Histopathological Regression Research Articles

Clinical and histopathological characteristics of a family with R1141X mutation of pseudoxanthoma elasticum – presymptomatic testing and lack of carrier phenotypes

Pseudoxanthoma elasticum (PXE) is a heritable ectopic mineralization disorder affecting cutaneous, ocular, and cardiovascular systems, caused by mutations in the ABCC6 gene. PXE presents with a marked clinical and genetic heterogeneity. Furthermore, heterozygous carriers may present with limited histopathological features. This study was conducted to investigate a patient with PXE and her family members clinically, histopathologically, and genetically. Clinical and histopathological examinations and mutation analyses of ABCC6 gene were performed. Lesional skin biopsy of the patient with PXE demonstrated clumping and fragmentation of elastic fibers, and calcification in the dermis. Non-lesional axillary skin samples of the husband, daughter, and older son were histopathologically normal. The skin from a similar region of a younger son revealed elastic fibers with some fragmentation and clumping but no mineralization. The patient with PXE was homozygous for the R1141X mutation in the ABCC6 gene. The husband had wild-type alleles, while all children were heterozygous carriers. Daily treatment of antioxidant therapy with tocopherol acetate and ascorbic acid was prescribed to the patient with PXE. After oneyear, both clinical and histopathological regression of the lesions was observed; however, lesions began to progress during the additional 6-month period of treatment. The mutation analyses of ABCC6 gene are important to determine the genotype of both patients with PXE and putative heterozygous carriers, as histopathological features of carriers may differ even in the same family. The role of antioxidant therapy for PXE is unclear, and there is a need for controlled clinical trials.

Histopathological regression grading matches excellently with local and regional spread after neoadjuvant therapy of rectal cancer

Histopathological regression grading has been shown to predict outcome in chemoradiated rectal cancer. Lymph node spread is still considered the most important single prognostic parameter. Therefore, we investigated the association of regression grading with tumor spread in a single center retrospective cohort.102 consecutive patients who had undergone neoadjuvant therapy for rectal adenocarcinoma were included. Surgery was performed, including total mesorectal excision. Pathological examination included UICC staging and Dworak's five-tier tumor regression grading.Histological complete response was achieved in 16.7% of cases. Dworak's regression grading and a simplified two tier scheme both correlated excellently with ypT, ypN and UICC stage. However, cases with poor histological response were strongly represented in ypN0.Tumor regression grading is a reliable method for assessment of response to neoadjuvant therapy, but the optimal cut-off for separating good and poor response remains to be established based on clinical outcome.

A prospective multicenter phase II study evaluating multimodality treatment of patients with peritoneal carcinomatosis arising from appendiceal and colorectal cancer: the COMBATAC trial

BackgroundPeritoneal carcinomatosis is regarded as a common sign of advanced tumor stage, tumor progression or local recurrence of appendiceal and colorectal cancer and is generally associated with poor prognosis. Although survival of patients with advanced stage CRC has markedly improved over the last 20 years with systemic treatment, comprising combination chemotherapy +/− monoclonal antibodies, the oncological outcome—especially of the subgroup of patients with peritoneal metastases—is still unsatisfactory. In addition to systemic therapy, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are specific treatment options for a selected group of these patients and may provide an additional therapeutic benefit in the framework of an interdisciplinary treatment concept.Methods/designThe COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase II trial investigating perioperative systemic polychemotherapy including cetuximab in combination with CRS and HIPEC patients with histologically proven wild-type KRAS colorectal or appendiceal adenocarcinoma and synchronous or metachronous peritoneal carcinomatosis. The planned total number of patients to be recruited is 60. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), perioperative morbidity and treatment-associated toxicity, feasibility of the combined treatment regimen, quality of life (QoL) and histopathological regression after preoperative chemotherapy.DiscussionThe COMBATAC trial is designed to evaluate the feasibility and efficacy of the combined multidisciplinary treatment regimen consisting of perioperative systemic combination chemotherapy plus cetuximab and CRS plus bidirectional HIPEC with intraperitoneal oxaliplatin.Trial registrationClinicalTrials.gov Identifier: NCT01540344, EudraCT number: 2009-014040-11

