We are faced with a situation of probable liver metastasis from a localized colon adenocarcinoma treated 2 years ago. Probable because we do not have histological confirmation, although as it usually happens, what else could it be? As this is a situation of oligometastasis and the treatments for advanced colon adenocarcinoma allow prolonged survival with good quality of life in these patients, if there is nothing to contraindicate surgery, this should be the first option (correct answer 3). I attach the algorithm proposed by the NCCN in situations of recurrence (http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf). In case of an unresectable situation, chemotherapy treatment would be considered with the intention of converting the single metastatic lesion into a resectable one. Since more than 12 months have passed since FOLFOX treatment, the same scheme could be used, although FOLFIRI+bevacizumab would also be useful. Capecitabine monotherapy, in the patient's current situation, would also not be a good starting option, since the responses are lower compared to FOLFOX or FOLFIRI plus antiangiogenic combinations. Hepatic radiotherapy could be considered, since there are SBRT techniques that achieve very good results, but in this case it is best to start by asking for an assessment by the surgeons and if they rule out surgery we would consider RT.

We are faced with a situation of probable liver metastasis from a localized colon adenocarcinoma treated 2 years ago. Probable because we do not have histological confirmation, although as it usually happens, what else could it be? As this is a situation of oligometastasis and the treatments for advanced colon adenocarcinoma allow prolonged survival with good quality of life in these patients, if there is nothing to contraindicate surgery, this should be the first option ([HIDDEN]). I attach the algorithm proposed by the NCCN in situations of recurrence (http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf). In case of an unresectable situation, chemotherapy treatment would be considered with the intention of converting the single metastatic lesion into a resectable one. Since more than 12 months have passed since FOLFOX treatment, the same scheme could be used, although FOLFIRI+bevacizumab would also be useful. Capecitabine monotherapy, in the patient's current situation, would also not be a good starting option, since the responses are lower compared to FOLFOX or FOLFIRI plus antiangiogenic combinations. Hepatic radiotherapy could be considered, since there are SBRT techniques that achieve very good results, but in this case it is best to start by asking for an assessment by the surgeons and if they rule out surgery we would consider RT.

A 57-year-old patient diagnosed with stage T3N1M0 adenocarcinoma of the colon. He was treated with resection followed by postoperative FOLFOX chemotherapy (fluorouracil, leucovorin and oxaliplatin) for 6 months. In a routine control, two years later, carcinoembryonic antigen (CEA) elevation to 30 ng/mL (previously less than 2 ng/mL) was detected. She has no symptoms, physical examination is unremarkable, chest X-ray is normal. CT scan shows a 3 cm mass in the right hepatic lobe that is captured on PET. No other alterations are observed in CT or PET. What is the most correct approach?

Chemotherapy with FOLFIRI (fluorouracil, leucovorin and irinotecan) plus bevacizumab.

Assessment for surgical resection of the hepatic lesion.

[Resection of a left obturator lymph node recurrence five years five months after surgery for rectal cancer].

A 62-year-old man with lower rectal cancer underwent abdominoperineal resection and dissection of the lateral pelvic lymph nodes. The cancer was staged at pT3pN0cM0, pStage II and did not show recurrence. Two years later, the patient had dysphagia and was diagnosed with esophageal cancer based on upper gastrointestinal endoscopy. Positron emission tomography-computed tomography (PET/CT) performed to detect distant metastasis revealed fluorodeoxyglucose (FDG) uptake in the left obturator lymph nodes, indicating rectal cancer recurrence. The patient received radiation therapy (60.4 Gy) for the recurrence. A PET/CT scan obtained 2 years 6 months after the initial rectal cancer resection revealed no FDG uptake. Uraciltegafur plus Leucovorin (UFT+LV) was started and continued for 6 months, but tumor enlargement was noted. Treatment was changed to LV, 5-fluorouracil, and irinotecan (FOLFIRI), but after 4 courses, the patient's carcinoembryonic antigen (CEA) levels rose. The patient then received 4 courses of bevacizumab plus FOLFIRI. A CT scan revealed tumor shrinkage, so the patient received 4 more courses of this regimen. Five years postoperatively, the patient's CEA levels rose again. A PET/CT scan 4 months later revealed FDG uptake in the left obturator lymph nodes, indicative of rectal cancer recurrence. One month later, the lymph nodes were resected. The patient was subsequently recurrence free. Tumor marker measurement and PET/CT helped to assess the patient's condition. When cancer recurs in the lateral pelvic lymph nodes with no involvement of the pelvis and R0 resection is possible, resection should be considered if the patient is capable of undergoing surgery.

The utility of FDG-PET/CT as an effective tool for detecting recurrent colorectal cancer regardless of serum CEA levels.

