Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: analysis of histopathology and outcome

To examine the histopathologic effect of neoadjuvant therapy and its impact on survival in patients with carcinoma of the pancreas, we retrospectively reviewed the records of 116 patients who underwent resections for pancreatic cancer from 1987 to 2000. Median follow-up of surviving patients was 19 mo(range 4-150 mo). Preoperative chemotherapy was administered in 61 patients (53%) and consisted of 5-fluorouracil/mitomycin C in 35 patients and gemcitabine in 26 patients, given concurrently with external beam radiation (5040 cGy). All resections were performed with curative intent (98 Whipples, 11 total, 6 distal, and 1 central pancreatectomy). Histopathologic examination included an estimation of the amount of fibrosis present in the tumor specimen (expressed as the percentage of fibrosis identified relative to the amount of neoplastic cells present). The mean fibrosis level for the series was 56% (range 5% to 100%). The administration of neoadjuvant therapy resulted in greater fibrosis (73%) than no preoperative treatment (38%) (p = 0.0001). Higher mean fibrosis levels were observed in patients with negative lymph nodes (p = 0.0006) and negative margins (p = 0.05). Factors associated with improved survival(log rank test) included: negative margins (p = 0.001), negative lymph nodes (p = 0.03), and use of neoadjuvant therapy (p = 0.03). Median survival in the neoadjuvant group was 23 mo vs 16 mo without preoperative therapy (p = 0.03). In conclusion, the use of neoadjuvant therapy resulted in a greater degree of fibrosis in the specimen. Patients with negative margins and negative lymph nodes had a greater amount of fibrosis present, and these were significant predictors of improved outcome. Although retrospective,this series suggests an improvement in survival in patients treated with neoadjuvant therapy.     

Surgical outcome of pancreatic cancer using radical antegrade modular pancreatosplenectomy procedure

AIM:To evaluate the surgical outcomes following radical antegrade modular pancreatosplenectomy (RAMPS) for pancreatic cancer. METHODS:Twenty-four patients underwent RAMPS with curative intent between January 2005 and June 2009 at the National Cancer Center, South Korea. Clinicopathologic data, including age, sex, operative findings, pathologic results, adjuvant therapy, postop-erative clinical course and follow-up data were retro-spectively collected and analyzed for this study. RESULTS:Twenty-one patients (87.5%) underwent distal pancreatectomy and 3 patients (12.5%) underwent total pancreatectomy using RAMPS. Nine patients (37.5%) underwent combined vessel resection, including 8 superior mesenteric-portal vein resections and 1 celiac axis resection. Two patients (8.3%) underwent combined resection of other organs, including the colon, stomach or duodenum. Negative tangential margins were achieved in 22 patients (91.7%). The mean tumor diameter for all patients was 4.09 ± 2.15 cm. The 2 patients with positive margins had a mean diameter of 7.25 cm. The mean number of retrieved lymph nodes was 20.92 ± 11.24 and the node positivity rate was 70.8%. The median survival of the 24 patients was 18.23 ± 6.02 mo. Patients with negative margins had a median survival of 21.80 ± 5.30 mo and those with positive margins had a median survival of 6.47 mo (P = 0.021). Nine patients (37.5%) had postoperative complications, but there were no postoperative mortalities. Pancreatic fistula occurred in 4 patients (16.7%):2 patients had a grade A fistula and 2 had a grade B fistula. On univariate analysis, histologic grade, positive tangential margin, pancreatic fistula and adjuvant therapy were significant prognostic factors for survival. CONCLUSION:RAMPS is a feasible procedure for achieving negative tangential margins in patients with carcinoma of the body and tail of the pancreas.     

Establishing the optimum lymph node yield for diagnosis of stage III rectal cancer

Background

The optimum lymph node yield for tumour staging following surgery for rectal cancer remains controversial. This study aimed to determine the optimum number of lymph nodes needed to accurately determine stage III rectal cancer.

Methods

Sixty-three thousand three hundred and eighty-one patients from the surveillance, epidemiology and end resulted database, who underwent surgery for rectal adenocarcinoma in 1995–2009, were included. The primary outcome was detection of stage III rectal cancer, assessed by multivariable logistic regression.

