Long-term survival of a patient with primarily unresectable liver metastasis from rectal cancer after neoadjuvant chemotherapy.Introduction
Resectability is the decisive factor for long-term survival of metastatic Metastatic
The term used to describe a secondary cancer, or one that has spread from one area of the body to another.
Mentioned in: Coagulation Disorders
pertaining to or of the nature of a metastasis. colorectal cancer colorectal cancer
Malignant tumour of the large intestine (colon) or rectum. Risk factors include age (after age 50), family history of colorectal cancer, chronic inflammatory bowel diseases, benign polyps, physical inactivity, and a diet high in fat. . Unfortunately, only approximately 10% of patients with colorectal liver metastases Metastasis (plural, metastases)
A tumor growth or deposit that has spread via lymph or blood to an area of the body remote from the primary tumor.
Mentioned in: Malignant Melanoma have resectable re·sect·a·ble
Suitable for resection. disease. In the past decade, there has been a paradigm shift A dramatic change in methodology or practice. It often refers to a major change in thinking and planning, which ultimately changes the way projects are implemented. For example, accessing applications and data from the Web instead of from local servers is a paradigm shift. See paradigm. in treatment strategies. Developments in chemotherapy have led to improvements in response rates and been able to induce resectability in patients with initially unresectable metastases with the result that patients who had been regarded as non-curable have achieved long-term survival.
Here we describe the case of a 45-year-old woman with rectal cancer and initially unresectable colorectal liver metastases.
In December 2001, a 45-year-old woman [Eastern Cooperative Oncology Group The Eastern Cooperative Oncology Group (ECOG) was established in 1955 as one of the first cooperative groups launched to perform multi-center cancer clinical trials. A cooperative group is a large network of researchers, physicians, and health care professionals at public and (ECOG ECOG Eastern Cooperative Oncology Group ) performance status 1] with no family history of cancer presented with weight loss of 6 kg during the previous 10 weeks, perianal perianal
around the anus.
under the skin outside the anal canal. Causes sufficient pain to inhibit defecation. blood loss and changes in defecation defecation
or bowel movement
Elimination of feces from the digestive tract. Peristalsis moves feces through the colon to the rectum, where they stimulate the urge to defecate. .
The colonoscopy revealed a tumour of the rectum 4.5 cm from linea dentata with an extension of about 10 cm. The tumour was found on further examination to be stage T3N1. Leukocyte count and alkaline phosphatase levels were increased, and computed tomography (CT) scan showed a single large liver metastasis (71 x 56 mm) in contact with the portal vein branch, as well as bile duct obstruction. The metastasis metastasis /me·tas·ta·sis/ (me-tas´tah-sis) pl. metas´tases
1. transfer of disease from one organ or part of the body to another not directly connected with it, due either to transfer of pathogenic microorganisms or to was regarded as non-resectable. After having decided against a palliative resection or a colostomy colostomy
Surgical formation of an artificial anus by making an opening from the colon through the abdominal wall. It may be done to decompress an obstructed colon, to allow excretion when part of the colon must be removed, or to permit healing of the colon. , the patient received argon plasma coagulation Argon plasma coagulation or APC is a medical endoscopic procedure used primarily to control bleeding from certain lesions in the gastrointestinal tract, and also sometimes to debulk tumours in the case of patients for whom surgery is not recommended. of the rectal tumor to reduce the bleeding 'in order to keep life-qualtity for a patient with such a limited perspective' (surgical report).
The patient received cetuximab and weekly irinotecan, folinic acid and 5-FU within a clinical trial . Staging examinations with CT scan after the first cycle of treatment showed a partial remission with reduction of the liver metastasis down to 51 x 33 mm, and with decreased obstruction of the intrahepatic biliary tract. After three complete cycles of chemotherapy, the liver metastasis had reduced in size to 31 x 20 mm. Colonoscopy also revealed downstaging of the primary. The levels of tumour marker carcinoembryonic antigen (CEA CEA carcinoembryonic antigen.
CEA (Carcinoembryonic antigen) ) normalised from 260 ng/ml in January 2002 to 2.8 ng/ml in July 2002.
The primary tumor was resected in September 2002 by anterior resection and protective colostomy [pT3pN1(2/12) G2], whereas the liver metastasis was resected in December 2002 by right hemihepatectomy. Histological examination of the liver metastasis specimen revealed necrotic material but no vital tumour tissue. Adjuvant adjuvant /ad·ju·vant/ (aj?dbobr-vant) (a-joo´vant)
1. assisting or aiding.
2. a substance that aids another, such as an auxiliary remedy.
3. radiotherapy was not considered because of a recto-vaginal fistula fistula (fĭs`chlə), abnormal, usually ulcerous channellike formation between two internal organs or between an internal organ and the skin. .
Today, 5 years after hepatic resection, the patient is still in complete remission.
