Treatment of locoregional recurrence after intentional curative resection of pancreatic cancer.

In order to analyze the results of treatment of patients with locoregional recurrence after intentional curative resection of pancreatic cancer, a retrospective study was performed. During the period 1978-1988, 108 patients underwent an intentional curative resection fo the pancreas. In 34 patients locoregional recurrence occurred, all within a period of three years (cumulative recurrence rate 56%). Sixty-eight percent of the patients presented with upper abdominal pain, and 62% with weight loss. Survival was significantly better (p = 0.02) in the group of 18 patients without distant metastases (1-year survival 22%) than in the 16 patients with distant metastases (1-year survival 0%). Five patients without proven distant metastases were treated by resection or chemotherapy. The mean survival was 33 months (range 6-74) in the treated group, and 4 months (0.4-7 months) in the untreated group, p = 0.002. In this retrospective study the longest survival was seen after radical resection of locoregional tumor recurrence. We therefore recommend that patients with locoregional recurrence without distant metastases after intentional curative resection of pancreatic cancer be treated.     

Multimodale Therapie des kolorektalen Karzinoms

Adjuvant chemotherapy for resected stage III colon cancer is indicated for all patients, including elderly patients >70 years. In general, adjuvant oxaliplatin-fluoropyrimidine chemotherapy should be started within 6 weeks after tumor resection and should be given for a period of 6 months. However, patients aged >70 should receive fluoropyrimidine mono-chemotherapy. This mono-therapy, but not an oxaliplatin-based combination, can also be considered for patients with standard risk stage II tumors without microsatellite instability. In stage II patients with a high risk constellation adjuvant oxaliplatin-fluoropyrimidine combination therapy should be considered. Patients with stage II and III rectal cancer require neoadjuvant radiochemotherapy with fluoropyrimidine followed by adjuvant fluoropyrimidine treatment. There is no role for the use of VEGF- or EGFR-antibodies in the adjuvant therapy of colon cancer or in neoadjuvant therapy of rectal cancer. The prognosis of patients with primary resectable colorectal liver metastases may be improved by adjuvant or perioperative chemotherapy, while neoadjuvant systemic chemotherapy frequently facilitates potential curative resection of initially non-resectable liver metastases.     

Chemotherapy for pancreatic cancer]

Chemotherapy is expected to play an important role in the treatment of pancreatic cancer because most of pancreatic cancers are being discovered at locally advanced or metastatic stages and recurrence rate is high even after the curative resection. Gemcitabine is a key agent for the first-line therapy of advanced pancreatic cancer. It can enhance the quality of life and prolong the survival of patients. Combination of erlotinib or capecitabine with gemcitabine showed a marginal survival benefit over single-agent gemcitabine. If patient's performance state is good, gemcitabine-based platinum combination therapy showed overall survival benefit compared with gemcitabine monothrapy. If the first-line palliative chemotherapy fails, 5-FU, capcitabine, or tegafur with or without combination can be used as the second-line agents. Adjuvant chemotherapy using 5-FU or gemcitabine after curative resection has overall survival benefit. However, neoadjuvant chemotherapy has not been proven to be effective in the treatment of pancreatic cancer.     

Xelox (capecitabine plus oxaliplatin) as neoadjuvant chemotherapy of unresectable liver metastases in colorectal cancer patients

Complete resection of liver metastasis may provide long term survival in patients with colorectal cancer. Increased number of studies on successful resection after neoadjuvant chemotherapy with initially unresectable liver metastasis has been reported. We evaluated retrospectively the results of 35 patients with unresectable liver only metastases from colorectal cancer treated with capecitabine plus oxaliplatin combination (XELOX). Treatment consisted of IV oxaliplatin 130 mg/m2 day 1 and oral capecitabine 1000 mg/m2 day twice daily on days 1 to 14 followed by 7 days of rest repeated every 3 weeks. After chemotherapy, 13 (37, 2 %) patients showed partial clinical response. Among them, 7 patients were considered suitable for surgery but 2 patients refused the surgery. While one of 5 patients had unresectable disease at surgery, the remaining 4 patients (11, 4 %) had a complete resection. There was one postoperative mortality due to sepsis within 2 months after surgery. Our data suggests that XELOX regimen seems to be useful in unresectable liver only metastases from colorectal cancer because of its activity, feasibility and tolerability. Further studies of XELOX in combination with bevacizumab and/ or cetuximab are warranted in this setting.     

