Prediction of surgical resectability in patients with hepatic colorectal metastases.

OBJECTIVE: To evaluate the efficacy of two distinct imaging techniques to predict, before operation, unresectability compared with standard computed tomographic scan (CT). SUMMARY BACKGROUND: Accurate preoperative identification of the number, size, and location of hepatic lesions is crucial in planning hepatic resection for colorectal hepatic metastases. Although infusion-enhanced CT is the standard, its limitations are the imaging of relatively isodense and/or small (< 1 cm) lesions. The increased sensitivity of CT arterial portography (CTAP) may be offset by false-positive results caused by benign lesions and flow artifacts. METHODS: Fifty-eight selected patients considered to be eligible for resection by standard CT had laparotomy. Before operation and in addition to CT, all patients had CT arterial portography and hepatic artery perfusion scintigraphy (HAPS) using radiolabeled macroaggregated albumin. Early studies showed an increased sensitivity for detecting small lesions using the invasive CTAP. Similarly, the HAPS study has detected malignant lesions not observed by standard CT. RESULTS: Of 58 patients having laparotomy, 40 were resectable by either lobectomy (22) or trisegmentectomy (1) and the rest by single or multiple wedge resections. Eighteen patients could not be resected because of combined intra- and extrahepatic disease or the number and location of metastases. Standard CT detected 64% of all lesions (12% of lesions less than 1 cm). Unresectability was accurately predicted by CTAP and HAPS in 16 (88%) and 15 (83%), respectively, of the 18 patients considered ineligible for resection at laparotomy. Of the 40 patients who had resection for possible cure, CTAP and HAPS falsely predicted unresectability in 6 of 40 patients (15%) and in 10 of 40 patients (25%), respectively. The positive predictive value for unresectability of CTAP and HAPS was 73% and 60%, respectively. False-positive lesions after CTAP included hemangiomas, cysts, granulomas, and flow artifacts. False-positive HAPS lesions included patients in whom no tumor was found at surgery but with some identified by intraoperative ultrasound, blind biopsy, and blind resection. CONCLUSIONS: False-positive results by HAPS and CTAP may limit the ability of these tests to accurately predict unresectability before operation and may deny patients the chance for surgical resection. The HAPS study does, however, detect small lesions not seen by CT or CTAP. Standard CT, although less sensitive, followed by surgery and intraoperative ultrasound, does not necessarily preclude patients who could be resected.     

Use of OncoScint scan to assess resectability of hepatic metastases from colorectal cancer.

Patients with limited hepatic metastases from colorectal cancer can potentially be cured by resection. A number of patients deemed resectable by standard imaging procedures are found to have extrahepatic disease at laparotomy and are thus unresectable. A test capable of identifying these patients would assist in better patient selection. OncoScint (Cytogen Corp, Princeton, NJ) scan targets colorectal cancer by interacting with a tumor-associated glycoprotein. Can OncoScint scan be used to reliably identify patients with extrahepatic disease preoperatively? Between February 1996 and August 1998 eight patients with colorectal metastases to the liver were enrolled prospectively. All patients received preoperative OncoScint scan (indium-111) and underwent laparotomy. The laparotomy findings were correlated with the results of OncoScint scan. In four of eight patients (50%) OncoScint scan showed no extrahepatic disease. This was confirmed at laparotomy. All of these patients underwent hepatic resection. One of eight patients (12.5%) had OncoScint findings suggestive of extrahepatic disease pathologically confirmed during laparotomy. Three of eight patients (37.5%) had OncoScint findings of extrahepatic disease not confirmed by laparotomy. All three patients underwent hepatic resection. One of the three patients is still disease free for more than 48 months after hepatic resection. If OncoScint scan had been used to determine resectability this patient with false positive scan would have been denied a potentially curative operation. Because of the unacceptably high false positive rate the study was terminated after eight patients. Because of its high false positive rate (37.5%) OncoScint scan is not a reliable test for the assessment of extrahepatic disease. Other tests need to be developed to accurately stage extrahepatic disease with an acceptably low false positive rate to prevent exclusion of patients who can potentially be cured.     

