What to do after R1-resection of adenocarcinomas of the esophagogastric junction?

BACKGROUND AND OBJECTIVES: The management of R1-resected adenocarcinoma of the esophagogastric junction (AEG) is unclear. We aimed to identify risk factors and prevalence of R1 resections, their recurrence and prognosis, and efficacy of postoperative therapy. METHODS: A single center cohort of 766 consecutive patients undergoing curative intent resection for AEG was analyzed retrospectively. RESULTS: R1-resection rate was 13%. Poorer tumor differentiation, higher T-, N-, and UICC/AJCC-stages were associated with R1-resections. Compared to R0-resected patients, R1-resected patients had a higher incidence of tumor recurrence (77% vs. 32%; P < 0.001) and worse overall survival (5-year overall survival 43% vs. 10%; P < 0.001). The pattern of recurrence did not differ between R0- and R1-resections with distant metastases in 90% and 87% of patients with tumor recurrence. We found a trend towards better overall survival for R1-resected patients receiving postoperative therapy compared to R1-resected patients without postoperative therapy (median 17.4 vs. 14.6 months, P = 0.056). CONCLUSIONS: The association of R1-resections with poor tumor characteristics allows for identification of patients at risk for R1-resection. As in R0-resections, tumor recurrence in R1-resections is mainly systemic, not local. The potential benefit of additive local postoperative therapies in R1-resected patients must be balanced against overall prognosis and therapy-specific morbidity and mortality. J. Surg. Oncol. 2016;114:428-433. © 2016 Wiley Periodicals, Inc.

Small bowel pleomorphic liposarcoma: a rare cause of gastrointestinal bleeding.

In this case report we present a 60-year-old male patient with overt midgastrointestinal bleeding of a primary ileal pleomorphic liposarcoma diagnosed by video capsule endoscopy (VCE). Clinical work-up for final diagnosis and the pathological background of this uncommon tumorous entity of the small bowel will be discussed in this paper.

A multifactorial histopathologic score for the prediction of prognosis of resected esophageal adenocarcinomas after neoadjuvant chemotherapy.

BACKGROUND: For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system. PATIENTS AND METHODS: We evaluated esophageal adenocarcinoma specimens following cis/oxaliplatin-based therapy from two separate centers (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3 = 2 points; ≤ 50 % residual tumor/tumor bed = 1 point; >50 % residual tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of these factors (group A: 3; group B: 4-5; group C: 6) and was correlated with patients' overall survival (OS). RESULTS: The PRSC groups showed significant differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7-2.8]), which could also be demonstrated in both cohorts separately (center 1 p < 0.0001; HR 2.48 [95 % CI 1.8-3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1-2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1-1.2]), and assessment of two goodness-of-fit criteria (Akaike Information Criterion and Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC over the UICC staging. CONCLUSION: The proposed PRSC clearly identifies three subgroups with different outcomes and may be more helpful for guiding further therapeutic decisions than the UICC staging system.

Prevalence and topography of lymph node metastases in early esophageal and gastric cancer.

OBJECTIVE: To determine the prevalence and localization of lymph node metastases in patients with pT1 carcinoma of the esophagus, esophagogastric junction, and stomach. BACKGROUND: Retrospective analysis and topographic description. METHODS: We included 793 consecutive patients with pT1 carcinomas who underwent primary surgery for squamous cell carcinoma (SCC) of the esophagus, adenocarcinomas of the esophagogastric junction (AEG), or gastric cancer (GC). Clinical records and pathology reports were reviewed, and the prevalence and topography of lymph node metastases were identified. RESULTS: The prevalence of lymph node metastases in SCC, AEG, and GC was 7%, 0%, and 5% for pT1a tumors and 24%, 18%, and 14% for pT1b tumors, respectively. Positive lymph node status was associated with worse overall survival (P<0.001). Not only infiltration of the submucosa (P=0.002) but also lymphatic vessel invasion (P<0.001), multifocal tumor growth (P=0.001), lower patient age (P=0.001), and poor tumor differentiation (P=0.05) were associated with nodal disease. These 5 parameters allowed the compilation of a nomogram to estimate the individual risk of lymph node metastases. In SCC, lymph node metastases were found from the neck to the celiac axis. In AEG, nodal disease was limited to the lower mediastinum and the D1 compartment. In GC, lymphatic spread exceeded the D1 compartment in 7% of node positive patients. CONCLUSIONS: Risk estimation for lymph node metastases should not be based on depth of tumor infiltration alone but additional clinicopathological parameters should also be considered. The extent of lymphadenectomy in surgical procedures should respect the presented topography of lymph node metastases.

