Resectability and outcome with anti-EGFR agents in patients with KRAS wild-type colorectal liver-limited metastases: a meta-analysis

Background

Cetuximab (C) and panitumumab (P) increase response rate and survival in KRAS wild-type metastatic colorectal cancer (mCRC). We performed a meta-analysis of randomised controlled trials (RCTs) to assess their effect on overall response rate (ORR), the rate of radical resection (R0) and survival in patients with liver-limited initially unresectable mCRC.

Materials and methods

We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for RCTs comparing first-line chemotherapy plus or minus C or P and reporting data in patients with KRAS wild-type, unresectable liver-limited mCRC. Relative risks (RRs) with 95% confidence interval were calculated. Meta-analysis of hazard ratios (HRs) for progression-free and overall survival (PFS and OS) was also performed.

Results

Four RCTs involving 484 KRAS wild-type patients were included. Compared to chemotherapy alone, the addition of C or P significantly increased the ORR (RR 1.67, p?=?0.0001), the R0 resection rate from 11% to 18% (RR 1.59, p?=?0.04) and PFS (HR 0.68, p?=?0.002), but not OS (p?=?0.42).

Conclusions

The addition of C and P increased the R0 resection rate by 60% and reduced the risk of progression by 32% in patients with mCRC and unresectable liver-limited disease. This combination represents one of the preferred choices as conversion therapy in KRAS wild-type patients with unresectable liver metastases.     

Inferior head resection of the pancreas for intraductal papillary mucinous neoplasms

Background

Previous reports have suggested that patients with intraductal papillary mucinous neoplasm (IPMN) have a favorable prognosis after surgical resection. Thus, a variety of types of partial pancreatic resections have been advocated for treating these low-grade malignant tumors. However, the surgical outcome of IPMN after such limited pancreatectomy has not been fully clarified.

Methods

We performed a retrospective review of the clinicopathologic features and surgical outcome in 15 patients who underwent inferior head resection for IPMN at the Chiba University Hospital and National Cancer Center Hospital East between July 1994 and January 2007.

Results

There were 13 patients with noninvasive IPMNs (10 adenomas and 3 noninvasive carcinomas) and 2 patients with minimally invasive intraductal papillary mucinous carcinoma (minimally invasive IPMN). Complete tumor removal (R0 resection) was performed in four patients (80%) with intraductal papillary mucinous carcinoma. Subsequent pancreatoduodenectomy was performed in one patient because of noninvasive carcinoma with multiple mucous lakes in the pancreatic parenchyma. Values for N-benzoyl-l-tyrosyl-p-aminobenzoic acid excretion test results before (n?=?13) and after (n?=?13) the operation were 70.7 and 66.1, showing no significant difference. The 2-h glucose levels in the 75?g oral glucose tolerance test before (n?=?13) and after (n?=?13) the operation were 133 and 146?mg/dl, respectively, showing no significant difference. Pancreatic fistula occurred in 7 (47%) patients. Overall morbidity and mortality rates were 67 and 0%, respectively. The overall 1-, 3-, 5-, and 10-year survival rates for the 15 patients were 100, 79, 79, and 71%, respectively. The 1-, 3-, 5-, and 10-year survival rates for patients with noninvasive IPMN (n?=?13) and those with minimally invasive IPMN (n?=?2) were 100, 92, 92, and 83%; and 100, 0, 0, and 0%, respectively. There was a significant difference in survival between patients with noninvasive IPMN and those with minimally invasive IPMN (p?=?0.0005). No patient with noninvasive IPMN developed recurrent disease. One patient with minimally invasive IPMN died of recurrent peritoneal dissemination 18?months after margin-positive R1 resection. Two patients died of pancreatic ductal adenocarcinoma, 30 and 78?months after inferior head resection.

