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Chemotherapy and radiotherapy treatment regimens for gastrointestinal, peritoneal and pelvic tumours can disrupt the intestinal microbiome and intestinal epithelia. Such disturbances can provoke symptoms such as diarrhoea, nausea and vomiting. Chemotherapy and radiotherapy induced gastrointestinal toxicity aggravating intestinal microbiome dysbiosis is postulated to adversely alter the intestinal microbiome, with a consequent induced pro-inflammatory effect that disrupts the intestinal microbiome-epithelia-mucosal immunity axis. Although not widely recognised, the intestinal mucosa is the largest and most densely and dynamically populated immune-environment. Cancer treatment adverse effects that affect intestinal and mucosal cells inadvertently target and disrupt resident intestinal macrophages, the cells that marshal immune activity in the intestinal mucosa by shaping pro-inflammatory and anti-inflammatory activities to control and eradicate infectious insults and maintain local homeostasis. Pathobionts (bacteria capable of pathogenic pro-inflammatory activity) and noxious environmental and bacterial antigens use the intestinal epithelia and gap junctions as a point of entry into the systemic circulation. This translocation movement promotes toxic sequelae that obstruct intestinal macrophage functions resulting in uncontrolled local and systemic pro-inflammatory activity, loss of phagocytic function and loss of expression of tight junction proteins. Probiotic bacteria as an adjunctive treatment shows efficacy in ameliorating enteropathies such as mucositis/diarrhoea resulting from chemotherapy or radiotherapy regimens. As such we posit that an important benefit that warrants a further focused research effort is the administration of adjuvant probiotics to help reduce the incidence of febrile neutropenia.

Possible toxic effects following radiation and chemotherapy of gastrointestinal tumours may cause a depletion of the mucosal barrier within the radiation volumes with severe mucositis. Diarrhoea, nausea, emesis and severe malabsorption followed by infections with dehydration and electrolyte disorders have to be encountered. For prevention and treatment of oropharyngeal mucositis an oral care protocol, oral cryotherapy together with benzydamine mouthwash may be recommended. Lower gastrointestinal diarrhoea is best treated by Octreotide (>100 μg s.c. bid) if loperamide is ineffective and amifostine (340 mg/m(2) IV) to prevent radiation proctitis. Enteral nutrition may be necessary with severe malnutrition or no enteral food intake for >7days or insufficient intake (<60%) for >10 days. With severe generalized mucositis or severe radiation induced enteritis parenteral nutrition will be initiated. Following the application of highly emetogenic chemotherapy regimen, 5-HT3 antagonists, dexamethasone and aprepitant, whereas in moderate risk levels 5-HT3 antagonist plus dexamethasone may be sufficient., (Copyright © 2016. Published by Elsevier Ltd.)

Approximately 50% of all patients with cancer receive radiotherapy (RT) at some point during their treatment. Despite the advent of modern imaging and advances in planning and delivering highly-conformal and precise RT, further dose escalation to improve clinical outcome is often limited by the potential side-effects to adjacent tissues. Addition of chemotherapy to radiotherapy (CRT) has led to significant clinical improvements in many gastrointestinal malignancies but at the expense of increased toxicity as most chemotherapy drugs lack specificity. Targeted agents modulate specific biological pathways and can potentially enhance RT efficacy. However, so far, the majority of clinical studies incorporating targeted agents into RT and CRT have produced disappointing results in gastrointestinal malignancies. Also, we lack validated biomarkers and methods for monitoring and predicting the efficacy of these agents when combined with RT/CRT. In the present article, we will review the most important targeted therapies, and examine the efficacy and toxicity of these agents when combined with RT/CRT in gastrointestinal malignancies. The shortcomings as well as future challenges and perspectives for the successful use of these compounds with RT/CRT in future trials will also be outlined., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients' quality of life (QOL). This study described the subjective experience of patients with radiation-induced nausea and vomiting (RINV) and its relation to QOL., Methods: Forty-eight patients treated with abdominal radiotherapy alone or with concomitant chemoradiotherapy were followed in a prospective study. All episodes of nausea, vomiting, and antiemetic use were recorded daily for the treatment period and the week following completion of therapy. QOL was assessed weekly using the Functional Living Index-Emesis QOL Tool (FLIE) and the EORTC QLQ-C30 core questionnaire (C30)., Results: In total, 351 episodes of nausea severity, duration, onset time, and 154 outcomes of vomiting onset times and contents were documented. The median nausea severity experienced per episode was 5 (on a scale from 1 to 10), and the most common durations of nausea were 30 min or less and constant nausea all day and night. The most common location of nausea was the abdomen. Longer nausea duration, great nausea severities, and the location of nausea experienced had significant adverse relationships to multiple QOL items on both the FLIE and the C30. In addition, the onset timing and number of vomiting episodes were related to the majority of all FLIE and QOL scores., Conclusion: Patient's subjective experiences of RINV directly correlated to the worsening of QOL outcomes. The identification and amelioration of these RINV experiences could improve QOL.

