Colorectal Cancer (CRC) Epidemiology, Risk Factors Symptoms, Stages, Therapy 3) Molecular Biology & Pathology Screening. Background: is an online support network developed in partnership with the American Cancer Society that helps help cancer patients, survivors. ASKEP ca SAP CA ASKEP CA ASKEP ca ASKEP CA ASKEP CA COLON (Definisi, Etiologi).
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Colorectal cancer CRC is a common neoplasia in the Western countries, with considerable morbidity and mortality. Traditionally approached surgically, by resection of the primitive tumor or stoma, the management to incurable stage IV CRC patients has significantly changed over the last three decades and is nowadays multidisciplinary, with a pivotal role played by chemotherapy CHT.
This latter have allowed for a dramatic increase in survival, whereas the role of colonic and liver surgery is nowadays matter of debate. Although any aslep is difficult, two xa situations are considered, asymptomatic or minimally symptomatic and severely symptomatic patients needing aggressive management, including emergency cases.
In asymptomatic patients, new CHT regimens allow today long survival in selected patients, also exceeding two years.
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Secondary surgery of liver metastasis is gaining acceptance since, under new generation CHT colob, an increasing amount of patients with distant metastasis initially considered non resectable become resectable, with a significant increase in long term survival.
Obstruction is traditionally approached surgically by colonic resection, stoma or internal by-pass, although nowadays CRC stenting is a feasible option. Nevertheless, CRC stent has peculiar contraindications and complications, and its long-term cost-effectiveness is questionable, especially in the light of recently increased survival.
Bleeding and other CRC-related symptoms pain, tenesmus, etc. Every fifth patient presents with metastatic disease, which is usually not resectable. In asymptomatic patients, new chemotherapy regimens allow long survival and, potentially, conversion of non resectable liver metastasis in resectable ones, with a significantly improved prognosis. Obstruction is traditionally approached by colonic resection, stoma or internal by-pass, although nowadays stenting is a feasible option.
Bleeding and other symptoms pain, tenesmus are managed mini-invasivally by radiotherapy, laser therapy and other transanal procedures. Colorectal cancer CRC is the third most common askwp estimated 1. Ten-fold differences in incidence between the different regions of the world, being the highest in Australia, Western Europe and North America, are reported[ 1 ]. Traditionally managed surgically, by resection of the primitive tumor, intestinal bypass or stoma[ 6 – 8 ], the palliative approach to incurable stage IV CRC patients has significantly changed over the last three decades and is nowadays multidisciplinary, with a pivotal role played by chemotherapy CHT [ 9 – 11 ].
Such a multimodal management of incurable CRC is responsible for a significant increase in survival of patients affected by incurable CRC in general, which has passed from 8 to 14 mo over the last two decades[ 3 ], but has colno reported to exceed two years in selected populations following the sequential use of various dolon of treatment including the newest chemotherapeutic agents[ 1213 ].
Differently from potentially curable patients, where overall survival and disease-free survival are the main outcome and measured variable of any treatment, the short residual life of these patients radically change the perspective. From such a changed point of view, individual, psychological, ethical issues gain importance in deciding for the best management of any singular patient. The multimodal approach to initially non-resectable liver metastasis, including systemic CHT[ 121415 ], intraarterial CHT[ 1617 ], portal embolization[ 1819 ] and secondary surgery[ 2021 ], and its impact on survival[ 22 ], will be treated in a dedicated paragraph.
Extrahepatic CRC metastasis do not systematically imply a palliative management anymore, either. The indication to surgical resection of other extrahepatic CRC disease, in particular peritoneal metastasis, is also matter of debate: Although it is not among the aims of the present paper, imaging modalities for resectability assessment are briefly summarized.
MRI is reported to be superior to CT in the preoperative evaluation of colorectal metastasis both in normal liver[ 35 ], copon it has higher sensitivity Usually diagnosed endoscopically, primary CRC resectability is normally assessed by CT[ 38 ], endoscopic ultrasound[ 39 ] and MRI[ 40 ], these two latter having a pivotal role in defining the resectability of rectal cancer. Identifying peritoneal metastasis by imaging is one of the major issues in advanced CRC.
Thus, peritoneal metastasis is still, often, an intraoperative diagnosis.
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First appeared in scientific literature in the mid-twentieth century[ 4647 ], the management of incurable metastatic CRC still represent a matter of debate askwp oncologists, and surgeons. Unfortunately, most of those papers askepp single-center, small-sized, retrospective series, extremely heterogeneous concerning patients, clinical scenarios and aakep, metastatic pattern, primary tumor location, and management surgery, CHT, stenting etc.
In the absence of randomized trials, in recent years, the efficacy of colonic resection has been assessed by larger retrospective series, metanalysis and literature reviews[ 54 – 56 ]. As a matter of fact, such a various literature on the subject, prevent even nowadays from definitive conclusions concerning the best approach to incurable stage IV patients, in particular concerning the role of palliative resection of the primary CRC.
