Metastases, rather than primary tumours, are responsible for most cancer deaths. To prevent these deaths, improved ways to treat metastatic disease are needed. Blood flow and other mechanical factors influence the delivery of cancer cells to specific organs, whereas molecular interactions between the cancer cells and the new organ influence the probability that the cells will grow there. Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy.

Dissemination and growth of cancer cells in metastatic sites

Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.

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Chronic inflammation in the etiology of disease across the life span

The use of laparoscopy for liver surgery is increasing rapidly. The Second International Consensus Conference on Laparoscopic Liver Resections (LLR) was held in Morioka, Japan, from October 4 to 6, 2014 to evaluate the current status of laparoscopic liver surgery and to provide recommendations to aid its future development. Seventeen questions were addressed. The first 7 questions focused on outcomes that reflect the benefits and risks of LLR. These questions were addressed using the Zurich-Danish consensus conference model in which the literature and expert opinion were weighed by a 9-member jury, who evaluated LLR outcomes using GRADE and a list of comparators. The jury also graded LLRs by the Balliol Classification of IDEAL. The jury concluded that MINOR LLRs had become standard practice (IDEAL 3) and that MAJOR liver resections were still innovative procedures in the exploration phase (IDEAL 2b). Continued cautious introduction of MAJOR LLRs was recommended. All of the evidence available for scrutiny was of LOW quality by GRADE, which prompted the recommendation for higher quality evaluative studies. The last 10 questions focused on technical questions and the recommendations were based on literature review and expert panel opinion. Recommendations were made regarding preoperative evaluation, bleeding controls, transection methods, anatomic approaches, and equipment. Both experts and jury recognized the need for a formal structure of education for those interested in performing major laparoscopic LLR because of the steep learning curve.

Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system 1 2 was adopted to define the strength of recommendations and the quality of evidence. Main recommendations
 1 ESGE recommends endoscopic en bloc resection for superficial esophageal squamous cell cancers (SCCs), excluding those with obvious submucosal involvement (strong recommendation, moderate quality evidence). Endoscopic mucosal resection (EMR) may be considered in such lesions when they are smaller than 10 mm if en bloc resection can be assured. However, ESGE recommends endoscopic submucosal dissection (ESD) as the first option, mainly to provide an en bloc resection with accurate pathology staging and to avoid missing important histological features (strong recommendation, moderate quality evidence). 2 ESGE recommends endoscopic resection with a curative intent for visible lesions in Barrett’s esophagus (strong recommendation, moderate quality evidence). ESD has not been shown to be superior to EMR for excision of mucosal cancer, and for that reason EMR should be preferred. ESD may be considered in selected cases, such as lesions larger than 15 mm, poorly lifting tumors, and lesions at risk for submucosal invasion (strong recommendation, moderate quality evidence). 3 ESGE recommends endoscopic resection for the treatment of gastric superficial neoplastic lesions that possess a very low risk of lymph node metastasis (strong recommendation, high quality evidence). EMR is an acceptable option for lesions smaller than 10 – 15 mm with a very low probability of advanced histology (Paris 0-IIa). However, ESGE recommends ESD as treatment of choice for most gastric superficial neoplastic lesions (strong recommendation, moderate quality evidence). 4 ESGE states that the majority of colonic and rectal superficial lesions can be effectively removed in a curative way by standard polypectomy and/or by EMR (strong recommendation, moderate quality evidence). ESD can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion that is based on two main criteria of depressed morphology and irregular or nongranular surface pattern, particularly if the lesions are larger than 20 mm; or ESD can be considered for colorectal lesions that otherwise cannot be optimally and radically removed by snare-based techniques (strong recommendation, moderate quality evidence).

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Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.

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NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors

An original technique for performing endoscopic thyroidectomy using a breast approach to avoid an operative scar in the neck was developed. The subcutaneous space in the breast area and the subplatysmal space in the neck were bluntly dissected through a 15-mm incision between the nipples, and CO2 was insufflated at 6 mm Hg to create the operative space. Three trocars were inserted at the breast, and dissection of the thyroid and division of the thyroid vessels and parenchyma were performed endoscopically using an ultrasonically activated scalpel. Four hemithyroidectomies and one partial resection of the thyroid for five female patients with thyroid adenomas 5 to 7 cm in diameter were successfully performed using this procedure. There were no conversions to open surgery or complications. No scars were apparent in the neck, and all patients were fully satisfied with the cosmetic results. Endoscopic thyroidectomy using a breast approach and low-pressure subcutaneous CO2 insufflation is a feasible and safe procedure, which results in satisfactory cosmetic results.