Evaluation of Clinical and Histopathologic Prognostic Factors for Survival in Canine Osteosarcoma of the Extracranial Flat and Irregular Bones

Osteosarcoma is the most common bone tumor in dogs. However, current literature focuses primarily on appendicular osteosarcoma. This study examined the prognostic value of histological and clinical factors in flat and irregular bone osteosarcomas and hypothesized that clinical factors would have a significant association with survival time while histological factors would not. All osteosarcoma biopsy samples of the vertebra, rib, sternum, scapula, or pelvis were reviewed while survival information and clinical data were obtained from medical records, veterinarians, and owners. Forty-six dogs were included in the analysis of histopathological variables and 27 dogs with complete clinical data were included in the analysis of clinical variables. In the histopathologic cox regression model, there was no significant association between any histologic feature of osteosarcoma, including grade, and survival time. In the clinical cox regression model, there was a significant association between the location of the tumor and survival time as well as between the percent elevation of alkaline phosphatase (ALP) above normal and survival time. Controlling for ALP elevation, dogs with osteosarcoma located in the scapula had a significantly greater hazard for death (2.8) compared to dogs with tumors in other locations. Controlling for tumor location, every 100% increase in ALP from normal increased the hazard for death by 1.7. For canine osteosarcomas of the flat and irregular bones, histopathological features, including grade do not appear to be rigorous predictors of survival. Clinical variables such as increased ALP levels and tumor location in the scapula were associated with decreased survival times.

Neoadjuvant treatment improves capsular integrity and the width of the fibrous capsule of high-grade soft-tissue sarcomas

BackgroundNeoadjuvant treatment is thought to improve resection with margin-negative surgery in locally advanced soft-tissue sarcomas (STS). Treatment-induced alterations of the tumor peripheryhave not yet been microscopically evaluated. ObjectiveThis histopathological study compared limb STS with primary resection and those that had undergone neoadjuvant treatment, emphasizing microscopic changes of the fibrous capsule (FC) and reactive zone (RZ) after neoadjuvant treatment. Patients and methodsPatients with primary high-grade limb sarcomas (N = 76) which have not previously been treated were included. Of those, 37 were primarily resected and 39 were treated with one of the following neoadjuvant treatment modalities: 7x chemotherapy (CTX), 3x radiotherapy (RT), 15x isolated limb perfusion (ILP), 8x CTX + RT, and 6x CTX + ILP. Sizes of the FC and RZ were microscopically measured, and FC-integrity was documented. Histopathologic regression was expressed as a percent. ResultsOnly 35.1% of untreated sarcomas showed an intact FC. We observed significantly higher capsular integrity after treatment (76.9%). Additionally, the average width of the FC (0.21 mm vs. 0.61 mm) and RZ (0.67 mm vs. 1.48 mm) increased significantly. The extent of histopathologic regression showed a correlation with capsular integrity and width. The combination of two treatment modalities (CTX + RT or ILP) showed strongest effects at the tumor periphery. ConclusionsNeoadjuvant treatment stabilizes the tumor periphery in STS (e.g., the capsule). Concerning local treatment strategies, these novel histopathologic insights might significantly influence the decision as to whether primary resection is advisable in advanced local soft-tissue sarcoma.

