A case of multiple hepatic metastases from colorectal cancer effectively treated by arterial infusion therapy with Leucovorin/5-FU

We report a patient with multiple hepatic metastases from colorectal cancer effectively treated by hepatic arterial infusion therapy (5-FU/LV therapy). The patient was a 55-year-old man with sigmoid colon cancer and multiple hepatic metastases, 5 cm in diameter, in both lobes of the liver. First, we locally controlled the sigmoid colon cancer by sigmoid colectomy (with D3 lymph node dissection). After resection of the primary cancer lesions and dissection of the lymph nodes, we treated the patient by systemically administering 4 courses of Leucovorin/5-FU (once weekly for 6 weeks per course) from a port-catheter system during hospital stay and in the outpatient clinic after hospital discharge. Assessment of therapeutic effects by CT showed CR in the patient. CEA levels, which were abnormal before and after surgery, decreased to normal at the end of chemotherapy. After 1 year, neither CT evidence of tumor enlargement in the liver nor re-increase in CEA levels has been noted. Although the patient experienced side effects such as pigmentation, grade 1 loss of appetite, and leukopenia, he was able to maintain his QOL in the absence of severe side effects.     

A case whose lung metastasis was detected and resected eleven years after resection of primary colon cancer

In July 1999, a 79-year-old man underwent sigmoidectomy and D3 lymphadectomy for sigmoid colon cancer (ss, n(-), stage II, cur A). In September 2000, hepatectomy of right lobe and cholecystectomy were performed for his liver metastasis. Every three to six months follow-up had been kept since adjuvant chemotherapy (200 mg/day of 5-FU per os for two years) completed. Eleven years and two months after sigmoidectomy (in September 2010), a chest X-ray examination detected a small nodule in upper area of his right lung, which was diagnosed as either primary lung cancer or metastatic lung tumor followed by chest CT scan and PET-CT examination. In November 2010, laparoscopy-assisted partial resection of his right lung was performed. Histochemical examination of the resected lung tumor resulted cytokeratin 7(-), cytokeratin 20(+) and TTF-1(-), confirming its final diagnosis as lung metastasis from sigmoid colon cancer. He has been alive for six months without any recurrence since resection of his lung metastasis. It was a very rare case to have more than ten-year interval between colon cancer resection and detection of its lung metastasis. However, when we diagnosed the patient with lung tumor, who had undergone a colorectal resection, we should consider if he had a lung metastasis from colorectal cancer.     

A case of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.     

A case of multiple liver metastases from colon cancer successfully treated with pharmacokinetic modulating chemotherapy

The present patient was a 54-year-old woman with anemia. After examination to identify the cause of anemia, she was diagnosed with sigmoid colon cancer and multiple liver metastasis. Sigmoid colectomy and insertion of an intra-hepatic arterial catheter were carried out. Histopathological examination of the resection specimen revealed well-differentiated adenocarcinoma, with a depth of tumor invasion of ss and positive lymph node metastasis. Pharmacokinetic modulating chemotherapy (PMC) was performed after the operation. The PMC consisted of oral UFT 300 to 400 mg/day every day and continuous arterial infusion of 5-FU 750 to 1,000 mg/24 h once a week. On a CT scan of the abdomen performed 6 months after the operation, the liver metastasis had disappeared and the patient was in complete remission (CR). PMC was continued, but the hepatic artery became occluded 1 year and 11 months after the operation, and so PMC was replaced by systemic chemotherapy of 5-FU plus levofolinate at 2 years after the operation. This chemotherapy was discontinued after 3 courses. At present, 2 years and 10 months after the operation, the patient remains in CR and is followed as an outpatient.     