Tumor recurrence of colorectal cancers (CRC) is generally followed up by analyses of the serum carcinoembryonic antigen (CEA) levels. However, recent evidence suggests that tumor recurrence can also be visualized by 18F-fluoro-deoxyglucose emission tomography/computed tomography (FDG-PET/CT) in patients with normal CEA levels. We retrospectively evaluated the diagnostic performance of FDG-PET/CT in patients with suspected recurrence of CRC by comparing PET/CT performance in patients with normal CEA levels with PET/CT performance in patients with elevated CEA levels. A total of 235 patients with CRC who had been treated with surgery and/or chemotherapy/radiotherapy underwent PET/CT for the detection of tumor recurrence. The patients [96 females and 139 males; age (mean ± SD) 59.9 ± 12.6 years; range 18-85] were divided into 2 groups based on whether their CEA levels were normal (<5 ng/ml) (Group 1, n = 118) or elevated (>5 ng/ml) (Group 2, n = 117). All of the patients had suspected recurrence based on raised CEA levels, clinical symptoms, and/or tumor detection using other imaging modalities. Of the 235 patients, 172 (73.1 %) had disease recurrence confirmed by a pathological examination (either biopsy or surgical exploration) or clinical follow-up studies. The FDG-PET/CT study yielded a true positive in detecting recurrence in 169 (71.9 %) patients, a true negative in 53 (22.5 %) patients, a false negative in 3 (1.2 %) patients and a false positive in 10 (4.2 %) patients. CRC recurrence was detected in 64.4 % (76/118) and 88 % (103/117) patients in Group 1 and Group 2 with FDG-PET/CT, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the FDG-PET/CT study for establishing recurrence were 100, 84, 89.4, 100 and 93.2 %, respectively, for Group 1; by contrast, these parameters were 97.1, 84.6, 98, 78.5 and 95.7 %, respectively, for Group 2. The number of patients with hepatic and extra-hepatic metastases, such as lung and abdominal lymph node metastasis, detected with FDG-PET/CT was significantly different in Group 1 than in Group 2; however, the number of patients with local recurrence and peritoneal implants detected with FDG-PET/CT was not different between the two groups. FDG-PET/CT can accurately detect tumor recurrence in patients with suspected recurrent CRC, even for patients with normal CEA levels.

Scan? Cure? Sure!

A 61-year-old man undergoes a sigmoid colectomy for a T3N1 (two of 18 nodes) adenocarcinoma of the sigmoid colon. He recovers well and receives 6 months of adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) uneventfully. At his first follow-up visit, the oncologist recommended every 3 month visits for a physical, liver function tests, and carcinoembryonic antigen (CEA) measurement; every 6 month chest, abdomen, and pelvic computed tomography (CT) scans for 3 years; and aspirin, vitamin D supplementation, and exercise. Is CT scanning appropriate in the follow-up of colon cancer patients? (This case was presented at Massachusetts General Hospital Cancer Center.).

Metastatic liver disease

Diagnosis Hemoglobin decrease Liver function test: ALP elevated, bilirubin elevated, albumin decrease Carcinoembryonic antigen for colorectal secondaries Ultrasound scan CT scan Biopsy under ultrasound control Treatment Treatment can consist of surgery (hepatectomy), chemotherapy and/or therapies specifically aimed at the liver like radiofrequency ablation, transcatheter arterial chemoembolization, selective internal radiation therapy and irreversible electroporation. For most patients no effective treatment exists because both lobes are usually involved, making surgical resection impossible. Younger patients with metastases from colorectal cancer confined to one lobe of the liver and up to 4 in number may be treated by partial hepatectomy. In selected cases, chemotherapy may be given systemically or via hepatic artery.

Carcinoembryonic Antigen -- Clinical Significance -- Post Resection Detection of Liver Metastasis/Oligometastases

CEA measurement is the most sensitive detector of liver metastasis from colorectal cancers that can be resected surgically. [23] There is evidence that colon cancer patients with liver metastasis with preoperative CEA less than or equal to 30 µg/L have more likelihood of having resectable metastatic lesions and hence more prolonged survival. [24] When monitored along with CT scans, CEA has proven to detect the metastasis in surgically curable stage than either modality alone.

[A case of rectal cancer with multiple liver metastases successfully treated by repeated hepatectomy].

A 61-year-old man was diagnosed with rectal cancer with multiple liver metastases in December 2009, and low anterior resection of the rectum was performed. Postoperative adjuvant chemotherapy with 6 courses of oxaliplatin, Leucovorin, and 5-FU (FOLFOX4) and bevacizumab was initiated, followed by 5 courses of fluorouracil, Leucovorin, and irinotecan (FOLFIRI) and bevacizumab. Right posterior segment (S6, S7) hepatectomy with enucleation of S2, S3 and S5 was performed, and chemotherapy with FOLFOX4 (11 courses) was administered. New metastases in the S5 segment were observed in August 2011 and right hepatic lobectomy was performed. The patient then underwent 8 courses of adjuvant chemotherapy with FOLFOX4. However, left hepatic lobe lateral segment and caudate lobe metastases then appeared. Subsequent repeated chemotherapy with FOLFIRI plus cetuximab (3 courses) and irinotecan plus cetuximab was interrupted in August 2013 owing to adverse events resulting in rapid growth of hepatic metastases. The patient underwent hepatic left lateral segmentectomy and left caudate lobectomy. The postoperative course was uneventful and the patient has currently survived 4 years and 7 months after the initial surgery.

Oncologic emergencies secondary to advanced colorectal cancer successfully treated with oxaliplatin/5-fluorouracil/leucovorin: report of three cases.

Metastatic/advanced colorectal cancer is considered a resistant disease and oncologic emergencies secondary to advanced disease may be regarded with a nihilistic attitude. The objective of this report is to emphasize the efficacy of the oxaliplatin/5-fluorouracil/leucovorin regimen (FOLFOX-4) in three patients presenting oncologic emergencies secondary to advanced colon cancer. The first case was a 40-year-old man with severe respiratory insufficiency due to massive carcinomatous lymphangitis; subsequently a cecal adenocarcinoma was diagnosed. The patient's conditions became life-threatening and he was admitted to the intensive care unit. The second case was a 41-year-old woman presenting with fever, abdominal mass and pain. Ultrasound and CT-scan revealed two hepatic masses (13 x 15 and 15 x 20 cm), diagnosed as liver metastases from colon cancer. The patient's condition deteriorated with intestinal obstruction secondary to the large left liver mass. The third case was a 58-year-old woman presenting with hepatic mass, fever and weight loss. Ultrasound and CT-scan showed a liver lesion occupying the right lobe (12 x 14 cm). Ultrasonically-guided biopsy and colonoscopy showed liver metastases from cecal cancer. A 5-fluorouracil/leucovorin regimen failed to improve her clinical condition and she had disease progression, inferior vena cava neoplastic thrombosis and right hydronephrosis. All three patients rapidly improved after a few cycles of oxaliplatin-containing chemotherapy. These cases demonstrate that even patients with advanced colorectal cancer presenting with oncologic emergencies and life-threatening conditions can be successfully treated with the FOLFOX-4 regimen.

