TREATMENT OF RECTAL ADENOCARCINOMA WITH …



TREATMENT OF RECTAL ADENOCARCINOMA WITH METASTATIC HEPATIC NODULES: CLINICAL CASE

R. Pugliese, D. Maggioni, C. Brambilla, S. Di Lernia, G.Ferrari, A. Costanzi

General Surgery and Videolaparoscopy Niguarda-Ca’ Granda Hospital, Milano

Abstract

A 50 year old female patient came under our care because of 4 month diarreha and consistent weight loss. A CT scan showed an etheroplastic lesion of the rectal wall and two metastatic hepatic nodules localized in the Iind-IIrd and VIIIth segment. A Total Mesorectal Excision was performed associated with Resection of the II° and III° segment. The histologic findings confirmed the diagnosis of rectal adenocarcinoma pT3N2M1. The postoperative course was complicated only by a pericardic effusion. The patient was succesively treated with chemotherapy and when there was the evidence of a reduction of the residual hepatic lesion, she underwent a resection of the 8ht hepatic segment.

Clinical case

At the beginning of June 2006 a 50 year old female patient came under our care because of 4 month diarrhea (up to 10 discharges a day) and weight loss (about 15 kg).

The anamnesis pointed out an appendectomy (1966) and the removal of pelvic endometrial tissue (1992). The patient didn’t take domiciliary therapy and reported an allergy to NSAID, Acetaminophen, Rociverin and other unspecified antibiotics.

The doctors decided to carry out a coproculture to search for faecal parasites on 6 specimens, that turned out to be negative. The hematochemical exams showed just a slight anaemia (Hb 11.4 mg/dL), while ESR, electrophoresis, hepatic, renal, thyroidal function and tumorous markers were within the norm.

The CT total body carried out on the 9th of June 2006 revealed, at level of the abdomen, a nonuniform etheroplastic thickening of the walls of the rectum and on the rectum-sigmoid region, an irregular volumetric decrease of the bowel lumen and a thickening of the perirectal fatty tissue where multiple tumefactions of the lymph nodes could be recognized (fig.1). Besides three hypodense solid nodular focal lesions were revealed in the liver (fig.2):

1 nodule (diameter: 3 cm) in the 2nd and 3rd segment

1 nodule ( diameter: 12 mm) in the 7th segment

1 nodule (diameter: 3 cm) in the 8th segment

In order to complete the diagnosis the patient underwent rectosigmoidoscopy that confirmed – 8 cm away from the anal fessure- the presence of a vegetating, ulcerated and multimamillated lesion rostrad extended up to about 15 cm from the anus. The colonoscopist reported that carrying out the colonoscopy hadn’t been possible due to the patient’s lack of compliance. The lesion was biopsied in three points whose histological report was unvaried: ulcerated and infiltrating adenocarcinoma.

The patient also underwent a rectal and pelvic echoendoscopy that found secondary lymph nodes involvement in the mesorectum and metastases in the hypogastric stations on both sides and in the rectouterine cleavage plane, signs of infiltration of the hypogastric vessels, of the vaginal and uterine walls were ruled out instead. To conclude the survey of the patient and rule out possible bone metastases, she underwent a lumbosacral CT that turned out to be negative. The preoperative staging was T3N2M1, that excluded the inclusion in the neoadjuvant chemo-radiotherapy protocol.

The operation was performed in stages: at first resection of the primary tumour, temporary protective ileostomy and resection of the hepatic metastasis of the left lobe, more easily removable through mini-invasive technique to let the patient recover more rapidly and favour a lesser postoperative immunodepression. Later on the patient would be treated with adjuvant chemotherapy and, in a third stage, she would undergo the resection of the remaining hepatic metastases associated with intestinal recanalization. The antalgic therapy started before the operation was : Tramadol 3 vials iv deluted in 500 ml of normal saline solution three times a day, replaced with morphin 1 vial and Tramadol 1 vial in 250 cc of normal saline solution one week before the operation.

6/26/2006 the first operation of videolaparoscopic anterior resection of the rectum (fig.3) associated with total mesorectal excision, videolaparoscopic hepatic resection of the second and third segment and temporary protective ileostomy placed in the right iliac fossa (video).

The histological findings confirmed the diagnosis of moderately differentiated rectal adenocarcinoma infiltrating perivisceral adipose tissue with images of perineural and intravascular invasion. Besides they revealed metastases in 14 out of 28 lymph nodes isolated from the perivisceral adipose tissue. The postoperative staging therefore was T3N2M1, corresponding to the 4th stage in accordance with Dukes’s classification, modified by Astler and Coller.

The postoperative course proceeded regularly from a surgical point of view: the first day the nasogastric tube was removed, the second day the catheter was removed and immediately active and spontaneous diuresis started again; the patient was mobilized and fed with a light diet.

From the operation until the 6th postoperative day the patient was given morphin 3 vials, hydrochlorate ondansetron 1 vial, metoclopramide 1 vial in 500 ml of normal saline solution 20 ml/h.