Conclusions

Pancreatic endocrine and exocrine function was well preserved after inferior head resection. Pancreatic fistula occurred more frequently after inferior head resection than with conventional pancreatoduodenectomy. Patients with noninvasive IPMN had favorable survivals after this procedure. However, one patient with minimally invasive IPMN with margin-positive R1 resection died of recurrent disease. Thus, margin-negative R0 resection should be performed for IPMN.     

Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese Society of Pancreatic Surgery

Background

Optimal treatment types and prognosis for patients with borderline resectable pancreatic cancer (BRPC) remain unclear because of the lack of studies involving large series of patients.

Methods

We retrospectively analyzed various prognostic factors for 624 BRPC (pancreatic head/body) patients treated from June 2002 to May 2007, by distributing questionnaires to member institutions of the Japanese Society of Pancreatic Surgery in 2010. BRPC was defined according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2009).

Results

Among 624 patients, 539 (86.4 %) underwent curative-intent resection, showing an R0 resection rate of 65.9 %. The 3- and 5-year survival rates were 16.1 and 9.9 % in all patients, 22.8 and 12.5 % in the resected patients, and 4.4 and 0 % (P < 0.0001) in the unresected patients, respectively. The following factors influencing survival in all patients were selected as independent prognostic factors using multivariate analysis: major arterial involvement on imaging study; preoperative treatment; surgical resection; and postoperative chemotherapy. Among the resected cases, multivariate analysis revealed that major arterial involvement and remnant tumor status were independent prognostic factors.

Conclusion

BRPC included two distinct categories of tumors influencing survival: those with portal vein/superior mesenteric vein invasion alone and those with major arterial invasion, which was the most exacerbating factor in the analysis.     

Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis

Background

Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis.

Methods

We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum.

Results

Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1–P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection.

Conclusions

P1–P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.     

Should isolated peritoneal carcinomatosis from colorectal cancer be sub-classified into stage IVB in era of modern chemotherapy?

Background

According to the 7th edition of the TNM staging system, stage IV metastatic colorectal cancer (CRC) at the time of initial diagnosis is sub-classified into stage IVA or IVB disease. Peritoneal carcinomatosis (PC), considered to have a dismal prognosis, is exclusively sub-classified into stage IVB, even though other metastases to a sole organ are sub-classified into stage IVA, which is considered to be associated with better survival. This retrospective study was undertaken to investigate the overall survival in metastatic CRC patients, focusing on PC patients.

Methods

We reviewed data on patients with metastatic CRC at initial diagnosis surgically treated between January 2006 and June 2011. A survival analysis was performed paying special attention to PC and sub-classifying patients with PC into three categories according to metastatic sites.

Results

There were 69 stage IVA patients (IVA group) and 83 stage IVB. Among stage IVB patients, 20 had isolated PC (PC-I group), 28 had PC with one or more other sites of metastasis (PC-II group), and 35 had at least 2 metastatic without peritoneal involvement (NPC group). Of 152 stage IV patients, 132 (87 %) underwent resection of the primary tumor and 19 (12 %) underwent radical resection of metastatic disease with microscopic free margins (R0 resection) including 5/20 (25 %) patients in the PC1 group. A total of 139 patients received oxaliplatin-based chemotherapy in a palliative (n = 125), neoadjuvant (n = 3), or adjuvant setting after R0 resection (n = 11). Compared with 36.6 months in the PC-I group, median survival was 32.5 months (P = 0.48) in the IVA group, 14.7 months (P = 0.07) in the PC-II group, and 12.9 months (P < 0.01) in the NPC group.

Conclusions

The sub-classification of isolated PC into stage IVA instead of IVB might be more appropriate in the era of modern chemotherapy. Further investigation is warranted.     

Survival after resection of liver and lung colorectal metastases in the era of modern multidisciplinary therapy

Purpose

Despite recent improvement of the outcomes of colorectal cancer (CRC), the benefits of resection and appropriate selection criteria in patients with both liver and lung metastases remain controversial. The aim of this study was to analyze the outcomes and prognostic factors for survival in patients who underwent both hepatic and pulmonary resection for CRC metastases in the era of modern multidisciplinary therapy.