Chylothorax after esophagectomy for cancer: impact of the surgical approach and neoadjuvant treatment: systematic review and institutional analysis.

BACKGROUND: Esophagectomy is a challenging operation with considerable potential for postoperative complications, including chylothorax. METHODS: Because no randomized controlled trial or metaanalysis is available to clarify the incidence of chylothorax in esophageal cancer surgery, the authors analyzed their own institutional data for 1,856 patients and performed a systematic review using the MEDLINE database (9,794 patients) to identify risk factors, compare success rates of therapeutic approaches, and investigate long-term outcomes. RESULTS: The overall institutional chylothorax rate was 2 % (n = 39). Reoperation was performed for 69 % of the patients. No significant difference was noted between the transthoracic and transhiatal approaches. Regression analysis showed neoadjuvant treatment (odds ratio [OR], 0.302; p = 0.001) and tumor type (OR, 0.304; p = 0.002) to be independent risk factors. The systematic review included 12 studies. Chylothorax occurred for 2.6 % of the patients. Treatment favored reoperation in five studies (70-100 %) and a conservative approach in four studies (58-72 %), with equal mortality rates. No significant difference was found between the transthoracic and transhiatal approaches. CONCLUSION: Chylothorax rates are low in high-volume centers (2-3 %). No significant difference was noted between the transthoracic and transhiatal approaches. Neoadjuvant treatment and tumor type were shown to be independent risk factors. Treatment concept (reoperation vs conservative treatment) did not affect long-term survival.

Effect of preoperative radio(chemo)therapy on long-term functional outcome in rectal cancer patients: a systematic review and meta-analysis.

BACKGROUND: Preoperative radio(chemo)therapy (pR(C)T) significantly reduces the local recurrence risk and is therefore recommended in stage II/III rectal cancer. However, this multimodal treatment approach may be associated with late adverse effects. To determine the impact of pR(C)T on long-term anorectal, sexual, and urinary function, we performed a systematic review and meta-analysis. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for studies reporting on long-term functional outcome after rectal cancer resection with pR(C)T. Only studies that reported anorectal, sexual, and/or urinary function after rectal cancer resection in TME-technique with pR(C)T were eligible for inclusion. RESULTS: Twenty-five studies, including 6,548 patients, were identified. Methodological quality of the eligible studies was low. The majority of studies reported higher rates of anorectal (14/18 studies) and male sexual dysfunction (9/10 studies) after pR(C)T. Few studies examined female sexual dysfunction (n = 4). Meta-analysis revealed that stool incontinence occurred more often in irradiated patients (risk ratio (RR) = 1.67; 95 % confidence interval (CI), 1.36, 2.05; p < 0.0001) and manometric results were significantly worse after pR(C)T (mean resting pressures (weighted mean difference (WMD) = 15.04; 95 % CI, 0.77, 29.31; p = 0.04) and maximum squeeze pressures (WMD = 30.39; 95 % CI, 21.48, 39.3; p < 0.0001)). Meta-analysis of erectile dysfunction revealed no statistical significance (RR = 1.41; 95 % CI, 0.74, 2.72; p = 0.3). Six of eight studies and meta-analysis demonstrated no negative effect of pR(C)T on urinary function (RR = 1.05; 95 % CI, 0.67, 1.65; p = 0.82). CONCLUSIONS: Although quality of studies on long-term functional outcome is limited, current evidence demonstrates that pR(C)T negatively affects anorectal function after TME.

Adenocarcinomas of the esophagogastric junction are more likely to respond to preoperative chemotherapy than distal gastric cancer.