Repeated resections for originally unresectable liver metastasis from colorectal cancer after multiagent chemotherapy

We describe the case of a 74-year-old man with liver resection for originally unresectable liver metastasis from colorectal cancer after multiagent chemotherapy. Eleven bilobar liver metastases appeared four months after curative resection for double cancer of sigmoid colon and upper rectum. After 6 courses of multiagent chemotherapy (mFOLFOX 6 with bevacizumab), the number of liver metastasis decreased from 11 to 5. The patient underwent curative resection for liver metastasis. A new lesion of 7 mm in the segment 6 appeared 8 months after an initial liver resection. After 3 months' observation, two more liver metastases appeared. All liver metastases were resected. Solitary lung metastasis appeared 10 months after the second liver resection. The lung metastasis was also resected. The patient was alive with no evidence of disease in 33 months after the initial liver resection. We experienced the case with repeated liver resections after multiagent chemotherapy for originally unresectable bilobar liver metastasis. The therapeutic strategy which combines surgical resection with cytotoxic chemotherapy will be important more than ever.     

A case of pathologically by complete response in advanced sigmoid colon cancer with multiple metastases of lung and Liver, left hydronephrosis after chemotherapy including bevacizumab/FOLFOX6

A 61-year-old complaining of anorexia and general fatigue was admitted to our hospital for further examination. She was diagnosed as advanced sigmoid colon cancer with multiple metastases of lung, liver, and left hydronephrosis. Since curative surgery was not deemed possible, we started chemotherapy with bevacizumab/FOLFOX6 (bi-weekly drip infusion). After the 6th course, colonoscopy revealed a significant tumor reduction and changes to the scar tissues. CT did not reveal a complete disappearance, but found some reductions in metastases of lung and liver. Sigmoidectomy and lymph node resection (D1) were performed. We did not disappeared any dissemination and the histological diagnosis revealed a complete disappearance of cancer cells in the main tumor. She was discharged 13 days after surgery, following chemotherapy which included bevacizumab and XELOX. The chemotherapy using bevacizumab/FOLFOX6 is a candidate for the standard treatment strategy for inoperable advanced colon cancer. Herein we report this rare case with a review of the literature.     

A case report of thyroid gland metastasis associated with lung metastasis from colon cancer

Thyroid gland metastasis of malignant tumors is observed in 1.9% to 9.5% of histologically examined autopsy cases. Thyroid metastasis from colon cancer is extremely rare and the prognosis is poor. Here we report a case of lung metastasis and thyroid gland metastasis following sigmoid colon cancer surgery. In 2000, a 58-year-old woman underwent a sigmoid colectomy for sigmoid colon cancer. In 2005, a metastatic lung tumor was detected by chest CT. The patient underwent a partial thoracoscopic resection of the left lung in April 2005. On a CT scan taken 3 years and 4 months after the lung resection, a tumor mass was observed in the left lung and a low-absorption region with an unclear border was seen in the left lobe of the thyroid gland. Thyroid aspiration cytology showed adenocarcinoma, and a diagnosis of thyroid gland metastasis from sigmoid colon cancer was made. In April 2008 a subtotal thyroidectomy was performed. Following surgery, the patient underwent chemotherapy with mFOLFOX6 and bevacizumab. Nevertheless a number of lung metastases and expressions of lung metastasis were subsequently observed. Histopathological examination revealed a number of metastases of differentiated papillary adenocarcinoma in the thyroid gland from colon cancer.     

A case of colorectal cancer effectively treated with UFT/LV

5-FU/LV therapy has been standard chemotherapy for advanced and recurrent colorectal cancer. Several studies reported that a new alternative chemotherapy, UFT/LV, had anti-cancer effects the same as with conventional 5-FU/LV therapy. We report a patient who had advanced and recurrent colorectal cancer treated with UFT/ LV. This 70-year-old male was admitted to our hospital because of a right lower abdominal mass, which was diagnosed as a peritoneal recurrence of transverse colon cancer by abdominal CT. UFT/LV therapy was started on an outpatient basis. After one course of chemotherapy, the intra-abdominal mass disappeared, and this therapy was continued for three courses. He did not suffer from any adverse effect during chemotherapy. Although this therapy was resumed because of the recurrence at the same site after nine months, it was refractory to chemotherapy. Thereafter, surgical resection was performed, and it was diagnosed as lymph node metastasis of previous surgery.     

