Bone marrow-disseminated tumor cells in patients with carcinoma of the esophagus or cardia

BACKGROUND: The long-term prognosis after surgical therapy for esophageal carcinoma depends on tumor stage and completeness of resection. Similarly to other epithelial tumors, the presence of micro deposits of neoplastic cells in the bone marrow may indicate residual disease and the potential for recurrence. This study assesses the prevalence of bone marrow-disseminated tumor cells in patients undergoing surgical resection for esophageal carcinoma. In addition, we investigated the agreement between immunohistochemical and molecular techniques for the detection of micrometastases in a subgroup of patients. METHODS: Between January 1998 and November 1999, forty-eight patients with adenocarcinoma of the esophagogastric junction (n = 29) or squamous cell carcinoma of the thoracic esophagus (n = 19) and no evidence of overt metastatic disease entered the study. An immunohistochemical assay (capable of detecting 1 carcinoma cell in 7 x 10(5) bone marrow cells) was used to test bone marrow obtained by flushing a resected rib or by needle aspiration either of the iliac crest or of a rib. A polymerase chain reaction (PCR) molecular technique was also used to identify bone marrow and peripheral blood epithelial cells. RESULTS: Cytokeratin-positive cells were found in 79.1% of the bone marrow samples obtained from the rib, and in only 8% of the needle aspirates either from the iliac crest or from a contiguous rib: This difference is probably explained by the improved removal of metastatic cells with the flushing of the rib. Comparable results were obtained at a qualitative level by the PCR technique on bone marrow. In addition, PCR-positive results were found in 3 of 18 peripheral blood samples. There was no association with tumor type, neoadjuvant therapy, or lymph node status. Patients with a pT3 or pT4 tumor showed, at a borderline statistical level, a higher proportion of cytokeratin-positive cells in the flushed rib. CONCLUSIONS: Bone marrow-disseminated tumor cells are present in the resected rib of a high proportion of patients undergoing esophagectomy for carcinoma, and immunohistochemistry seems to be the method of choice for their quantitative assessment. However, the prognostic and therapeutic implications of this finding need further investigation.     

Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas

Background: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer.Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT.Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months.Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15-18, 2001.     

Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer

Background Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. Methods Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.Results The estimated overall survival (median±SE) in the entire group of patients undergoing resection was 23±4.2 months, with an estimated 3-year survival of 37%±6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.Conclusions Histological response to neoadjuvant CRT—as measured by residual tumor load—may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.     

Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases

OBJECTIVE: To examine the prognostic significance of disseminated tumor cells in blood and bone marrow of patients undergoing surgical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Despite curative hepatic resection of colorectal liver metastases, a high percentage of patients develop tumor recurrence. These recurrences probably originate from disseminated tumor cells released into the circulation before or during surgery. METHODS: Thirty-seven patients with potentially curative (R0) resection of colorectal liver metastases were prospectively enrolled into the study. Preoperative bone marrow samples and preoperative, intraoperative, and postoperative blood samples were examined for disseminated tumor cells by CK20 RT-PCR. RESULTS: Tumor cells were detected in preoperative blood samples in 11 of 37 (30%) patients, in intraoperative blood samples in 17 of 37 (46%) patients, and in postoperative blood samples in 8 of 37 (22%) patients. Four of 25 (16%) patients tested positive for disseminated tumor cells in bone marrow samples. Median follow-up time for all patients was 38 months (range, 10-63 months). Multivariate analysis confirmed tumor cell detection in intraoperative blood (P = 0.009) and in bone marrow samples (P = 0.013) to be independent prognostic factors of tumor relapse. CONCLUSIONS: This is the first study demonstrating that detection of hematogenous tumor cell dissemination during hepatic resection of colorectal cancer metastases predicts tumor relapse. Detection of disseminated tumor cells may help to individualize adjuvant therapy for patients with colorectal liver metastases and to develop surgical strategies to prevent intraoperative hematogenous tumor cell shedding.     

Neoadjuvant therapy reduces the incidence of nodal micrometastases in esophageal adenocarcinoma

Background

We evaluated the impact of neoadjuvant chemoradiotherapy (CRT) on nodal micrometastases (NMMs) in esophageal adenocarcinoma (EAC) patients with histologically negative nodes ([y]pN0).