Detection of recurrences during follow-up after liver surgery for colorectal metastases: both carcinoembryonic antigen (CEA) and imaging are important.

The follow-up of patients treated for colorectal liver metastases (CRLM) is not standardized. The accuracy of an increase in carcinoembryonic antigen (CEA) levels for finding recurrences after treatment for CRLM is compared in this retrospective cohort study with the accuracy of routine imaging modalities of liver and chest. Data from all patients in follow-up after intentionally curative treatment for CRLM from 1990 to 2010 were analyzed. All patients underwent the same follow-up schedule. The way in which recurrences became apparent (i.e., CEA increase, routine imaging, or both) was registered. The specificity and sensitivity of increases in CEA before finding recurrent disease were calculated by receiver operating characteristic (ROC) curves. An economic evaluation of the cost per resectable tumor recurrence was performed. ROC curves showed that a significant CEA increase was defined as a 25 % increase from the previous value. Recurrences were detected in 46 % of the procedures through CEA increase concomitant with positive imaging, in 23 % through CEA increase without positive findings on routine imaging, and in 31 % through positive imaging without an increase in CEA. The resectability of recurrences did not differ between triggers. Cost per curable recurrence was <euro>2,196 for recurrences found via CEA alone and <euro>6,721 for recurrences found with imaging and CEA. In the follow-up of patients after liver surgery for CRLM, a 25 % increase in CEA serum level can accurately detect recurrences, but routine imaging is indispensable. In patients with CRLM, we advocate both CEA monitoring and imaging in the follow-up after liver surgery.

Metastasectomy

Preoperative evaluation involves imaging of the liver and its metastases, for example with ultrasound, computed tomography or magnetic resonance imaging. Positron emission tomography can be useful to check the entire body for metastases, although the test can be falsely normal with small lesions or preoperative chemotherapy. Baseline blood tests typically include liver function tests and tumour markers. During surgery, intraoperative ultrasound can aid the surgeon to find additional metastases. A clinical risk score first proposed by Fong et al. is often used to assess the risk of recurrence after hepatic resection. The score assigns one point to each of the following: CEA level >200 ng/ml Disease-free interval from primary to metastasis <12 months Node-positive primary More than one liver metastasis Largest hepatic tumor >5 cm The median survival for each score is:

Yield of routine imaging after curative colorectal cancer treatment.

The use of imaging in the follow-up of patients after curative colorectal cancer resection is much debated. The American Society of Colon and Rectal Surgeons did not recommend routine imaging. This retrospective study assesses the yield of routine imaging to detect recurrent disease. In 1998, 108 consecutive patients underwent curative resection for colorectal carcinoma. Minimum followup in our institution was 3 years. Multidisciplinary follow-up at a joint clinic consisted out of a history, clinical examination, serum carcinoembryonic antigen (CEA), chest X-ray and abdominal ultrasound, at least every 6 months. Colonoscopy was performed within 1 year after operation and every 3 to 5 years thereafter. The incidence, timing, means of detection and resectability of recurrence were studied. The recurrence rate was 22% (24 patients): liver metastases (11), extra-hepatic recurrence (10) and combined recurrence (3). Recurrent disease occurred in stage II or III cancer, except for two patients. It was diagnosed at a median of 21.5 months (range 4-79) after surgery. Means of detection were: symptoms in 2 (peritoneal disease, 8%), increasing CEA in 15 (63%), routine imaging in 6 (25%), and abdominal CT-scan in one patient. Curative resection of recurrent disease was possible in ten patients (42%): in 6/15 recurrences detected by CEA, in 3/6 recurrences detected by routine imaging, in 1 liver metastasis detected by CT and in none of the symptomatic patients. A CEA level increasing above 5.0 microg/L was the most important diagnostic tool. However, one quarter of the recurrences were detected by routine imaging and half of them could be resected for cure. These data support routine imaging during follow-up.

Staged Double Hepatectomy, Double Total Vascular Exclusion, and Double Venous Reconstruction by Peritoneal Patches in One Patient with Colorectal Liver Metastases.

Surgical resection is the best treatment for colorectal liver metastases with good response to chemotherapy and in the absence of extrahepatic disease.1 With the amelioration of surgical technique, primary and recurrent colorectal liver metastases with venous invasion can be resected safely under short total vascular exclusion (TVE), and associated right thoracotomy can have a major benefit if resection at the hepato-caval junction is planned.2 The availability of the peritoneum as an autologous graft for venous reconstruction considerably facilitates the task of the surgeon.3 In this video, we present a patient who had staged double liver resection, double TVE, and double venous reconstruction by a peritoneal graft on the vena cava and the hepatic vein. In March 2017, a 47-year-old female was diagnosed with rectal cancer and synchronous liver metastases, microsatellite stability, and Kras mutation. The patient received folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy, with good response and a decrease in tumor markers. After chemotherapy, a computed tomography (CT) scan showed one lesion located on the right liver with lateral invasion of the vena cava, and another lesion located in segment I. A liver-first strategy was decided and, in October 2017, the patient had a right hepatectomy extended to segment I and partially on the diaphragm, with lateral resection of the vena cava under isolated clampage of the vena cava and reconstruction with a peritoneal graft (60 mm). The patient received FOLFOX adjuvant chemotherapy for 3 months, and, while under radiotherapy for the rectal cancer, recurrence was diagnosed on the left liver lobe (two lesions), with lateral invasion of the left hepatic vein. Chemotherapy was shifted to folinic acid, fluorouracil, and irinotecan (FOLFIRI)-Avastin, with good response, allowing resection of the primary (T3N0M1), followed by adjuvant chemotherapy. In May 2019, the patient underwent two large resections on the left liver, including one under TVE, with opening of the diaphragm and intrathoracic control of the vena cava. The left hepatic vein was reconstructed laterally with a peritoneal graft (30 mm). Postoperative outcome was uneventful and the two hospital stays were 12 and 15 days, respectively. For the first hepatectomy, pathological examination showed two lesions (80 and 50 mm) with a residual tumor at 10% and R0 resection, and, for the second resection, pathological examination showed two lesions (18 and 20 mm) with residual tumor at 40-60% and R0 resection. In both cases, the tumor was in contact with the resected vein without wall infiltration. The reconstructed vena cava and hepatic vein were patent without stenosis. The patient is disease-free 3 years after the diagnosis. Improvements in surgical technique combined with short TVE and associated thoracotomy allow some complicated liver resections to be performed safely. The use of the peritoneum for venous reconstruction is of great benefit in relation to safety and availability, especially in 'redo' liver surgery where intense adhesions can be encountered.