The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

Patients with well-differentiated neuroendocrine tumours of the gastrointestinal tract often present with metastases and hormonal symptoms. These patients can be palliated by interventional tumour reduction and medical treatment with somatostatin analogues; no effective chemotherapy is available. Radionuclide therapy via somatostatin receptors is one new therapeutic alternative. The recognition that neuroendocrine tumours express specific receptors for growth factors and chemokines, which are of importance for tumour growth, vascularization, and spread, may open the way for new therapeutic approaches. The signalling pathways in carcinoid tumours are incompletely explored. This review summarizes potential new treatment strategies from clinical and experimental studies, e.g. inhibition of angiogenesis, targeting of growth factors or their receptors by tyrosine kinase inhibitors, interference with specific cellular pathways (mTOR, PI3K, RAS/RAF, Notch), and also inhibition of the proteasome and histone deacetylation. Combining targeted therapy with chemotherapy, or using drugs to sensitize for radionuclide therapy, may enhance the treatment outcome.

Chemoradiotherapy (CRT) is one of the effective modalities for the local control of gastric cancer. Advances in CRT as an adjuvant treatment have been made in the West. The INT0116 trial demonstrated that postoperative chemotherapy with 5-fluorouracil (FU) plus leucovorin and concomitant 45-Gy radiation significantly improved the survival of gastric cancer patients who received gastrectomy with D0 or D1 lymph node dissection. As the result of this trial, the standard treatment for curable gastric cancer in the United States has been considered as a combination of surgery and postoperative CRT. The great interest in CRT in the adjuvant setting for gastric cancer has induced oncologists, particularly in the West, to conduct new clinical trials using various kinds of anticancer drugs. However, there is no rationale for adjuvant CRT after D2 dissection. Large-scale randomized controlled trials in Japanese patients have shown significant improvement of overall survival brought about by postoperative adjuvant chemotherapy with S-1. The results of these studies have suggested that even D2 surgery alone brings about much better survival for patients than limited surgery plus adjuvant CRT. Thus, strategies for the postoperative treatment of gastric cancers should be classified according to the degree of surgery.

Purpose of Review: The present review is timely owing to the previous paucity of biomarkers, particularly functional noninvasive tests, to evaluate the extent and severity of gastrointestinal toxicity in both animal models of chemotherapy and in cancer patients undergoing chemotherapy., Recent Findings: The most recent findings using noninvasive functional biomarkers now allow longitudinal monitoring of the time course of damage and repair that occurs in the gastrointestinal tract following radiotherapy and chemotherapy. This monitoring has in turn enabled collection of objective evidence for efficacy of new antimucositis agents using animal models and, more importantly, for use in future randomized, double-blind, placebo-controlled clinical trials., Summary: In the past 12 months the C sucrose breath test has been applied to a series of animal models of chemotherapeutic damage, showing rapid monitoring of the efficacy of particular bioactive molecules is now possible at different stages of the damage and repair cycle. This biomarker has also been applied to childhood cancer studies of mucositis and now needs to be used in adult cancers for eventual adoption in routine clinical management of mucositis. An exciting possibility would be extension of the biomarker use to predict damage in other regions of the gastrointestinal tract, including oral mucosa.

Surgical therapy of any malignancy always attempts the complete removal of a cancer from the organism. An adjuvant chemotherapy has the goal to remove remaining tumor-cells, to prevent recurrence of the disease and to improve long term survival. Within the last years there has been a substantial improvement in prognosis due to multi-modal therapeutic regimens including combination-chemo-therapy and innovative radiation-protocols. This review aims to present and to critically review current concepts in the treatment of selected tumors of the gastrointestinal tract.

Response to perioperative chemotherapy or chemoradiation can hardly be predicted on the basis of molecular marker analyses. In contrast, by means of metabolic and molecular imaging using positron emission tomography, response can be assessed as early as 14 days after the start chemotherapy for many tumors. There is no doubt that the prognosis of patients with surgically resected tumors is much better in the case of a response to chemotherapy or chemoradiation. Important consequences can be deduced from this regarding the indications for perioperative therapies, the radicality of surgery or the surgical indications per se. In the following, we delineate the current knowledge on response prediction and early response evaluation in selected tumor entities and draw possible conclusions for clinical practice and future clinical studies.