Methods

Of 48 consecutively treated patients with neoadjuvant CRT, we selected 20 EAC ypN0 patients (group 1). These patients were matched with 20 pN0 EAC patients who had surgery alone (group 2). Harvested (y)pN0 lymph nodes were examined immunohistochemically (anti-CK8/18 [CAM 5.2]) according to a validated sentinel node protocol. A 3rd group (n = 11) staged as ypN1 after neoadjuvant CRT was used as the control group.

Results

Upstaging to NMM+ occurred in 2 patients (10%) in group 1 and in 8 patients (40%) in group 2 (P = .028). Disease-free and overall survival rates in NMM+ patients in group 1 were worse compared with NMM− patients (P = .014 and P = .003, respectively) but comparable with ypN1 patients (n = 11).

Conclusions

A 30% reduction of NMM+ was obtained after neoadjuvant treatment in (y)pN0 patients. NMM+ after CRT had a negative impact on survival in ypN1 patients. These data warrant further investigation in larger prospective datasets.     

Multidisciplinary approach to esophageal and gastric cancer

Despite marked advances in surgical therapy for patients with esophageal, esophagogastric, and gastric cancers, the overall prognosis of these patients has not markedly improved during the past decades. Multidisciplinary approaches using adjuvant postoperative and neoadjuvant preoperative therapeutic principles have received increasing attention with regard to the management of these patients. A series of randomized, prospective trials has demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a convincing survival advantage after complete tumor resection in esophageal, esophagogastric junction, or gastric cancer. The available data on the role of neoadjuvant preoperative therapy are not yet conclusive. Although neoadjuvant therapy may reduce the tumor mass in many patients, several randomized, controlled trials have shown that, compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, that is, potentially resectable, tumors. In contrast, in patients with locally advanced tumors, that is, patients in whom complete tumor removal with primary surgery seems unlikely, neoadjuvant therapy increases the likelihood of complete tumor resection on subsequent surgery, but only patients with objective histopathologic response to preoperative therapy seem to benefit from this approach. Consequently, in the future, improvements in the overall survival of patients with esophageal, esophagogastric junction, or gastric cancer most likely will be achieved only by tailored therapeutic strategies that are based on the individual tumor location, tumor stage, and consideration of established prognostic factors. A clear classification of the underlying tumor entity, a profound knowledge of the prognostic factors applicable, a thorough preoperative staging, and identification of parameters that allow for the prediction of response to preoperative therapy will become essential for the selection of the optimal therapeutic modality for individual patients.     

K-ras mutations detection in paraaortic lymph nodes and its prognostic value after the surgical treatment of pancreas cancer

Survival after surgery of pancreas carcinoma is still poor. Despite an apparently curative resection, tumor rapidly recur. Thus, the arsenal of diagnostic means should be enriched by sensitive methods to detect the minimal residual disease. The frequency of micrometastases in corresponding paraortic lymph nodes after an apparently curative operation was detected using routine histological, immunohistological and polymerase chain reaction for mutated K-ras methods. Tumor tissue was used for the control. 3 cases out of 69 revealed a positive tumor histological reaction, and 5--immunohistological staining. K-ras mutations are detected in 42 (61%) patients, 12 (17%) of those revealed a positive tumor reaction. Only one patient of a control group showed K-ras mutation. All K-ras positive patients revealed a poor survival prognosis and had a tumor relapse after resection.     