The value of routine serum carcino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer.

This analysis aims to evaluate routine carcino-embryonic antigen (CEA) and computed tomography (CT) of thorax, abdomen, and pelvis as part of protocol-specified follow-up policy for colorectal cancer (CRC). Patients with resected stage II and III CRC were randomly assigned to bolus fluorouracil/leucovorin or protracted venous infusion fluorouracil. Following completion of chemotherapy, patients were seen in clinic at regular intervals for 5 years. CEA was measured at each clinic visit, and CT of thorax, abdomen, and pelvis was performed at 12 and 24 months after commencement of chemotherapy. Between 1993 and 1999, 530 patients were recruited. The median follow-up was 5.6 years. Disease relapses were observed in 154 patients. Relapses were detected by symptoms (n = 65), CEA (n = 45), CT (n = 49), and others (n = 9). Fourteen patients, whose relapses were detected by CT, had a concomitant elevation of CEA and were included in both groups. The CT-detected group had a better survival compared with the symptomatic group from the time of relapse (P =.0046). Thirty-three patients (21%) proceeded to potentially curative surgery for relapse and enjoyed a better survival than those who did not (P <.00001). For patients who underwent hepatic or pulmonary metastatic resection, 13 (26.5%) were in the CT group, eight (17.8%) in the CEA group, and only two (3.1%) in the symptomatic group (CT v symptomatic, P <.001; CEA v symptomatic, P =.015). Surveillance CT and CEA are valuable components of postoperative follow-up in stage II and III colorectal cancer.

A 5-year recurrence-free survivor with over ten colorectal liver metastases undergoing FOLFOX plus bevacizumab followed by two-stage hepatectomy.

A 62-year-old male was admitted because of lower left abdominal pain and diarrhea. The patient was diagnosed with rectal cancer and multiple liver metastases. First, the laparoscopic Hartmann operation with a D3 lymph node dissection was performed. After five cycles of folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and bevacizumab, and one additional FOLFOX, the tumor markers dramatically decreased; with carcinoembryonic antigen levels ranging from 1096.3 to 7.6 ng/ml and carbohydrate antigen 19-9 levels ranging from 3248.0 to 42.1 U/ml. Computed tomography showed a bilateral 14 colorectal liver metastases which indicated stable disease by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria and optimal morphologic response. A two-stage hepatectomy was performed to complete a curative resection because of the insufficient remnant liver volume. Five partial hepatic resections in the left liver and the right portal vein ligation were performed during the first operation. Thirty-four days later, a right hepatectomy was successfully performed. Pathologically, there was tumor necrosis in 90 percent of the area of the metastasized liver, and viable cells were detected in only a marginal part of the liver. The patient had an uneventful postoperative course and was discharged fifteen days after the second operation. Uracil-tegafur plus leucovorin was administered for 6 months as an adjuvant chemotherapy treatment. The patient is currently alive and has remained disease-free for more than 5 years. In conclusion, an ideal combination of perioperative chemotherapy and curative resection may provide a chance of long-term survival without recurrence of disease for selected patients with more than ten bilateral colorectal liver metastases.

CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma.

Since 1971, serial carcinoembryonic antigen (CEA) levels have been measured to monitor patients after primary resection of colorectal cancer. Based solely on a rise in CEA level above the baseline established after primary resection, 146 patients were readmitted to the hospital. Chest films, liver-spleen scan, colonoscopy, bone scan, abdominal and pelvic CAT scan, and hepatic arteriograms were performed, and elevated CEA levels were confirmed before reexploration was undertaken. In the 146 patients, 139 (95%) had recurrences, and 81 (58%) of these were resectable for potential cure. Two of the first 22 patients re-explored between 1971 and 1975 are still living 11 and 14 years after second look; of 45 patients reoperated upon from 1976 through 1979 and followed for at least 5 years, 14 (31%) are still living. A rise in CEA above the baseline established after primary resection proved to be a sensitive indicator of recurrence and prompted reexploration before symptoms developed. Early alternative therapy was begun in patients with unresectable recurrences.

Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy.

Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan (folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer (NK) cells (35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

Application and Indication of Carcinoembryonic Antigen Triggered 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scanning in the Detection of Relapse of Colorectal Cancer Patients After Curative Therapy.

This study aimed to explore the characteristics of patients with colorectal cancer (CRC) following curative therapy that may benefit from fluorine-18-2-uoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) scanning, evaluate the application of carcinoembryonic antigen (CEA)-triggered F-FDG PET/CT scanning, and provide referential indicators. This retrospective study included 56 CRC patients who received a PET/CT scan as a primary examination because of rising CEA levels after curative therapy and who had not received any other radiological examinations previously. The rate of recurrence or metastasis was 75.0% by PET/CT scan but was 69.6% with follow-up treatment. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 94.9%, 70.6%, 87.5%, 88.1%, and 85.7%, respectively. TNM (tumor, node, metastasis) stage, body mass index, and CEA level were significant prognostic factors. Positron emission tomography/CT can be selectively applied as a primary examination in CRC patients with asymptomatic elevation of CEA. High CEA levels, increased body mass index, and advanced TNM staging are risk factors for relapse.