Review article: the reversibility of cirrhosis

Cirrhosis is the end result of many types of chronic liver diseases. Recent developments in the understanding of the process of hepatic fibrogenesis have revealed that the process is a dynamic one and a capacity for recovery from any degree of fibrosis including those associated with cirrhosis is plausible. To review current evidence of histopathological reversibility following drug therapy of more common aetiologies of cirrhosis. A PubMed search was performed and the evidence for histopathological regression of advanced fibrosis/cirrhosis following drug therapy was reviewed as of the end of February 2012. There is abundant clinical evidence in support of the idea of the reversibility of cirrhosis in patients with different aetiologies of advanced hepatic disease including viral, autoimmune and metabolic/infiltrative liver disease. The concept of cirrhosis has changed from being a form of static and irreversible entity to a dynamic and reversible diseases stage. Novel therapeutic strategies are under investigation to target specific steps in the process of fibrogenesis with the aim of reversing advanced fibrosis/cirrhosis.

Preoperative concurrent chemoradiotherapy for stages II–IV oral squamous cell carcinoma: a retrospective analysis and the future possibility of this treatment strategy

This study evaluated survival in 154 patients with stages II–IV oral squamous cell carcinoma (OSCC) treated with preoperative concurrent chemoradiotherapy and assessed the future use of this treatment strategy. 14 patients exhibited advanced stage II, 73 exhibited stage III and 67 exhibited stage IV. All patients received 40Gy irradiation and concurrent cisplatin-based chemotherapy in two courses. Radical surgery was undertaken after 2–6 weeks. The clinical tumour response, histopathologic regression grade, residual tumour grade (RGrade) in the primary tumour and the level of residual pN+ were associated with prognosis. 90% of patients with complete response and 73% of patients with good partial response in the primary tumour were RGrade 0 (no residual tumour cells) or RGrade 1 (viable tumour cells remained within central superficial portion). In patients with complete response in the neck, residual pN+ was only seen in levels IB (8%) and IIA (8%); the higher the level of residual pN+, the lower the survival rate (p<0.0001). This treatment strategy was excellent for stages II–IV OSCC. It may be possible to perform minimally invasive surgery in which the extent of resection in primary tumour and neck is reduced in patients who achieve good response following preoperative chemoradiotherapy.

Possible predictors of histopathological response to neoadjuvant chemoradiotherapy for rectal cancer

The response to neoadjuvant chemoradiotherapy (CRT) varies greatly in patients suffering from locally advanced rectal cancer. Our aim was to correlate the response to CRT with the pre-treatment expression of heat shock protein 90 (Hsp90), small heat shock protein 16.2 (sHsp 16.2), phospho-Akt (p-Akt), growth hormone-releasing hormone receptor (GHRH-R) and heme-binding protein 2 (SOUL) in order to try to identify one or more as a predictive marker. Sixty-nine patients receiving combined CRT for locally advanced rectal cancer were examined retrospectively. Surgical resection was carried out 6-9weeks following CRT. The histopathological response to neoadjuvant treatment was determined according to the modified Mandard score. Using immunohistochemistry, we investigated the relationship between the expression of the five cited proteins in the pre-operative samples as well as various clinical parameters and the histopathological regression of the tumors. Thirty-one patients (48%) were good responders, and 33 patients (52%) were found to respond poorly to neoadjuvant therapy. Among patients undergoing surgery 7weeks following CRT, there were significantly more good responders than among patients who underwent surgery sooner (63% vs. 37%). High levels of expression of GHRH-R and Hsp90 were shown to be significantly correlated with minor or absent histological regression. GHRH-R and Hsp90 were found to be independent predictive factors of histopathological response to neoadjuvant RCT. Since GHRH-R antagonists and Hsp90 inhibitors are currently being tested as potential anticancer agents, our study implies the possible elaboration of an effective and individualized treatment of poor responders.