Results

Each additional node examined increased the chance of stage III diagnosis by 3.9 % (adjusted odds ratio 1.039, p < 0.001). Optimum histopathological stage was reached following retrieval of 18 nodes in patients treated without neoadjuvant radiotherapy (n = 49,162) and 16 nodes in those treated with neoadjuvant radiotherapy (n = 14,219). For stage I and II cancer, retrieval of a minimum of 8 and 14 nodes, respectively, was associated with optimum five-year overall survival. For stage III cancer, increasing number of positive lymph nodes and increasing lymph node ratio (>0.5) were independent negative predictors of survival; total lymph node yield did not correlate with survival.

Conclusions

Eighteen lymph nodes for those treated without neoadjuvant radiotherapy and 16 nodes for those treated with it were needed to prevent stage migration in rectal cancer. These findings provide further evidence of the importance of the technique of proctectomy and of careful pathologic assessment.     

Absence of Lymph Nodes in the Resected Specimen After Radical Surgery for Distal Rectal Cancer and Neoadjuvant Chemoradiation Therapy: What does it Mean?

Purpose The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. Methods Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. Results Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P < 0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P = 0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P = 0.2), and both were significantly better than patients with ypN+ disease (30 percent; P < 0.001). Conclusions Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality. Presented at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer

Background The value of immunohistochemical detection of disseminated tumor cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer is still of uncertain prognostic value. We therefore evaluated the immunohistochemical detection rates and their prognostic value comparing three different monoclonal antibodies.Methods A total of 170 lymph nodes of 85 patients with curatively resected colorectal carcinoma at UICC stage I or II were evaluated for disseminated tumor cells. Frozen sections of each lymph node were immunohistochemically stained using three antibodies directed against CEA, CK20, and Ber-EP4. The detection rates were compared with histopathological tumor parameters and with the patients survival. The median follow-up time was 86 months.Results CEA-, CK20-, and Ber-EP4-positive disseminated tumor cells were identified microscopically in lymph nodes of 23 patients (27%), 24 patients (28%), and 23 patients (27%), respectively. In 18 patients (21%) disseminated tumor cells were found in consecutive sections and stained positive for all three monoclonal antibodies. The lymph nodes of 10 of 18 patients (56%), which developed tumor recurrence, contained CEA- and CK20-positive disseminated tumor cells. Ber-EP4-positive cells were present in lymph nodes of 9 of 18 patients (50%) with tumor recurrence. The 5-year overall survival of the 23 patients with CEA-positive disseminated tumor cells was 72% compared to 91% of the patients without immunohistochemical evidence of tumor cells (p<0.01). While the identification of CK20-positive tumor cells was also correlated significantly with a worse overall patient survival (p<0.01), the application of Ber-EP4 failed to reach significance (p=0.057). Multivariate analysis identified the tumor site (colon versus rectal cancer) (p<0.006) and the presence of CEA-positive disseminated tumor cells (p<0.03) as independent prognostic factors.Conclusion In colorectal carcinoma, the immunohistochemical detection of disseminated tumor cells in histopathologically pN0 peritumoral lymph nodes allows the identification of a subgroup with a significantly worse prognosis. Nevertheless, the prognostic value of immunohistochemically detected disseminated tumor cells remains controversial due to the nonuniform data in the literature.     

The survival rate and prognostic factors in 26 perforated colorectal cancer patients

Purpose The treatment for perforated colorectal cancer is not easy and the prognosis for this disease is not so predictable. There are some controversies about performing radical operations because colorectal cancer perforation was considered as an advanced stage disease due to the possibility of tumor cell dissemination through the perforation site. Methods We selected and enrolled 26 patients with perforated colorectal cancers among the 1,227 patients who underwent operation for colorectal cancer. These cases were retrospectively analyzed by using their medical records and clinicopathological data. Results Twenty-eight cases (2.3%) with perforated colorectal cancers were studied and the overall operative mortality rate was 11%. The overall 5-year survival rate was 57.8% when excluding the operative mortality. The overall 5-year cancer-free survival rate was 52.8%. There were significant differences in the survival rate and the cancer-free survival rate between the stages (p=0.008 and p<0.001, respectively). A univariate analysis of the prognostic factors revealed that the number of the metastatic lymph nodes (p=0.018) and the perforation proximal to the cancer (p=0.005) were significantly correlated to worse survival, and the higher number of the metastatic lymph nodes was correlated to a poorer cancer-free survival rate (p<0.001). Conclusion For the perforated colorectal cancers, the stage, the perforation proximal to the cancer, and the number of the metastatic lymph nodes were correlated, with the survival and the cancer-free survival as factors of a poor prognosis. The surgical approach selected for perforated colorectal cancer should be in line with the principles of an appropriate cancer operation because the clinical pathway of perforated colorectal cancer is similar to that of uncomplicated colorectal cancer.     