A Case of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis Treated with Preoperative FOLFOX Chemotherapy Followed by Radical Subtotal Gastrectomy and D2 Lymph Node Dissection.

We report the case of a 73-year-old female who was diagnosed with advanced gastric cancer. Esophagogastroduodenoscopy was used to diagnose Borrmann type 3 advanced gastric cancer located at the gastric antrum. A biopsy revealed poorly differentiated adenocarcinoma. Abdominopelvic computed tomography (CT) and <sup18</supF-fluorodeoxyglucose positron emission tomography-CT (FDG-PET-CT) scans demonstrated multiple lymph node metastases, including the para-aortic lymph nodes. Systemic chemotherapy with 5-fluoruracil (5-FU), oxaliplatin, and leucovorin (FOLFOX) was initiated. An abdominopelvic CT scan taken after 4 cycles of chemotherapy showed improvement in the ulceroinfiltrative gastric lesion and marked regression of several enlarged lymph nodes. Consequently, we performed a subtotal gastrectomy with D2 lymphadenectomy. The postoperative histopathological report was early gastric carcinoma with no lymph node metastasis in the 48 resected lymph nodes. Another 4 cycles of FOLFOX chemotherapy were performed after surgery. A FDG-PET-CT scan taken 12 months postoperatively showed no definite evidence of local recurrence or distant metastasis, and the previously noted retroperitoneal lymph nodes had disappeared. A FDG-PET-CT taken 16 months postoperatively showed multiple lymph node metastases, including the left supraclavicular lymph node. Despite 8 cycles of secondary chemotherapy with 5-FU, irinotecan, and leucovorin (FOLFIRI) and radiotherapy, the patient died 38 months after the operation.

Assessment of serial carcinoembryonic antigen: determinations to monitor the therapeutic progress and prognosis of metastatic liver disease treated by regional chemotherapy.

It is difficult, time-consuming, and expensive to evaluate the therapeutic efficacy of regional chemotherapy of metastatic liver disease by means of imaging procedures. Therefore it was the aim of this study to find out whether serial carcinoembryonic antigen (CEA) determinations yield reliable data on the therapeutic progress and the individual prognosis of these patients. Since there exists no generally accepted modality to assess CEA curves of patients receiving chemotherapy, we developed our own criterion and tested it in a group of 35 patients. For each patient an individual reference level (CEA-means) was fixed which was obtained as the arithmetical mean of serial CEA values taken during the first three courses of chemotherapy (reference time). On the basis of CEA-means the marker curves of the 35 patients could be divided into two groups. After the reference time the CEA values of group 1 (12 patients) never decreased below CEA-means. Survival of these patients was significantly (P = 0.00001) shorter than that of the 23 patients (group 2) who showed a decrease in their CEA curves below CEA-means after the reference time. Beyond this it could be observed that the improvement in survival was significantly greater in those patients who showed a CEA decrease below CEA-means for a prolonged period (3 months). This difference in prognosis is not an artefact due to different pretherapeutic conditions but is a sign of different responses to therapy. The decrease in CEA values below the individual reference level (CEA-means) is a certain sign of the efficacy of the chosen chemotherapy. A continuous rise of the CEA curve above CEA-means signifies an ineffective intrahepatic chemotherapy or extrahepatic tumor manifestation. In this case an intensive diagnostic workup of the patient and possibly a modification of the therapy are indicated.

Colorectal cancer

If cancer has spread to the lymph nodes or distant organs, which is the case with stage III and stage IV colon cancer respectively, adding chemotherapy agents fluorouracil, capecitabine or oxaliplatin increases life expectancy. If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative. Typically in this setting, a number of different chemotherapy medications may be used. Chemotherapy drugs for this condition may include capecitabine, fluorouracil, irinotecan, oxaliplatin and UFT. The drugs capecitabine and fluorouracil are interchangeable, with capecitabine being an oral medication and fluorouracil being an intravenous medicine. Some specific regimens used for CRC are CAPOX, FOLFOX, FOLFOXIRI, and FOLFIRI. Antiangiogenic drugs such as bevacizumab are often added in first line therapy. Another class of drugs used in the second line setting are epidermal growth factor

What is the most accurate whole-body imaging modality for assessment of local and distant recurrent disease in colorectal cancer? A meta-analysis : imaging for recurrent colorectal cancer.

The objective of this study was to compare the diagnostic performance of positron emission tomography (PET), PET/CT, CT and MRI as whole-body imaging modalities for the detection of local and/or distant recurrent disease in colorectal cancer (CRC) patients who have a (high) suspicion of recurrent disease, based on clinical findings or rise in carcinoembryonic antigen (CEA). A meta-analysis was undertaken. PubMed and Embase were searched for studies on the accuracy of whole-body imaging for patients with suspected local and/or distant recurrence of their CRC. Additionally, studies had to have included at least 20 patients with CRC and 2 × 2 contingency tables had to be provided or derivable. Articles evaluating only local recurrence or liver metastasis were excluded. Summary receiver-operating characteristic (ROC) curves were constructed from the data on sensitivity and specificity of individual studies and pooled estimates of diagnostic odds ratios (DORs) and areas under the ROC curve (AUCs) were calculated. To test for heterogeneity the Cochran Q test was used. Fourteen observational studies were included which evaluated PET, PET/CT, CT and/or MRI. Study results were available in 12 studies for PET, in 5 studies for CT, in 5 studies for PET/CT and in 1 study for MRI. AUCs for PET, PET/CT and CT were 0.94 (0.90-0.97), 0.94 (0.87-0.98) and 0.83 (0.72-0.90), respectively. In patient based analyses PET/CT had a higher diagnostic performance than PET with an AUC of 0.95 (0.89-0.97) for PET/CT vs 0.92 (0.86-0.96) for PET. Both whole-body PET and PET/CT are very accurate for the detection of local and/or distant recurrent disease in CRC patients with a (high) suspicion of recurrent disease. CT has the lowest diagnostic performance. This difference is probably mainly due to the lower accuracy of CT for detection of extrahepatic metastases (including local recurrence). For clinical practice PET/CT might be the modality of choice when evaluating patients with a (high) suspicion of recurrent disease, because of its best performance in patient based analyses and confident prediction of disease status.