Significance of Histopathological Tumor Regression After Neoadjuvant Chemotherapy in Gastric Adenocarcinomas

An increasing number of patients with locally advanced gastric carcinomas (GC) are being treated with preoperative chemotherapy before surgery. Histopathological tumor regression may have an important prognostic impact in addition to the UICC-TNM classification system. We evaluated the histopathological tumor regression in 480 surgical resection specimens of GC after neoadjuvant cisplatin-based chemotherapy, using an established system encompassing three tumor regression grades based on the estimation of the percentage of residual tumor tissue at the primary tumor site in relation to the macroscopically identifiable former tumor bed. Tumor regression was correlated to clinicopathological characteristics and patient survival. Of the patients in this study, 102 (21.2%) had complete or subtotal tumor regression (<10% residual tumor), 121 (25.2%) had partial tumor regression (10-50% residual tumor), and 257 (53.5%) had minimal or no regression (>50% residual tumor). Tumor regression was significantly associated with posttreatment tumor category (pT), lymph node status (pN), lymphatic invasion status (pL), and resection status (P < 0.001). Major histopathological regression was less frequent in tumors of the distal stomach and tumors of nonintestinal type (P = 0.003). Tumor regression (P = 0.009) and postoperative Lymph node status (P < 0.001) were independent prognostic factors for survival in a multivariate analysis of tumor regression, ypT/N/L category, resection status, grading and Lauren´s classification. Assessment of histological tumor regression after preoperative chemotherapy in GC provides objective and highly valuable prognostic information in addition to posttherapeutic lymph node status. A standardized tumor regression grading system should be implemented in pathological reports of these tumors.

Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy

Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer. Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3-4/N+) were treated with preoperative treatment: 1-patients receiving induction Ch or 2-neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor. There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high-body mass index (BMI > 25 kg/m(2) ) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; χ(2) , P = 0.0024). Preoperative treatment with Ch or ChRT for locally advanced gastric cancer can be performed safely with an acceptable operative morbidity and low operative mortality rate with careful consideration of the added risk associated with BMI and surgical resection of the pancreas and spleen. Ch and ChRT is feasible and effective in terms of pathological response and R0 resection.

Tumor vascularization and histopathologic regression of soft tissue sarcomas treated with isolated limb perfusion with TNF‐α and melphalan

Isolated limb perfusion (TM-ILP) achieves high response rates in soft tissue sarcomas (STS). Some tumors show an insufficient association between radiological and pathological response. We investigated STS after TM-ILP with a primary emphasis on histologic regression patterns. In 53 patients with STS, TM-ILP with subsequent tumor resection was performed. Regression was assessed by the Salzer-Kuntschik regression scale. Microvessel density (MVD) of primary biopsies of 37 patients was determined by immunohistochemistry. Tumor regression was correlated with MVD of primary biopsies and other clinico-pathological parameters. Regression presented mainly as necrosis or fibrosis/sclerosis upon histopathology. MFH, leiomyosarcoma, or clear cell sarcoma (CCS) responded well; whereas liposarcomas, synovial sarcomas, or MPNST were poor responders. MFH often had abundant necrosis; while other STS mainly presented with fibrosis/sclerosis. MVD had no influence on regression grade but modulated histologic regression patterns. Excellent regression demonstrated a trend toward an association with improved survival and local control. TM-ILP yielded high response rates in STS. Regression after TM-ILP exhibits MVD-dependent histopathologic patterns and variable efficacy in different sarcoma types. Complete regression seems to be a favorable prognostic factor. A concerted consideration of histopathology and clinical findings may contribute to a better clinical assessment of regression after TM-ILP.

Metabolic turn over of amyloid fibrils and post-treatment regression of amyloid deposits in systemic amyloidosis with polyneuropathy

Systemic amyloidosis that includes familial transthyretin (TTR)-related amyloid polyneuropathy (FAP) and primary systemic immunoglobulin light chain (AL)-derived amyloidosis was long considered to be an incurable disease, but effective therapeutic approaches developed during 20 years ago: liver transplantation for FAP and high dose melphalan with autologous peripheral blood stem cell transplantation (Auto-PBSCT). Systemic amyloidosis is characterized by the presence of an amyloid precursor protein in serum and both treatments can cease the production of amyloid precursor proteins in serum. After transplantation the progression of FAP symptoms certainly stopped, and the patients who were in an early stage of the disease and underwent successful operation showed considerable improvement in their quality of life. Similar clinical recovery was seen in primary systemic AL amyloidosis patients with polyneuropathy after high dose melphalan with auto-PBSCT. Histopathological regression of amyloid deposits on aspirated abdominal fat tissues and/or gastroduodenal mucosa was demonstrated in the patients with long post-treatment courses, indicating that an amyloid precursor protein is dynamically turned over in the lesions with amyloid deposits.