Methods

A retrospective analysis of 43 consecutive patients who underwent both liver and lung resections for metastatic CRC at our institute from 2003 to 2011 was performed. All patients in this study had achieved cancer-free status after resection of the second metastatic site.

Results

Of the patients, 24 (56 %) had synchronous metastatic disease with their primary tumor. Twenty-seven patients had developed recurrence after resection of the second metastatic site. In 14 cases, re-metastasectomy was performed for recurrence. Fourteen patients received palliative chemotherapy after recurrence, and all of these patients received oxaliplatin and/or irinotecan-based chemotherapy. After resection of the second metastatic organ, the 5-year relapse-free and overall survival rates were 29.6 and 70.0 %, respectively. Patients with multiple lung metastases had worse relapse-free survival than patients with solitary lung metastases at first lung resection (p?=?0.046).

Conclusions

Aggressive surgical resection and a combination of modern chemotherapeutic agents improve the survival of patients with lung and liver metastases from CRC. The presence of multiple lung metastases at resection suggests a poor prognosis.     

Short term chemotherapy followed by radiofrequency ablation in stage III pancreatic cancer: results from a single center

Background

Neo-adjuvant chemotherapy (CHT) has gained increasing importance in resectable and borderline resectable pancreatic cancer leading to a better performing surgery when we look at negative resection margins and selection of patients with less aggressive disease. We apply this principle to patients with Stage III (LAC) pancreatic cancer undergoing RFA and try to select patients who may benefit from a local treatment.

Methods

All patients affected by LAC were treated with RFA for a stable disease after a short CHT. Postoperative morbidity and mortality were evaluated together with overall survival (OS) and disease specific survival (DSS).

Results

We consecutively treated 57 patients affected by LAC. Median duration of CHT before RFA was 5 months. The postoperative mortality rate was zero. Overall morbidity was 14 % with RFA-related morbidity of 3.5 %. The OS and DSS were 19 months and when compared to a similar population who received RFA as up front treatment, there was no difference.

Conclusions

Our results do not support the adoption of a short CHT as a way to identify patients to treat with RFA with the most benefit. Based on this and by knowing the role of immune modulation after RFA and its specific involvement in pancreatic carcinoma, we can propose RFA as upfront treatment.     

Adjuvant chemotherapy with gemcitabine and S-1 after surgical resection for advanced biliary carcinoma: outcomes and prognostic factors

Background/Purpose

The aims of this study were to evaluate long-term outcomes and to determine prognostic factors for survival in patients with resected biliary carcinoma who received adjuvant gemcitabine plus S-1 chemotherapy.

Methods

Seventy patients with International Union Against Cancer (UICC) stage II, III, or IV biliary carcinoma received postoperative adjuvant chemotherapy consisting of intravenous gemcitabine 700?mg/m² on day 1 and oral S-1 60–100?mg/body for seven consecutive days, followed by a 1-week pause of chemotherapy. Patients received up to ten 2-week cycles. Long-term outcomes and predictors of survival with this adjuvant chemotherapy regimen were analyzed.

Results

The median duration of follow-up was 47?months. Fifty-six percent of patients had node-positive disease, and 80% of patients underwent R0 resection. Overall and disease-free survival rates were 91 and 81% at 1?year, 56 and 55% at 3?years, and 40 and 46% at 5?years, respectively. Lymph node status (p?=?0.025) and surgical margin status (p?=?0.033) were independently associated with long-term survival by multivariate analysis.

Conclusions

Adjuvant gemcitabine plus S-1 chemotherapy may be a promising strategy for patients with resected biliary carcinoma, and nodal status and surgical margin status may be predictors of survival with this treatment strategy.     