FOLFOX

FOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs folinic acid (leucovorin, FOL), fluorouracil (5-FU, F), and oxaliplatin (Eloxatin, OX). FOLFOX4 Adjuvant treatment in patients with stage III colon cancer is recommended for 12 cycles, every two weeks. The recommended dose schedule is as follows: Day 1: Oxaliplatin 85 mg/m2 intravenous (IV) infusion in 250-500 mL D5W and leucovorin 200 mg/m2 IV infusion in D5W administered concurrently over 120 minutes in separate bags using a Y-line, followed by fluorouracil (5-FU) 400 mg/m2 IV bolus given over 2–4 minutes, followed by 5-FU 600 mg/m2 IV infusion in 500 mL D5W (recommended) as a 22-hour continuous infusion. Day 2: Leucovorin 200 mg/m2 IV infusion over 120 minutes, followed by 5-FU 400 mg/m2 IV bolus given over 2–4 minutes, followed by 5-FU 600 mg/m2 IV infusion in 500 mL D5W (recommended) as a 22-hour continuous infusion.

16. FDG-PET in the Detection of Recurrence in Colorectal Cancer Based on Rising CEA Level. Experience in 72 Patients.

Purpose: A rising CEA level after the resection of colorectal cancer is an early indicator of tumour recurrence. However, conventional imaging techniques have limited sensitivity for detecting recurrent disease in such patients. Our group has evaluated the role of Positron Emission Tomography with 18F-Fluorodeoxiglucose (FDG-PET) in this clinical situation.Material and Methods: Seventy-two patients with abnormal CEA levels and normal results of conventional methods of tumour detection were studied with FDG-PET. The PET results were compared with pathologic findings (n = 25) long-term radiological (n = 9) and clinical follow-up (n = 38). Influence of PET findings in therapeutic management was also considered in this study.Results: PET detected lesions in 63/72 patients (87.1%). Metabolic imaging showed metastases in the liver (44.1%), ganglionar nodes (27.5%), local recurrence (20.4%) and lung metastases (8%). Overall, the sensitivity of PET was 94.4%, specificity was 83.3%, the positive-predictive value was 97.1%, the negative-predictive value was 71.4% and the diagnostic accuracy was 92.8%. FDG-PET findings change therapeutic decision in 68/72 patients (94.1%)Conclusion: When conventional examinations are normal, FDG-PET is a valuable imaging tool in patients who have rising CEA level after colorectal surgery. Metabolic imaging represents a very cost-effectiveness diagnostic procedure in this clinical situation, avoiding unnecessary invasive techniques.

[A case of hepatic resection after chemotherapy for metastatic colon cancer of the liver with invasion of the inferior vena cava and hepatic vein].

A 61-year-old man presented with lower abdominal pain. Further examination revealed descending colon cancer and multiple liver metastases (S1, S2, and S5). The largest metastatic lesion in S1 showed massive invasion to the inferior vena cava (IVC) and was considered unresectable. Resection of the primary colon cancer was performed in January 2011, followed by several types of systemic chemotherapy(12 courses of capecitabine plus oxaliplatin [XELOX] + bevacizumab[Response Evaluation Criteria In Solid Tumors{RECIST}: PD], 5 courses of folinic acid, fluorouracil, and irinotecan [FOLFIRI] + bevacizumab[RECIST: SD], and 13 courses of FOLFIRI+ panitumumab). After these regimens, the lesions in S1 and S2 substantially decreased in size (RECIST: PR), and the lesion in S5 was no longer visible. The extent of invasion to the IVC significantly reduced, and liver resection(extended left lobectomy)and partial IVC resection were performed in November 2013 without reconstruction of the IVC by using a vascular prosthesis. The patient was discharged uneventfully on postoperative day 16, and administration of tegafur-uracil-Leucovorin (UFT/UZEL) was initiated. After 4 months, a recurrent lesion was found in S5, and partial liver resection was performed. In addition, FOLFIRI+panitumumab was reinitiated for the multiple lung metastases. The patient is alive without progression of disease 3 years and 4 months after colectomy.

Carcinoembryonic antigen assay: an adjunct to liver scanning in hepatic metastases detection.

The radionuclide liver scan is a valuable study for detection of hepatic metastases; however, it has a false-negative rate of between 10 and 30%. In a double-blind study involving 377 patients, we assessed the value of CEA assay as an adjunct to liver scanning for detection of hepatic metastases. Fifty-seven patients studied by both methods were ultimately proven to have liver metastases. All patients with CEA levels above 9 ng/ml and focal defects on liver scan had hepatic tumor involvement, while only 4 of 291 patients with CEA values less than 9 ng/ml and negative scans were later shown to have liver metastases. CEA and liver scan results were discordant for 29 patients with proven hepatic metastases: the radionuclide study was positive in 21 cases with false-negative CEA results, while the CEA assay suggested the presence of metastatic disease in eight of the 12 patients with false-negative liver scans.