Indications and outcome of salvage surgery for oesophageal cancer

OBJECTIVE: Some patients with localised oesophageal cancer are treated with definitive chemoradiotherapy (CRT) rather than surgery. A subset of these patients experiences local failure, relapse or treatment-related complication without distant metastases, with no other curative treatment option but salvage oesophagectomy. The aim of this study was to assess the benefit/risk ratio of surgery in such context. METHODS: Review of a single institution experience with 24 patients: 18 men and 6 women, with a mean age of 59 years (+/-9). Histology was squamous cell carcinoma in 18 cases and adenocarcinoma in 6. Initial stages were cIIA (n=5), cIIB (n=1) and cIII (n=18). CRT consisted of 2-6 sessions of the association 5-fluorouracil/cisplatin concomitantly with a 50-75 Gy radiation therapy. Salvage oesophagectomy was considered for the following reasons: relapse of the disease with conclusive (n=11) or inconclusive biopsies (n=7), intractable stenosis (n=3), and perforation or severe oesophagitis (n=3), at a mean delay of 74 days (14-240 days) following completion of CRT. RESULTS: All patients underwent a transthoracic en-bloc oesophagectomy with 2-field lymphadenectomy. Thirty-day and 90-day mortality rates were 21% and 25%, respectively. Anastomotic leakage (p=0.05), cardiac failure (p=0.05), length of stay (p=0.03) and the number of packed red blood cells (p=0.02) were more frequent in patients who received more than 55 Gy, leading to a doubled in-hospital mortality when compared to that of patients having received lower doses. A R0 resection was achieved in 21 patients (87.5%). A complete pathological response (ypT0N0) was observed in 3 patients (12.5%). Overall and disease-free 5-year survival rates were 35% and 21%, respectively. There was no long-term survivor following R1-R2 resections. Functional results were good in more than 80% of the long-term survivors. CONCLUSION: Salvage surgery is a highly invasive and morbid operation after a volume dose of radiation exceeding 55 Gy. The indication must be carefully considered, with care taken to avoid incomplete resections. Given that long-term survival with a fair quality of life can be achieved, such high-risk surgery should be considered in selected patients at an experienced centre.     

Analysis of Anal Sphincter Preservation Rate According to Tumor Level and Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients

The anal sphincter preservation rate (ASPR) according to tumor level and neoadjuvant chemoradiotherpy (CRT) has not been fully evaluated. Therefore, the aim of this study was to evaluate the correlation between the tumor level, neoadjuvant CRT, and the ASPR in rectal cancer patients. We studied 544 patients (tumor level, 0–6 cm) who underwent curative resection for rectal cancer between 1991 and 2005. Patients were divided six into groups according to tumor level over 1-cm intervals, and the ASPR was evaluated in patients with and without neoadjuvant CRT according to tumor level. Sphincter preservation surgery was performed in 191 patients, and 86 patents underwent neoadjuvant CRT. The overall ASPR was 43.0% (37/86) in patients with neoadjuvant CRT and 33.6% (154/458) in patients without neoadjuvant CRT (P = 0.094). In an analysis according to tumor level, the ASPR was 0.0 vs 0.0% in ≤1 cm, 0.0 vs 2.1% in 1 ≤ 2 cm (P = 0.589), 11.8 vs 16.8% in 2 ≤ 3 cm (P = 0.599), 55.6 vs 20.2% in 3 ≤ 4 cm (P = 0.001), 57.7 vs 45.9% in 4 ≤ 5 cm (P = 0.227), and 66.7 vs 69.5% in 5 ≤ 6 cm (P = 0.827). Neoadjuvant CRT did not increase the ASPR in tumor level within ≤6 cm. However, for the tumor level (3 ≤ 4 cm), neoadjuvant CRT significantly increased the ASPR. Presented at the 20th Annual meeting of International Society for Digestive Surgery in Rome, Italy, November 29–December 2, 2006 (oral presentation in Grassi Prize Session).     

A Highly Active and Tolerable Neoadjuvant Regimen Combining Paclitaxel,Carboplatin, 5-FU,and Radiation Therapy in Patients with Stage II and III Esophageal Cancer

BACKGROUND: The present phase II study aimed to assess the feasibility and efficacy of a new paclitaxel-based neoadjuvant chemoradiation regimen followed by surgery in patients with stage II-III esophageal cancer. METHODS: From January 2002 to November 2004, 50 patients with a potentially resectable stage II-III esophageal cancer received chemotherapy with paclitaxel, carboplatin, and 5-FU in combination with radiotherapy 45 Gy in 25 fractions. Surgery followed 6-8 weeks after completion of neoadjuvant treatment. RESULTS: Patient characteristics: male/female: 44/6, median age 60 years (34-75), median WHO 1 (0-2), adenocarcinoma (n = 42), squamous cell carcinoma (n = 8). Toxicity was mild, and 84 % of the patients completed the whole regimen. Forty-seven patients underwent surgery with a curative intention (transhiatal n = 44, transthoracic n = 3). Pathologic complete tumor regression was achieved in 18 of 47 operated patients (38%). R0 resection was achieved in 45 of 47 operated patients (96%). There were four postoperative deaths (8.5). Postoperative complications were comparable with other studies. After a median follow-up of 41.5 months (21-59) estimated 3- and 5-year survival on an intention-to-treat basis was 56 and 48%. Estimated 3-year survival in responders was 61%, in nonresponders 33%. CONCLUSION: This novel neoadjuvant chemoradiation regimen for treatment of patients with stage II-III esophageal cancer is feasible. Results are encouraging with a high pathologic complete tumor regression and R0 resection rate and an acceptable morbidity and mortality. Preliminary survival data are very promising.     