Perihilar lymph nodes in patients with primary sclerosing cholangitis with and without cholangiocellular carcinoma

Objective. Enlarged perihilar lymph nodes have been described in patients with primary sclerosing cholangitis (PSC). The aim of the study was to determine the clinical relevance of perihilar lymph nodes in PSC patients with and without cholangiocellular carcinoma (CCC). Material and methods. The status of perihilar lymph nodes was investigated in 117 patients with PSC using “high-end” ultrasound. Thirty-five of the 117 PSC patients had histologically proven CCC. Lymph node status was correlated with the presence of CCC and inflammatory bowel disease (IBD). Results. Seventy-three percent of PSC patients without CCC and 86% of patients with CCC had enlarged perihilar lymph nodes (NS). In CCC patients, the width of lymph nodes was significantly larger (12±6 mm versus 8±4 mm; p=0.0001), and the length:width ratio (2.15±0.7:1 versus 2.5±0.6:1; p=0.004) of the lymph nodes was significantly lower. Thirty-seven percent of PSC patients without CCC and 57% of patients with PSC and CCC had multiple perihilar lymph nodes (p=0.04). In all patients, the presence versus absence of IBD had no influence on the number (84% versus 74%,) and size of perihilar lymph nodes (length: 21±10 mm versus 19±7 mm). Lymph node status did not correlate with the number of episodes of cholangitis. Conclusions. Enlarged perihilar lymph nodes are characteristic of patients with PSC. Since perihilar lymph nodes are not predictive of the presence of complicating CCC, such patients should not be excluded from liver transplantation.     

The role of adjuvant chemotherapy in esophageal cancer patients after neoadjuvant chemotherapy plus surgery

Background

Esophageal cancer typically has a poor prognosis. While neoadjuvant chemotherapy (NAC) is reported to be effective for esophageal cancer patients, the prognosis of patients for whom NAC is ineffective remains poor.

Methods

In total, 113 patients with thoracic esophageal squamous cell carcinoma who were treated between January 2006 and December 2015 were enrolled. These patients received NAC followed by radical surgery and had three or more pathologic positive lymph nodes. The effectiveness and feasibility of adjuvant chemotherapy (AC) were evaluated.

Results

Forty patients received AC (AC(+) group) and 73 patients did not (AC(?) group). Two-year relapse-free survival (RFS) rates of the AC(+) and AC(?) groups were 30.0% and 28.8%, respectively (p?=?0.47). These patients were further divided into two subgroups, i.e., those with 3–6 positive lymph nodes (3–6 subgroup) and those with?≥?7 positive lymph nodes (≥?7 subgroup). Within the 3–6 subgroup (72 patients), 2-year RFS rates of the AC(+) and AC(?) groups were 38.5% and 33.9%, respectively (p?=?0.31). Within the?≥?7 subgroup (41 patients), 2-year RFS rates of the AC(+) and AC(?) groups were 25.9% and 7.1%, respectively (p?=?0.04).

Conclusions

AC may offer a significant additional benefit to the prognosis of esophageal cancer patients who have many positive lymph nodes even after NAC.

     

The total number of lymph nodes harvested is associated with better survival in stages II and III colorectal cancer

Background

Lymph node status is important in staging colorectal cancer (CRC). Presence of metastatic nodes differentiates stage III from stage II. The role of adjuvant therapy is still unclear in stage II CRC. Inadequate node sampling may result in inaccurate staging.