A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases.

Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy. In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.

Is carcino-embryonic antigen useful in the follow-up management of patients with colorectal liver metastases?

The role of carcino-embryonic antigen (CEA) in monitoring early detection of recurrent or metastatic colorectal cancer, and its impact on resectability rate and patient survival remains controversial. Our objective was to determine any association between the preoperative level of CEA and prognosis, and the resectability and survival by method of diagnosis of colorectal hepatic metastases. We analyzed patients who underwent exploration for hepatic resection for metastatic colorectal cancer over a 15-year period. The patient population consisted of those patients who had undergone primary colon or rectal resection and were followed up with serial CEA levels and of patients who were followed up with physical examination, liver function tests (LFTs) or computed tomography (CT) of the abdomen and pelvis that led to the diagnosis of liver metastases. Also included in the study were patients who were diagnosed with liver metastases at the time of the primary colon or rectal resection and underwent planned hepatic resection at a later time. Three hundred and one (301) patients who underwent a total of 345 planned hepatic resections for metastatic colorectal cancer between January 1978 and December 1993 were included in this analysis. The median preoperative CEA level was 24.8 ng/mL in the resected group, 53.0 ng/mL in the incomplete resection group, and 49.1 ng/mL in the nonresected group (P = 0.02). More of the patients who had a preoperative CEA < or =30 ng/mL were in the resected group, while those who had a preoperative CEA >30 ng/mL were likely to be in the nonresected group (P = 0.002). The median survival was 25 months for patients with a preoperative CEA level < or =30 ng/mL and 17 months for patients with a preoperative CEA >30 ng/mL (P = 0.0005). The resectability rate and the survival of patients by method of diagnosing liver metastases-rising CEA versus history and physical, elevated LFTs, CT scan versus diagnosis at the time of primary resection-was not significant (P = 0.06 and P = 0.19, respectively). Given the nonstandardized retrospective nature of the study cohort and relative small groups of patients, the power to detect small differences in survival by method of diagnosis is limited. In the complete resection group of patients with unilobar liver disease (5-year survival of 28.8%) there was no difference in survival between those patients who had normal preoperative CEA and those who had elevated preoperative CEA, and approximately 90% of them had an abnormal preoperative serum CEA level. CEA is useful in the preoperative evaluation of patients with hepatic colorectal metastases for assessing prognosis and is complimentary to history and physical examination in the diagnosis of liver metastases. Patients with colorectal liver metastases and preoperative CEA < or =30 ng/mL are more likely to be resectable, and they have the longest survival.

Chemotherapy rechallenge in metastatic colon cancer: A case report and literature review.

Colorectal cancer (CRC) is the third leading cause of cancer-related death in males and females in the United States. Approximately, 20%-22% of patients have metastatic disease at the time of presentation, and 50%-60% will develop metastasis over the course of their disease. Despite advances in systemic therapies, there remains a paucity of effective third- and later-line therapies for patients with ongoing disease progression. However, rechallenging chemo-resistant CRC tumors with previously administered therapies is an emerging concept that may be a life-prolonging option for heavily treated metastatic colorectal cancer (mCRC). A 41-year-old man with no previous medical history initially presented with worsening diffuse abdominal tenderness. Computed tomography was significant for a splenic flexure mass and hepatic lesions concerning for metastatic disease. He underwent a colectomy with anastomosis. Postoperative pathology was diagnostic for moderately to well-differentiated adenocarcinoma (T4bN1bM1a). He received adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), but therapy was discontinued due to the development of atrial fibrillation. Additional workup indicated a carcinoembryonic antigen level of 508.2 ng/mL, and mutational analysis found that the tumor was microsatellite instability-high and <iKRAS</i/<iBRAF</i wild-type. He was started on irinotecan with oxaliplatin (IROX), and bevacizumab (14 cycles), developed disease progression, was transitioned to FOLFOX and cetuximab, and then eventually three cycles of pembrolizumab. Following disease progression, he was rechallenged with IROX therapy, as he previously responded well to oxaliplatin-based therapy. The IROX rechallenge provided this patient with a ten-month survival benefit, decreased metastatic burden, and marked improvement in his clinical condition. Rechallenge of previous lines of well-tolerated systemic chemotherapy regimens may be a valuable therapeutic strategy in patients with heavily-treated mCRC.

Positron emission tomography for evaluation of colorectal carcinoma.

Evaluation of patients with known or suspected recurrent colorectal carcinoma is now an accepted indication for FDG PET imaging. FDG PET does not replace imaging modalities such as CT for preoperative anatomic evaluation but is indicated as the initial test for diagnosis and staging of recurrence and for preoperative staging (N and M) of known recurrence that is considered to be resectable. FDG PET imaging is valuable for differentiation of posttreatment changes from recurrent tumor, differentiation of benign from malignant lesions (indeterminate lymph nodes, hepatic and pulmonary lesions), and evaluation of patients with rising tumor markers in the absence of a known source. Addition of FDG PET to the evaluation of these patients reduces overall treatment costs by accurately identifying patients who will and will not benefit from surgical procedures. Although initial staging at the time of diagnosis is often performed during colectomy, FDG PET imaging is recommended for a subgroup of patients at high risk (with elevated CEA levels) and normal CT and for whom surgery can be avoided if FDG PET shows metastases. Screening for recurrence in patients at high risk has also been advocated. FDG PET imaging seems promising for monitoring therapy, but larger studies are necessary.

[A CASE OF ASCENDING COLON CANCER RECURRENCE WITH INTRALUMINAL URETERAL DISSEMINATION MIMICKING PRIMARY URETERAL CANCER, DETECTED DURING INVESTIGATION FOR FEVER].