A case of recurrent colon cancer with complete response to modulation chemotherapy using low-dose leucovorin and 5-fluorouracil]

We experienced a case of lymph node recurrence from colon cancer with complete response to modulation chemotherapy using low-dose leucovorin and 5-FU. The patient was a 68-year-old male. He underwent sigmoid colon resection for sigmoid colon cancer in October 1993. In June 1994, he complained of left lower abdominal pain. Swelling of retroperitoneal lymph node was detected by CT scan and cytology revealed cancer cells in urine. He was diagnosed as having lymph node recurrence. He then was given modulation chemotherapy of 30 mg of leucovorin and 500 mg of 5-FU that were bolus injected intravenously for 5 days. After 2 cycles of this regimen, the recurrent mass disappeared completely for further examination. Until May 1998, he had received 14 cycles. Since this regimen started, his survival period has been 46 months, and his response duration 42 months.     

Complete remission in a case of sigmoid colon cancer with multiple liver metastases-treatment with arterial chemotherapy and percutaneous microwave coagulation therapy

A 59-year-old man was admitted to our hospital for advanced sigmoid colon carcinoma with synchronous multiple liver metastases. The patient received sigmoidectomy with regional lymph node dissection on June 8, 1998. We started intra-arterial combination chemotherapy on July 1, 1998. MMC (4 mg/body) was administered via rapid intra-arterial infusion on day 1. After MMC administration, 5-day intra-arterial continuous infusion of 5-FU at 500 mg/body/day was performed with oral administration of LV (30 mg/body/day). The treatment cycle was defined as every three weeks. The patient was treated with 4 courses of chemotherapy. From September 30, he received intra-arterial infusion of bolus MMC 4 mg/body, LV 6 mg/body and 5-FU 1,000 mg/body/4 hrs every two weeks with oral administration of Tegafur-uracil 400 mg/day. After 4 intra-arterial chemotherapy sessions, the metastatic liver tumors disappeared except for a focus in the right lobe. Therefore we decided to give the remnant liver metastasis percutaneous microwave coagulation therapy (PMCT). He obtained a complete remission in the liver metastases after two PMCT (70 W, 60 sec) sessions. Intra-arterial chemotherapy is effective for unresectable metastatic liver tumors from colon cancer. If a patient shows a partial response on the metastatic tumors through the chemotherapy, one must consider other modalities such as PMCT.     

Successful treatment of liver metastasis and extrahepatic metastasis with hepatic arterial infusion of CDDP, CPT-11, and 5-FU

A 63-year-old man, who had been operated with right hemicolectomy 1 year and 3 months ago, had giant liver metastasis, lung metastasis, and local dissemination tumor due to ascending colon cancer. He was treated by systemic chemotherapy with 5-FU and the treatment evaluation was PD on CT. After admission to our hospital, he was treated by hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU. After 3 courses of the treatment, each recurrent lesion decreased on CT and the CEA level decreased. There were no side effects except mild diarrhea. We believe hepatic arterial infusion chemotherapy with CDDP, CPT-11, and 5-FU may be an effective strategy against liver metastasis and extrahepatic metastsis due to colon cancer.     

A case of sigmoid colon cancer invading urinary bladder treated with preoperative mFOLFOX6 and urinary bladder conserving surgery

A 69-year-old man visited our hospital because of melena and anemia. Colonoscopy revealed a type 3 tumor at sigmoid colon, and by abdominal CT, we detected a sigmoid colon cancer invading the urinary bladder with a single liver metastasis. The patient required sigmoidectomy with partial hepatectomy and total urinary bladder resection. Preoperative chemotherapy with mFOLFOX6 was initiated as a part of multidisciplinary therapy. After the 6th course was completed, CT revealed a reduction in the primary tumor's size and the disappearance of liver metastasis. After the 8th course was completed, we performed urinary bladder conserving sigmoidectomy. The pathological diagnosis of the surgical specimen was tub1, pSS, ly0, v0, pN0, and pStage II. Down-sizing chemotherapy might improve the quality of life(QOL)of colon cancer patients with extensive invasion of the urinary bladder.     

