Pancreatic cancer–Neoadjuvant therapy

In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only potential monomodal cure for pancreatic adenocarcinoma. However only 10%–20% of patients present with tumors that are amenable to resection, and even after resection of localized cancers, long term survival is rare. The addition of chemoradiation therapy significantly increases median survival. To achieve long-term success in treating this disease it is therefore increasingly important to identify effective neoadjuvant/adjuvant multimodality therapies. Preoperative chemoradiation for potentially resectable pancreatic cancer has the following advantages: (1) neoadjuvant treatment would eliminate the delay of adjuvant treatment due to postoperative complications; (2) neoadjuvant treatment could avoid unnecessary surgery for patients with metastatic disease evident on restaging after neoadjuvant therapy; (3) downstaging after neoadjuvant therapy may increase the likelihood for negative surgical margins; and (4) neoadjuvant treatment could prevent peritoneal tumor cell implantation and dissemination caused during surgery. This review systematically summarizes the current status, controversies, and prospects of neoadjuvant treatment of pancreatic cancer.     

Neoadjuvant Treatment for Esophageal Cancer

Because the conflicting data currently available from the performed randomized trials it is verydifficult to provide strict guidelines for the treatment of patients with locoregional advanced esophagealcancers.Surgery however,remains the standard of care for potentially resectable disease.Preoperativechemotherapy is still controversial with two large randomized trials resulting in two different conclusionsregarding the survival benefit.Preoperative chemoradiation is also controversial since only one randomizedtrial showed a clear survival benefit however,the patients treated with surgery alone in this trial had anunusually poor outcome.And the study by Urba et al was not powered enough to show a clear survivalbenefit for patients treated with neoadjuvant chemoradiation.The results of three metaanalysis of theserandomized studies show lower rate of resection,higher rate of RO-resection,more often postoperativemortality and better prognosis for patients with neoadjuvant radiochemotherapy.As a consequence one mayconsider offering neoadjuvant chemotherapy or neoadjuvant radiochemotherapy to patients with locally-advanced disease under the premise that patients have a good performance status and understand thecontroversies about this therapeutic option.Larger trials with sufficient power to clearly detect survivalbenefits for patients treated with neoadjuvant chemotherapy or radiochemotherapy are necessary beforethis therapeutic option will be the standard of care.     

The liver in Hodgkin's disease—I. Clinico-pathological relations

A retrospective analysis of staging results from 308 patients with Hodgkin's disease (HD) was performed in order to relate clinico-pathological findings with respect to the liver to other staging results and to prognosis. Thirty-four patients had clinically enlarged liver, 80 had increased serum-enzyme levels indicating possible liver damage, but only 10 patients had biopsy-proven histologic evidence of HD in the liver (7 primary biopsies, 3 re-biopsies). Among the prognostic correlations not only advanced stage and liver infiltrates were connected to poor prognosis, but also—even in early stages—elevated serum enzyme values (S-GOT and alkaline phosphatase).     

Neoadjuvant chemoradiation for rectal cancer: is more better?

Neoadjuvant chemoradiation is now considered the clear preferable adjuvant standard of care in the management of stage II/III rectal cancer. Neoadjuvant fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU plus radiation therapy. Recent nonrandomized comparative studies have shown that capecitabine (Xeloda) plus radiation result in downstaging and pathologic complete responses equivalent to those of 5-FU plus radiation, making this combination an acceptable alternative neoadjuvant treatment. The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy appears to result in more favorable pathologic responses in phase I/II trials. These combinations should be investigated further in larger phase III studies before they are endorsed in the routine neoadjuvant treatment of rectal cancer. This article will review the progress of chemoradiation over the past 2 decades, current standards of care, and investigational treatments in the neoadjuvant treatment of rectal cancer.     

Neoadjuvant Therapy of Pancreatic Cancer: The Emerging Paradigm?