A 69-year-old woman visited our hospital with a chief complaint of fever. Five years ago, she was diagnosed as ascending colon cancer and received right hemi-colectomy. One year later, local recurrence with right hydronephrosis was detected, and she received chemotherapy -4 cycles of modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab, and 12 cycles of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab- for two years. Local recurrence and right hydronephrosis disappeared on positron emission tomography performed 4 years postoperatively. This time, abdominal computed tomography for investigation of fever showed a relapse of right hydronephrosis and pyonephrosis. Cystoscopy revealed non-papillary tumor from the right ureteral orifice. Pelvic magnetic resonance imaging showed multiple tumors in the right ureter, and the distal lesion projecting into the bladder. After the general condition became well by right nephrostomy for infection control, transurethral resection of bladder tumor was performed. Histological examination of the specimen revealed a metastatic tubular adenocarcinoma (colon origin). Although right nephrectomy was performed for pyonephrosis control, she died of local progression of ascending colon cancer 10 months after first visit. Intraluminal ureteral progression of carcinoma originating from organs other than urinary tract is very rare. To our knowledge, this is the 9th report in the English or Japanese literature. In this case we could not rule out primary ureteral cancer preoperatively, and histological examination revealed intraluminal ureteral dissemination of ascending colon cancer.

Positron emission tomography for the evaluation of patients with colorectal cancer.

Approximately 40% of patients treated with curative intent for colorectal carcinoma eventually recur. In about one third of these patients, the lesion is localized and potentially resectable. Typically, the recurrence is characterized by findings on diagnostic imaging studies and may be accompanied by a rise in the serum carcinoembryonic antigen (CEA) levels. In a few patients, however, the asymptomatic rise in CEA is not accompanied by diagnostic findings on computed tomography (CT). We report a case herein, of a patient with rising CEA, noted 1 year after completion of adjuvant chemotherapy for node-positive colorectal cancer. CT and laparoscopic exploration were nondiagnostic. In order to further evaluate the rise in CEA, positron emission tomography (PET) was performed. PET revealed an area of increased uptake in the right lobe of the liver. Resection of the metastatic liver lesion resulted in a subsequent drop in the CEA levels.

Response to chemotherapy in metastatic colorectal cancer after exposure to oxaliplatin in the adjuvant setting.

Oxaliplatin with 5-fluorouracil (5-FU) and leucovorin (FOLFOX and FLOX) or capecitabine (XELOX) is the standard adjuvant treatment for colonic cancer. In metastatic disease, 5-FU/leucovorin/irinotecan (FOLFIRI) and FOLFOX are equivalent in respect to response rates, progression-free and overall survival. Little data are available to compare their efficacy after exposure to oxaliplatin-containing adjuvant chemotherapy. We carried out a retrospective study of patients who underwent surgery and FOLFOX adjuvant chemotherapy, followed by FOLFIRI or FOLFOX for metastatic disease. Exclusion criteria were: metastatic disease at presentation and no oxaliplatin in adjuvant chemotherapy. The end-point was the overall response rate (ORR) to first-line chemotherapy for metastatic disease after three months, as assessed by computed tomography (CT). A total of 205 patients received FOLFOX as adjuvant treatment for colorectal adenocarcinoma between 2006 and 2010. Metastatic disease was diagnosed later in 32 cases after a median follow-up of three years (range=1-5.5 years). The median time between the beginning of adjuvant chemotherapy and onset of metastatic disease was 1.7 years (range=0.5-5.5 years). Twenty-eight patients were evaluable for effects of treatment: six patients received FOLFOX plus bevacizumab and 22 FOLFIRI plus bevacizumab. The ORR was 17% in the FOLFOX group versus 36% in the FOLFIRI group (p=0.22). This difference was not statistically significant, despite a trend in favor of FOLFIRI. Metastatic disease after exposure to oxaliplatin in the adjuvant setting tends to occur early and can be characterized by partial resistance to this agent. Despite insufficient statistical power, our results suggest that FOLFIRI may result in higher response rates than FOLFOX in this situation. However, oxaliplatin re-challenge can also lead to radiological responses and disease stabilization.

Value of ¹⁸F-FDG PET-CT in surveillance of postoperative colorectal cancer patients with various carcinoembryonic antigen concentrations.

To evaluate the value of positron emission tomography (PET)/computerized tomography (CT) in surveillance of colorectal cancer (CRC) patients with different carcinoembryonic antigen (CEA) concentrations. One hundred and six postoperative CRC patients who had suspected recurrence or metastasis and received fluorodeoxyglucose (FDG) PET/CT within one week were included in this study. The final diagnosis was confirmed by histological examination or clinical follow-up over at least six months. The sensitivity, specificity, and accuracy of FDG PET/CT were 95.2%, 82.6%, and 92.5%, and 94.8%, 81.4% and 92.8%, respectively, in the case- and lesion-based analyses. The sensitivity and accuracy of FDG PET/CT significantly differed from CT in both analyses (χ(2) = 8.186, P = 0.004; χ(2) =6.201, P = 0.013; χ(2) =13.445, P = 0.000; χ(2) =11.194, P = 0.001). In the lesion-based analysis, the sensitivity, specificity, and accuracy of FDG PET/CT in the abnormal CEA group were 97.8%, 82.6%, and 95.6%, compared with 81.3%, 80%, and 80.6% for patients with normal CEA levels. In case-based analysis, the sensitivity, specificity, and accuracy of FDG PET/CT were 97.2%, 77.8%, and 95% in abnormal CEA group. Only in lesion-based analysis, the sensitivity and accuracy of FDG PET/CT in the abnormal CEA group were significantly superior to those in the normal CEA group (χ(2) =6.432, P = 0.011; χ(2) =7.837, P = 0.005). FDG PET/CT changed the management in 45.8% of patients with positive scans. FDG PET/CT showed superior diagnostic value and is an advisable option in surveillance of postoperative CRC patients with a vague diagnosis.