or CT scan every 6 months during the first 2 years. · Digital rectal examination, proctoscopy, CEA every 6 months + MRI or CT scan annually from the 3rd to the 5th year. · If we have evidence of relapse during follow up, salvage surgery should be offered at any time. 5. Published results According to the international watch & wait database: · Local regrowth occurred with a 2-year rate of 25.2%. · 88% of local regrowth was diagnosed within the first 2 years. · Local regrowths were located in the bowel wall in 97%. · 78% of patients with local regrowth had TME resection, 99% with curative intention. · In those who underwent salvage surgery: R0 resection in 88%, in 6% tumor margins were positive (R+) and in 6% margin involvement was unknown. · Distant metastases were diagnosed in 8% of patients during follow-up. Most frequently located in lungs (62%), followed by liver (41%). · For patients with a sustained clinical complete response, the 5-year disease-specific survival was 97.3% and 5-year overall survival was 87.9%. For patients with local regrowth, the 5-year disease-specific survival was 84% and 5-year overall survival 75.4%
Published
Jun 2020
Rectal cancer is the third most commonly diagnosed cancer in males and the second in females, only after lung, prostate and breast cancer. In 2018, 1.8 million new cases of colorectal cancer were diagnosed, while rectal cancer comprised about 700,000 new cases, the 8th cancer in terms of incidence. 310,000 deaths in 2018 make it the 10th most deathly. Only in Spain, rectal cancer claimed more than 4 thousand lives. The 5-year survival rate for rectal cancer is currently more than 75, with a 35% risk for metastatic diseases and local recurrence as low as 10-5%. It can be classified into clinical features like: Age: advanced ages are not associated with a poor prognosis. Performance status. CEA: the best tumor marker available to be used as an independent prognostic factor and as a monitor for recurrence of disease after primary tumor resection. Clinical stage: determined by TNM.Comorbidities. Histology: some variants, such as signet ring and mucinous, are associated with a worse prognosis, and also with a poor response to neoadjuvant treatment. Peritoneal involvement: associated with a decreased overall survival. Molecular markers: any genetic and epigenetic alterations that negatively affect the process of regulation, control of cell proliferation and differentiation, apoptosis, and angiogenesis. Neoadjuvant chemoradiotherapy (nCRT) + total mesorectal excision (TME) is considered nowadays the standard treatment for locally advanced rectal cancer. Since TME was described by Heald in the 80s, local recurrence has decreased from 30% to 10-5%, but still some advanced tumors had an adverse prognosis. That’s why some therapies like CRT are implemented. When we refer to neoadjuvant therapy (NAT), we’re practically talking about radiotherapy and chemo is administered as a radiosensitizer. Some countries advocate for classifying rectal tumors in categories (GOOD, BAD and UGLY), according to some characteristics which confer good or bad prognosis. According to this, patients are enrolled into 3 possible treatments: primary surgery, short course RT, long course RT. Summarizing, neoadjuvant therapy indications are: T4 tumors, N positive or with some adverse prognostic factors: Presence of extramural vascular invasion (EMVI) Suspicious mesorectal lymph nodes Circumferential resection margin <1mm Tumor height - Tumor in the anterior quadrant We deliver neoadjuvant therapy for the following reasons: Increasing downstaging Increasing the sphincter preserving procedures Increasing R0 resections Increasing the pathological complete response rate Increasing the pathological complete response rate: Short course radiotherapy, with immediate or delayed surgery Long course radiotherapy with conconcurrent chemotherapy and Total neoadjuvant treatment with both There’s currently an ongoing debate regarding the appropriate interval from the end of NAT and surgery that allows to achieve higher rates of pathological complete response (pCR). 8 weeks is considered standard, but interestingly some questions are yet to be answered: Do longer intervals increase the pCR? Is there any difference in DFS, OS or morbidity? The GRECCAR-6 study demonstrated that waiting for extended intervals does not increase the pathological complete response rate but increases technical difficulties during surgery and is associated with a higher complication rate. Probst et al on the contrary reflects that the key for obtaining a higher pathological complete response rate is increasing the interval from the end of NAT to surgery, without increasing the complications rate. It’s important to be aware of two concepts: Clinical complete response (cCR): no evidence of tumour when assessed by digital rectal examination (DRE), endoscopy-biopsy and MRI. Near Complete Response (nearCR): minor or equivocal findings during clinical examination which cannot be defined as cCR nor clinical bad response. We have several tools to evaluate the response to NAT: Endoscopy with a poor sensitivity of 50% and a negative predictive value of 11%, which can be explained by geographic misses when doing the biopsy. Digital rectal exam. MRI: has a special role, based on the tumor regression grade. PET TC: for the assessment of the metabolic response. Shows an accuracy of 91% which could be increased by a combination with clinical assessment. CEA levels. Endoscopy findings suggesting