Method

Records of 131 patients with stages II and III CRC who underwent curative resection, having five or more lymph nodes harvested from the specimen, were prospectively followed up and analyzed. The Kaplan–Meier method was used to analyze survival, based on groups of serially ascending values of lymph nodes harvested. Regression analysis was performed by Cox proportional hazards ratio model with right-censored CRC survival data at a 10 % significance level. The effect of nodal harvest on survival was adjusted for age, sex, preoperative carcinoembryonic antigen (CEA) level, neoadjuvant chemoradiation, pathological tumor stage, histological type, differentiation, margin positivity, angioinvasion, perineural invasion, and lymphovascular infiltration.

Results

The total population showed improved survival with 14 or more nodes harvested (p=?0.005). For both rectal (n=?83; p=?0.03) and colon cancers (n=?46; p=?0.08), most significant survival benefits were seen with over 14 nodes harvested, irrespective of the stage. With multiple regression analysis, advanced age (p=?0.003), male sex (p=?0.017), lymphovascular infiltration (p=?0.015), and preoperative CEA levels (p=?0.096) were found to be other significant factors. The lymph node effect remained significant (HR?=?0.19, p=?0.004) after adjusting for the above factors.

Conclusion

A lymph node harvest of 14 or more resulted in better survival outcome from CRC in this population. Staging of the disease could be accurate with increased nodal harvesting.     

Adenocarcinoma of the rectum treated by abdominoperineal excision: multivariate analysis of prognostic factors

The aims of this study were to describe the results of 100 consecutive abdominoperineal excisions, and to try to define homogeneous subgroups of survivors using the Cox regression analysis model. There was one postoperative death. No patient was lost to follow-up. Overall 5-year survival rate was 45%. Multivariate analysis selected 3 prognostic factors: lymph node involvement (p<0.001), local tumour extent (P=0.08), and extension to adjacent organs (p=0.03). Four subgroups of patients were defined. Best survival was observed in patients (n=43) with tumour invading into the subserosa (W1) or less and without lymph node metastasis (N0), with a 5-year survival of 82% (group 1). Patients in Group 2 (n=18) had a tumour invading into the muscularis propria or less with lymph node metastasis (W0 N+), or into the serosa or perirectal fat without lymph node invasion (W2 N0), with a 5-year survival of 51%. Patients in Group 3 (n=17) had a tumour invading into the subserosa with lymph node invasion (W1 N+) or extension to adjacent organ without lymph node invasion (W3 N0) with a 5-year survival of 24%. Patients in group 4 (n=22) had extension into the serosa or perirectal fat or more with lymph node invasion (W2 N+) with a 5-year survival of 2%. This scoring system is simple, practical and easy to apply. If it can be confirmed by other studies, its routine adoption could be justified.     

Colorectal liver metastasis surgery: analysis of risk factors predicting postoperative complications in relation to the extent of resection

Background/aims  Despite advances in diagnosis and treatment, the rate of complications after resection for colorectal liver metastases remains high. An awareness of risk factors is essential for the rates of morbidity and mortality to fall to optimal levels. Materials and methods  Of the 240 patients who underwent resection for the first manifestation of colorectal liver metastases, 49 patients with lobectomy or extended hepatectomy (major resections) and 58 with wedge resections within only one liver segment (minor resections) form the basis of this report. A total of 16 variables were analyzed to find the risk factors linked to postoperative morbidity and mortality. Results/findings  Thirty-four patients (31.8%) suffered postoperative complications, and one patient died during the hospital stay (0.9%). In the major resection group, multivariate analysis showed that neoadjuvant chemotherapy [odds ratio (OR): 2.4; p = 0.005], vascular clamping (OR: 1.4; p = 0.008), and intraoperative blood loss with transfusion of three to six packed red cell units (OR: 1.2; p = 0.029) were significantly associated with postoperative morbidity. Vascular clamping was an independent predictor for biliary fistula (OR: 1.2; p = 0.029). Postoperative temporary liver failure was influenced by neoadjuvant chemotherapy (OR: 3.4; p = 0.010), vascular clamping (OR: 1.5; p = 0.015), and requirement of blood transfusion (OR: 2.1; p = 0.016). After minor resections, only a decreased postoperative serum cholinesterase B level was an independent predictor for complications (OR: 2.2; p = 0.001), as well as for hemorrhage (OR: 1.6; p = 0.023). Postoperative mortality was not predicted by any of the factors that were analyzed. Interpretation/conclusion  Factors for complications differ depending on the extent of colorectal liver metastasis resection. Only knowledge and particular consideration of these factors may provide for an optimal postoperative outcome for the individual patient. Ralf Konopke and Stephan Kersting contributed equally to this work     