Histopathological regression grading versus staging of rectal cancer following radiotherapy

To compare histological grading of rectal cancer radiotherapy response with pathological staging as a prognostic indicator. Histological tumour regression was five tier graded in 102 rectal cancer patients treated with preoperative radiotherapy [short course (n = 34), long course (n = 68)]. Differences between these grades and between the two radiotherapy regimes were assessed. These variables, pTMN staging and others were correlated with relapse free survival at 3 years. 22 patients suffered disease recurrence and four died during a mean post-operative follow-up of 40.3 months. There were 52 good responders (tumour regression grades 1-3) and 50 poor responders (tumour regression grades 4-5). Regression was greater following the long course regime (p < 0.0001). Otherwise, there were no significant differences between the response groups and between the two regimes, including the number of lymph nodes found in the resected bowel. Only the pN status correlated with relapse free survival on multivariate analysis (p = 0.0004; HR = 4.26, 95%CI = 1.66-10.93 for pN2 versus pN0). The number of lymph nodes found for staging was not influenced by either the extent of primary tumour regression or the type of radiotherapy. pN status, but not tumour regression grade, is a reliable predictor of survival.

Preoperative radiotherapy with capecitabine and mitomycin C in locally advanced rectal carcinoma

To evaluate the efficacy and safety of preoperative radiotherapy with capecitabine and mitomycin C in patients with locally advanced rectal cancer. A prospective, open-label, non-randomized, phase II study was performed on 49 patients with locally advanced rectal cancer. Preoperative radiotherapy was conducted on linear accelerators (15 or 18MV) with a tumor dose of 45Gy in 25 fractions over 5weeks, combined with mitomycin C 7mg/m(2) on days 1 and 29 and oral capecitabine 825mg/m(2) twice daily on days 1-35. Surgery was performed 5-6weeks after the end of chemoradiation. The primary study endpoint was histopathological complete regression rate (pCR; Dworak grade 4). Disease stage at diagnosis was T3 in 34 patients (69%) and T4 in 15 patients (31%). Positive lymph nodes were diagnosed in 28 patients (57%). Toxicity (all grades) was documented in 35 patients (71%). Grade 3 toxicities were radiation dermatitis (25%), diarrhea (2%), neutropenia (2%), and granulocytopenia (2%). No patient experienced grade 4 toxicity. A pCR was seen in 8 (16%, 95% CI 9-29%) patients, a major response was noted in 24 (49%) patients and a minor response in 14 (29%) patients. R0 resection was performed in 46 patients (93.9%) and R1 in 3 patients (6.1%). Histopathological tumor downstaging was documented in 26 patients (53%). One-year disease-free survival was 93.3% and 1-year survival was 97.7%. Preoperative chemoradiation with capecitabine and mitomycin C appeared to be effective with low toxicity in patients with locally advanced rectal cancer.