Neoadjuvant and adjuvant therapy in relation to surgery for colorectal liver metastases

Liver resection is associated with prolonged survival in patients with colorectal liver metastases. At diagnosis, 15-20% of patients have resectable colorectal liver metastases whereas other patients have too advanced disease to enable surgical treatment and receive chemotherapy. In patients undergoing resection of colorectal liver metastases, disease relapse occurs in up to 70%. Therefore, a combined approach including preoperative or postoperative chemotherapy or both has been tested to improve outcome after surgery. In patients with unresectable colorectal liver metastases, chemotherapy is initially the sole treatment option. The considerable improvement of the efficacy of anticancer agents has contributed to increase the response rate in patients with advanced colorectal cancer. In case of major response to chemotherapy, surgery with curative intent can be offered to patients with initially unresectable liver metastases.     

Surgery for local recurrence of rectal carcinoma

PURPOSE: This study was designed to evaluate results, especially mortality and morbidity, of surgical resection with curative intent for patients with a local recurrence of rectal cancer, in combination with radiotherapy. METHODS: Consecutive medical records of 163 patients with local recurrence of rectal carcinoma after previous “curative” therapy for primary rectal cancer were reviewed. Although 35 patients had an exploratory laparotomy, only 27 had local recurrence amendable to resection (6 irresectable locoregional recurrences and 2 distant metastases found at laparotomy). Twenty-one patients received radiotherapy. There was no perioperative mortality. Median follow-up time was 42 (range, 22–92) months. RESULTS: Local rerecurrence occurred in 16 (59 percent) patients. Ten patients are alive, of whom nine have good local control. Estimated five-year survival (Kaplan-Meier) is 20 percent. Survival was significantly better in patients without a second recurrence, but radicality of the resection was not influential. Good local control could be obtained in 12 (44 percent) patients, and 1 patient is living with symptoms. CONCLUSIONS: In selected patients with local recurrence of rectal carcinoma, reoperation with irradiation may result in good palliation and possibly cure.     

The multidisciplinary management of gastrointestinal cancer. Multimodal treatment of gastric cancer

Although radical surgical R0 resections are the basis of cure for gastric cancer, surgery alone only provides long-term survival in 20-30% of patients with advanced-stage disease. Thus, in Western and European countries, advanced gastric cancer has a high risk of recurrence and metachronous metastases. Very recently, multimodal strategies combining different neoadjuvant and/or adjuvant protocols have improved the prognosis of gastric cancer when combined with surgery with curative intent. As used in palliative regimens, the combination of cisplatin with intravenous or oral fluoropyrimidines has been the integral component of such (neo)adjuvant strategies. However, the cytotoxic agents docetaxel, oxaliplatin and irinotecan and new targeted biologicals such as cetuximab, bevacizumab or panitumumab are currently under investigation, with or without irradiation, in multimodal treatment regimens. These studies may further increase R0 resection rates, and prolong disease-free and overall survival times in the treatment of advanced gastric cancer. This article reviews the most relevant literature on multimodal treatment of gastric cancer, and discusses future strategies to improve locoregional failures.     