A case of colon cancer with liver and lung metastases-efficacy of CPT-11/5-FU/l-LV (IFL) as part of ambulatory treatment

In July 2003, a 59-year-old man underwent a right hemicolectomy for sigmoid colon cancer. Hepatic intraarterial injection therapy with 5-FU/CDDP was not only ineffective against a liver metastasis but a lung metastasis was also found, and therefore systemic chemotherapy with CPT-11/5-FU/l-LV (IFL) was administered. After onetime IFL therapy, the CPT-11 was withheld due to ileus. Although 5-FU/l-LV therapy was administered, it was ineffective. IFL therapy was again performed, with the dose decreased by 20%, as part of ambulatory treatment. Not only the liver metastasis but also the lung metastasis decreased significantly in size after one course. In addition, no severe adverse reactions were observed during the treatment, which enabled the therapy to be continued as part of an ambulatory regimen. The results suggest that IFL therapy is effective against colon cancer with lung/liver metastasis and can be administered as part of ambulatory treatment.     

A successful case of preoperative intermittent hepatic arterial infusion of high-dose 5-FU and pharmacokinetic modulating chemotherapy against unresectable liver metastasis of colon cancer

A 46-year-old adult who underwent a sigmoidectomy for sigmoid colon cancer at the age of 44 was found to have a liver tumor 2 years after the first operation. His CEA was elevated to 158.8 ng/ml. An abdominal CT showed a huge mass of 10 x 7 x 7 cm in the anterior segment of right lobe of the liver invading into segment 4 and 7, which compressed the left hepatic vein and the umbilical portion of the portal vein. We diagnosed an unresectable liver metastasis of sigmoid colon cancer. Intermittent hepatic arterial infusion of high-dose 5-FU was started on a weekly schedule and oral UFT was added as pharmacokinetic modulating chemotherapy 4 weeks after the initial chemotherapy. Chemotherapy was continued for 13 weeks and the tumor shrunk up to 64%. An extended right hepatectomy was performed. Pathological examination showed residual cancer cells in the central part of the tumor, but fibrous degeneration and calcification were observed in the surrounding area and considered to be the effect of chemotherapy.     

A case of hepatic metastasis from colon cancer successfully treated with 5-FU, levofolinate (l-LV) and low-dose CPT-11

The patient was a 67-year-old man in whom hepatic metastasis from transverse colon cancer was detected 15 months after transverse colectomy (D2). We treated the patient by systemically administering 2 courses of 5-FU 750 mg/day with l-LV 350 mg/day (once weekly for 6 weeks per course). Assessment of therapeutic effects by CT showed PD in the patient. As a second-line therapy, we treated the patient by systemically administering 3 courses of 5-FU 750 mg/day, l-LV 350 mg/day and CPT-11 40 mg/day x 3 days (once a week for 4 weeks per course). After 3 courses of this chemotherapy, CT examination revealed a reduction in the tumor size of the liver, and CEA levels decreased at the end of this chemotherapy. This chemotherapy also showed no high-grade toxicities. l-LV/5-FU/low-dose CPT-11 seems to be effective for metastatic colon cancer, and safe from the toxicity standpoint.     

Adjuvant chemotherapy for stages II, III and IV of colon cancer

Colorectal cancer is the third most frequent malignant neoplasm in Western countries. After complete resection, 5-year overall survival varies according to the initial stage. Adjuvant chemotherapy (CT) is indicated in patients with colon cancer at high-risk stage II, stage III and after complete resection of metastases. 5-Fluorouracil (5FU), alone or modulated with levamisol or leucovorin (LV), oral fluoropyrimidines, raltitrexed, irinotecan and oxaliplatin have been studied as adjuvant therapy for colon cancer. Nowadays, oxaliplatin-based regimens, FOLFOX or FLOX, are considered as the standard adjuvant CT. If there are contraindications for oxaliplatin, the best alternatives are capecitabine or continuous infusion of 5FU/LV. The role of monoclonal antibodies, cetuximab and bevacizumab, combined with oxaliplatin/fluoropyrimidine-based CT is under investigation in clinical trials. This article reviews the state of the art and the future perspectives of adjuvant therapy in colon cancer. Prognostic and predictive factors are also commented on.     