Patients with incurable CRC may be asymptomatic or present with a variety of symptoms and clinical scenarios ranging from moderate anaemia to cllon troubles, to lower gastrointestinal GI bleeding to life-threatening conditions, including obstruction and perforation, needing emergency management.
In fact, in asymptomatic patients, the management is aimed to slow down cancer progression, thus prolonging long-term survival and preventing cancer-related complications.
Differently, in emergency and severely symptomatic patients, it is focused in solving cancer-related complications, which may be rapidly fatal or imply intolerable symptoms. Obviously, the two proposed managements are not indefinitely exclusive, as an emergency patient may become asymptomatic after a life-threatening condition has been treated, and, conversely, an asymptomatic patient may become severely symptomatic under CHT.
Algorithm for the management of incurable asymptomatic or minimally symptomatic stage IV colorectal cancer patients. Algorithm for the management of severely symptomatic incurable stage IV colorectal cancer patients including emergency cases.
In recent times, copon main role in the management of non-emergency patients affected by incurable CRC has passed from surgery to CHT. Accordingly, international guidelines suggest nowadays to avoid surgery in the case akep patients with incurable metastasis from CRC, unless in the presence of or in the imminent risk of complications such as obstruction or significant coolon 33 ]. Nevertheless, the approach to patients with incurable CRC is extremely various, as two thirds of them undergo surgery in United Asiep 63 ], whereas they are mostly non-operated on in the Netherlands[ 64 ].
Although the purpose of the paper is not technical, here we coloon a brief summary of the surgical procedures performed for palliation. Since healing process may be poor in end-stage CRC, and neoplastic ascites may predispose to eventrations and early ventral hernias, the abdominal wall should be accurately closed plane by plane.
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Cloon general, it should be reminded that any complication, even minor, may significantly affect the short residual life. Laparoscopy may be as effective as laparotomy[ 65 ] with better early outcome and less long-term complications[ 6667 ]. Differently from ileal stomas, that present the main drawback of high volume, very irritating, liquid stools, colonic stomas have the advantage of lower-volume, solid stools, are normally easier to manage postoperatively and have lower morbidity, thus representing the ideal solution for palliation[ 68 ].
Normally performed in the transverse colon or sigma, stoma fashioning may be preceded by laparoscopic exploration, which can facilitate the dissection of the chosen segment and the identification of the colostomy placement[ 69 ].
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Whenever general anaesthesia is contraindicated, stomas may also be performed under spinal or loco-regional anaesthesia in the lower abdomen. Resective surgery for palliation[ 2747 xskep, 7071 ] include classic procedures performed for CRC, such as right colectomy, left colectomy, Hartmann procedure left segmental colectomy associated with proximal stump colostomy and closure of the distal stumpproctocolectomy, low anterior resection and abdominoperineal resection.
Since technical standards for palliative CRC resection are not the same as for curative ones, limited colonic resections including ileocecal resection and segmental colectomy are generally accepted, being margin-free, R0 primary CRC resection the main criterion to be respected. Moreover, D2 lymphadenectomy required for oncological reasons and correct staging, including the dissection of vascular pedicles at the origin and the total mesorectal excision for rectal tumorsis not needed in the case of palliation.
The vascularisation of the colonic remnant must be respected, and any manoeuvre aimed to avoid any tension at the anastomosis-site should be performed, including colonic dissection and inferior mesentery vein division, if needed. The anastomosis should be performed avoiding any contamination of the abdomen and abdominal wall, which should be adequately protected, since both neoplastic cell dissemination and infectious complications may occur.
Extended resections for CRC infiltrating contiguous organs, including anterior and posterior pelvic exenteration[ 7273 ], and hemicorporectomy[ 74 ] are not indicated in a palliative context anymore. Transanal procedures are discussed in the paragraph dedicated to bleeding and other symptoms. Strategy in surgical palliation: Importantly, if the non-resectability is due to distant metastasis, technical difficulty of resection is comparable to asksp surgery, whereas, if the reason of non resectability is the primary, surgery may results in a very challenging situation.
CRC site also influences the surgical strategy also concerning cw type of surgery resective vs non-resective.
In fact, clinical impact and morbidity of CRC resection are generally considered to increase from proximal to distal, being maximum for the lower third of the rectum. Palliative ileocecal resection is considered a low-complexity, short-lasting procedure which may be accomplished even under spinal anaesthesia, thus reducing the stress of surgery.
On the contrary, left-sided procedures are more time-consuming and associated to higher morbidity[ 75 ], including leakage and pelvic abscess[ 76 ]. Rectal cancer deserves a particular mention. Also owing to intrinsic technical difficulty and morbidity of surgery, and the fact that stoma is often necessary thus cancelling one advantage of resectiondeciding to perform a palliative resection of low rectal tumors should be carefully pondered.