Pancreatic cancer remains one of the deadliest cancers due to difficulty in early diagnosis and its high resistance to chemotherapy and radiation. It is now clear that even patients with potentially resectable disease require multimodality treatment including chemotherapy and/or radiation to improve resectability and reduce recurrence. Tremendous efforts are currently being invested in refining preoperative staging to identify optimal surgical candidates, and also in developing various neoadjuvant or adjuvant regimens to improve surgical outcome. Although at present no studies have been done to directly compare the benefit of neoadjuvant versus adjuvant approaches, accumulating evidence suggests that the neoadjuvant approach is probably beneficial for a subset of the patient population, particularly those with borderline resectable disease in which complete surgical resection is almost certainly unachievable. In this article, we review the literature and rationales of neoadjuvant chemotherapy and chemoradiation, as well as their potential limitations and caveats. We also review the pathological findings following neoadjuvant therapies, and potential surgical complications that may be associated with neoadjuvant therapies.     

Neoadjuvant chemotherapy for epithelial ovarian cancer—role of apoptosis

Background Ovarian cancer is one of the most frequently fatal gynecological cancers because most cases are diagnosed at an advanced stage. Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumor progression. Little is known about the effect of various treatment regimens on the distribution of molecular markers of apoptosis in epithelial ovarian cancer. The objective of this study was to compare the expression levels of both proapoptotic and antiapoptotic proteins p53, p73, Bcl-2, Bcl-XL and survivin in the ascitic cells and tumor samples of patients undergoing treatment with two different regimens.Methods A total of 24 patients with untreated epithelial ovarian cancer were randomized into two groups of 12 each. Group 1 patients received three cycles of chemotherapy prior to surgery and three cycles after surgery and group 2 patients received six cycles of chemotherapy prior to surgery. The expression of apoptosis-related proteins was analyzed in ascitic fluid and tumor samples by Western blotting and immunohistochemistry. The apoptotic index was also determined in these samples by the TUNEL assay.Results Significant decreases in antiapoptotic bcl-2 and survivin were seen, accompanied by increases in apoptotic index in tumors that had undergone chemotherapy as compared to the baseline ascites samples. No significant change in bcl-XL was observed. A significant decrease in proapoptotic p53 was also seen. No expression of p73 was observed in tumors or ascites. The findings were similar in groups 1 and 2 patients and were not statistically significantly different, perhaps due to the small sample size (n=12) of each group.Conclusions The above findings indicate that chemotherapy in ovarian carcinoma leads to an increase in apoptosis by a p53-independent pathway, which involves the downregulation of antiapoptotic Bcl-2 and survivin but not Bcl-XL. Furthermore, administering neoadjuvant chemotherapy (six cycles) as an alternative form of therapy for advanced epithelial ovarian cancer is more effective in inducing apoptosis than three cycles. However, the findings of this study need to be corroborated using a larger sample.     

‘I know they are distressed. What do I do now?’

Significant advances have been made in our understanding of psychological adjustment to cancer over the last 40 years. Most clinicians now recognise the importance of psychosocial factors and the need for skills in emotional support. In the first phase of psycho‐oncology, pioneering work in the 1970s and 1980s mapped the extent of psychological morbidity in cancer. This has been followed by a second phase where clinical trials have demonstrated that psychological treatments are effective. But although clinicians may feel more confident in identifying distress and listening to the patient, they rarely feel confident that they possess the skills to help. This paper will review the progress through the first two phases and argue that we are now in the third phase where we can begin to examine methods for delivering cost‐effective psychological care. One of these methods is to equip staff with basic skills to understand and manage psychological distress. This paper will also describe a programme over the last 10 years to evaluate the effectiveness and clinical impact of such training for palliative care professionals. Copyright © 2013 John Wiley & Sons, Ltd.     