The utilization and impact of adjuvant therapy following neoadjuvant therapy and resection of pancreatic adenocarcinoma: does more really matter?

BackgroundAlthough neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined.MethodsThe National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated.ResultsOf patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005).ConclusionThis analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection.     

Liver transplantation for hilar cholangiocarcinoma

The most appropriate treatment for Klatskin tumor(KT)with a curative intention is multimodal therapy based on achieving resection with tumour-free margins(R0resections)combined with other types of neoadjuvant or adjuvant treatment(the most important factor affecting KT survival is the possibility of R0 resections,achieving 5-year survival rate of 40%-50%).Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%.In irresectable non-disseminated KT patients,using liver transplantation without neoadjuvant treatment,the 5-year survival rate increase to 38%,reaching 50%survival in early stage.In selected cases,with liver transplantation and neoadjuvant treatment(chemotherapy and radiotherapy),the actuarial survival rate is 65%at 5 years and 59%at 10 years.In conclusion,correct staging,neoadjuvant treatment,living donor and priority on the liver transplant waiting list may lead to improved results.     

Comparison of clinical stage, therapy response, and patient outcome between squamous cell carcinoma and adenocarcinoma of the esophagus

Purpose: To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus. Patients and Methods: We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS. Results: Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA. Among the ACA patients, a significantly larger proportion was male (93% vs 7%; p<0.001), whereas sex was distributed similarly among SCC patients (55% male vs 45% female; p=0.5). A significantly larger percentage of SCC patients were classified as lower TN and overall stage than ACA patients (T2=41% vs 28%, p<0.0001; N0=69% vs 48%, p=0.01; stage II=76% vs 55%, p<0.001). A significantly greater portion of SCCs was categorized as pathologic N0 after treatment (71% vs 65%; p=0.02). Among the pathCR patients in clinical stage II, there were significantly greater proportion of SCC patients (77% vs 63%; p<0.001) than ACA patients. Among the pathCR patients in clinical stage III patients, a significantly greater proportion were ACA patients (38% vs 23%; p<0.001) than SCC patients. The median and 5-yr OS was 53±11 mo and 39% for ACA patients and 35±14 mo and 37% for SCC (median OS, p=0.3). Among pathCR patients, median OS of ACA patients (133 mo) was longer than that of SCC patients but nonsignificant (29 mo; p=0.07); results were similar for non-pathCR patients. DFS results were similar in all subgroups. Among the whole cohort, incidence of local-regional recurrence and distant metastases did not vary significantly. The median time to distant metastases did not vary significantly for pathCR and non-pathCR patients. Conclusions: We believe this is the first study that compares failure outcome of ACA and SCC patients with similar clinical stage after trimodality therapy. Our data suggest that significant differences in clinical stage and post-therapy pathologic stage exist between ACA and SCC. Frequent presence of malignant nodes in the resected specimens of ACA patients resulted in a shorter time-to-metastases suggesting that ACA patients need better systemic control.     

Prognostic significance of the endoscopic ultrasound defined lymph node metastasis count in esophageal cancer