Malignant gastrointestinal tumors are still worldwide a very common cause of death from cancer. Even though the surgical techniques and the neoadjuvant/adjuvant therapies have improved over the last years and multimodal concepts in cancer treatment have been established, these types of tumors remain a challenge. Therefore predictive/prognostic markers need to be established, to be able to tailor chemotherapies and therefore improve efficacy of neoadjuvant/adjuvant treatment. Over the last years potential predictive/prognostic factors have been characterized by molecular-biological technologies: the tumor suppressor gene p53, the cell-cycle regulatory proteins p21 and p27, the marker of proliferation Ki-67, the epidermal growth factor receptor, HER2/neu, angiogenetic factors (the vascular endothelial growth factor, cyclooxygenase 2, thymidine phosphorylase), enzymes involved in the DNA-repair-system (ERCC1), enzymes involved in the 5-fluorouracil-metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase) or other genetic alterations, like the loss of heterozygosity or the microsatellite instability. The results of the mainly retrospective studies are promising but prospective studies are needed to validate those markers in the therapy of gastrointestinal tumors. The goal is that we will be able to predict when and with what to treat.

New combinations of chemotherapy with radiotherapy for gastrointestinal cancers are showing evidence that improved outcomes may result from toxicity profiles associated with "targeted" systemic radiosensitizing agents. These new agents are also clinically attractive owing to such factors as oral bioavailability and patient dosing schedules, making them practical and convenient compared with older intravenous administration requirements. Several new classes of radiosensitizing agents are discussed here and underscore aspects of molecular activation in tumors rather than normal tissues because of differences in pathways of metabolism or based on the process of tumor-associated angiogenesis.

Objective: To study on Fuzheng Baozhen Decoction (FZBZD) enhancing effect of radio- and chemotherapy for malignant tumors., Methods: One hundred and Seventeen cases of malignant tumors treated with chemotherapy or/and radiotherapy, 55 cases treated together with FZBZD (group A), comparing with 30 cases treated with radio- and chemotherapy plus Zhenqi Fuzheng Granules (group B) and 32 cases radio- and chemotherapy alone (group C). Mechanism of FZBZD enhancing effect of chemotherapy on transplanted human lung adenocarcinoma (SPC-A-1) and sarcoma (S180) bearing mice was conducted., Results: Effective rates (CR + PR) of group A, B, C were 63.6%, 43.3%, 37.5% respectively, that of group A was the best (P < 0.05). The survival quality of life was improved best in group A (P < 0.05). After being treated, the level of the peripheral blood (WBC, Hb, PLT) of group A was the highest (P < 0.05); CD3, CD4, NK activity, interleukin-2 were also improved significantly in group A (P < 0.01). Animal experiment showed that FZBZD could improve chemotherapy effect of inhibitory action on tumor growth (P < 0.01), increase cAMP/cGMP ratio (P < 0.01) by adding cAMP level in cancer tissue, and enhance of G0/G1 phase cells and decrease S phase cells., Conclusions: FZBZD inhibited tumor growth and enhanced the effect of radio- and chemotherapy by improving immune and hematopoietic function, cAMP/cGMP ratio and stagnating tumor cells in G0/G1 phase.

A critical review of adjuvant therapies of gastrointestinal tumors shows that this is a field of active clinical investigation. Unfortunately the results that have been achieved until now have not fulfilled the expectations. Neoadjuvant therapies of squamous cell carcinomas of the esophagus and the anus in many cases lead to pathologically documented complete remissions. After a 10 years follow-up, it is evident that for anal carcinoma such pathological complete remissions translate into longterm remissions and eventually cures. The same conclusion, however, can not yet be drawn for esophageal cancer. The role of adjuvant chemotherapy in gastric carcinoma remains unclear. The results of the current FAM-studies are eagerly awaited. In pancreatic cancer the combination of radiotherapy and 5-FU may probably prolong disease-free survival and survival for a limited time period. Many adjuvant studies have been done in colonic cancer, without any conclusive data regarding the role of chemotherapy. Some indications point to biological response modifiers, immuno- and regional therapies to be effective in the adjuvant situation. The results of adjuvant chemotherapy in rectal cancer after radiotherapy or radiochemotherapy are easier to judge. They show that some patients profit from adjuvant therapy. But the most efficient combinations and the role of newer modalities remain to be elucidated (Fig. 8 a-8c).

A multidisciplinary approach consisting of surgery, radiotherapy, chemotherapy, and immunotherapy is now being used in both early and advanced stages of carcinoma. Positive and constructive approaches available today vary from adjuvant studies for early or primary disease to combinations of radiotherapy and chemotherapy for advanced disease. Methods of treatment considered to hold significant promise are discussed.