Individual Radiosensitivity and Correlation with Tumoral Regression

On the one hand, higher individual radiosensitivity increases the risk for side effects of radiotherapy, on the other hand it could also lead to improved tumor response after neoadjuvant chemoradiation. Our point of interest was the correlation of individual radiosensitivity (γH2AX as a reliable factor of radiosensitivity) and regression of the rectal cancer. We investigated a total of 22 patients (19 male, 3 female, all in stage T3 N0/N + M0) with locally advanced rectal adenocarcinoma. All patients received neoadjuvant chemoradiation (RCT) followed by resection. Before treatment, 2ml of blood was collected, lymphocytes were isolated and irradiated with 2 Gy. After 24 hours, lymphocytes were stained with γH2AX antibodies. We compared our results with untreated lymphocytes of the same patient. At least 500 lymphocytes (and the included γH2AX -foci) were microscopically analyzed per patient. Subsequently, we statistically evaluated the correlation of the number of γH2AX foci (γH2AX as a sign for unrepaired DNA DSB), and tumor regression (RG) by Dworak et al. (RG 0 to 4; RG 0: no regression, RG 4: complete regression). Five of 22 (23%) had a complete (RG 4), and 11 (50%) patients an almost complete tumoral regression (RG 3); However, 6 patients showed only a minor regression (RG1-2). In the untreated lymphocytes an average of 0.36 (± 0.21) foci was counted; after irradiation with 2 Gy and a 24 hour delay 2.25 Foci were still present. Tumoral regression (RG 3 + 4 vs. RG 0-2) correlated positively (p = 0.05) with the number of γH2AX-foci. However, regression did not correlate with other parameters such as age, weight, tumor size, dose and volume. In patients with adenocarcinoma of the rectum there is an obvious positive correlation of remaining γH2AX foci in peripheral lymphocytes and histopathological regression of primary tumor. These findings could be an indication that patients of rectal cancer with increased radiosensitivity benefit of better response to neoadjuvant RCT.

Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer

The current study was conducted to evaluate the maximum tolerable dose of weekly gemcitabine administered simultaneously with radiation and cisplatin in patients with locally advanced nonsmall cell lung cancer (NSCLC). Patients with stage IIIA/B NSCLC received concurrently 63 grays radiation and 20 mg/m² cisplatin Day 1 to 3 in Weeks 1 and 5, plus weekly gemcitabine at escalating doses (150-700 mg/m²) on Fridays after radiation to avoid radiosensitization. The authors assessed dose-limiting toxicities according to Common Toxicity Criteria. The primary endpoint was maximum tolerated dose (MTD) of gemcitabine. Tumor resectability, survival, and disease-free survival (DFS) were also determined. Forty-two patients were accrued, of whom 95% received radiation and 66% cisplatin as above. Weekly doses of gemcitabine were escalated to 700 mg/m². Grade 3 dysphagia and 1 case of fatal, probably treatment-related pulmonary deterioration established the MTD of gemcitabine at 550 mg/m² weekly. Twenty-five patients underwent surgery, and histopathological complete regression was documented in 26% of these patients. Overall, median actuarial survival and DFS were 23.8 and 12.4 months, respectively. Gemcitabine at doses up to 550 mg/m² weekly can be given simultaneously with radiation and cisplatin to patients with locally advanced NSCLC. Radical resection thereafter is feasible. The impact of this aggressive therapy should be evaluated further.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

The objective of this study was to evaluate positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients. FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik. FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS. FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Association of the VEGF 936C&gt;T Polymorphism with FDG Uptake, Clinical, Histopathological, and Metabolic Response in Patients with Adenocarcinomas of the Esophagogastric Junction

The MUNICON trial confirmed prospectively the usefulness of early response evaluation by 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography (FDG-PET) . Metabolic responders (R) showed initially a higher FDG uptake compared with nonresponders (p = 0.018). An association of the vascular endothelial growth factor (VEGF) 936C>T polymorphism and FDG uptake was reported for breast cancer. Therefore, we investigated the VEGF 936C>T polymorphism for an association with response and survival. The study was based on 110 patients included in the MUNCON trial (103 male, seven female; 75 AEG I, 35 AEG II, event-free survival (EFS) median 21.1 ± 4.6 months). Response was significantly associated with EFS. The VEGF 936C>T polymorphism was determined by PCR and restriction fragment length polymorphism analysis. For analysis, the T-variants were combined. One hundred two patients were evaluable. Seventy-two patients showed the CC, 24 the CT, and six the TT genotype. Median EFS was 29.3 months for CC and 11.7 months for CT/TT (p = 0.04). No association of the genotypes (CC or CT/TT) with the SUV or response was found. Multivariate analysis revealed histopathological regression (p = 0.003) and genotype (p = 0.04) as independent prognostic factors. A combination of genotype and PET response (Gen-PET) defines three prognostic groups early in the course of treatment (p = 0.002). Cox regression analysis including clinical and histopathological response and Gen-PET reveals Gen-PET as independent prognostic factor (p = 0.003). The VEGF 936C>T polymorphism is a prognostic factor in patients undergoing neoadjuvant chemotherapy, although it is not associated with FDG uptake and response. The combination of metabolic response and VEGF 936C>T polymorphism defines three different prognostic groups. These findings need to be confirmed prospectively. This study has been registered in the European Clinical Trials Database as trial 2007-003356-11.