Hepatic colorectal metastases: methods of improving resectability

Surgery is the best treatment modality for colorectal liver metastases. When initially unresectable, hepatic resection of metastases after downstaging by chemotherapy can provide a hope of long-term survival similar to that of primarily resected patients. Definitions of resectability have evolved with the emerging principle that if metastases can be completely resected regardless of their size and number,resection should be performed as the sole mean of achieving long-term survival.Specific surgical techniques can be combined to improve resectability. If the tumor is considered unresectable, recent developments make possible to render some tumors surgically resectable. Depending on the tumor size, number and location, neoadjuvant treatments, mainly chemotherapy, can be used, followed by resection. Resection may be contraindicated if the residual volume of liver is inadequate to avoid liver failure. This may be changed either by PVE or two-stage hepatectomy, both of which use the natural regenerative capacity of the liver. Local destructive therapies such as cryosurgery and radio-frequency can also be used in conjunction with resection for patients in whom all metastases are not surgically resectable. The present use of these ablative techniques is improving the percentages of unresectable patients considered for surgery. All of the above-described methods can be combined to achieve a surgical strategy that is as curative as possible, increasing the number of patients primarily unresectable, with a long-term survival hope similar to that of primarily resectable patients. To achieve this objective, a close collaboration between oncologists, radiologists, and surgeons is mandatory, with routine re-evaluation of patients for an adequate timing of each treatment.     

Systemic irinotecan and regional floxuridine after hepatic cytoreduction in 185 patients with unresectable colorectal cancer metastases

Background This study evaluated our 7-year experience treating unresectable colorectal cancer (CRC) hepatic metastases refractory to systemic 5-fluorouracil. Methods A total of 185 patients with unresectable 5-fluorouracil-resistant CRC hepatic metastases underwent surgical cytoreduction. Postoperatively patients received either hepatic arterial floxuridine (FUDR) and systemic irinotecan as part of a phase II trial or no further treatment. Results Of the 185 patients undergoing surgical cytoreduction. 71 patients received adjuvant irinotecan/FUDR. There were no appreciable differences in synchronous or metachronous lesions or the median number or size of lesions between treatment groups. At a median follow-up of 20 months, there were fewer recurrences in patients treated with postoperative irinotecan/FUDR compared with untreated patients for both hepatic and extrahepatic recurrences. Progression-free and overall survival were longer for patients who received irinotecan/FUDR compared with patients who did not receive adjuvant therapy. The 2-year survival rate was significantly better for patients receiving adjuvant therapy compared with patients receiving no additional treatment. Predictors of improved survival included a preoperative carcinoembryonic antigen level <100 ng/dl, >30% postoperative reduction in carcinoembryonic antigen level, and adjuvant therapy. Conclusions Combined therapy with irinotecan/FUDR may improve the results of surgical cytoreduction for unresectable CRC hepatic metastases. Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Operative ultrasound establishes resectability of metastases by major hepatic resection

In this study, the utility of intraoperative ultrasound in the surgical management of hepatic colorectal metastases requiring hepatic resection has been demonstrated. The intraoperative ultrasound technique has been described as a method to accurately monitor curative resection of large colorectal metastases requiring anatomical procedures such as right hepatic trisegmentectomy, bisegmentectomy, and hepatic lobectomy. Preoperative analysis of the patients reported utilizing either computed tomography, ultrasound, or magnetic resonance imaging demonstrated very well the extent of tumor but could not define a major anatomical resection along normal tissue planes. In the 3 patients demonstrated, intraoperative ultrasound was able to confirm a normal hepatic parenchymal dissection overlying the extensive tumors and enabled completion of the curative resections. Furthermore, we have described the intraoperative ultrasound criteria for assessment of resectability. These included a definition of the proximity of the major portal and hepatic venous structures, exclusion of simultaneous minimal metastatic disease in the remaining parenchyma, and the distinction between marginal resectability and resectability for cure along the proposed parenchymal dissection plane. We conclude that intraoperative ultrasound is important in the surgical management of metastatic colorectal cancer and can provide for a more complete clinical staging and appropriate selection of patients for curative major hepatic resection.

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Resumen El presente estudio demuestra la utilidad de la ultrasonografía intraoperatoria en la resección quirúrgica de las metástasis hepáticas del cáncer colorrectal. La técnica de ultrasonografía intraoperatoria ha sido descrita como un método que permite la monitoría de la resección curativa de grandes metástasis de cancer colorrectal por medio de procedimientos anatómicos tales como la trisegmentectomía hepática derecha, la bisegmentectomía, y la lobectomía. Aunque el estudio preoperatorio de los pacientes por tomografía computadorizada, ultrasonografía, o imagenología por resonancia magnética demostró muy bien la extensión del tumor, fue posible la definición de las resecciones anatómicas mayores de acuerdo a los pianos tisulares. En los pacientes que aquí se informan, la ultrasonografía intraoperatoria fue capaz de confirmar la presencia de parenquima hepático normal ubicado sobre tumores muy extensos, con lo cual fue posible completar las resecciones curativas. Tambien se describen los criterios ultrasonográficos intraoperatorios, de resectabilidad. Estos incluyen la definición de la proximidad de las estructuras venosas portales y hepáticas principales, la identificación de metástasis minimas en el parenquima residual, y la distinción entre una resección marginal y una disección para curación a lo largo del propuesto piano de disección. Nuestra conclusión es que la ultrasonografía intraoperatoria es importante en el tratamiento quirúrgico del cáncer colorrectal metaásico y que hace posible una más completa definición del estado cliico y una más apropiada selección de los pacientes para resecciones curativas mayores del hígado.