Clinical outcomes of adult and childhood rhabdomyosarcoma treated with vincristine, d-actinomycin, and cyclophosphamide chemotherapy

Background

Outcomes in adult patients with rhabdomyosarcoma are poor, with a 5-year survival rate of approximately 30?%. The current study aimed to compare the clinical outcomes of adult and childhood rhabdomyosarcoma patients with local and metastatic disease and to examine the impact and timing of local therapy on metastasis.

Methods

Clinicopathological features and patient outcomes were reviewed retrospectively for rhabdomyosarcoma patients receiving chemotherapy between 1981 and 2010 at our institution. Adults were defined as those aged 21?years or older.

Results

Of the 98 patients identified, 36 were adults (median age, 29; range, 21–72) and 62 were children (median age, 11; range, 0.6–20). Median progression-free survival of localized and metastatic disease for children and adults was as follows: localized disease, 166.9 versus 22.4?months (p?=?0.005), and metastatic disease, 13.3 versus 13.3?months (p?=?0.949), respectively. Multivariate regression analysis revealed that older age (≥21 vs. <21) was a significant poor prognostic factor in localized disease. Conversely, age was not related to survival in metastatic disease. Receiving radiotherapy to the primary site was an independent factor indicating a better prognosis. An analysis of the optimal timing of local therapy was performed for 53 patients; however, its significance on survival could not be determined.

Conclusions

Age was a negative prognostic factor in rhabdomyosarcoma patients with localized disease, but it did not affect the survival in metastatic disease. For metastatic disease, although local therapies may be effective for survival, the timing of such therapies should be determined individually.     

Liver resection in selected patients with metastatic breast cancer: a single-centre analysis and review of literature

Purpose

Despite the development of modern chemotherapeutics and target-specific drugs as well as improved surgical techniques, prognosis of metastatic breast cancer remains poor. Only a small number of selected patients will be eligible for liver resection and/or alternative metastatic ablation. Data on prognostic factors for patients with surgically resectable liver metastases of breast cancer are scarce at present.

Methods

From 1997 to 2010, 50 patients with hepatic metastases of breast cancer have undergone laparotomy with the intention to undergo a curative liver resection at our institution. Data from these patients were collected in a prospectively maintained standardized liver resection data base.

Results

Liver resection was performed in 34 patients. Resection margins were clear in 21 cases (R0). Nine patients lived for more than 60 months after liver resection. The observed 5-year survival rate was 21 % for all 50 patients, 28 % for resected patients and 38 % after R0-resection. On univariate analysis, survival rates of the resected patients were statistically significantly influenced by R-classification, age, extrahepatic tumour at the time of liver resection, size of metastases and HER2 expression of liver metastases. Multivariate analysis revealed absence of HER2 expression, presence of extrahepatic tumour and patient’s age ≥50 years as independent factors of poor prognosis.

Conclusions

Breast cancer patients younger than 50 years with technically resectable hepatic metastases, minimal extrahepatic tumour and positive HER2 expression appear to be suitable candidates for liver resection with curative intent. An aggressive multi-disciplinary management of those patients including surgical treatment may improve long-term survival.     

ALK expression is absent in pancreatic ductal adenocarcinoma

Purpose

It has not yet been clearly defined whether anaplastic lymphoma kinase (ALK) expression can be detected in pancreatic ductal adenocarcinoma (PDAC).

Methods

Within a retrospective study, archival PDAC surgical specimens were screened for ALK expression in tumor and normal tissue by immunohistochemistry (IHC) with the use of a specific ALK detection kit on a tissue microarray (TMA).

Results

PDAC tumor tissue was available from 99 resected cases: fifty-eight out of 99 patients (59 %) had nodal-positive disease, and 80 patients (81 %) had pT3 tumors. Forty-nine patients underwent R0 resection, and in 48 cases, resection status was classified R1. Regarding ALK expression, five cases showed faint immunoreactivity on TMA, which was negative on whole mount sections. All other 94 cases showed no ALK expression.