Ergebnisse der primär chirurgischen Therapie beim Adenokarzinom des ösophagogastralen Übergangs

INTRODUCTION: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide, and classification systems and resection procedures are being controversially discussed. METHODS AND PATIENTS: We report on 225 AEG patients undergoing primary resection in our unit (1986-2000) with a special focus on perioperative morbidity, mortality, and long-term prognosis under consideration of the AEG type (Siewert classification) and operative procedure performed (subtotal esophagectomy with proximal gastric resection in AEG I, total gastrectomy with distal esophageal resection in AEG II and AEG III). RESULTS: Types I, II, and III carcinomas were found in 32%, 42%, and 26% of the patients, respectively, with R(0) resections in 65%, 69%, and 51% ( P=0.039). The overall 5-year survival rates were 29%, 31%, and 14% ( P=0.068), respectively; in R(0)-resected patients, they were 40%, 41%, and 27% ( P=0.771). In univariate analysis, the TNM classification ( P<0.001), R classification ( P<0.001), and tumor stage ( P<0.001) were relevant prognostic factors. In multivariate analysis, only the R classification ( P=0.003), LN ratio ( P=0.012), and N stage ( P=0.027) were independent prognostic factors. In 35 of 177 patients resected with curative intent, R(0) resections could not be achieved, mainly because of residual tumor in the circumferential plane (22/35=63%). Only in 37% of cases (13/35) was the R(1) situation due to exclusive positive oral or aboral resection margins. Therefore, in only 7% of all patients resected with curative intent (13/177) did the question arise of whether the R(1) resection could have been avoided by a different surgical approach. Surgical, pulmonary, and cardiac complications were found in 33%, 26%, and 10%, respectively. The mortality within 30 days was 4%. CONCLUSIONS: Failure of R(0) resection in patients treated with curative intent is mostly caused by residual tumor in the circumferential plane. Therefore, different surgical approaches with varying oral and aboral resection margins are of minor importance for reducing the frequency of R(1) resections. Downstaging of tumors by neoadjuvant treatment may increase the R(0) resection rate.     

Short-term outcomes of laparoscopically assisted surgery for rectal cancer following neoadjuvant chemoradiotherapy: a single-center experience

Objective

The efficacy of laparoscopic treatment of rectal cancer remains unclear, and little is known about its effect on sphincter preservation. We compared short-term outcomes of laparoscopically assisted and open surgeries following neoadjuvant chemoradiotherapy (CRT) for mid and low rectal cancer.

Methods

This study enrolled 137 patients with mid-low rectal cancer who underwent curative resection, 51 by laparoscopically assisted (Lap group) and 86 by conventional open (Open group) surgeries, following neoadjuvant CRT from July 2007 to July 2012. The clinical and surgical findings of the two groups of patients were prospectively collected and analyzed.

Results

Three patients (5.9%) in the Lap group were converted to an open procedure. The mean operating times were similar in both groups. The Lap group had a significantly higher rate of sphincter preservation (62.7% versus 41.9%, P = 0.018) and significantly lower mean blood loss than the Open group. Mean times to first flatus, start of a normal diet, and overall postoperative hospitalization were longer for open surgery. The complication rate (11.8% versus 31.4%, P = 0.009) was significantly lower in the Lap group. Mean distal resection margin, involvement of the circumferential resection margin (2.0% versus 3.5%, P = 1.000), and mean lymph nodes harvested (12 versus 11; P = 0.242) were equivalent in the two groups.

