Successful outcome after combined chemotherapeutic and surgical management in a case of esophageal cancer with breast and brain relapse

INTRODUCTION Esophageal cancer (EC) is a highly lethal disease, with an estimated annual incidence of 14 550 new cases and 13 770 related deaths in 2006 in the USA[1]. Approximately 50% of patients present with metastatic disease and most patients with lo…     

Chemotherapy in breast cancer patients with brain metastases: have new chemotherapic agents changed the clinical outcome?

Brain metastasis occurs in 15-40% of cancer patients and is present in approximately 10-16% of patients with metastatic breast disease. However, little is known about prognostic factors enabling the early identification of breast cancer patients at risk of CNS metastases. Therapy for brain metastases should be based on several parameters, such as the assessment of prognostic variables, the extent of neurological and systemic disease, and its chemo-sensitivity to previously administered chemotherapy treatments. In view of the known close correlation between metastatic and primary tumor chemosensitivity, the type of chemotherapy chosen should depend more on the tumor histology than on the cerebral distribution of the single drug. More recent drugs with a high impact on the clinical outcome of metastatic breast cancer patients, such as taxanes or trastuzumab, play only a limited role in the treatment of brain metastases.     

Chemotherapy in breast cancer patients with brain metastases: Have new chemotherapic agents changed the clinical outcome?

Brain metastasis occurs in 15–40% of cancer patients and is present in approximately 10–16% of patients with metastatic breast disease. However, little is known about prognostic factors enabling the early identification of breast cancer patients at risk of CNS metastases. Therapy for brain metastases should be based on several parameters, such as the assessment of prognostic variables, the extent of neurological and systemic disease, and its chemo-sensitivity to previously administered chemotherapy treatments. In view of the known close correlation between metastatic and primary tumor chemosensitivity, the type of chemotherapy chosen should depend more on the tumor histology than on the cerebral distribution of the single drug. More recent drugs with a high impact on the clinical outcome of metastatic breast cancer patients, such as taxanes or trastuzumab, play only a limited role in the treatment of brain metastases.     

Neoadjuvant therapy for resectable esophageal cancer

BACKGROUND: Surgical excision remains the only therapeutic approach with curative potential in patients with localized esophageal cancer. Due to the presence of lymph node metastases upon diagnosis in a large percentage of patients with locally advanced tumors and/or the presence of considerable co-morbidity, only a limited number of patients are amenable to surgery. These facts have prompted us to evaluate approaches including perioperative therapy modalities. METHODS: By means of a computer-supported search (MEDLINE, ASCO Proceedings) as well as a manual literature search, randomized clinical trials and meta-analyses evaluating preoperative therapy plus surgery in patients with resectable esophageal cancer were identified. RESULTS: Twenty-three randomized clinical studies and five meta-analyses were identified. Interpretation--especially of the older studies--however, is hampered by the lack of a stringent application of modern examination techniques allowing for exact specification of tumor stage (resectable/locally advanced) as well as the inclusion of patients with different histological entities (squamous cell/adenocarcinoma), different surgical techniques and the low number of patients. There were no significant differences for the following perioperative therapy modalities regarding tumor-related mortality: preoperative radiotherapy versus postoperative radiotherapy, preoperative and postoperative radiotherapy versus postoperative radiotherapy (higher mortality in preoperative and postoperative radiotherapy arm), preoperative radiotherapy versus surgery, preoperative chemotherapy versus surgery, preoperative and postoperative chemotherapy versus surgery. In terms of 3-year mortality, statistically significant differences could be found for the following therapy modalities: preoperative radiochemotherapy versus surgery (preoperative therapy superior), preoperative chemotherapy versus preoperative radiotherapy (preoperative radiotherapy superior). CONCLUSION: Judging from these data, no clear recommendation for a standard multimodality approach outside clinical studies can be given for patients with resectable esophageal cancer. Neoadjuvant therapy, therefore, can only be recommended in centers with a maximum surgical expertise and in the context of multidisciplinary study protocols.     

Risk and patterns of brain metastases in colorectal cancer

PURPOSE: In patients with colorectal cancer, brain metastasis is infrequent. This study aims to elucidate the risk, pattern of occurrence, and survival time after different treatment modalities. METHODS: A retrospective review of all patients with colorectal cancer admitted to the Veterans General Hospital-Taipei between 1970 and 1996 from our hospital was performed. Univariate analysis for survival determination was performed. RESULTS: Brain metastases developed subsequent to surgery for colorectal cancer in 53 well-documented patients, at a median of 36 months after surgery. Brain metastases were more commonly seen in rectal cancer and often occurred concurrently with lung metastases. Forty of these patients received active intervention in terms of surgery, chemotherapy, or radiotherapy, with surgical intervention achieving a significantly increased mean survival time (+/- standard deviation) compared with chemotherapy or radiotherapy or both of 86.6 +/-17.35 vs. 2.9 +/- 0.59 months (P < 0.05). CONCLUSION: Increased awareness of the possibility of brain metastases, early diagnosis, and aggressive therapy can provide increased survival time for patients with colorectal cancer with brain metastases.     