Complete resection of unresectable liver metastases from colorectal cancer without deterioration of liver function after cetuximab and irinotecan: two case reports

Complete resection for colorectal metastases is the only treatment that can provide long-term survival and may lead to cure. Recent reports have shown that liver resection following systemic chemotherapy in patients with initially unresectable metastases from colorectal cancer may also result in a good long-term survival, and rescue surgery after chemotherapy has become a strategy of choice. A 29-year-old male and a 35-year-old female with unresectable liver metastases from colorectal cancer underwent complete resection after administration of third-line combination therapy of cetuximab and irinotecan. Although systemic chemotherapy may decrease liver function, which may make liver resection unfeasible, in the two cases reported, liver function did not deteriorate after cetuximab plus irinotecan. The indocyanine green retention rate at 15 minutes, which is useful in deciding the safe limit of hepatectomy, was optimal after the administration of cetuximab plus irinotecan in both patients. Cetuximab plus irinotecan may be beneficial as neoadjuvant chemotherapy for metastatic colorectal cancer, not only because of its oncological efficacy but also for preservation of liver function.     

Current preventive treatment for recurrence after curative hepatectomy for liver metastases of colorectal carcinoma： A literature review of randomized control trials

To review the preventive approaches for recurrence after curative resection of hepatic metastases from colorectal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy, systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in post-hepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and disease free survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conducted to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy. Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.     

Chirurgische Therapie des hepatozellulären Karzinoms

Surgical treatment with complete resection of the hepatocellular carcinoma and liver transplantation can lead to a long term cure. If needed both surgical approaches can be incorporated into a neoadjuvant concept. In certain cases locoregional tumor treatment with curative intent can establish tumor control. Patients with established diagnosis are assigned to the corresponding surgical curative, neoadjuvant or palliative therapeutic approach according to the tumor stage and degree of parenchymal liver damage. The individual resection requirements to achieve tumor control and the acceptable limit of remnant liver volume to maintain liver function, define the individual feasibility of liver resection. For this reason sequence and choice of the therapeutic measures are determined by the extent of chronic functional impairment of the liver.     

Management of borderline and locally advanced pancreatic cancer: Where do we stand?

Many patients with pancreas cancer present with locally advanced pancreatic cancer (LAPC). The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound, axial imaging with computed tomography and magnetic resonance imaging, and diagnostic laparoscopy. The definition of resectability has historically been vague, as there is considerable debate and controversy as to the definition of LAPC. For the patient with LAPC, there is some level of involvement of the surrounding vascular structures, which include the superior mesenteric artery, celiac axis, hepatic artery, superior mesenteric vein, or portal vein. When feasible, most surgeons would recommend possible surgical resection for patients with borderline LAPC, with the goal of an R0 resection. For initially unresectable LAPC, neoadjuvant should be strongly considered. Specifically, these patients should be offered neoadjuvant therapy, and the tumor should be assessed for possible response and eventual resection. The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad, ranging from 3%-79%. The different modalities of neoadjuvant therapy include single or multi-agent chemotherapy combined with radiation, chemotherapy alone, and chemotherapy followed by chemotherapy with radiation. This review focuses on patients with LAPC and addresses recent advances and controversies in the field.     

Rectal excision and colonic pouch-anal anastomosis for rectal cancer

PURPOSE: Preservation of the anal sphincter is now accepted as a primary aim in surgical treatment of rectal cancer. The use of colonic J-pouch-anal anastomosis after complete rectal excision is one method that permits retention of continence without compromising oncologic principles. This study aimed to assess carcinologic results of rectal excision followed by colonic J-pouch anal anastomosis, with particular reference to rate of locoregional recurrence. METHOD: From 1984 to 1990 complete rectal excision and colonic pouch-anal anastomosis were performed in 167 patients for cancer of the middle or low rectum. A total of 154 patients were followed for this study for a minimum of five years, with evaluation of the frequency of locoregional recurrence. RESULTS: Sixty-five patients died during the period of surveillance, giving a five-year survival rate of 68.8 percent. Twenty patients (13 percent) presented with locoregional recurrence at an average of 31 months after surgery. In 11 cases (7 percent) the local recurrence was not associated with metastatic disease, and six of these patients underwent further curative surgery. CONCLUSIONS: These results confirm that coloanal anastomosis after complete rectal excision is a valuable option in the surgical treatment of rectal cancer and is accompanied by a frequency of isolated locoregional recurrence of less than 7 percent, of which half underwent surgical resection with curative intent.Presented at Journées Francophones de Pathologie Digestive, Lille, France, March 23 to 27, 1996.     