Conclusions

Laparoscopically assisted surgery following neoadjuvant CRT is safe for patients with rectal cancer and provides favorable short-term benefits but without compromising oncologic outcomes. This sphincter-preserving procedure may be a treatment of choice for patients with lower rectal cancer.     

The effects of neoadjuvant chemoradiation on pTNM staging and its prognostic significance in esophageal cancer

For esophageal cancer, it is not clear if pathologic TNM staging after chemoradiation and resection will have the same prognostic significance compared with patients who undergo resection only. From 1995 to 2004, prospectively collected data from 279 patients with intrathoracic squamous cell cancers were analyzed. Patients were given chemoradiation either as part of a randomized trial comparing neoadjuvant chemoradiation with surgical resection alone, or because of advanced disease at presentation. One hundred seventy patients had surgical resection only (surgery), and 109 had neoadjuvant chemoradiation (CRT plus surgery). In the surgery group, pT1, 2, 3, and 4 disease was found in 15, 17, 104, and 34 patients, respectively; their respective pN1 rates were 13.3%, 29.4%, 57.7%, and 64.7%, P<0.01. In CRT plus surgery, pT0, T1, 2, 3, and 4 were found in 48, 12, 23, 21, and 5 patients, respectively; their respective pN1 rates were 31.3%, 16.7%, 21.7%, 52.4%, and 20%, P=0.44. Logistic regression analysis of factors predictive of pN1 showed that pT stage correlated with pN1 status (P=0.005) in the surgery group, but not for the CRT plus surgery group. Cox regression analysis demonstrated that in the surgery group, pT, pN, and R category, and overall pTNM stage, were independent prognostic factors, whereas pN, R category, and gender were identified as relevant for CRT plus surgery. After chemoradiation, pT and overall pTNM stage groupings were not as clearly prognostic as in patients without prior therapy. Nodal status remains an important prognostic factor. Presented at the Forty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, California, May 20–24, 2006 (oral presentation).     

Neoadjuvant chemotherapy in stage III breast cancer

Neoadjuvant chemotherapy in advanced breast cancer can potentially downstage disease prior to definitive surgery. In this study, a doxorubicin-based neoadjuvant regimen was administered to stage III breast cancer patients to assess 1) primary tumor response, 2) tumor involvement of resection margins, and 3) predictive value in cancer outcome. Eighty-two patients with stage IIIA and IIIB breast cancer diagnosed between 1990 and 2003 were studied. All patients received similar chemotherapy regimens, consisting of doxorubicin, cisplatin, and 5-fluorouracil, plus surgery and radiation therapy. End points measured include primary tumor response [complete response (CR) = 100%, partial response (PR) > 50%, or no response (NR) < or = 50%], resection margins for tumor, disease-free, and overall survival. Kaplan-Meier and log-rank tests were performed. Of the 82 patients studied, 34 received neoadjuvant therapy, 48 received conventional postoperative treatment. Seventy-two per cent of the stage IIIB and 22 per cent of the stage IIIA patients received neoadjuvant therapy. In the neoadjuvant group, 29 (85%) patients demonstrated tumor response, 9 (26%) of which were CR. Tumor-free resection margins were achieved in 94 per cent of the neoadjuvant group. Survival analysis demonstrated no benefit comparing neoadjuvant versus postoperative adjuvant therapy but hints at improved disease-free survival in neoadjuvant CR patients (log-rank test, P = 0.07). Eighty-five per cent of patients with stage III breast cancer treated with neoadjuvant chemotherapy experienced clinical response, with 26 per cent CR, and 97 per cent tumor-free resection margins. CR may portend a better cancer outcome.     

Surgical conservation planning after neoadjuvant chemotherapy for stage II and operable stage III breast carcinoma