The key prognostic factor which predicts outcome after esophagectomy for cancer is the number of malignant lymph node metastases, but data regarding the accuracy of endoscopic ultrasound (EUS) in determining and predicting the metastatic lymph node count preoperatively are limited. The aim of this study was to assess the prognostic significance of EUS defined lymph node metastasis count (eLNMC) in patients diagnosed with esophageal cancer. Two hundred and sixty‐seven consecutive patients (median age 63 years, 187 months) underwent specialist EUS followed by stage directed multidisciplinary treatment (183 esophagectomy [64 neoadjuvant chemotherapy, 19 neoadjuvant chemoradiotherapy], 79 definitive chemoradiotherapy, and 5 palliative therapy). The eLNMC was subdivided into four groups (0, 1, 2 to 4, >4) and the primary measure of outcome was survival. Survival was related to EUS tumor (T) stage (P < 0.0001), EUS node (N) stage (P < 0.0001), EUS tumor length (p < 0.0001), and eLNMC (P < 0.0001). Multivariable analysis revealed EUS tumor length (hazard ratio [HR] 1.071, 95% CI 1.008–1.138, P= 0.027) and eLNMC (HR 1.302, 95% CI 1.133–1.496, P= 0.0001) to be significantly and independently associated with survival. Median and 2‐year survival for patients with 0, 1, 2–4, and >4 lymph node metastases were: 44 months and 71%, 36 months and 59%, 24 months and 50%, and 17 months and 32%, respectively. The total number of EUS defined lymph node metastases was an important and significant prognostic indicator.     

Grading of tumor regression in non-small cell lung cancer : morphology and prognosis.

OBJECTIVE: Different types of multimodality therapy, including chemoradiotherapy and surgery, increasingly are being used for the treatment of patients with locally advanced non-small cell lung cancer (NSCLC; stages IIIA and IIIB). In this context, the applicability of a morphologic regression grading and its prognostic value were investigated. PATIENTS AND METHODS: In a multicenter phase II trial, 54 patients with locally advanced NSCLC received neoadjuvant bimodality treatment (ie, two cycles of ifosfamide, carboplatin, and etoposide, followed by twice-daily radiation up to 45 Gy with simultaneous administration of carboplatin and vindesine). Forty patients underwent resections. Using the corresponding resection specimens of the primary and regional lymph nodes, the following regression grading was established: grade I, no regression or only spontaneous tumor regression; grade II, morphologic evidence of therapy-induced tumor regression with at least 10% (grade IIa) or < 10% (grade IIb) vital tumor tissue; and grade III, complete tumor regression with no evidence of vital tumor tissue. Regression grading then was correlated with the survival time. RESULTS: Three tumors were classified as regression grade I, 10 were classified as regression grade IIa, 20 were classified as regression grade IIb, and 7 were classified as regression grade III. Patients with tumors of regression grades IIb or III showed significantly longer survival times than those with tumors of regression grades I or IIa (median survival time, 36 vs 14 months, respectively; 3-year survival rate, 52% vs 9%, respectively; p = 0.02). These survival times were also compared for patients who had undergone complete resection (median survival time, not reached vs 23 months, respectively; 3-year survival rate, 56% vs 11%, respectively; p = 0.03). The presurgical clinical response after patients had received neoadjuvant multimodality therapy had no predictive value in assessing the extent of therapy-induced tumor regression in the resection specimen. CONCLUSIONS: After neoadjuvant therapy of patients with NSCLC, the proposed tumor regression grading was of predictive value for long-term survival. Beyond the achievement of complete tumor resection (R0), a therapy-induced tumor regression of < 10% of vital tumor tissue is pivotal for superior long-term outcomes.     

Prognostic value of positive lymph nodes in rectal cancer

Abdominal curative resections for rectal cancer in 109 patients with positive lymph nodes were prospectively studied. The best subdivision of patients for predicting outcome was into 1–3 and >3 positive lymph node groups. Comparison with patients with >3 positive lymph nodes demonstrated that patients with 1–3 positive nodes had less local (35.0 percent vs. 13.0 percent;P =0.007) and less distant recurrences (45.0 percent vs.26.0 percent;P =0.04) and had much better crude five-year survival (58.2 percent vs.17.0 percent; P < 0.0001). For predicting postsurgical outcome in patients with positive lymph nodes, the results justify subdividing patients into the following two prognostic subgroups: 1) those with 1–3 involved lymph nodes and 2) those with metastatic tumor in four or more lymph nodes.     