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Résumé Dans cette étude nous avons démontré que l'échographie peropératoire est utile dans le traitement chirurgical des métastases hépatiques d'origine colorectale demandant une résection hépatique majeure. L'échographie peropératoire guide les résections à titre curatif des métastases colorectales comme l'hépatectomie droite élargie, les lobectomies ou les hépatectomies. L'imagerie préopératoire par tomodensitométrie, échographie ou résonance magnétique, même si elle montre extrêment bien l'étendue de la tumeur, ne peut définir les plans de résection utiles pour cette chirurgie. Pour les 3 cas rapportés ici, l'échographie peropératoire a permis de vérifier que la résection passait en zone saine à côté des tumeurs: elle a ainsi permis d'effectuer des résections à visée curative. Nous avons décrit les critères d'échographie peropératoire pour évaluer la résectabilité. Ceux-ci comprennent la proximité de la tumeur et les éléments principaux portes et hépatiques veineux, l'élimination de la possibilté de métastases dans le parenchyme restant, et la distinction entre la résectabilité au plus près et celle à distance permettant de parler de résection à visée curative. Nous concluons que l'échographie peropératoire est très importante dans la tactique thérapeutique des métastases hépatiques d'origine colorectale. Elle complète le bilan clinique et permet de sélectionner les patients susceptibles de bénéficier d'une résection hépatique majeure.

     

胃肠肿瘤根治联合肝移植术治疗晚期胃肠肿瘤并肝脏广泛转移

目的 总结胃肠肿瘤根治联合肝移植治疗晚期胃肠肿瘤并发肝脏多发转移的近期疗效。方法 1例胃癌和2例直肠癌并发肝脏多发转移患者，分别接受胃癌和直肠癌根治、联合原位同种异体肝移植手术，其中1例因肺结核同时行左上肺部分切除术。结果 3例患者无围手术期死亡。随访5-7个月，胃癌患者术后5个月死于肿瘤复发；1例直肠癌并肺结核患者术后7个月死于肝功能衰竭，无肿瘤复发；另1例直肠癌患者已完成3个月化疗，术后半年无复发，肝功能和血常规正常，精神食欲好，已恢复工作。结论 胃肠肿瘤根治联合肝移植为部分晚期肿瘤患者提供了生存的希望，远期效果有待进一步观察。     

Effect of risk factors in colorectal cancer hepatic metastases

The risk factors, influencing late results of surgical treatment, were analyzed in 69 patients, suffering a colorectal cancer hepatic metastases. The significance of clinico-morphological (the metastases maximal size, quantity, localization, the tumor grade, the hepatic affection synchronicity with primary tumor appearance, the hepatoduodenal ligament lymph nodes affection, microvascular invasion, the resection edges) and molecular (CK 20, beta-cat, Ki 67, Muc 2 and 5A) factors of prognosis was studied up. The hepatic resection variant was chosen, depending on the largest metastasis size present, the tumor nodes quantity and localization, the extrahepatic foci present, the lymph nodes affection and hepatic functional reserve secured. Basing on estimation of the level and type of expression for molecular factors there was determined correlation with the tumor recurrence rate. High degree correlation was established for the CK 20, beta-cat, Ki 67 expression and the recurrence rate, but it was not true for the Muc 2 and 5A expression. One, three and five years have survived 85, 50 and 31% of patients accordingly, and without recurrences--68, 27 and 14% accordingly. No one of clinico-morphological factors, but the metastasis grade, have had influenced the disease prognosis.     