The postoperative course was complicated by a pericardic effusion detected by an echocardiogram showing that it was ubiquitous and ruling out any sign of heart tamponade.

The control total body CT carried out after the operation (7/10/2006) showed that in the 8th hepatic segment there was a considerable dimensional increase of the known lesion whose maximum transversal diameter was 4.3 x 3.1 cm compared with the previous diameter (2.8 x 2.4 cm), while the lesion whose diameter was 1 cm in the 7th segment hadn’t changed.

7/13/2006: the patient underwent another control echocardiogram that confirmed the resolution of the effusion. The patient was discharged from the surgery ward on 7/16/2006 and came under the care of Oncology operative unit, where she was treated with Oxaliplatin 140 mg (total dose), Lederfolin 150 mg (total dose) on the first day and 5-Fluorouracil 650 mg as bolus iv and 1000 mg through continous pump infusion in accordance with Folfox-4 scheme. Between July and October 2006 the patient was treated with 6 courses of associative chemotherapy on day hospital in accordance with Folfox-4 scheme. After an episode of G2 degree leukopenia the treatment for the following courses was reduced to Oxaliplatin 100 mg (total dose), Lederfolin 150 mg (total dose) the first day and 5-Fluorouracil 600 mg as bolus iv and 1000 mg through continous pump infusion .

The control CT (10/24/2006) showed the volumetric decrease of the lesion in the 8th segment (from 4.3 x 3.1 to 3.8 x 3.2), while the one in the 7th segment didn’t change.

Since the state of the lesion was nearly stable, from November 2006 to January 2007 four other courses of chemotherapy were carried out in accordance with Folfox 4 scheme to monitor a possible evolution of the disease.

After the last course of chemotherapy a hepatic NMR was prescribed to check the remaining metastatic nodules’ dimensions: the lesion in the 8th segment seemed to be further decreased (27 x 24 mm in comparison with previous 38 x 32); the lesion in the 7th segment hadn’t changed instead and, due to its appearance at T2 weighed sequences it was considered to be consistent with angioma.

Since the clinical state was good, we decided to perform a second surgical operation (1/30/2007): resection of the 8th hepatic segment through laparotomy after verifying the sight of the lesion through intraoperative echography, associated with the removal of the ileostomy and intestinal recanalization (fig. 3, fig.4, fig.5, fig.6). The postoperative course was complicated by the development of serosanguineous effusion characterized by gradual organization and subsequent spontaneous resolution around the site of the resection, and by a serious leukopenia due to probable myelotoxicity because of the intake of cephalosporins. During the ambulatory follow-up these problems seemed to be on the road to resolution.

10 months after the diagnosis the patient is currently free from the disease and in good health.

A nonuniform etheroplastic thickening of the walls of the rectum and of the rectosigmoid region, an irregular volumetric decrease of the bowel lumen and a thickening of the perirectal fatty tissue.

Fig.1 Rectal preoperative CAT

At level of the hepatic parenchyma three hypodense solid nodular focal lesions are recognizable

Fig.2 Liver preoperative CAT showing the lesions in the 8th segment and in the left lobe.

After the incision of the peritoneum from the promontory to the duodeno-jejunal flexure, the section of the inferior mesenteric artery and the incision of the left parietocolic semicanal, the rectum is prepared as far as the levators’plane. Rectal excision was performed and end-to-end transanal colorectal anastomosis was constructed.

Fig.3 Laparoscopic section of the rectum, distal compared with the tumour. Video

The edges of the excision of the 8th segment are marked on the Glisson’s capsule.

Fig.4 Incision of the Glisson’s capsule in order to perform the resection of the 8th segment

The intraoperative echography confirms the presence of a lesion whose diameter was about 3 cm in the 8th segment and rules out further lesion in the other hepatic segments.

Fig.5 Metastatic nodule of the 8th segment after the removal.

All the nodular metastatic lesions localized in the 2nd , 3rd , 8th segment have been removed.

Fig.6 The residual liver after the resection of the 8th segment.

DISCUSSION

Colorectal cancer is the second more frequent cause of death in western society. The diagnosis shows that from 15 to 25% of the patients already have hepatic metastases and besides, almost half of patients is going to suffer from that. The liver is the most frequent site of colorectal tumour metastatic dispersion and once the disease metastasizes, survival rate without any treatment is only eight months.

The results provided by several reports in medical literature about surgical treatment of the colorectal carcinoma hepatic metastases with 30-50% 5-year survival rate and 1-2% surgical mortality explain the reason why nowadays surgery is gold standard treatment, the only one prospect of radical cure. On this point it’s worth underlining how the overall survival rate in patients who underwent that kind of procedure and don’t relapse within 4 years corresponds to that in people, of the same sex and of the same age, not suffering from cancer.

However, resectability percentage of hepatic metastases, even if it ranges from 10% to 20-25% of the patients, thanks to the introduction of neoadjuvant chemotherapy in the clinical practice and the change in time of the resectability criteria , is still low in the “traditional” case histories.

The set resectability criteria are the number of the metastases (less than 4), unilobar distribution, dimensions ................
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