Neoadjuvant treatment strategies for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC) is the second most common primary liver malignancy and is increasing in incidence. Long-term outcomes are optimized when patients undergo margin-negative resection followed by adjuvant chemotherapy. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Furthermore, recurrence rates are high even among patients who undergo surgical resection. The delivery of systemic and/or liver-directed therapies prior to surgery may increase the proportion of patients who are eligible for surgery and reduce recurrence rates by prioritizing early systemic therapy for this aggressive cancer. Nevertheless, the available evidence for neoadjuvant therapy in ICC is currently limited yet recent advances in liver directed therapies, chemotherapy regimens, and targeted therapies have generated increasing interest its role. In this article, we review the rationale for, current evidence for, and ongoing research efforts in the use of neoadjuvant therapy for ICC.     

Hepatocellular carcinoma: locoregional and targeted therapies

HCC is a leading cause of morbidity and mortality worldwide. Advances in cancer screening and surveillance have allowed for earlier detection of tumors, affording greater treatment potential. The advent of locoregional therapies has generated greater treatment options for patients with HCC. Either alone or in combination as an adjuvant or neoadjuvant therapy, these novel approaches continue to hold promise for improving morbidity and/or mortality of patients with HCC. The emergence of systemic molecular targeted therapies increases the role of translational science. Whereas surgical resection and transplantation conventionally form the cornerstone of curative approaches, the advancement of locoregional therapies holds great promise in adding to the curative armamentarium.     

Low toxic neoadjuvant cisplatin, 5-fluorouracil and folinic acid in locally advanced gastric cancer yields high R-0 resection rate

Purpose Neoadjuvant chemotherapy in locally advanced gastric cancer is effective, but is often associated with severe side effects, including fatal outcome. This study evaluates a combination of cisplatin, folinic acid and 5-fluorouracil (PLF) in terms of efficacy (R-0 resection rate) and toxicity.Methods Twenty-five patients with locally advanced gastric cancer who after extensive staging were deemed not suitable for curative resection underwent neoadjuvant chemotherapy. Three or four cycles of cisplatin (50 mg/m² days 1 and 15), folinic acid (200 mg/m² days 1, 8, 15 and 22), and 5-fluorouracil (2,000 mg/m² days 1, 8, 15 and 22) were administered. Cases with progressive disease were taken off the study. Two weeks after finishing chemotherapy resection was performed and all patients were enrolled in a structured follow-up.Results Of the patients, 22/25 finished chemotherapy and 20 of those underwent laparotomy. In 13/25 patients (52%) a R-0 resection and in three cases a R-1 resection were achieved. Four patients stayed irresectable. During 76 completed cycles of chemotherapy we observed five cases of WHO grade-III toxicity and no grade-IV toxicity.Conclusions The presented PLF protocol yields R-0 resection rates comparable to protocols like EAP (etoposide, adriamycin, platinum), but with a better safety profile allowing administration in an outpatient setting. Our study supports PLF as a reference neoadjuvant treatment for gastric cancer even outside of clinical studies.     

Sequential endoscopic ultrasound identifies predictive variables for relapse-free follow-up after neoadjuvant chemotherapy in gastric cancer

Background: The accuracy of endosonographic tumor staging after neoadjuvant therapy is less reliable than in primary staging. Therefore, the value of sequential endosonographic examinations after neaodjuvant chemotherapy in gastro-esophageal cancer is discussed controversially. Previous data suggest, that endoscopic ultrasound (EUS) after neoadjuvant treatment using other variables than classic uTN-criteria may identify patients with a better prognosis.