Scarless Endoscopic Thyroidectomy: Breast Approach for Better Cosmesis

The role of the sentinel lymph node in gastrointestinal cancer.

We have applied two different laparoscopic surgical techniques for early gastric cancer and have successfully treated 111 patients since March 1992. The indications are: 1) preoperative diagnosis of mucosal cancer; 2) lesion size of < 25 mm if the protruding type; and 3) lesion size < 15 mm and UI (-) if the depressed type. The first technique is laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 93). The gastric wall around the cancerous lesion is exposed laparoscopically. The abdominal wall and gastric wall in the vicinity of the lesion are pierced using a 12-G sheathed needle. A small metal rod with a fine wire is introduced into the stomach through the outer sheath. By retracting the metal rod, the lesion can be lifted precisely (i.e., lesion-lifting method). Wedge resection at a sufficient distance from the metal rod is carried out using an endoscopic stapler. The second technique is referred to as laparoscopic intragastric mucosal resection (n = 18). Three balloon trocars are placed in the stomach laparoscopically. The stomach is then insufflated with CO2, and surgical instruments are introduced. The mucosal and submucosal layers around the lesion are resected with sufficient surgical margins. The selection of the laparoscopic technique depends on the site of the cancerous lesion. In our series of 111 patients, sufficient horizontal (mean 15 +/- 5 mm and 8 +/- 4 mm, respectively, using the first and second technique) and vertical surgical margins were achieved. There was no mortality and no major complications in patients undergoing either surgical technique. There have been two recurrences, both mucosal lesions found 2 years after the initial surgery, which were successfully treated with gastrectomy and laser irradiation. All patients have survived for 3 to 96 months, and there has been no trocar site recurrence. In conclusion, these laparoscopic procedures are curative and minimally invasive treatments for early gastric cancer.

Curative Laparoscopic Surgery for Early Gastric Cancer: Five Years Experience

Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases

There is a need for a clinically useful drug-response assay for cancer patients to individualize their chemotherapy. Collagen sponge-gel-supported histoculture has been shown to maintain tissue architecture and function in vitro and has been utilized to develop the histoculture drug-response assay (HDRA) for individualizing chemotherapy. In order to evaluate the HDRA with the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide end point for clinical use, chemosensitivity to mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin of 107 advanced gastric and 109 advanced colorectal cancers was determined in vitro in a correlative clinical trial. Two hundred eight (96.3%) of 216 of the patient specimens were evaluable in the HDRA. Thirty-eight patients with remaining measurable lesions after surgery were evaluable for comparison of the effects of chemotherapy in the HDRA with clinical outcome. Their overall response in the HDRA to all four drugs correlated to published historical data. Twenty-nine patients were treated with drugs shown to be ineffective in the HDRA, and all 29 cases showed clinical chemoresistance. In nine patients treated with drugs shown to be effective in the HDRA, six showed clinical chemoresponse and three showed arrest of disease progression. The correlation rate of the assay to clinical drug-sensitivity response was thus calculated to be 92.1% (35/38), with 100% (29/29) true-negative and 66.7% (6/9) true-positive rates, 100% (6/6) sensitivity, and 90.6% (29/32) specificity. Thirty-two patients with stage III and IV gastric cancer without remaining measurable tumor lesions after surgery were treated with mitomycin C and a fluoropyrimidine adjuvantly. The survival rate of 10 patients whose tumors were sensitive to either mitomycin C and/or 5-fluorouracil in the assay was significantly (P < 0.005) better than that of 22 patients whose tumors were shown to be insensitive to both drugs. Twenty-nine patients with stage III and IV colorectal cancer without remaining measurable tumor lesions after surgery were treated with fluoropyrimidines adjuvantly. The recurrence-free survival rate of 7 patients whose tumors were sensitive to 5-fluorouracil in the assay was significantly (P < 0.05) better than that of 22 patients whose tumors were insensitive. Thus the HDRA with the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide end point should be of clinical value to choose optimal chemotherapy for response as well as for survival.

https://clincancerres.aacrjournals.org/content/clincanres/1/3/305.full.pdf

Toshiharu Furukawa

Papers

Scarless Endoscopic Thyroidectomy: Breast Approach for Better Cosmesis

The role of the sentinel lymph node in gastrointestinal cancer.

Curative Laparoscopic Surgery for Early Gastric Cancer: Five Years Experience

Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases

Clinical applications of the histoculture drug response assay