a pCR: Normal mucosa Whitening of the mucosa Telagiectasia Absence of tumor In reference to the MRI role, TRG referring to a classification of cancer response to preoperative treatment, can predict a prognosis of survival. It depends on what the radiologist sees in the images. It has its equivalent in the pathology report. TRG 1 and 2 are considered good response. Keon Jang et al in their meta-analysis evaluate the role of TRG. mrTRG1 for detecting pCR: Sensitivity: 32%. Specificity: 93%. They recommend using it as just ONE of the parameters for deciding to perform a less radical excision. Still more studies are needed, but the fact is that mrTRG is q0 times more likely to detect a pCR than proctoscopy/biopsy. Even though NAT is important for obtaining better oncological outcomes, it’s not harmless. This is demonstrated by the high rates of bowel dysfunction evidenced in patients treated by preoperative chemoRT, with various symptoms ranging from incontinence to anal blood or mucus loss, compared with those patients treated by surgery alone. Also they are more likely to develop some wound complications, hernias or bowel obstruction. Radical excision of the rectum entails a heavy burden for the patient: 28-40% of associated morbidity, 2% of mortality and also bowel, anorectal and sexual dysfunction. LARS or Low Anterior Resection Syndrome is defined as a disordered bowel function after rectal resection, leading to a detriment in quality of life. Comprises a bunch of symptoms like clustering of stools or fecal incontinence. Patients should expect some improvement over the first year, particularly in the first 6 months. The greater improvement in bowel function is in the first year and will never return to baseline. It’s worrying that 87% of patients are aware of their survival data, but only 53% were aware of functional alterations. POLARS, or the Pre-Operative Low Anterior Resection Syndrome score take into account 6 items for determining the risk of developing LARS: Age (older patients might have some functional bowel alterations that make them more likely to perceive the symptoms as minor), gender (more likely in women), Type of surgery (frequent in total mesorectal excision), Tumor Height (more in low and ultralow rectal tumors), Stoma (after reconstruction), and preop RADIOTHERAPY. The POLARS could help us to better inform patients and to decide the best treatment option for them. So, how to avoid morbidity? By selective use of radiation AND/OR increased adoption of nonoperative management and Watch & Wait. Pathological complete response (pCR) is seen in up to 20% after NAT. These patients could benefit from organ sparing management. There are a lot of studies trying to demonstrate the role of non-operative management in rectal cancer. Habr-Gamma, Garcia-Aguilar, Brown are obtaining great results with this strategy. Reported in the literature, watch and wait could obtain a 6% of local recurrence, 93% of disease free survival, 85% overall survival. There’s an international W&W database. The most striking result is the 24% local recurrence, knowing that these recurrences are mostly early recurrences (first 2 years), 97% endoluminal recurrences, and 88% of regrowths were treated with salvage surgery. On the other hand they reported 94% 5 year DSS. The follow up proposal during W&W is: 1rs/2nd year: DRE, Proctoscopy, CEA every 1-2 months + MRI/CT every 6 months. 3er-5th year: DRE, Proctoscopy, CEA every 6 months + MRI/CT annually. And if detection of relapse at any time, you should perform salvage surgery. The other way to avoid morbidity is the better selection of patients who received NAT. MERCURY and OCCUM are two studies that aim to demonstrate that delivery of Nat could be reduced so that we can reduce organ injury: MERCURY: evaluate primary surgery alone in MRI-predicted stage II or less and in MRI “good prognosis” stage III. 33% surgery alone, overall survival: 68%, Disease free survival: 85%, local recurrence: 3%.. OCCUM: reduce patients receiving NAT to 39.5%, found a Circumferential Resection Margin positive in 2.5% (surgery), 8.6% (NAT). R0: 99.2% (surgery), 96.8% (NAT). 5y-LRR and OS: awaited. Patients with locally advanced rectal cancer currently have a 30-35% risk of distant metastatic recurrence, which is the most frequent cause of cancer related death in this population. For solving this problem, the concept of TOTAL NEOADJUVANT THERAPY emerged. Consist in deliver chemotherapy as induction or consolidation concomitant with the conventional chemoRT. It has the following advantages: Improved delivery of planned therapy Increased downstaging Earlier introduction of optimal systemic chemotherapy Delivery of all chemotherapy preoperatively Reduce duration with a diverting ileostomy Based on two types of local recurrence, pelvic and in the lateral lymph nodes of the pelvis: the first associated with residual tumor cells in the pelvis and the second to lymph drainage. Pelvic recurrence is related to CRM & Histology and LPLN with CEA & swelling. Lateral pelvic lymph node dissection is perform in some Eastern countries like Japan. They demonstrated a 5-year relapse free survival similar in TME alone and TME plus LPLND (73.4% vs. 73.3%), explaining why they perform this procedure systematically. On the other hand it carries the risk of longer operation time and more complications. nCRT is recommended for avoiding pelvic recurrence and LPLND for LPLN recurrence.
Published
Feb 2020
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