BACKGROUND: This study was performed to investigate the extent of tumor downstaging achieved in women with operable breast cancer treated with neoadjuvant chemotherapy and breast-conservation surgery, develop recommendations for effective surgical planning, and report local-regional recurrence rates with this approach. METHODS: One hundred nine patients with stage II or III (T3N1) breast cancer were treated in three prospective trials utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC, n = 72) or paclitaxel (n = 37) followed by segmental resection (n = 109) and axillary node dissection (n = 94). Postoperatively, patients received 4 additional cycles of FAC followed by irradiation of the breast. The median follow-up was 53 months. RESULTS: The median tumor size was 4 cm (range 1.1 to 9 cm) at presentation and only 1 cm (range 0 to 4.5 cm) after four cycles of chemotherapy. The primary tumor could not be palpated after chemotherapy in 55% of 104 patients presenting with a palpable mass and therefore required needle localization or ultrasound guidance for surgical resection. Of the 34 patients clinically deemed to have no residual carcinoma in the breast after chemotherapy and before surgery, only 50% of these patients were found to have no residual carcinoma on pathologic examination after surgery. Patients with primary tumors < or =2 cm were significantly more likely than patients with larger tumors to have complete eradication of the primary tumor prior to surgery (P <0.001). The 5-year local-regional recurrence rate was 5%. CONCLUSIONS: Tumor downstaging is marked in patients with operable breast cancer and requires close monitoring during chemotherapy. We recommend placement of metallic tumor markers when the primary tumor is < or =2 cm to facilitate adequate resection and pathologic processing. Resection of the tumor bed remains necessary in women deemed to have a complete clinical response to ensure low rates of recurrence.     

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??Optimal timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer CAO Jian, YE Ying-jiang??WANG Shan. Department of Gastrointestinal Surgery, Beijing University People’s Hospital, Beijing 100044, China
Corresponding author: YE Ying-jiang, E-mail: yjye101@sina.com
Abstract The standard treatment for locally advanced rectal cancer??LARC?? is curative surgical resection??combined with neoadjuvant chemoradiation therapy ??nCRT?? and additional adjuvant therapy if indicated. But the optimal interval between CRT and surgery is still unclear. Prolonging the interval to 12 weeks may lead to significantly higher rates of tumor downstaging and pathologic complete response??pCR??. However??delayed surgery may increase the technical difficulty??and reduce the quality of surgery. Whether prolonged interval can improve long-term outcome is uncertain. Individualized treatment strategies should be based on the patient's condition.     

Carcinoma of the Ampulla of Vater: Patterns of Failure Following Resection and Benefit of Chemoradiotherapy

Background

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery.

Methods

A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan?CMeier method.

Results

A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n?=?43) or neoadjuvant (n?=?18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P?=?.03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8?years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P?=?.001) with trend toward 3-year DFS (66% vs 48%, P?=?.09) and OS (62% vs 46%, P?=?.074) benefit in patients receiving CRT.

Conclusions

Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.     

Surgical results on N2 lung cancer with special reference to correlation between tumor size and extension of lymph node metastases]

Systematic lymph node dissection was performed for every patients undergoing surgical intervention. Since 1981, there were 218 stage IIIA-N2 patients who underwent resection with two operative mortality. The five-year survival rate of whole cases was 22.6%, and that of 152 completely resected cases was 30.0%. Favorable factors on long-term survival of pN2 patients were cN0, T1-2 N2M0, single mediastinal node involvement, and tumor less than 20 mm or less. The five-year survival rates of stage IIIA-N2 patients with tumor diameter of < or = 20 mm, 21-30 mm, 31-50 mm, and > or = 51 mm were 48.1%, 27.7%, 31.2%, and 16.7%, respectively. When micrometastases to lymph node in the p-stage I patients (diagnosed by H-E staining) were examined by immunohistochemical staining, 36 patients (27%) out of 132 verified micrometastases in the lymph nodes.     

Magen- und Adenokarzinome des ?sophagogastralen ��bergangs

According to the current European and German S3 guidelines, neoadjuvant chemotherapy is now an integral part of the treatment of locally advanced gastric cancer and adenocarcinoma of the esophagogastric junction. Neoadjuvant therapy seeks to achieve downsizing of the primary tumor, lowering of the T and N categories and eradication of micrometastases. As the indications for neoadjuvant treatment are based on pretherapeutic information alone, a sophisticated clinical staging plays a central role. Despite all progress made in the field of diagnostic work-up, clinical staging often fails. Despite this fact, controlled randomized trials showed that neoadjuvant chemotherapy enhances the rate of curative (R0) resections and reduces the likelihood of systemic relapse. Overall, survival can be improved by neoadjuvant chemotherapy. The current research is focused on the molecular prediction of response and early response monitoring with functional imaging. New targeted drugs are being integrated into the peri-operative treatment.