T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival

PURPOSE: Preoperative chemoradiation therapy is used widely in the treatment of rectal cancer. The predictive value of response to neoadjuvant remains uncertain. We retrospectively evaluated the impact of response to preoperative and, specifically, of T-level downstaging, nodal downstaging, and complete pathologic response after chemoradiation therapy on oncologic outcome of patients with locally advanced rectal cancer. METHODS: There were 88 patients with ultrasound Stage T3/T4 midrectal (n = 37) and low rectal (n = 51) cancers (63 males; mean age 62.6 years). All patients were treated by preoperative 5-fluorouracil-based chemotherapy and pelvic radiation followed by surgical resection in six weeks or longer (56 sphincter-preserving resections). RESULTS: T-level downstaging after neoadjuvant treatment was demonstrated in 36 (41 percent) of 88 patients, and complete pathologic response was observed in 16 (18 percent) of the 88. Of the 42 patients with ultrasound-positive nodes, 27 had no evidence of nodal involvement on pathologic evaluation (64 percent). The overall response rate (T-level downstaging or nodal downstaging) was 51 percent. At a median follow-up of 33 months, 86.4 percent of patients were alive. The overall recurrence rate was 10.2 percent (three patients had local and six had metastatic recurrences). Patients with T-level downstaging and complete pathologic response were characterized by significantly better disease-free survival (P = 0.03, P = 0.04) and better overall survival (P = 0.07, P = 0.08), according to Wilcoxons test comparing Kaplan-Meier survival curves. None of the patients with complete pathologic response developed recurrence or died during the follow-up period. CONCLUSION: T-level downstaging and complete pathologic response after preoperative chemoradiation therapy followed by definitive surgical resection for advanced rectal cancer resulted in decreased recurrence and improved disease-free survival. Advanced rectal cancers that undergo T-level downstaging and complete pathologic response after chemoradiation therapy may represent subgroups that are characterized by better biologic behavior.     

Oncologic Outcomes of Salvage Surgery for Epidermoid Carcinoma of the Anus Initially Managed With Combined Modality Therapy

PURPOSE: Primary chemoradiation failure for epidermoid carcinoma of the anus is treated by surgical resection. This study evaluates the outcome of salvage surgery at one institution.METHODS: All patients (n = 177) with a diagnosis of epidermoid carcinoma of the anus undergoing surgery since 1980 were reviewed. After criteria-based exclusion (n = 115), the remaining patients (n = 62) were analyzed. Kaplan-Meier survival analysis was performed on abdominoperineal resection/low anterior resection patients. Variable comparisons were made using log-rank and Cox regression analyses. Inguinal lymph node dissection patients (n = 5) were analyzed separately.RESULTS: Median follow-up was 24.2 months. Actuarial five-year survival in all abdominoperineal resection/low anterior resection patients (n = 57) was 33 percent (median, 34.1 months). Univariate predictors of decreased survival were tumor size > 5 cm or adjacent organ involvement at salvage, positive nodal disease at salvage, and positive margins. Independent predictors of decreased survival were the same except for tumor size or adjacent organ involvement at salvage (not significant). Patients undergoing potentially curative resections (n = 47) had an actuarial five-year survival of 40 percent (median, 49 months). The univariate and multivariate predictors of both decreased survival and recurrence in this subgroup included: disease persistence after chemoradiation and nodal disease at salvage. Tumor size > 5 cm or adjacent organ involvement at salvage predicted recurrence with only univariate analysis. Interestingly, actuarial five-year survival after potentially curative resection for recurrence after chemoradiation was 51 percent (as opposed to 31 percent for persistence). After potentially curative resections, most documented recurrences (79 percent) occurred within two years and were locoregional (74 percent). Actuarial five-year recurrence-free survival was 46 percent. Three of five inguinal lymph node dissection patients were alive without disease at 21.2, 81.7, and 84.3 months.CONCLUSIONS: Salvage surgery after failed chemoradiation therapy has a reasonable chance of cure. Favorable independent prognostic factors include recurrence (vs. persistence) after chemoradiation (when salvage is potentially curative), absence of nodal disease at salvage, and negative margins. Salvage inguinal lymph node dissection after failed chemoradiation therapy also is potentially curative.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Smoking is associated with steatosis and severe fibrosis in chronic hepatitis C but not B

Objective. The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC. Material and methods. The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded. Results. In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028–1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356–11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003–1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001–1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286–96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted. Conclusions. Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.