Our case is not unusual today--and this very normality illustrates the enormous changes of recent years and the shift in treatment of patients with potentially resectable colorectal cancer. Today, patients such as the woman described above are clearly regarded as having a chance of curative treatment; however, it may be worth remembering that this patient would have had a very poor prognosis in the era of 5-fluorouracil (5FU) monotherapy when, according to a prognostic model, life expectancy would have been only 6 months  and liver resections were rare .
In this case, the surgeon acted on the assumption that the patient had very limited options in a strictly palliative situation. The primary tumour was not resected, and the patient began chemotherapy. Retrospective analyses have shown no survival advantage for resection in patients with lack of bowel obstruction in comparison to systemic treatment [4-6]. By contrast, resection may delay systemic treatment, which is the only treatment option with proven survival benefit.
Only a few years before the start of treatment of the patient in our case report, the first larger reports of patients with liver resection after neoadjuvant chemotherapy were published by Bismuth bismuth (bĭz`məth) [Ger. Weisse Masse=white mass], metallic chemical element; symbol Bi; at. no. 83; at. wt. 208.9804; m.p. 271.3°C;; b.p. about 1,560°C;; sp. gr. 9.75 at 20°C;; valence +3 or +5. et al.  and Giacchetti et al. , which increased the awareness of secondary resectability. However, in 2001, when colorectal liver metastases were diagnosed in our patient, neoadjuvant treatment and especially an intensive approach with chemotherapy and targeted therapy was not the standard treatment. During the following years, several single-arm studies were performed which confirmed the possibility of resecting initially non-resectable liver metastases [9-12]. This approach results in relatively favourable long-term survival. Adam and co-workers reported a 10-year survival rate of 23% . However, they also reported prognostic factors that clearly showed the differences in patients without any risk factor [more than two metastases, large metastases >10 cm, elevated carbohydrate antigen (CA) 19-9 and rectal primary; calculated 5-year survival, 59%] compared to those with unfavourable factors (more than two risk factors; calculated 5-year survival, [less than or equal to] 1%) .
Discussions have continued regarding the optimal chemotherapy, especially as most patients in the first reports [7,8] were treated with oxaliplatin-containing schedules. Pozzo and coworkers demonstrated that irinotecan-containing schedules gave similar results to combinations with oxaliplatin in a smaller patient group . Today, we know that leucovorin, 5FU and irinotecan (FOLFIRI FOLFIRI Folinic Acid, Fluorouracil & Irinotecan (chemo treatment) ) combined with cetuximab is an effective therapy that significantly prolongs progression-free survival and increases response rate in first-line therapy . Combinations of leucovorin, 5FU and oxaliplatin (FOLFOX FOLFOX 5-Fluorouracil, Leucovorin and Oxaliplatin (chemo treatment) ) with cetuximab  and the four-drug combination leucovorin, 5FU, oxaliplatin and irinotecan (FOLFOXIRI)  may also increase the response rate. When FOLFIRI/cetuximab  or FOLFOXIRI  were compared to FOLFIRI alone, the concept that increased response rates induce a higher probability of liver resection was confirmed .
When our patient showed a good partial response, resection of the liver metastasis was possible and took place without peri-operative complications. Early multidisciplinary discussion during chemotherapy is crucial in this group to enable the patient to undergo early liver surgery, thus avoiding unnecessary preoperative pre·op·er·a·tive
Preceding a surgical operation.
preceding an operation.
the preparation of a patient before operation. exposure to chemotherapy which is related to higher peri-operative mobidity . A further reason against long-duration pre-operative chemotherapy is that even a complete remission shown on CT scan is of no advantage as approximately 85% of 'disappeared' metastases do not have pathological complete response (if resected) or recur during the first year after resection .
In this case, adjuvant radiotherapy was not discussed because of a recto-vaginal fistula. However, in general the value of radiochemotherapy might be reduced after resection of simultaneous liver metastases if the risk of local recurrence is weighed against the risk of systemic relapse.
Liver metastases of colorectal cancer and the management of patients with simultaneous metastases of colon and particularly rectal cancer remains a very interesting field of multidisciplinary research.
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1. one of three offspring produced at one birth.
2. a combination of three objects or entities acting together, as three lenses or three nucleotides.
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ASCO Association of Schools and Colleges of Optometry (since 1941; Rockville, Maryland)
ASCO Australian Standard Classification of Occupations
ASCO Automatic Switch Company , 2004, 23, Abstr. 3593.
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tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment. phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial. Proc ASCO, 2007, 25, Abstr. 4000.
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n. pl. pen·nae
A contour feather of a bird, as distinguished from a down feather or a plume.
[Latin, feather; see pet- in Indo-European roots. C, Amin-Hashem M et al. Influence of preoperative chemotherapy on the risk of major hepatectomy hep·a·tec·to·my
Excision of liver tissue.
surgical excision of liver tissue.
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Katharina Sprenger and Gunnar Folprecht
Medical Department I, University Hospital Dresden, Germany
Correspondence to: Katharina Sprenger (email: firstname.lastname@example.org)