The pathogenesis and treatment of brain metastases: a comprehensive review

Brain metastases are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. The role of surgery in the management of multiple brain metastases is still controversial. As more than 70% of patients have multiple metastases at the time of diagnosis, whole brain radiotherapy is the treatment of choice in most cases. Brain metastases are an ideal target for stereotactic radiosurgery, as they are better circumscribed than primary brain tumors. Currently, chemotherapy has a limited role in the treatment of most brain metastases. Several new therapies, with a good penetration through the blood brain barrier, such as temozolomide, have been used in brain metastases with different results depending on the histology of the primary tumor. A better understanding of the complex processes underlying the development of brain metastasis will enable us to develop more satisfactory targeted treatments.     

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.     

Pathological complete response of synchronous multiple liver metastases associated with advanced gastric cancer to gastrectomy and prompt S-1 treatment in combination with fractional cisplatin: report of a case

Systemic chemotherapy is the treatment recommended for prolonged survival in cases of metastatic gastric cancer. There have been a number of clinical reports of surgical resection of liver metastasis in selected patients with gastric cancer. Here, we report on a case of treatment of far advanced gastric cancer with synchronous multiple liver metastases with prompt S-1 in combination with fractional cisplatin sandwiched between twostage surgery. Metastases including peritoneal dissemination and extensive lymph node involvement were absent so it was feasible to completely remove all of the macroscopic liver metastases. Each step of the chemotherapy progressed satisfactorily and histological examination after the hepatectomy yielded a pathologically complete response of liver metastases from the gastric cancer. This strategy provides a promising treatment for far advanced gastric cancer with a limited number of synchronous liver metastases. The referral to surgical oncology is a crucial step for the documentation of pathological complete response.     

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.     

Factors affecting recurrence in node-negative advanced gastric cancer

Background and Aim:  Prognostic factors of lymph node-negative gastric adenocarcinoma after curative resection have been discussed. Recurrent pattern of advanced lymph node-negative gastric cancer after curative resection has rarely been described.
Methods:  Recurrent sites and correlated clinicopathological factors of 372 patients with lymph node-negative advanced gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were analyzed.
Results:  Recurrence was noted in 51 (13.7%) patients. Recurrent rates according to site of recurrence were 26 peritoneal seeding (51.0%), 26 locoregional (51.0%), 17 hematogenous (33.3%), and 4 lymph node metastasis (7.8%). Clinicopathological factors to predict peritoneal seeding were serosal exposure, lymphovascular invasion, Lauren's diffuse type differentiation and scirrhous stromal reaction. Serosal exposure, tumor size, microscopic infiltrating growth type predicts locoregional recurrence. Tumor had only lymphovascular invasion predict hematogenous spreading.
Conclusion:  Node-negative advanced gastric cancer has more peritoneal seeding and locoregional recurrence. Aggressive cell behavior predicted the route of tumor cell spreading.     

Recurrent colorectal cancer after endoscopic resection when additional surgery was recommended

AIM: To evaluate the type of recurrence after endoscopic resection in colorectal cancer patients and whether rescue was possible by salvage operation.METHODS: Among 4972 patients who underwent surgical resection at our institution for primary or recurrent colorectal cancers from January 2005 to February 2015, we experienced eight recurrent colorectal cancers after endoscopic resection when additional surgical resection was recommended.RESULTS: The recurrence patterns were: intramural local recurrence(five cases), regional lymph node recurrence(three cases), and associated with simultaneous distant metastasis(three cases). Among five cases with lymphatic invasion observed histologically in endoscopic resected specimens, four cases recurred with lymph node metastasis or distant metastasis. All cases were treated laparoscopically and curative surgery was achieved in six cases. Among four cases located in the rectum, three cases achieved preservation of the anus. Postoperative complications occurred in two cases(enteritis).CONCLUSION: For high-risk submucosal invasive colorectal cancers after endoscopic resection, additional surgical resection with lymphadenectomy is recommended, particularly in cases with lymphovascular invasion.     