Role of Chemoradiotherapy in Oesophageal Cancer — Adjuvant and Neoadjuvant Therapy

Despite low postoperative mortality rates, the long-term outcomes from surgical-based treatment for oesophageal cancer remain poor. Chemoradiotherapy (CRT), either given before surgical resection as neoadjuvant therapy or after resection as adjuvant therapy, has been postulated to improve these outcomes. This systematic review examines the evidence for these approaches. The evidence for postoperative radiotherapy is limited and conclusions are difficult, but it may have a role in patients at high risk of local relapse (positive margins). The addition of chemotherapy is recommended when possible. Patient selection is important due to the associated toxicities. The evidence for neoadjuvant treatment is stronger and based on the current evidence neoadjuvant CRT can be recommended as a treatment approach in T2–T4, N1–3 oesophageal cancer for both adenocarcinoma and squamous cell carcinoma, but further work is needed to establish its superiority over neoadjuvant chemotherapy alone, particularly for adenocarcinoma. We recommend that further studies divide the two histologies and they should be treated as two separate diseases.     

Neoadjuvant endocrine therapy for breast cancer: an overlooked option?

For many oncologists, neoadjuvant treatment for breast cancer is synonymous with preoperative cytotoxic chemotherapy, regardless of tumor characteristics. Preoperative therapy with an endocrine agent is generally considered suitable only for the frail elderly or the medically unfit. However, favorable information regarding third-generation aromatase inhibitors in the treatment of all stages of breast cancer prompts a reconsideration of this bias. In light of the fact that neoadjuvant therapy with aromatase inhibitors is restricted to postmenopausal women with strongly estrogen-receptor-positive tumors, the assumption that neoadjuvant combination chemotherapy is more efficacious than a third-generation aromatase inhibitor can be reasonably questioned. It is particularly remarkable that the outcome of a comparison of adjuvant tamoxifen vs anastrozole (Arimidex)--the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial--in more than 6,000 patients was predicted by a neoadjuvant trial that showed an efficacy advantage for a third-generation aromatase inhibitor (letrozole [Femara]) compared to tamoxifen in a sample of 337 patients after only 4 months of treatment. The potential of the neoadjuvant setting in efforts to identify new biologic agents that could build on the effectiveness of adjuvant aromatase inhibitors is therefore beginning to be appreciated. Finally, neoadjuvant therapy with an aromatase inhibitor could be considered a sensitivity test of endocrine therapy that might be incorporated into strategies to individualize treatment according to response. For this possibility to be realized, however, a better understanding of the relationship between surrogates from the neoadjuvant setting and the long-term outcome of adjuvant aromatase inhibitor therapy will have to be established through practice-setting clinical trials.     

Breast Cancer Patients: Who Would Benefit from Neoadjuvant Chemotherapies?

Neoadjuvant chemotherapy (NACT) was developed with the aims of shrinking tumors or stopping cancer cells from spreading before surgery. Unfortunately, not all breast cancer patients will benefit from NACT, and thus, patients must weigh the risks and benefits of treatment prior to the initiation of therapy. Currently, the data for predicting the efficacy of NACT is limited. Molecular testing, such as Oncotype DX, MammaPrint, and Curebest 95GC, have been developed to assist which breast cancer patients will benefit from the treatment. Patients with an increased level of Human Leukocyte Antigen-DR isotype, tumor-infiltrating lymphocytes, Fizzy-related protein homolog, and a decreased level of tumor-associated macrophages appear to benefit most from NACT.     

100mm片I.I胃间接摄影用作胃癌筛检的价值——附12,046人次分析

日本自1971年以来,胃间接摄影集团检查采用高分辨率影象增强器和100mm胶片,使得图象质量和诊断质量有了显著提高。1984年在中日胃癌学术交流会议上,土井伟誉报道,目前日本用流动车普查胃癌的检出率为0.1％,其中早期癌占39.7％。84年我国第一台国产F·Z·WC·01型胃间接摄影机问世。同年本市又从日本引进岛津AO-20型I·I胃间