Effect of hepatic artery chemotherapy on survival of patients with hepatic metastases from colorectal carcinoma treated with cryotherapy

Thirty-eight patients with unresectable multiple liver metastases from colorectal carcinoma were treated with either hepatic artery chemotherapy (HAC) and cryotherapy (n=27) or cryotherapy alone (n=11). Follow-up survival data were summarized using Cox regression. Allowing for the effect of the pathology of the primary tumor and the preoperative carcinoembryonic antigen (CEA) level, those patients who did not receive HAC after cytoreduction were three times as likely to die as those given HAC (RR 3.3, 95%; CI 1.2–9.3). The estimated median survival of patients treated with cryotherapy alone was 245 days, whereas for those given more than 3 months of HAC plus cytoreduction therapy it was 570 days. It is recommended that all patients who receive cryotherapy for multiple liver metastases from colorectal rectal carcinoma be given subsequent hepatic artery chemotherapy.

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Resumen En el presente estudio, 38 pacientes con metástasis hepáticas múltiples y no resecables de carcinoma colo-rectal fueron tratados con quimioterapia administrada en la arteria hepática (HAC) y crioterapia (n=27) o crioterapia sola (n=11). Los datos del seguimiento fueron resumidos según el método de regresión de Cox. Teniendo en cuenta el efecto de la patología del tumor primario y el nivel preoperatorio de antígeno carcino-embrionario, se halló que aquellos pacientes que no recibieron HAC luego de la citorreducción tuvieron una probabilidad de muerte 3 veces mayor que los que recibieron HAC (RR 3.3, 95% CI 1.2 a 9.3). La sobrevida media estimada de los pacientes tratados con crioterapia sola fue de 245 días, en tanto que aquellos que recibieron HAC por tres meses y terapia de citorreducción fue de 570 días. Se recomienda que todos los pacientes que reciben crioterapia para metástasis hepáticas múltiples de carcinoma colo-rectal reciban luego quimioterapia por vía de la arteria hepática.

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Résumé Trente-huit patients ayant des métastases hépatiques multiples non reséquables d'origine colorectale ont été traités soit par chimiothérapie par voie artérielle (CVA) associée à la cryothérapie (n=27) soit par cryothérapie seule (n=11). Les survies ont été analysées selon la méthode d'analyse du Modèle de Cox. En tenant compte de l'effet de la pathologie de la tumeur primitive et du niveau préopératoire de l'ACE, les patients n'ayant pas eu de de décéder que ceux qui en ont eu (RR 3.3, 95% IC 12 à 9.3). L'estimation de la survie médiane des patients traités par la cytoréduction seule a été de 245 jours, alors que celle des patients traités par les deux avec une CVA d'au moins trois mois, a été de 570 jours. On recommande que tous les patients ayant des métastases multiples du foie à partir des cancers colorectaux aient une CVA par la suite.

     

Strategies to increase the resectability of liver metastases from colorectal cancer

Liver resection can provide long-term survival and cure for patients with colorectal liver metastases but is feasible in only 15-25% of patients. In the last few years several major developments have contributed to increase this resectability rate. Neo-adjuvant chemotherapy can provide response rates as high as 50%, allowing surgery in about 10-15% of patients initially deemed unresectable. Patients requiring extensive liver resections with an anticipated small residual liver volume can undergo portal vein embolization to reduce the risk of postoperative liver failure by inducing hypertrophy of the remnant liver. Extensive bilobar disease can be treated by two-stage hepatectomy, with an interval to allow liver regeneration. Ablation techniques can be combined with hepatic resection to reduce local recurrence from incomplete surgical resection margins or to destroy contralateral tumor deposits. Finally, for patients with tumors involving the inferior vena cava or the hepatic veins, in which conventional resection is not feasible, in situ hypothermia or bench resection with reimplantation are suitable for very selected patients. Downstaging strategies may increase the resectability rate of colorectal liver metastases by over 20%.     

结肠直肠癌肝转移灶手术切缘距离及其对预后的影响

结肠直肠癌是最常见的恶性肿瘤之一。在美国,结肠直肠癌居所有肿瘤死亡原因的第二三位。而肝脏是结肠直肠癌最常见的转移部位．25％的结肠直肠癌病人在剖腹探查时发现伴有同时性肝转移,另有50％的病人在切除结肠直肠癌原发肿瘤后发生异时性肝脏转移。手术切除肝转移灶是目前可能治愈结肠直肠癌肝转移的唯一手段阳,而手术切缘状况是影响结肠直肠癌肝转移病人手术治疗预后的重要因素之一。因此．本文就结肠直肠癌肝转移手术切缘的研究综述如下。     

Effect of hepatic cryotherapy on serum CEA concentration in patients with multiple inoperable hepatic metastases from colorectal cancer

Eleven patients with multiple hepatic metastases from colorectal cancer, all judged inoperable, were treated by cryotherapy using a probe through which liquid nitrogen was circulated using a single freeze thaw sequence. Localization of metastases, positioning of the probe and monitoring of ice ball size was by intra-operative ultrasound. Serum carcinoembryonic antigen (CEA) was measured in these patients: there was a postoperative fall in all but two. In all but one, there has been a subsequent rise. Speed and degree of rise of CEA varied between patients. Serial CEA may be an effective means of monitoring the effect of hepatic cryotherapy.     