Meta-analysis: Perioperative regional liver chemotherapy for improving survival and preventing liver metastases in patients with colorectal carcinoma

OBJECTIVE: To evaluate the effect of prophylactic regional liver chemotherapy during the perioperative period on improving survival and preventing liver metastases in patients with colorectal cancer (CRC). METHODS: A comprehensive retrieval of the relevant literature was performed by searching major biomedical database, mainly from Medline and Embase. Studies reported in the selected literature were categorized into two subgroups according to the type of therapy: a perioperative hepatic artery infusion subgroup and a perioperative portal vein infusion subgroup. Mortality and liver metastasis were analyzed using a fixed-effects model. Statistical analysis was performed using Review Manager software. RESULTS: The results of this meta-analysis illustrated that survival and the rate of liver metastasis in patients receiving perioperative hepatic artery infusion (HAI) chemotherapy were significantly better than for those receiving surgery alone (pooled relative risk 0.46 [95% CI: 0.31–0.69] and 0.44 [95% CI: 0.28–0.68], respectively, P= 0.0002), while survival and the rate of liver metastasis in patients receiving perioperative portal vein infusion (PVI) chemotherapy were not significantly different from those receiving surgery alone (pooled relative risk 0.98 [95% CI: 0.89–1.09], P= 0.73 and 0.86 [95% CI: 0.72–1.02], respectively. P= 0.08). CONCLUSION: As a method of regional liver chemotherapy, HAI might be able to improve survival and reduce the rate of liver metastasis in patients with advanced CRC.     

结直肠癌肝转移综合治疗进展

虽然手术仍是目前唯一有可能治愈结直肠癌肝转移的手段,但是在结直肠癌肝转移的诊疗方面发展迅速。多学科团队综合治疗和分组治疗逐渐成为诊疗规范。对可切除的结直肠癌肝转移患者,在围手术期也应实施标准化疗,是否加用靶向药物尚无定论。实施转化性化疗时应选择高效化疗方案,并尽量缩短疗程,且一旦转移灶转化为可切除,就应积极安排手术。肝转移灶不可切除的患者,是否切除原发灶也存在争议。在肝转移灶局部治疗方面的新技术发展迅速,可改善患者生存。     

Neoadjuvant treatment with cetuximab, 5-Fluorouracil, folinic Acid and oxaliplatin in unresectable retroperitoneal recurrent colon cancer

Some patients with initially unresectable hepatic colorectal cancer metastases can be effectively treated with neoadjuvant chemotherapy to allow operative resection in curative intent. Here, we report on a patient with unresectable locoregional recurrence of colon cancer, which was down-staged using combination chemotherapy with infusional 5-fluorouracil, folinic acid, oxaliplatin and cetuximab. After 12 weeks of therapy a partial response was documented and 3 weeks later the tumor was completely resected without increased perioperative morbidity. Therefore, neoadjuvant treatment with molecular targeted agents in combination with chemotherapy can also be an option to enable selected patients with locoregional recurrence to undergo surgical resection in curative intent.     

Effectiveness of preoperative chemotherapy for far advanced gastric cancer

We herein report a case in which preoperative chemotherapy with cisplatin and 5-fluorouracil was found to effectively treat far advanced gastric cancer invading the pancreas forming a huge mass with regional and distant lymph node metastases. As a result of this treatment regimen, a potentially curative resection was performed which led to a substantially increased survival. The patient was treated with 10 mg of cisplatin and 1000 mg of 5-fluouracil each day preoperatively. After the continuous administration of these drugs for 28 days, the findings of extensive pancreas invasion and lymph node metastases dramatically disappeared. The tumor could be curatively resected by a total gastrectomy with lymph nodes dissection, combined with a distal pancreatectomy and splenectomy. A histological study of a resected specimen showed some cancer cell infiltration remaining within the muscularis propria with fibrous change. There was no evidence of either pancreas invasion or lymph node metastasis. As a result, postoperative adjuvant chemotherapy was performed, 14 months later lymph nodes recurrence was detected and the patient died 20 months after surgery. Our findings suggest that preoperative chemotherapy may thus be effective for the treatment of gastric cancer by both reducing the tumor burden and prolonging survival.     

Resection of localized recurrences after hepatectomy of colorectal cancer metastases

BACKGROUND/AIMS: Hepatectomy is generally considered the only mode of curative treatment available for patients with colorectal liver metastases, even though recurrence occurs in more than 60% of the patients. METHODOLOGY: This is a retrospective study examining the survival of 11 patients undergoing surgical excision of recurrences gained from 46 patients undergoing initial hepatectomy for metastatic colorectal cancer. These 46 patients had curative hepatectomy and no extrahepatic metastasis. RESULTS: Cancer recurred in 29 of the 46 patients after a median follow-up time of 29.5 months (range 2-183 months), and 11 had curative resection of localized recurrences. In 6 patients, the liver was the only site of recurrence and 4 patients had isolated lung metastases. One patient had liver and lung metastases. There was no perioperative mortality. The median survival time and cumulative 5-year survival rate for 11 patients after the repeated resection were 28 months and 43.8%, respectively. These results were comparable to the survival for 46 patients after the initial hepatectomy, in which the median survival was 29.5 months and the 5-year survival rate was 49.0%. CONCLUSIONS: In appropriately selected patients with colorectal cancer, surgical excision of localized recurrences after hepatectomy may be effective in prolonging survival.     

