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Aim Clinical staging is vital for selecting appropriate candidates and designing neoadjuvant treatment strategies for advanced tumors. The aim of this review was to evaluate diagnostic abilities of clinical TNM staging for gastrointestinal, gastrointestinal cancers. Methods We conducted a systematic review of recent publications to evaluate the accuracy of diagnostic modalities on gastrointestinal cancers. A systematic literature search was performed in PubMed/MEDLINE using the keywords “TNM staging,” “T4 staging,” “distant metastases,” “esophageal cancer,” “gastric cancer,” and “colorectal cancer,” and the search terms used in Cochrane Reviews between January 2005 to July 2020. Articles focusing on preoperative diagnosis of: (a) depth of invasion; (b) lymph node metastases; and (c) distant metastases were selected. Results After a full‐text search, a final set of 55 studies (17 esophageal cancer studies, 26 gastric cancer studies, and 12 colorectal cancer studies) were used to evaluate the accuracy of clinical TNM staging. Positron emission tomography–computed tomography (PET‐CT) and/or magnetic resonance imaging (MRI) were the best modalities to assess distant metastases. Fat and fiber mode of CT may be useful for T4 staging of esophageal cancer, CT was a partially reliable modality for lymph node staging in gastric cancer, and CT combined with MRI was the most reliable modality for liver metastases from colorectal cancer. Conclusion The most reliable diagnostic modality differed among gastrointestinal cancers depending on the type of cancer. Therefore, we propose diagnostic algorithms for clinical staging for each type of cancer., We conducted a systematic review of recent publications to evaluate the accuracy of diagnostic modalities on gastrointestinal cancers. Such systematic review on all three cancer types—esophageal cancer, gastric cancer, colorectal cancer—cannot be found in recent publications on PubMed. We believe that this review may be fundamental information to design clinical studies related to neoadjuvant therapy for gastrointestinal cancers.

Surgeons have increased physical stress during laparoscopic surgery due to operative site constraints. We developed a wearable device to reduce the physical stress on surgeons' lower extremities. The device mechanically facilitates maintaining a near-upright posture. The surgeon's knees are gently bent by a knee-joint locking mechanism, and fixing and releasing are performed independently on each side. The subjects were one female and two male surgeons, who wore the device during laparoscopic inguinal hernia repair or high anterior resection. Surface electromyogram (EMG) was conducted for both iliopsoas muscles. Control values were determined with the subject not wearing the device. Participants completed a post-procedure questionnaire. With the device, EMG activity had a tendency to decrease in the left iliopsoas muscle (P = .055), but it changed little on the right (P = .406). The post-procedure questionnaire showed an overall positive impression, although subjects reported some difficulty walking. This device decreases EMG activity and may improve a surgeon's work environment.

Background Carbon-ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC). Methods Thirty-one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made. Results Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1-, 3-, and 5-year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively. Conclusions CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events. J. Surg. Oncol. 2012; 105:750–755. © 2011 Wiley Periodicals, Inc.

We investigated the feasibility, safety, biological activity and therapeutic efficacy of adenovirus-mediated p53 gene transfer in patients with chemoradiation resistant advanced esophageal carcinoma. Eligible patients were not surgical candidates and had measurable, advanced squamous cell carcinoma of the esophagus that was resistant to chemoradiation therapy. On a 28-day cycle, intratumoral injections of Ad5CMV-p53 (INGN 201; ADVEXIN) were administered on days 1 and 3 at four dose levels (10 x 10(11) particles to 25 x 10(11) particles) and treated for up to five cycles. Ten patients received a total of 26 cycles with no dose-limiting toxicity. Administration of multiple courses was feasible and well-tolerated. Local tumor responses revealed stable disease in nine cases and progressive disease in one case. The overall responses were stable in six and progressive in four cases. Using polymerase chain reaction (PCR) analyses, gene transfer and p53 specific transgene expression were detected in tumor biopsy tissue from all patients. mRNA levels of p53, p21 and MDM2 increased in all but one case. Three patients showed absence of disease upon repeat biopsies. Substantial improvement in swallowing was observed in one patient with stenotic lesions. Intratumoral injection of Ad5CMV-p53 is safe, feasible and biologically active when administered in multiple doses to patients with esophageal cancer. Observations from this study indicate that this treatment results in local antitumor effects in chemoradiation resistant esophageal squamous cell carcinoma.

We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers.