A case of hepatic metastasis and local recurrence from rectal cancer responding to hepatic arterial infusion and systemic chemotherapy

A 71-year-old man underwent low anterior resection for rectal cancer. Two years after the surgery, liver metastasis and local recurrence were found on the CT scan. The first-line treatment was systemic chemotherapy (CPT-11 and 5'-DFUR). Effect was satisfactory for local recurrence, but a new liver tumor was found on the CT scan. The second-line treatment was a hepatic arterial infusion (5-FU) and systemic chemotherapy (UFT). After 4 courses, the liver metastasis was reduced, but after 5 courses, the liver tumors had enlarged. The third-line treatment was a hepatic arterial infusion (5-FU + levofolinate) and systemic chemotherapy (UFT). After 5 courses, the liver tumor disappeared, and no other recurrence was found on the CT scan.     

A case report of colon cancer with liver and lung metastases responding to combination chemotherapy with l-LV, 5-fluorouracil and CPT-11

A 58-year-old man who had colon cancer with liver and multiple lung metastases underwent ileocecal resection on May 10, 2002. MTT assay of 5-FU and CPT-11 was performed with resected material, with both medicines accepted for sensitivity. On June 4, he received combination chemotherapy with CPT-11 + 5-FU/l-LV. The liver metastasis disappeared and was judged CR from a CT of the abdomen. Almost all the multiple lung metastases had disappeared or were decreased in size. They were therefore judged NC from a CT of the chest. Moreover, CEA and CA19-9 decreased to within normal limits. While he was receiving bimonthly chemotherapy with only CPT-11 as a maintenance therapy, liver and lung metastases did not change. Combination chemotherapy with CPT-11 + 5-FU/l-LV is effective. The anticancer drug sensitivity examination is only one index, however. Considering adverse effects and medical costs, individualized therapy based on the sensitivity test for anticancer drugs should be performed.     

Metastatic rectal cancer responding to third-line therapy employing bevacizumab after failure of oxaliplatin and irinotecan: case report

A 61-year-old female with surgically treated rectal cancer that had metastasized to lung and lymph nodes was treated with bevacizumab (BV) plus 5-fluorouracil (5-FU) and leucovorin (LV) as third-line chemotherapy after treatment failures with infusional 5-FU, LV and oxaliplatin (FOLFOX regimen); and infusional 5-FU, LV and irinotecan (FOLFIRI regimen). After four cycles of treatment, a computed tomography scan revealed reduced sizes of the lung and lymph node metastases. Tumor response has still been maintained after six cycles of treatment, and the chemotherapeutic response was evaluated as partial response according to the Response Evaluation Criteria In Solid Tumor guidelines. Manageable toxicity included grade 2 hypertension, grade 1 epistaxis and grade 1 stomatitis. Although there are no clinical trial results supporting the use of BV-containing therapy as third-line chemotherapy for advanced colorectal cancer, BV plus 5-FU and LV was effective and feasible in our patient with colon cancer that had progressed after treatment with 5-FU, irinotecan and oxaliplatin.     

A case of recurrent sigmoid colon cancer with adrenal and para-aortic lymph node metastasis successfully treated by operation and chemotherapy

We report a case of 57-year-old woman suffering from advanced sigmoid colon cancer with adrenal and para-aortic lymph node recurrence. Sigmoidectomy was performed for sigmoid colon cancer in January 2002. Pathological staging was Stage II (pT3, pN0, pM0, Cur A). She received a UFT + CPT-11 regimen as preoperative chemotherapy for liver metastasis (S2, S7) from December 2002. A partial liver resection (S2, S7) was performed for liver metastasis in July 2003, and the UFT + CPT-11 was introduced as adjuvant chemotherapy. However, adrenal and para-aortic lymph node recurrence was detected in February 2007, and mFOLFOX6 was performed as preoperative chemotherapy. Right adrenalectomy and para-aortic lymph node dissection was performed in July 2007. mFOLFOX6 as postoperative chemotherapy was done, mFOLFOX6 + bevacizumab was started because of CEA increase. The chemotherapy was performed for 23 courses and temporarily stopped due to adverse reactions, such as peripheral neuropathy (grade 2), general fatigue (grade 1), and nausea (grade 1). She had no recurrence for almost 3 years after a resection of adrenal and para-aortic lymph node metastasis.