Conclusion

In 99 PDAC cases, no ALK expression was detected by IHC; ALK thus may not serve as a relevant drug target in PDAC.     

Adjuvant arterial infusion chemotherapy after resection of hepatocellular carcinoma with portal thrombosis: a pilot study

Background/Purpose

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombosis of the main trunk or major branches of the portal vein (mPVTT) is extremely poor, even if it is curatively resected. Uncontrollable multiple metastases to the residual liver are often observed within several months after the operation. We report here the results of a pilot study, showing the efficacy of adjuvant arterial infusion chemotherapy after the resection of HCC with mPVTT.

Methods

Twelve patients had curative resection of HCC with mPVTT. Six of the patients were treated by the arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port after curative resection of HCC with mPVTT. The initial course consisted of the daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU). This was followed by the weekly or biweekly administration of CDDP and subsequent infusion of 5-FU until the cumulative dose of 5-FU reached 15?g.

Results

The median overall survival time was 58.0 months with adjuvant chemotherapy and 8.0 months without adjuvant chemotherapy. The median disease-free interval was 15.0 months with adjuvant chemotherapy and 4.0 months without adjuvant chemotherapy. Adverse reactions were tolerable nausea and loss of appetite.

Conclusions

This chemotherapeutic regimen achieved favorable results and may be useful as adjuvant chemotherapy in treating patients after curative resection of HCC with mPVTT.     

A phase II study of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus: The Japan Clinical Oncology Group (JCOG) Trial (JCOG 9905-DI)

Background

This phase II study evaluated the efficacy and toxicity of combination chemotherapy with nedaplatin and 5-fluorouracil (5-FU) for metastatic esophageal squamous cell carcinoma.

Methods

Eligibility criteria included squamous cell carcinoma with organ metastasis, ECOG performance status (PS) 0–2, ≤ 75 years, measurable disease, and adequate organ function. Chemotherapy consisted of 5-FU (800 mg/m²/day) on days 1–5 and a 2-h infusion of nedaplatin (90 mg/m²) on day 1, repeated every 4 weeks. Therapy was continued until disease progression or intolerable adverse events. The primary end point was response rate. Secondary end points included overall survival, progression-free survival, and toxicities.

Results

Forty-two patients (39 men, 3 women; median age 59 years; range 44–70 years) were enrolled. Twenty-one, 21, and 0 patients had PS 0, 1, and 2, respectively. 23, 6, 3, and 18 patients had a history of surgical resection, radiotherapy, adjuvant chemotherapy, and no therapy, respectively. Among the 38 eligible patients, 1 and 14 complete and partial responses were observed, respectively; the overall response rate was 39.5 % (90 % confidence interval: 26.1–54.1 %). The median survival time was 8.8 months. The one-year survival rate was 32.9 %. Grade 4 neutropenia and thrombocytopenia were observed in 7 and 2 % of 41 patients, respectively. Grade 3 nausea, diarrhea, and stomatitis were observed in 12, 2, and 2 %, respectively.

Conclusion

Combination therapy with nedaplatin and 5-FU is highly active and well tolerated in metastatic or recurrent esophageal squamous cell cancer and is therefore a chemotherapy option for esophageal squamous cell carcinoma.     

Clinical impact of radiotherapy for locally advanced pancreatic cancer

Background

Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC.

Patients

Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n = 30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n = 28, or gemcitabine, n = 19, as a radiosensitizer) at Aichi Cancer Center Hospital.

Results

Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3–4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy.

Conclusions

Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy.     

Long-term outcomes after resection of para-aortic lymph node metastasis from left-sided colon and rectal cancer

Purpose

Para-aortic lymph node (PALN) metastasis from colorectal cancer is rare and often not suitable for surgery. However, in selected patients, radical resection may bring about longer survival. The aim of this study was to evaluate long-term outcomes of resection of left-sided colon or rectal cancer with simultaneous PALN metastasis.