BACKGROUND: Preoperative chemotherapy has been shown to improve outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) and gastric cancer (GC), and histopathologic response has been identified as an independent prognostic parameter in these patients. A recent meta-analysis has identified patients with AEG as benefiting more from preoperative chemotherapy than patients with GC. The aim of this retrospective analysis was to prove these findings in an experienced single-center large patient cohort because there are currently no recruiting prospective clinical trials. METHODS: In a single center, 551 patients underwent preoperative platin-based chemotherapy followed by oncologic surgery for locally advanced AEG and GC. Pretherapeutic clinical parameters were correlated with histopathologic response to preoperative chemotherapy. RESULTS: Histopathologic response (<10% of residual tumor) was found in 130 patients (24%) and was significantly correlated with overall survival (P<0.0001). Tumor localization at the esophagogastric junction (GE junction), lower baseline cT stage, and baseline cN0 stage were significantly associated with histopathologic response (P=0.034, P=0.015, and P=0.002, respectively). In subgroup analyses, the latter two predictive parameters were confirmed only for AEG (n=378) but not for other GC (n=173). AEG patients who were pretherapeutically staged as having cT3/4, cN0 disease (n=73) were identified as the subgroup with the highest rate of histopathologic response (48%). CONCLUSIONS: AEG is more likely to respond to preoperative chemotherapy than GC, a finding that might help identify patients who would benefit from preoperative chemotherapy.

How to classify adenocarcinomas of the esophagogastric junction: as esophageal or gastric cancer?

BACKGROUND: To evaluate whether so-called cardiac adenocarcinomas (adenocarcinomas of the esophagogastric junction type II and III, ie AEG II and III) are better staged as cancers of the esophagus or as cancers of the stomach. METHODS: A single-center cohort of 1141 patients operated for AEG II and III is staged according to the seventh edition of the TNM classification for cancers of the esophagus and cancers of the stomach. Kaplan-Meier and Cox regression analyses are used to evaluate the prognostic performance of these 2 staging schemes. RESULTS: For so-called cardiac adenocarcinomas, the esophageal T classification is monotone. That is, it defines subgroups with continuous decreasing survival with increasing T stage. And it is distinct. That is, survival of these monotonic subgroups differs significantly. The gastric T classification is monotone but not distinct for pT2 versus pT3 (P=0.641) and for pT4a versus pT4b tumors (P=0.130). The type of infiltrated adjacent structure matters with significant differences in prognosis between the esophageal subgroups T4a and T4b (P<0.001). For the N classification, both the esophageal and gastric schemes are monotone and distinct, with decreasing prognosis with increasing number of lymph node metastases. The subclassification of N3a and N3b disease according to the gastric scheme defines 2 subgroups with significant differences in prognosis (P<0.01). Both the gastric and esophageal schemes include heterogeneous stage groups (2 and 1, respectively) and are not distinctive between several stage groups (4 and 3, respectively). CONCLUSIONS: Neither the esophageal nor the gastric scheme proves to be clearly superior over the other, and neither is perfect for AEG II and III. Our analysis includes further hints that so-called cardiac adenocarcinomas have different biological properties compared with genuine gastric and genuine esophageal cancers.

Long-term outcome of 2920 patients with cancers of the esophagus and esophagogastric junction: evaluation of the New Union Internationale Contre le Cancer/American Joint Cancer Committee staging system.