Methods: In 67 patients with locally advanced gastric cancer treated in curative intent, we performed EUS before and after neoadjuvant chemotherapy. Endosonographic yTN-stage was compared to pathohistological yTN-stage after curative resection. The uTN-stage, yuTN-stage, maximal tumor thickness and maximal lymph node diameter as well as the shift of these variables after neoadjuvant therapy were analyzed for their usefulness to predict recurrence-free follow-up.

Results: Accuracy of EUS for yTN-staging after neoadjuvant therapy was poor, especially in lower tumor stages. However, three heavily correlated variables analyzed by sequential EUS could be used for the prediction of prognosis: low endosonographic tumor stage (yuT0–2) after neoadjuvant chemotherapy, a decrease of two or more steps in uT-stage and a maximal tumor thickness of <15?mm after chemotherapy were significantly associated with recurrence-free follow-up. Endosonographic T-stage before neoadjuvant therapy, as well as lymph node variables before or after chemotherapy, were of no predictive value.

Conclusion: In spite of poor concordance between endosonographic and pathohistological TN-stage after neoadjuvant treatment, sequential EUS, performed before and after neoadjuvant therapy, possibly identify patients at risk for tumor relapse after multimodal treatment in gastric cancer. This finding should be validated in a larger patient cohort.     

Recurrence patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years

BACKGROUND/AIMS: To investigate the recurrence patterns and interval from initial surgery in patients with curatively resected colorectal cancer followed for a minimum of 10 years. METHODOLOGY: We retrospectively reviewed 418 patients who had undergone curative resection for colon cancer (n = 246) or rectal cancer (n = 169). Follow-up periods ranged from 10 to 23 years. Main outcome measures were interval until recurrence, site of first recurrence, and influence of adjuvant chemotherapy. RESULTS: 26 (6%) had been lost to follow-up by 10 years and 143 (34%) had died. The most common site of recurrence was liver in colon cancer and locoregional in rectal cancer. The cumulative recurrence rate in colon cancer was 100% at 4 years. In rectal cancer, it was 89% at 5 years, 98% at 7 years and 100% at 10 years. The interval until recurrence was longer in rectal cancer (26.0 +/- 24.2 months) than in colon cancer (17.1 +/- 11.0 months) (p = 0.03). It was also longer in patients receiving than in those not receiving adjuvant chemotherapy (p < 0.01). The interval until lung metastasis was longer than that until liver metastasis in colon cancer (p = 0.04), and longer than that until locoregional recurrence in rectal cancer (p = 0.03). The interval until recurrence in the colon cancer was shorter for stage III than for stage II (p = 0.02). CONCLUSIONS: Surveillance for recurrences, particularly for relapses in the liver and lung, should be performed for at least 4 years in colon cancer patients. Patients with rectal cancer should be followed for a longer period than those with colon cancer, focusing on locoregional, liver and lung recurrence. It is particularly noteworthy that adjuvant chemotherapy may prolong the interval until recurrence and the interval until lung metastasis is relatively longer.     

Distant failure after treatment of postoperative locoregional recurrence of non-small cell lung cancer

BACKGROUND: The standard treatment for patients with locoregional recurrence of non-small cell lung cancer (NSCLC) after complete resection has not been established. The aim of this study was to evaluate clinicopathologic characteristics, type of locoregional recurrence, pattern of subsequent failure, and survival after the recurrence. METHODS: Of 743 patients undergoing pulmonary resection for NSCLC in the National Cancer Center Hospital between 1990 and 1995, we retrospectively reviewed the medical charts of the 43 patients (5.8 %) found to have locoregional recurrence without distant metastasis or pleural or pericardial involvement. RESULTS: The median time to locoregional recurrence was 13.6 months (range: 1.6 - 85.8 months). The most frequent site of recurrence was the mediastinal nodes in 21 of 43 patients (49 %). 33 patients (77 %) received further treatment for the recurrence: thoracic irradiation in 26, surgery in two, systemic chemotherapy in two, and a combination of the above in 3 patients. Subsequent distant failure was detected in 26 (68 %) of the 38 patients assessable for the analysis of failure pattern: lung in 11, brain in 6, bone in 5, and others in 13. The median interval from the recurrence to distant failure was 8.4 months (range: 1.7-56.4 months). The median survival time after diagnosis of the locoregional recurrence was 10.5 months (range: 0-74.0 months). A multivariate analysis showed that local therapy for the locoregional recurrence had no significant impact on postrecurrent survival or distant failure-free survival. CONCLUSIONS: Many patients with postoperative locoregional recurrence developed distant metastases early after the first recurrence. Systemic chemotherapy in addition to local therapy may be of benefit in this population.     