Histological Regression of Squamous Esophageal Carcinoma Assessed by Percentage of Residual Viable Cells after Neoadjuvant Chemoradiation is an Important Prognostic Factor

BackgroundWhether the TNM staging system is applicable after neoadjuvant chemoradiation in esophageal cancer is controversial. The aim of this study was to evaluate the prognostic value of histopathological regression of the primary tumor in postchemoradiated patients.Materials and MethodsThe pretherapeutic and pathological ypTNM stages of patients who have had neoadjuvant chemoradiation followed by esophagectomy were analyzed. The percentage of residual viable cells of the primary tumor (ypV) and other clinicopathological factors were tested for their prognostic value.ResultsOf 175 recruited patients, 55 (31.4%) achieved pathological complete response. The median survival of these 55 patients was significantly longer than those with other disease stages (124.8 vs 21.1 months) (P < .001). Gender, ypT, ypN, ypTNM, and ypV stage were significant prognostic factors in univariate analysis. In patients without nodal metastases, the median survival in patients with residual viable cells in the primary tumor (ypV+) was 24.6 months, compared with that of 124.8 months in those with no viable cells (ypV0) (P = .043). In those who had nodal metastases, the median survival of patients with ypV0 and ypV+ were 21.2 months and 17.4 months respectively (P = .37). Cox regression analysis showed that male gender, high percentage of residual viable cells (ypV), and positive nodal status (ypN1) were independent predictors of poor prognosis.ConclusionsIn patients who underwent neoadjuvant chemoradiation therapy, histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor in addition to nodal status and gender.

Analysis of patients with complete histopathological tumour regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Background: Our aim was to present the effect of the neoadjuvant chemoradiation therapy on the development of the complete histopathological tumour regression in patients with locally advanced rectal cancer and its influence on a five-year survival of these patients. Methods: In total, 223 patients were included in the analysis; 109 patients had the locally advanced rectal cancer; 75 patients received the neoadjuvant chemoradiation therapy, which was later followed by surgery; 34 patients were treated with the surgery alone. The surgical procedure was done 6 to 8 weeks after the chemoradiation therapy and it was preceded by haematology and biochemical analyses. In addition, patients were examined by ultrasound and MRI imaging of liver to evaluate the effects of neoadjuvant chemoradiation therapy. Accordingly, we had two patient groups: patients with the complete histopathological tumour regression and patients with the incomplete or no regression. We performed the statistical analysis of all locally advanced rectal cancer patients and determined their survival. Results: The complete histopathological tumour regression was found in 10.7% of 75 patients who were treated with preoperative chemoradiation. The down staging of the tumour appeared in 53.3% of patients. There were no stage changes in 21.3% of patients. The disease progressed into a more severe stage in 9.3% of patients, while the effects of the preoperative chemoradiation therapy could not be determined in 5.3% of patients. The survival of patients with the complete histopathological tumour regression was 70% in a five-year period, while it was 40% in patients with incomplete histopathological regression. Conclusion: The preoperative chemoradiation therapy leads to complete histopathological tumour regression and increases a five-year survival (70%). It also leads to the increase of the number of patients who undergo radical surgery.