Background and Objectives An increased serum C-reactive protein (CRP) level was found in patients with various malignant tumors and was associated with poor prognosis. The aim of this study was to analyze the clinicopathological significance and the prognostic value of preoperative CRP levels in patients with esophageal squamous cell carcinomas. Patients and Methods The preoperative CRP level was measured by enzyme-linked immunosorbent assay (ELISA) in 150 patients with primary esophageal squamous cell carcinomas. All patients underwent radical surgery without any preoperative therapy. The patients were divided into two groups using a cut-off value of 1.0 mg/dl. The pathological classifications of the tumor were examined according to the TNM/UICC classification. The associations between the clinicopathological factors and CRP level were determined. The prognostic value of CRP was determined using Cox's proportional hazards model. Results Thirty-five patients (23%) showed high CRP levels (more than 1.0 mg/dl). Statistically significant differences in CRP levels were observed depending on tumor depth (P = 0.022) and TNM/UICC stage (P = 0.001). A high CRP level was associated with poor survival (P = 0.005) and was confirmed by multivariate analysis. Conclusions A high CRP level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma. J. Surg. Oncol. 2003;83:248–252. © 2003 Wiley-Liss, Inc.

High preoperative serum midkine concentration is associated with poor survival in patients with esophageal cancer, even after radical surgery, and thus may have prognostic value. Midkine (MK), a heparin-binding growth factor, is expressed in numerous cancer tissues, and serum MK (S-MK) concentrations are increased in patients with various neoplasms. The aim of this study is to evaluate the clinical significance of S-MK in patients with esophageal squamous cell cancer (SCC). S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 93 patients with primary esophageal SCC before surgery. The serum concentrations of carcinoembryonic antigen (CEA), SCC antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated. All patients with esophageal SCC underwent radical esophagectomy. Tumor MK expression was assessed by immunohistochemistry in 14 fresh tumor specimens. To determine whether S-MK is of value as a prognostic factor, the authors conducted a survival analysis using Cox's proportional hazards model. S-MK values in patients with esophageal SCC were significantly higher than those in healthy controls (417 +/- 342 pg/ml vs. 154 +/- 76 pg/ml, P0.001). Using 300 pg/ml as the cut-off value (representing the mean + 2 standard deviations of the S-MK of healthy controls), 61% of patients with esophageal SCC were classified as positive. MK expression by the tumor was significantly associated with high level of S-MK. High S-MK (/= 300 pg/ml) was associated with tumor size, immunoreactivity and poor survival. Multivariate analysis indicated that S-MK was an independent prognostic factor. S-MK may be a useful tumor marker for esophageal SCC. Increased preoperative S-MK in patients with esophageal SCC is associated with poor survival.

BACKGROUND Serum cross-linked carboxyterminal telopeptide of Type I collagen (ICTP) is a metabolite of Type I collagen and has been reported to serve not only as a marker of bone metastasis but also as an indicator of treatment response and prognosis in several malignant tumors. The objective of this work was to evaluate the value of serum ICTP as a tumor marker in patients with esophageal squamous cell carcinoma (SCC). METHODS In this study, pretreatment serum ICTP concentrations were measured by double-antibody radioimmunoassay in 50 patients undergoing tumor resection, chemoradiotherapy, or palliation for newly diagnosed esophageal SCC. The cutoff value for positive ICTP levels was defined as 4.50 ng/mL. As a comparison, serum concentrations of SCC antigen, carcinoembryonic antigen, cytokeratin-19 fragment, alkaline phosphatase, and lactate dehydrogenase were simultaneously evaluated. The results were categorized according to several clinicopathologic variables. RESULTS Among the markers tested, ICTP showed the highest sensitivity (58.0%) in esophageal SCC sera. Positive ICTP levels were significantly correlated with tumor progression variables, such as tumor depth ≥ T2, regional lymph node metastasis (N1), distant metastasis (M1), TNM stage ≥ II, and maximal tumor length greater than 50 mm. Survival analyses of 29 patients who underwent curative resection demonstrated that patients who were positive for ICTP had significantly worse outcomes in terms of overall, disease specific, and disease free survival than those who were negative. Multivariate analyses confirmed that serum ICTP levels provided an independent prognostic indicator of overall and disease specific survival. However, serum ICTP values did not correlate with prognosis or treatment response in 17 unresectable cases treated by chemoradiotherapy. CONCLUSIONS Our results indicated that serum ICTP concentrations might be a novel prognostic tumor marker for assessing the progression of esophageal SCC. Cancer 2002;94:940–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10267