Repeat hepatic resection for recurrent colorectal liver metastases is associated with favourable long-term survival

BACKGROUND: The management of patients with recurrent colorectal liver metastases (RCLM) remains controversial. This study aimed to determine whether repeat liver resection for RCLM could be performed with acceptable morbidity, mortality and long-term survival. METHODS: Of 1121 consecutive liver resections performed and prospectively analysed between 1987 and 2005, 852 'curative' resections were performed on patients with colorectal liver metastases. Single liver resection was performed in 718 patients, and 71 repeat hepatic resections for RCLM were performed in 66 patients. RESULTS: There were no postoperative deaths following repeat hepatic resection compared with a postoperative mortality rate of 1.4 per cent after single hepatic resection. Postoperative morbidity was comparable following single and repeat hepatectomy (26.1 versus 18 per cent; P = 0.172), although median blood loss was greater during repeat resection (450 versus 350 ml; P = 0.006). Actuarial 1-, 3- and 5-year survival rates were 94, 68 and 44 per cent after repeat hepatic resection for RCLM, compared with 89.3, 51.7 and 29.5 per cent respectively following single hepatectomy. CONCLUSION: The beneficial outcomes observed after repeat liver resection in selected patients with RCLM confirm the experience of others and support its status as the preferred choice of treatment for such patients.     

Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases

BACKGROUND: Surgical resection of isolated hepatic or pulmonary colorectal metastases prolongs survival in selected patients. But the benefits of resection and appropriate selection criteria in patients who develop both hepatic and pulmonary metastases are ill defined. STUDY DESIGN: Data were prospectively collected from 131 patients with colorectal cancer who underwent resection of both hepatic and pulmonary metastases over a 20-year period. Median followup was 6.6 years from the time of resection of the primary tumor. Patient, treatment, and outcomes variables were analyzed using log-rank, Cox regression, and Kaplan-Meier methods. RESULTS: The site of first metastasis was the liver in 65% of patients, the lung in 11%, and both simultaneously in 24%. Multiple hepatic metastases were present in 51% of patients, and multiple pulmonary metastases were found in 48%. Hepatic lobectomy or trisegmentectomy was required in 61% of patients; most lung metastases (80%) were treated with wedge excisions. Median survival rates from resection of the primary disease, first site of metastasis, and second site of metastasis were 6.9, 5.0, and 3.3 years, respectively. After resection of disease at the second site of metastasis, the 1-, 3-, 5-, and 10-year disease-specific survival rates were 91%, 55%, 31%, and 19%, respectively. An analysis of prognostic factors revealed that survival was significantly longer when the disease-free interval between the development of the first and second sites of metastases exceeded 1 year, in patients with a single liver metastasis, and in patients younger than 55 years old. CONCLUSIONS: Surgical resection of both hepatic and pulmonary colorectal metastases is associated with prolonged survival in selected patients. Patients with a longer disease-free interval between metastases and those with single liver lesions had the best outcomes.     

Long-term results of treating hepatic colorectal metastases with cryosurgery

BACKGROUND: The purpose of this study was to determine the long-term efficacy of cryosurgery as an adjunct to hepatic resection in patients with colorectal liver metastases not amenable to resection alone. METHODS: Thirty patients met the following inclusion criteria: metastases confined to the liver and judged irresectable, ten or fewer metastases, cryosurgery alone or in combination with hepatic resection allowed tumour clearance. RESULTS: Median follow-up was 26 (range 9--73) months. Overall 1- and 2-year survival rates were 76 and 61 per cent respectively. Median survival was 32 months. Disease-free survival at 1 year was 35 per cent, at 2 years 7 per cent. Six patients developed recurrence at the site of cryosurgery; given that the total number of cryosurgery-treated lesions was 69 the local recurrence rate was 9 per cent. CONCLUSION: In patients with colorectal liver metastases, local ablative techniques can be used as an effective adjunct to hepatic resection to obtain tumour clearance.