OBJECTIVE: We analyzed the long-term outcome of patients operated for esophageal cancer and evaluated the new seventh edition of the tumor-node-metastasis classification for cancers of the esophagus. BACKGROUND: Retrospective analysis and new classification. METHODS: Data of a single-center cohort of 2920 patients operated for cancers of the esophagus according to the seventh edition are presented. Statistical methods to evaluate survival and the prognostic performance of the staging systems included Kaplan-Meier analyses and time-dependent receiver-operating-characteristic-analysis. RESULTS: Union Internationale Contre le Cancer stage, R-status, histologic tumor type and age were identified as independent prognostic factors for cancers of the esophagus. Grade and tumor site, additional parameters in the new American Joint Cancer Committee prognostic groupings, were not significantly correlated with survival. Esophageal adenocarcinoma showed a significantly better long-term prognosis after resection than squamous cell carcinoma (P < 0.0001). The new number-dependent N-classification proved superior to the former site-dependent classification with significantly decreasing prognosis with the increasing number of lymph node metastases (P < 0.001). The new subclassification of T1 tumors also revealed significant differences in prognosis between pT1a and pT1b patients (P < 0.001). However, the multiple new Union Internationale Contre le Cancer and American Joint Cancer Committee subgroupings did not prove distinctive for survival between stages IIA and IIB, between IIIA and IIIB, and between IIIC and IV. CONCLUSION: The new seventh edition of the tumor-node-metastasis classification improved the predictive ability for cancers of the esophagus; however, stage groups could be condensed to a clinically relevant number. Differences in patient characteristics, pathogenesis, and especially survival clearly identify adenocarcinomas and squamous cell carcinoma of the esophagus as 2 separate tumor entities requiring differentiated therapeutic concepts.

Clinical significance of the costimulatory molecule B7-H1 in Barrett carcinoma.

BACKGROUND: The costimulatory molecule B7-H1 (programmed death-1 ligand-1, PD-L1) has been implicated as a potential regulator of antitumor immunity in various human cancers. To date, no data are available on the role of B7-H1 in Barrett carcinoma. Therefore, we investigated the expression pattern and clinical significance of B7-H1 in a large cohort of patients with Barrett carcinoma. METHODS: Expression of B7-H1 was evaluated by immunohistochemistry in 101 patients with Barrett carcinoma. Expression data were correlated with clinicopathologic features, including TNM stage, UICC (Union Internationale Contre le Cancer) tumor stage, tumor grade, resection status, and survival, and with the number of tumor-infiltrating CD3(+), CD8(+), and CD45RO(+) T lymphocytes. RESULTS: Aberrant B7-H1 expression was found in Barrett carcinoma cells. High tumor B7-H1 expression was significantly associated with advanced T stage (p = 0.002), advanced UICC tumor stage (p = 0.022), and incomplete resection status (p = 0.009). The median survival of patients with high tumor B7-H1 expression was 38 months compared with 136 months for patients with no or low tumor B7-H1 expression. In the multivariable analysis, high tumor B7-H1 expression was significantly associated with an increased risk of death from Barrett carcinoma (hazard ratio, 3.50; 95% confidence interval, 1.66 to 7.38; p < 0.001). CONCLUSIONS: Our data suggest that B7-H1 may represent a new prognostic marker for patients with Barrett carcinoma. Furthermore, given its immune-inhibitory function, B7-H1 may represent a potential target in the treatment of Barrett carcinoma.

Healing occurs in most patients that receive endoscopic stents for anastomotic leakage; dislocation remains a problem.

BACKGROUND & AIMS: There is controversy about the best way to treat esophageal anastomotic leakage. We evaluated the effects of treatment with self-expanding metal stents in patients with esophageal anastomotic leakage after esophagectomy or gastrectomy for cancer. METHODS: We investigated outcomes and procedure-related complications of 115 patients who received endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy at a university hospital from 2004 to 2009. We also performed a systematic literature review on stent therapy and compared outcomes with that of other treatment regimens for esophageal anastomotic leakage. RESULTS: Among the 115 patients who received stents, the in-hospital mortality rate was 9% and complete anastomotic healing was achieved in 70% (95% confidence interval [CI], 64%-76%). Stent dislocation occurred in 53% of the patients (95% CI, 43%-62%), in all patients with esophagocolonostomy, in 61% with esophagojejunostomy, and in 49% with esophagogastrostomy. Three percent of patients (95% CI, 1%-5%) needed laparotomy to remove dislocated stents. Elective endoscopic stent removal was performed in 80% of the patients after a median of 54 days (range 17-427 d); 12% of these patients developed symptomatic anastomotic strictures after stent removal. CONCLUSIONS: Anastomoses completely heal in 70% of patients that receive endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy. Stent therapy should be used in the management of patients with adequately perfused esophageal anastomotic leakage. However, stent dislocation remains a common problem after surgery.