Methods

The study included 2122 patients with left-sided colon or rectal cancer (30 patients with and 2092 patients without PALN metastasis) who underwent resection with curative intent between 2002 and 2013. Clinicopathological characteristics, long-term outcomes of resection, and factors related to poor postoperative survival in patients with PALN metastasis were investigated.

Results

Of a total of 2122 total patients, 16 of 50 patients (32.0%) with lymph node metastasis at the root of the inferior mesenteric artery had PALN metastasis. The 5-year overall survival rates for 18 patients who underwent R0 resection and 12 patients who did not were 29.1 and 10.4%, respectively (p = 0.017). Factors associated with poor postoperative survival among patients who underwent R0 resection were presence of conversion therapy, lack of adjuvant chemotherapy, carcinoembryonic antigen >20 ng/mL, and lateral lymph node metastasis in rectal cancer patients. The 5-year recurrence-free survival rate was 14.8%.

Conclusions

Although recurrence was frequent, R0 resection for left-sided colon or rectal cancer with PALN metastasis was associated with longer survival than R1/R2 resection. Furthermore, the 5-year overall survival rate in the R0 group was relatively favorable for stage IV. Therefore, R0 resection may prolong survival compared with chemotherapy alone in selected patients.

     

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.     

Prognostic factors associated with primary cancer in curatively resected stage IV colorectal cancer

Purpose

The aim of this study is to evaluate the prognostic factors associated with primary cancer in patients with curatively resected stage IV colorectal cancer, based on lymph node status.

Methods

A total of 468 consecutive patients with curatively resected stage IV colorectal cancer from October 1994 to December 2010 were prospectively enrolled. Survival curves were constructed using the Kaplan–Meier method, and multivariate analysis assessed independent prognostic factors.

Results

During the median follow-up period of this study, which was 37 months (range 1–177), the 3- and 5-year overall survival rates were 66.5 and 52.1 %, respectively, and the 3- and 5-year disease-free survival rates were 43.0 and 38.2 %, respectively. According to multivariate analysis, adjuvant chemotherapy and the preoperative serum carcinoembryonic antigen (CEA) level were independent prognostic factors for overall survival, and primary tumor location and preoperative serum CEA level were independent variables for disease-free survival. For the patients with N0 and N1 tumors, the overall survival curves in the preoperative CEA groups differed significantly (P = 0.046 and P < 0.013, respectively). However, for patients with pN2 tumors, the overall survival did not differ significantly according to the preoperative CEA (P = 0.948).

Conclusion

The preoperative serum CEA level is a reliable predictor of recurrence and survival after curative surgery in patients with metastatic colorectal cancer. A multidisciplinary approach that combines both complete resection and adjuvant chemotherapy may achieve improved overall survival in these patients.     

Increased Rates of Duodenal Obstruction in Pancreatic Cancer Patients Receiving Modern Medical Management

Background

Duodenal obstruction from pancreatic cancer historically occurs in 2–25 % of patients without surgery, but with new advances in chemotherapy and radiation therapy, the life expectancy of pancreatic cancer has increased.

Aim

The aim of the study was to determine the rate of development of duodenal obstruction requiring intervention in patients with pancreatic head adenocarcinoma who do not undergo surgical resection, but receive modern chemoradiation.

Methods

It is a retrospective single center study. Inclusion criteria were patients with pancreatic cancer who underwent ERCP with metal biliary stent and then chemoradiation who subsequently developed symptomatic duodenal obstruction and underwent either metal duodenal stent placement or surgical duodenal bypass.

Results

Twenty-four of 63 patients (38 %, 95 % CI 26–50 %) with unresectable pancreatic cancer and biliary stents who received chemotherapy and/or radiation therapy developed duodenal obstruction. The average length of time from diagnosis of pancreatic adenocarcinoma to development of outlet obstruction was 11.4 ± 4.9 months (range 1.5–40 months). Average length of time from development of duodenal obstruction to death was 4.8 ± 2.1 months (range 0.5–60 months). Average survival time from diagnosis to death was 16.6 ± 5.6 months (range 4.5–58 months).