A national strategic change in treatment policy for rectal cancer--implementation of total mesorectal excision as routine treatment in Norway. A national audit

INTRODUCTION: Rectal cancer surgery has been characterized by a high incidence of local recurrence, an occurrence which influences survival negatively. In Norway there was a growing recognition that local recurrence rates were related to surgeon performance and that surgeons applying a standardized surgical technique in the form of total mesorectal excision could achieve better results. This contrasts with the prevailing argument voiced by many opinion leaders that local recurrence rates and possibly survival rates can only be improved by adjuvant or neoadjuvant treatment strategies. The Norwegian Rectal Cancer Project—initiated in 1993—aimed at improving the outcome of patients with rectal cancer by implementing total mesorectal excision as the standard rectal resection technique. METHODS: This observational national cohort study covers all new patients (3,319) with rectal cancer from a population of 4.5 million treated between November 1993 and August 1997. The main outcome measures were local recurrence, survival, and postoperative mortality and morbidity rates. The technique of total mesorectal excision was compared with conventional surgery. RESULTS: The proportion of patients undergoing total mesorectal excision was 78 percent in 1994, increasing to 92 percent in 1997. The observed local recurrence rate for patients undergoing a curative resection was 6 percent in the group treated by total mesorectal excision and 12 percent in the conventional surgery group. Four-year survival rate was 73 percent after total mesorectal excision and 60 percent after conventional surgery. Postoperative mortality rate was 3 percent and the anastomotic dehiscence rate was 10 percent. Radiotherapy was given to 5 percent and chemotherapy to 3 percent of the patients in the curative resection group. CONCLUSION: A refinement of the surgical resection technique for rectal cancer can be achieved on a national level, the technique of total mesorectal excision can be widely distributed, and surgery alone can give good results.     

Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer

Background:

Borderline resectable pancreatic cancers are technically amenable to surgical resection, but are associated with increased risk of locoregional recurrence. Patients with these tumours may be treated with neoadjuvant therapy in an attempt to improve margin-negative resection rates.

Methods:

The University of Cincinnati Pancreatic Cancer Database was retrospectively reviewed. Borderline resectable disease was defined by the following radiographic criteria: (i) short segment occlusion of the superior mesenteric vein (SMV), portal vein (PV) or SMV/PV confluence; (ii) short segment hepatic artery encasement, or (iii) superior mesenteric artery/coeliac artery abutment of <180 degrees. Patients with resectable disease who had questionable metastatic disease or poor performance status were also included.

Results:

Twenty-nine patients met the criteria. Of these, 26 underwent a full course of neoadjuvant therapy. Twelve (46%) underwent surgical resection and 14 had tumour progression or were deemed unresectable at laparotomy. The most common neoadjuvant therapy regimen was gemcitabine-based chemotherapy alone (58%). Of those undergoing surgery, 67% had margin-negative (R0) resections and 42% required venous resection. Median survival was 15.5 months for unresected patients and 23.3 months for resected patients.

Discussion:

Borderline resectable pancreatic tumours can be treated neoadjuvantly, resulting in margin-negative resection and survival rates similar to those in initially resectable disease.