Does a rectal cancer of the upper third behave more like a colon or a rectal cancer?

PURPOSE: This study aimed to evaluate whether cancers in the upper third of the rectum should be treated according to colon or rectal cancer guidelines. METHODS: We evaluated 499 patients with tumors located in the sigmoid colon (299 patients, 60%), the upper third of the rectum (95 patients, 19%), or the middle third of the rectum (105 patients, 21%), International Union against Cancer tumor stage II or III, no preoperative radiochemotherapy, and primary curative tumor resection between 1990 and 2006. Patients' surgical, histopathological, and prognostic parameters were compared. The median follow-up time was 80 months. RESULTS: Patients with sigmoid cancer showed a trend of significantly better estimated cause-specific survival (5-y value +/- 95% CI: 83.6 +/- 4.7%) compared with patients with rectal cancers of the upper third of the rectum (5-y value +/- 95% CI: 74.3 +/- 9.6%) or the middle third of the rectum (5-y value +/- 95% CI: 73.4 +/- 9.2%) (P = .063). Tumor location was an independent prognostic parameter (P = .036), with an increased risk of cause-specific death for rectal cancers of the upper third (hazard ratio, 1.87; P = .007) and of the middle third (hazard ratio, 1.43; P = .022) compared with sigmoid cancers. Stratification of upper third rectal cancers according to tumor grade, tumor infiltration depth (pT), and lymph node status (pN) identified a high-risk group. CONCLUSIONS: Cancers of the upper third of the rectum have more similarities with rectal cancers of the middle third of the rectum than with sigmoid cancers. A subgroup of patients with upper third rectal cancer can be identified who may require a more aggressive therapy than only primary resection followed by adjuvant therapy.

Pouch vs. no pouch following total gastrectomy: meta-analysis and systematic review.

OBJECTIVES: Whether reconstruction after total gastrectomy for gastric malignancies should be done with or without a pouch is a controversial issue in clinical research. There is still no consensus on the reconstruction technique of choice. The aim of this report was to assess the value of pouch formation as a gastric substitute after total gastrectomy compared with reconstruction techniques without a pouch. METHODS: A systematic literature search of the Medline database and the Cochrane Library was carried out and a meta-analysis executed according to the Quality of Reporting Meta-Analyses (QUOROM) statement. Only randomized controlled trials (RCTs) comparing reconstruction techniques with and without a pouch were eligible for inclusion. All trials were independently assessed by two authors. Data on perioperative parameters, postgastrectomy symptoms, eating capability, body weight, and quality of life were extracted from the RCTs for meta-analysis using random-effects models for the calculation of pooled estimates of treatment effects. RESULTS: Nine RCTs comparing Roux-en-Y reconstructions with and without pouch and four RCTs comparing jejunal interpositions with and without a pouch were included. The results of the meta-analyses show that additional pouch formation does not significantly increase morbidity or mortality and does not considerably extend the operating time or the hospital stay. Patients with a pouch complained significantly less of dumping and heartburn and showed a significantly better food intake postoperatively. Quality of life was significantly improved in patients with a pouch compared with patients without a pouch. This difference even increased over time from 6 to 12 and 24 months postoperatively. CONCLUSIONS: This meta-analysis highlights some clinical advantages of pouch reconstruction after total gastrectomy.

Defining a high-risk subgroup with colon cancer stages I and II for possible adjuvant therapy.