Conclusion

Thirty-eight percent of patients with unresectable pancreatic head adenocarcinoma and metal biliary stents who receive chemotherapy and/or radiation therapy eventually develop symptomatic duodenal obstruction requiring duodenal stent or surgical bypass. This rate of duodenal obstruction is nearly twice that of previous reports using older oncologic therapy and will likely increase as patients survive longer with advances in medical therapy for pancreatic cancer.     

Early Recurrence of Pancreatic Cancer after Resection and During Adjuvant Chemotherapy

Background/Aim:

Adjuvant chemotherapy for 6 months is the current standard of care after potentially curative resection of pancreatic cancer and yields an overall survival of 15–20 months. Early tumor recurrence before or during adjuvant chemotherapy has not been evaluated so far. These patients may not benefit from adjuvant treatment.

Patients and Methods:

Thirty-five patients with resection of ductal pancreatic carcinoma and adjuvant chemotherapy with gemcitabine were analyzed between 2005 and 2007. All patients had a computed tomography (CT) scan before and during adjuvant chemotherapy after 2–3 months, 12/35 patients had a histologically confirmed R1 resection. Recurrence of pancreatic cancer was determined by CT scan and the clinical course.

Results:

Median survival of 35 patients with resected pancreatic cancer was 19.7 months, and the 2-year survival was 44%. Thirteen (37%) of the 35 patients analyzed with a CT scan showed tumor recurrence during adjuvant chemotherapy. Overall survival of patients with tumor recurrence was 9.3 months with a 2-year survival rate of 13%, whereas median overall survival of patients without early relapse was 26.3 months (P<0.001). Local recurrence of pancreatic cancer occurred in 38% (5/13); 46% (6/13) of patients developed distant metastasis, and 38% (5/13) developed lymph node metastasis. Early tumor recurrence during or adjuvant chemotherapy did not correlate with R status (R1 vs R0, P=0.69), whereas histologically confirmed lymph node invasion (pN0 vs pN1) and grading showed a statistically significant correlation with early relapse (P<0.05).

Conclusion:

A significant fraction of patients with resected pancreatic cancer have early relapse during adjuvant chemotherapy, especially those with lymph node metastasis. Radiologic examinations prior to and during adjuvant chemotherapy will help to identify patients with tumor recurrence who are unlikely to benefit from adjuvant treatment and will need individualized palliative chemotherapy.     

Feasibility and short-term outcome of adjuvant FOLFOX after resection of colorectal liver metastases

Background

The role of adjuvant chemotherapy for stage IV colorectal cancer has so far been under-investigated. The aim of this study was to assess the feasibility and short-term outcome of adjuvant chemotherapy with the FOLFOX regimen following liver resection for patients with colorectal liver metastasis (CRLM).

Methods

From May 2005 to September 2010, 86 patients with CRLM underwent hepatic resection in the Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University. Of these patients, 24 received FOLFOX4 or modified FOLFOX6 as postoperative adjuvant chemotherapy.

Results

Nineteen male and 5 female patients received adjuvant chemotherapy following liver resection. Twenty-one (87.5 %) of these patients completed 6 cycles of adjuvant chemotherapy. Five patients required a dose reduction due to neutropenia, and the dose intensities of oxaliplatin and 5-FU were 93.6 and 94.1 %, respectively. There were no severe adverse events from the treatments. The median follow-up period was 48.4 months. Recurrences developed in 12 patients, and 3 patients died during the follow-up period. The 3- and 5-year disease-free survival and overall survival were 51.6 and 45.1 % and 95.5 and 76.0 %, respectively.

Conclusions

Adjuvant FOLFOX is feasible and might provide a good prognosis for CRLM patients who undergo liver resection.