The resective options are: Since APR implies a perineal wound which is associated to healing complications in roughly one half of the patients[ 77 ], sphincter-preserving techniques are generally preferred. For all these reasons, the general attitude is to be more aggressive for proximal tumors, and more oriented towards non-resective procedures for distal tumors. CRC extirpation and survival: In patients presenting without significant clinical symptoms or emergency conditions, the main question is whether they may benefit from primary CRC resection or a less aggressive management should be preferred.
Since [ 6 ], the debate as to the real effectiveness of palliative resection of primary CRC in prolonging survival has not given a definitive answer. Although, in the pre-CHT era, most authors[ 8477980 ] described a Since the nineties, the massive introduction of CHT in this class of patients, and the development of more and more effective CHT regimens, has rekindled the debate regarding the indication to palliative surgery in patients already undergoing a potentially non-inferior, less aggressive management.
Significantly, in their systematic review of papers comparing survival of patients undergoing the resection vs non-resection of the primary tumor, Verhoef et al[ 82 ] found that the resection of primary CRC was related to better prognosis in all papers including no or very few patients undergoing CHT[ 274779 ], whereas results were more ambiguous in series including patients undergoing CHT, where resective surgery resulted as being related to survival in some papers[ 5083 – 85 ] but not in others[ 485253617086 ].
Differently from procedures achieving an R0 resection no residual neoplastic tissue left after resectionleaving residual neoplastic tissue R1, R2 is related to the same dismal prognosis as no resection[ 5 ]. Since, in this latter case, the patient should suffer the drawbacks of both major colonic resection high morbidity and non-operative management short survivalthe abstention from CRC resection should be strongly recommended whenever an R0 resection may not be achieved.
Several others criteria have been found to be related to a poor prognosis or poor surgical outcome, thus being considered to be arguments against major surgical resection. Other parameters, including poor differentiation[ 525 ], high serum levels of CEA[ 4788 ] or lactic dehydrogenase[ 8588 ] have been also related to poor outcome.
Perioperative mortality and morbidity: Higher perioperative mortality and morbidity of CRC resection represent the counterpart of a supposed longer survival. Such an issue may be supposed as being even underestimated, since an intrinsic distress due to major colonic surgery with respect of clinical observation is undeniable although never measured and may be supposed to significantly affect the residual life.
Sincelaparoscopic surgery has been widely adopted in order to reduce the aggressiveness of surgery in incurable CRC patients[ 92 – 99 ]. Although a minimally invasive approach may seem intuitively not the main issue in patients with dismal prognosis, on the contrary, a prompt recovery during the weeks following surgery may significantly improve the quality of residual life.
As already observed in other fields of laparoscopy, a recent systematic review[ 56 ] found that laparoscopy allowed, in front of a prolonged operative time time median Although only two of reviewed papers[ 9697 ] found a difference in postoperative complication-rate, the pooled odd ratio allowed the authors to report a significantly lower morbidity after laparoscopy Interestingly enough, although in some cases it is reported to reach Interestingly, CRC-related morbidity results as being Moreover, it should be considered that surgical resection of the primary CRC may affect the following management by modifying CHT administration schedule: Pros and cons of operative and non-operative attitudes are difficult to assess, as they are likely to be related to the peculiar characteristics of the patient, tumor, and planned surgery.
Although curative management is not the aim of this review, nevertheless, the possibility to switch from a palliative context to a curative one is the most intriguing aspect of metastatic CRC management and will be briefly treated. Since, inAdam et al[ 20 ] first showed that the 5-year-survival rate of patients undergoing secondary resection was comparable to that of primary resection, resectability of liver meatastasis has become one of the purpose of new CHT agents.
Medical treatment for colon cancer has been radically modified in its aims and modalities in the last 30 years: Improvement of survival after various chemotherapic regimens for incurable stade IV colorectal cancer patients through the last three decades. Best supportive care; 5-FU: Folic acid Leucovorin ; OS: From the eighties to the nineties, with studies on fluoropyrimidines, some steps have been made towards a chemotherapeutic regimen active in advanced CRC[ 9- ].
These trials analyzed the use of infusional or bolus 5-fluorouracil 5-FU combined with folinic acid FA or levamisole, with different modulations; the results showed an enhanced effectiveness of 5-FU when combined with high-dose folinic acid, finally identifying a bimonthly schedule with continuous infusion of 5-FU after bolus as the more effective and less toxic schedule[ ].
A further trial showed the equivalence between oral 5-FU capecitabine and infusional 5-FU[ ]. During this long period of time, chemotherapy was considered as a palliative treatment and was administered only when surgery was no longer possible due to the presence of locally advanced or metastatic disease.
After years of attempts and modulation of approaches with fluoropyrimidines, a turning point was determined by the introduction of new drugs to be administered in association. The exploration of the activity of chemotherapeutic doublets with irinotecan and 5-FU was performed since the early s in large randomized phase III trials[ 10- ], establishing a new survival standard for metastatic CRC. Through the first decade of s, the choice concerning which one between oxaliplatin- or irinotecan-based regimens should have been employed as first or second line became a matter of debate.