AIM: Adjuvant therapy is not routinely recommended in UICC stages I and II colon cancer, but may be considered for high-risk patients. Our aim is to identify clinicopathologic characteristics in colon cancer stages I and II, which are associated with an increased risk of tumour recurrence and tumour-related death. METHODS: We analysed our prospectively documented clinical database of 775 patients with colon cancer stages I and II, which underwent curative resection between 1982 and 2006. No adjuvant chemotherapy was applied. The median follow-up time was 80 months. RESULTS: For the entire study group, 5- and 10-year tumour-specific survival probabilities were 94.8+/-0.9% and 91.0+/-1.4%, respectively. Multivariate analysis identified three tumour characteristics as independent prognostic factors: lymphatic vessel invasion (p=0.034), poor tumour grading (G3/G4) (p=0.020) and extended tumour length (6 cm) (p=0.042). Five-year (10-year) tumour-specific survival for patients without any of the poor prognostic tumour characteristics (ppTCs) was 96.0% (94.7%). There was a significantly increased risk for tumour-related death with increasing numbers of ppTCs (p<0.001). While patients with only one ppTC had a 5-year (10-year) tumour-specific survival of 94.8% (88.9%), it decreased to 88.9% (78.4%) for patients with two ppTCs (hazard ratio (HR) 3.69, 95% confidence interval (CI) 1.67-8.13) and to 87.5% (72.9%) for patients with all three ppTCs (HR 6.56, 95% CI 1.50-26.62). CONCLUSION: Patients with stage I or II colon cancer have a favourable prognosis after radical resection. The presence of two or three poor prognostic tumour characteristics identifies a small patient subgroup (12%) with an increased risk of tumour-related death that may be considered for adjuvant chemotherapy.

Testicular metastasis from adenocarcinoma of the esophagus.

We report the case of a 61-year-old patient, operated on for adenocarcinoma of the esophagus in 2002, who presented in 2007 with a hydrocele and palpable mass of the right testis. Operative exploration and orchiectomy were performed. Histopathology revealed a testicular and epididymidal metastasis from the esophageal adenocarcinoma. Only a few testicular metastases have been reported from gastrointestinal cancers. No case of testicular metastasis from esophageal cancer, including Barrett's carcinoma has been reported. In most cases, the testicular tumor was accompanied by a hydrocele. Therefore, cancerous and metastatic lesions should be considered in the management of hydrocele and testicular masses.

Management of verrucous carcinoma of the hand: a case report.

BACKGROUND: Verrucous carcinoma is a well-differentiated variant of squamous cell carcinoma seen on mucosa and skin, including the hands. METHODS: We report the case of a large verrucous carcinoma of the right palm which was completely resected with a fourth ray resection and remained without evidence of tumor recurrence or metastatic disease during follow-up for 11 years. On this basis, we reviewed all 15 previously published cases of verrucous carcinoma of the hand to define the peculiarities of this uncommon tumor and to give diagnostic and therapeutic recommendations. RESULTS: Verrucous carcinoma is defined by its characteristic clinical presentation as slowly but relentlessly enlarging "wart-like" tumor, by the typical histologic finding of local invasion with only minimal, if any, dysplasia and by the unique biological behavior with low incidence of metastases and good prognosis. For proper diagnosis, both careful physical examination and deep surgical biopsy must be performed. Radical resection is the treatment of choice with histologically confirmed tumor-free resection margins. Lymphadenectomy should only be performed in case of suspicious lymphadenopathy. CONCLUSIONS: Verrucous carcinoma may present a difficult diagnostic problem. After complete surgical resection, it has a good prognosis.

Reduced lymph node yield in rectal carcinoma specimen after neoadjuvant radiochemotherapy has no prognostic relevance.

BACKGROUND: In colorectal surgery UICC/AJCC criteria require a yield of 12 or more locoregional lymph nodes for adequate staging. Neoadjuvant radiochemotherapy for rectal carcinoma reduces the number of lymph nodes in the resection specimen; the prognostic impact of this reduced lymph node yield has not been determined. METHODS: One hundred two patients with uT3 rectal carcinoma who were receiving neoadjuvant radiochemotherapy were compared with 114 patients with uT3 rectal carcinoma who were receiving primary surgery followed by adjuvant radiochemotherapy. Total lymph node yield and number of tumor-positive lymph nodes were determined and correlated with survival. RESULTS: After neoadjuvant radiochemotherapy both total lymph node yield (12.9 vs. 21.4, p < 0.0001) and number of tumor-positive lymph nodes (1.0 vs. 2.3, p = 0.014) were significantly lower than after primary surgery plus adjuvant radiochemotherapy. Reduced total lymph node yield in neoadjuvantly treated patients had no prognostic impact, with overall survival of patients with 12 or more lymph nodes the same as that of patients with less than 12 lymph nodes. Overall survival of neoadjuvantly treated patients was significantly influenced by the number of tumor-positive lymph nodes with 5-year-survival rates of 88, 63, and 39% for 0, 1-3, and more than 3 positive lymph nodes (p < 0.0001). CONCLUSION: The UICC/AJCC criterion of a total lymph node yield of 12 or more should be revised for rectal carcinoma patients.

