Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.

The following on the treatments of adenocarcinomas in Barrett's esophagus contains commentaries on endo mucosal resection; choice between other ablative therapies; the remaining genetic abnormalities following stepwise endoscopic mucosal resection and possible recurrences; the Fotelo-Fotesi PDT; the CT TNM classification of early stages of Barrett's carcinoma; the indications of lymphadenectomy in intramucosal cancer; the differences in lymph node yield in transthoracic versus transhiatal dissection; video-assisted lymphadenectomy; and the importance of the length of proximal esophageal resectipon; and indications of sentinel node dissection.

Magnetic drug targeting is a new treatment principle for tumors using cytostatics coupled to ferromagnetic nanoparticles and extracorporeal magnets. Higher concentrations in tumor tissue with lower systemic concentrations and without damage of healthy organs should be achieved.

n = 42 adult Wag/Rij rats were transfected with rhabdomyosarcoma R(1)H in their right gastrocnemius muscle. In the biodistribution trial (n = 36) concentrations of mitoxantrone-iron oxide with and without an extracorporeal 0.6 tesla magnet and regular mitoxantrone were measured in plasma and tumor tissue for one- and two-dose administration. In the plasma iron trial (n = 6) iron concentrations were measured in plasma before, during, and up to 30 min after drug administration. Seven days after the trial liver, spleen and tumor samples were obtained and histologically assessed.

Mitoxantrone iron-oxide concentration in plasma was significantly (P < 0.05) lower when a magnet was placed over the tumor area and as low as uncoupled mitoxantrone. Mitoxantrone concentration in tumor tissue was always significantly higher with magnetic drug targeting when compared with uncoupled mitoxantrone. Two doses resulted in drug accumulation in tumor tissue. Plasma iron concentrations rose when the drug was first administered. Plasma levels fell below the starting level with a magnet applied. A rebound phenomenon with rising iron concentrations was observed after the magnet was removed. Tumors showed fresh necrosis and liver and spleen had detectable iron depositions but no necrosis 7 d after treatment. No allergies or toxic reactions were observed.

We showed that magnetic drug targeting achieves higher concentrations of cytostatics in tumor tissue compared with blood. During magnetic drug targeting, iron particles are quickly sliced and kept in the tumor area. Organs of the reticuloendothelial system are not affected by cytostatic damage.

Treatment of gastric cancer is more and more becoming an individualized decision. The choice of the optimal approach is based on prognostic factors, on the anatomic site of the tumor, and on expectations about the response to neoadjuvant treatment. Early gastric cancer that is limited to the mucosal layer is the domain of endoscopic resections. As soon as the submucosal layer is invaded, surgical strategies with adequate lymphadenectomy become necessary.

In many East Asian Centers and some other centers in the world, these tumors are resected by a laparoscopic approach. With a high experience, this can be done with excellent quality and outcome. In locally advanced gastric cancer, multimodal treatment can improve survival in comparison to surgery alone. However, the strategies differ significantly around the world. While adjuvant chemoradiotherapy is standard in the USA, in Europe, perioperative chemotherapy is the first choice, and in Japan, adjuvant chemotherapy is recommended. In Europe, three randomized phase III studies on the value of preoperative chemotherapy have been performed. Two of them have shown that perioperative chemotherapy does significantly improve the survival of patients with adenocarcinoma of the stomach and of the esophagogastric junction. The one including only preoperative chemotherapy failed to show a survival benefit for the combined treatment arm but showed excellent outcomes in both the surgery alone and the preoperative chemotherapy arms. Based on these studies, patients with stage II or stage III disease are now treated with perioperative chemotherapy. Additionally, it is generally accepted for more than 10 years now that responding patients have a significantly improved prognosis compared to nonresponding patients. The percentage of responding patients varies depending on the applied regimen between 20% and 45%. Therefore, early response evaluation or response prediction is an utmost important field of research. Proximal tumors are treated with a transhiatal extended gastrectomy, tumors in the middle third with a total gastrectomy, and distal tumors with a subtotal gastrectomy, if possible. Modified D2 lymphadenectomy avoiding splenectomy is now accepted as the standard procedure, providing improved prognosis for certain subgroups of patients. Individualized resection and lymphadenectomy techniques for early tumor stages and response-based neoadjuvant concepts for locally advanced tumors are the challenge for the future.

Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs.

From 1994 to 2000, data from a total of 61 patients with resectable gastric cancer were analyzed. Peritoneal cytology was performed before NAC at laparoscopy and at tumor resection. A minimum of 6 weeks of NAC, consisting of cisplatin, folinic acid, and fluorouracil, was administered. FPTCs were detected immunohistochemically with Ber-EP4 antibody.

No FPTCs could be detected in 42 patients (69%), compared to 19 (31%) with FPTCs before NAC. During chemotherapy, 10 (24%) of 42 patients developed FPTCs, and 7 (37%) of 19 patients reverted from positive to negative. Patients who became FPTC negative (n = 7) showed an improved median survival (36.1 months) and a longer 2-year survival (71.4%) compared to FPTC-positive patients before and after NAC (n = 12), with a median survival of 9.2 months and a 2-year survival rate of 25%. In contrast, patients who reverted from FPTC negative to positive during NAC (n = 10) had a median survival of 18.5 months and a 2-year survival of only 20%. Multivariate analysis identified ypN category and FPTC change as independent prognostic factors.

NAC for patients with positive cytology could lead to FPTC negativity in a subset of patients and improve their prognosis. However, NAC might be a risky strategy for almost one-quarter of patients whose disease develops positive cytology.

The prognosis of locally advanced gastric cancer remains poor. It has been shown that multimodal treatment can improve the outcome in comparison to surgery alone. Two randomized studies that have been performed in Europe have shown that peri-operative chemotherapy significantly improves the survival of patients with adenocarcinoma of the stomach and of the gastro-esophageal junction. These results have a profound effect on the treatment of patients presenting with stage II or stage III disease. For more than 10 years it has been accepted that responding patients have a significantly improved prognosis compared to non-responding patients. Therefore, (early) response evaluation or response prediction is of utmost importance. After neoadjuvant chemotherapy patients should undergo a D-2 lymphadenectomy due to the high probability of lymph node metastasis. Neither mortality nor complication rate are increased after neoadjuvant chemotherapy for gastric cancer. Patients with locally advanced gastric cancer should always be referred to experienced high volume centers, where the findings are discussed in a multidisciplinary tumor board.

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.