DCC protein as a predictor of distant metastases after curative surgery for rectal cancer

PURPOSE: The aim of this study was to determine the value of DCC (deleted in colorectal cancer) protein for predicting metachronous distant metastases after curative surgery for rectal cancer. The DCC protein—for which a gene has been located on chromosome 18q—has recently been reported to have a prognostic value in colorectal cancer. This finding might have implications for treatment of International Union Against Cancer Stage II rectal carcinoma, in which distant metastases will develop in 14 percent of patients despite optimal surgery. METHODS: Paraffin-embedded tissues from 85 patients who developed distant metastases, but no local recurrence, after curative surgery for rectal cancer were matched with 85 samples from patients who remained disease-free. Matching criteria were tumor stage, age, gender, and date of surgery. Expression of DCC protein was assessed using immunohistochemistry. End points of follow-up were recurrence of disease and death. Mean follow-up was 9.6 years. No patient received either local or systemic adjuvant therapy. RESULTS: The DCC protein was found to be expressed in 64.9 percent of tumor samples. Nonexpression of DCC protein had an negative influence on survival (P=0.03). For all tumor stages together, sensitivity of the test for subsequent occurrence of distant metastases was 42 percent and specificity was 71 percent. In Stage II cancers, the positive predictive value was 19 percent, and the negative predictive value was 88 percent. CONCLUSIONS: Our results confirm that DCC protein is a useful prognostic marker in patients with rectal carcinomas, but the positive predictive value of DCC protein for occurrence of metachronous metastases does not appear to be sufficient to justify adjuvant therapeutic measures in Stage II rectal cancer.     

A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation]

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.     

Surgical therapy for recurrent esophageal cancers at anastomoses after esophagectomy.

BACKGROUND/AIMS: The long-term prognosis of a recurrent esophageal cancer at the anastomosis after esophagectomy is generally unfavorable. We have experienced six cases in our institute where surgical treatment resulted in a good prognosis. METHODOLOGY: Between 1962 and 1997, 1720 patients underwent esophagectomy for esophageal cancers in our institute. Anastomotic recurrence was identified in 13 and surgical therapy was performed for six of these. Their clinical and histopathological features were examined with reference to control of anastomotic recurrent esophageal cancers. RESULTS: The six patients were all males with an average age of 61.5 years. Their median disease-free interval was 5.5 months. Three patients lived more than five years after the first esophagectomy. Histopathologically, regional lymph node metastases were found in four of the cases and cervical lymph node metastases were detected in two at the initial esophagectomy. Vessel invasion was evident in three cases, intraepithelial spread in one, and multiple cancers in two. There were no cases with intramural metastasis. Radiotherapy and/or chemotherapy were added for three cases. CONCLUSIONS: After esophagectomy for esophageal cancers, frequent examination of the anastomotic site using endoscopy and long-term follow-up studies are desirable. The option of surgery should not be ignored when a recurrent cancer appears only at the anastomosis.     

Rationale of the so-called extended resection for pancreatic invasive ductal carcinoma

It has generally been recognized that for adenocarcinoma of the pancreas, surgical resection provides the only chance for cure. In this study, we have analyzed the long-term survival of 141 patients with invasive ductal adenocarcinoma of the pancreas who received macroscopically curative resection. Multivariate analysis demonstrated that comprehensive stage of the tumor, curability of the resection, and adjuvant radiation therapy were independent prognostic factors. Pancreatectomy in this study was done with an extensive retroperitoneal clearance of para-aortic lymph node and nerve tissues, so-called extended resection. Survival curves of these patients revealed that the R0 resection is essentially necessary for long-term survival. Survival curve without microscopic lymph node metastasis was significantly better than that with node metastasis; however, 3 patients with node metastasis have been alive for more than 3 years. The survival curve of the patients who received adjuvant radiation therapy was better than of those who underwent surgery alone, and postoperative regional chemotherapy with continuous 5-FU infusion decreased hepatic metastases within 6 months. The results suggest that local recurrence of pancreatic cancer might possibly be controlled by extended resection and adjuvant irradiation, and early development of hepatic metastases might be controlled with regional chemotherapy.