The predictive value of metabolic response to preoperative radiochemotherapy in locally advanced rectal cancer measured by PET/CT.

BACKGROUND: To evaluate the value of positron emission tomography using fluorodeoxyglucose and computer tomography scan (FDG-PET/CT) for prediction of histopathological response of preoperative radiochemotherapy (RCTX) in patients with rectal carcinoma. METHODS: Thirty patients with uT3 rectal carcinoma were examined by FDG-PET/CT at baseline, 14 days after initiation, and after completion of preoperative RCTX. The FDG decreases seen with PET scanning from baseline to day 14 (early metabolic response) and after completion of therapy (late metabolic response) were compared with histopathological tumor response. One patient denied surgery after RCTX. RESULTS: The mean (+/-SD) reduction of tumor FDG uptake in histopathologically responding compared to non-responding tumors was -44.3% (+/-20.1%) versus -29.6% (+/-13.1%) (p = 0.085) at day 14 and -66.0% (+/-20.3%) versus -48.3% (+/-23.4%) (p = 0.040) after completion of RCTX. Best differentiation of histopathological tumor response was achieved by a cut-off value of 35% reduction of initial FDG uptake at day 14 and 57.5% after completion of therapy. Applying the cut-off values as a criterion for metabolic response, histopathological response was predicted with a sensitivity of 74% (14/19) at day 14 and 79% (15/19) after completion of therapy. The positive predictive value for early metabolic response was 82% (14/17) and for late metabolic response was 83% (15/18). Histopathological evidence of accumulated peritumoral inflammation cells was associated with a minor FDG decrease in five histopathologically responding patients, and influenced the results with negative predictive values of 58% (7/12) and 64% (7/11) at the early and late time points, respectively. CONCLUSIONS: Metabolic response to a preoperative RCTX using FDG-PET/CT in rectal cancer patients can be correlated with histopathological response, but FDG uptake of peritumoral inflammation cells limited the results and led to false negative results.

Prognosis of patients with colorectal cancer is associated with lymph node ratio: a single-center analysis of 3,026 patients over a 25-year time period.

OBJECTIVE: We examined the prognostic impact of lymph node ratio (relation of tumor-infiltrated to resected lymph nodes) in comparison to the pN category and other prognostic factors in patients with colorectal cancer. SUMMARY BACKGROUND DATA: Although the high prognostic impact of lymph node metastases and the total number of lymph nodes to be resected are well established, studies still report large differences in lymph node numbers. The lymph node ratios relevant for prognosis are not clearly defined and not routinely reported. METHODS: We analyzed the clinical and histopathological data of 3026 patients with colorectal cancer at a single surgical center over a 25-year time period (1982-2006). RESULTS: One thousand seven hundred sixty-three colon and 1263 rectal carcinomas were documented. The rate of curative resection was 77.4% and the median number of resected lymph nodes was 16. The optimal cut-off values for prognostic differentiation of LNRs were statistically calculated as 0.17, 0.41, and 0.69. The 5-year overall survival of patients without lymph node metastases was 87%. Patients with lymph node metastases had 5-year overall survival rates of 60.6%, 34.4%, 17.6%, and 5.3% with increasing LNRs (P < 0.001). Multivariate survival analysis identified both the LNR and the pN category, the number of resected lymph nodes, the patient's age, the tumor location (colon vs. rectum), the pT category, the pM status, the R status, the tumor grade, and the year of operation as independent prognostic factors. The LNR had better prognostic value than the pN category (P < 0.05). The analysis of the subgroup of patients separated into colon and rectal cancer patients confirmed the identified LNRs as independent prognostic factors (P < 0.001). CONCLUSIONS: The defined cut-off values of LNRs were strong independent prognostic factors for colorectal cancer patients and should be calculated for risk group stratification.