The use of an artificial intelligence algorithm for circulating tumor cell detection in patients with esophageal cancer.

Despite recent advances in multidisciplinary treatments of esophageal squamous cell carcinoma (ESCC), patients frequently suffer from distant metastasis after surgery. For numerous types of cancer, circulating tumor cells (CTCs) are considered predictors of distant metastasis, therapeutic response and prognosis. However, as more markers of cytopathological heterogeneity are discovered, the overall detection process for the expression of these markers in CTCs becomes increasingly complex and time consuming. In the present study, the use of a convolutional neural network (CNN)-based artificial intelligence (AI) for CTC detection was assessed using KYSE ESCC cell lines and blood samples from patients with ESCC. The AI algorithm distinguished KYSE cells from peripheral blood-derived mononuclear cells (PBMCs) from healthy volunteers, accompanied with epithelial cell adhesion molecule (EpCAM) and nuclear DAPI staining, with an accuracy of >99.8% when the AI was trained on the same KYSE cell line. In addition, AI trained on KYSE520 distinguished KYSE30 from PBMCs with an accuracy of 99.8%, despite the marked differences in EpCAM expression between the two KYSE cell lines. The average accuracy of distinguishing KYSE cells from PBMCs for the AI and four researchers was 100 and 91.8%, respectively (P=0.011). The average time to complete cell classification for 100 images by the AI and researchers was 0.74 and 630.4 sec, respectively (P=0.012). The average number of EpCAM-positive/DAPI-positive cells detected in blood samples by the AI was 44.5 over 10 patients with ESCC and 2.4 over 5 healthy volunteers (P=0.019). These results indicated that the CNN-based image processing algorithm for CTC detection provides a higher accuracy and shorter analysis time compared to humans, suggesting its applicability for clinical use in patients with ESCC. Moreover, the finding that AI accurately identified even EpCAM-negative KYSEs suggested that the AI algorithm may distinguish CTCs based on as yet unknown features, independent of known marker expression.

[Factors Contributing to Surgical Intervention for Subacute Subdural Hematoma Enlargement in Patients with Mild Head Injuries].

Delayed neurological deterioration following mild head injury(MHI)usually occurs within 24 hours. However, some cases require delayed surgical evacuation of an acute subdural hematoma(ASDH), owing to subacute progressive hematoma enlargement. This study aimed to determine radiological or clinical parameters associated with surgical intervention in ASDH cases in which surgery was not initially considered necessary. From 2010 to 2015, 64 patients were non-surgically treated for ASDH following MHI. We evaluated the various outcomes of eventual surgical ASDH evacuation after the first 48 hours following injury, due to hematoma enlargement and clinical deterioration. Univariate and multivariate analyses were applied to both the demographic and initial radiographic features to identify risk factors for ASDH progression and surgery. Overall, at the time of their last follow-up computed tomography, 57 patients(89%)demonstrated minimal ASDH or spontaneous hematoma resolution with conservative non-surgical management. The remaining 7 patients(11%)received delayed surgical ASDH evacuation a median of 5.1 days after the head trauma. There were no significant differences between the two groups for baseline characteristics, including age, prior history of anticoagulants, the presence of cerebral contusions, or subarachnoid hemorrhages. On multivariate analysis, use of antiplatelet drugs(p=0.013, OR=28, 95%CI=1.82-24)was independently associated with delayed hematoma evacuation. These data indicate that as much as 11% of patients with minimal ASDHs after MHI can deteriorate over the course of a week and then require surgical intervention, and that patients on concurrent antiplatelet medication require especially careful monitoring of hematoma progression.

Efficacy of double-scope endoscopic submucosal dissection and long-term outcomes of endoscopic resection for superficial pharyngeal cancer.

BACKGROUND AND AIM: Owing to increased awareness and use of narrow-band imaging, there are more opportunities to treat superficial pharyngeal cancer (SPC). The present study aimed to describe the short- and long-term outcomes of endoscopic resection (ER) for SPC. METHODS: This study included 166 consecutive SPC in 113 patients treated during 2006 to 2013 at one referral cancer center. In the first period, we treated patients using endoscopic mucosal resection (EMR), in the second period using conventional ESD (cESD) and in the recent period using double-scope ESD (dsESD), which involves a second thin endoscope for assistance to produce traction. Median follow-up period was 30 months. RESULTS: All lesions were diagnosed as squamous cell carcinoma. Complete resection rate of cESD and dsESD procedures was 56.4% and 82.3% (P < 0.01), and local recurrence rate was 2.6% and 0.0%, respectively. Procedure duration was significantly shorter for dsESD than for cESD (P < 0.05). Four cases of recurrent lymph node (LN) metastasis were observed; however, all patients with LN metastases survived to a 48-month median interval after neck dissection. Risk factors for LN metastasis included subepithelium invasion, tumor thickness >1000 µm, droplet infiltration, and lymphovascular invasion. Overall survival rate after 5 years was 79.5%; no patients died of SPC. Cumulative rate of metachronous SPC after 5 years was 46.5%. CONCLUSION: ER for SPC is a feasible and effective treatment, although metachronous SPC occurred frequently. For the technique of ER, dsESD was effective.

Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002).

We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.

Combination chemotherapy of carboplatin and paclitaxel for advanced/metastatic salivary gland carcinoma patients: differences in responses by different pathological diagnoses.

BACKGROUND: A standard chemotherapy for recurrent/metastatic salivary gland cancers has not been established. Combination chemotherapy of carboplatin and paclitaxel should be evaluated as a treatment option. METHODS: This study retrospectively reviewed salivary gland cancer patients who received combination chemotherapy of carboplatin and paclitaxel. The differences in objective responses and in the prognoses according to the different pathological diagnoses were evaluated. RESULTS: A total of 38 patients were enrolled in the study; of them, 18 had salivary duct carcinomas (SDCs), nine had adenoid cystic carcinomas (ACCs), and 11 had other pathological diagnoses. Objective responses were observed in 15 (39%) patients. The median progression-free survival (PFS) was 6.5 months, and the median overall survival (OS) was 26.5 months. ACC patients had relatively low response rates (9%), but there were no significant differences in PFS or OS compared to other sub-types. The treatment was well tolerated, with few adverse events. CONCLUSION: Salivary gland cancer patients showed a moderate clinical response to the combination chemotherapy of carboplatin and paclitaxel. The objective response rates differed according to the pathological diagnoses, but there were no significant differences in prognoses.

Delayed perforation after endoscopic submucosal dissection for early gastric cancer: Clinical features and treatment.

Perforation is an important procedural complication of endoscopic submucosal dissection (ESD) for early gastric cancer. Although the incidence of delayed perforation after ESD is low, extreme caution is necessary because many cases require surgical intervention. Among 1984 lesions of early gastric cancer treated in our hospital by ESD in 1588 patients from September 2002 through March 2015, delayed perforation developed in 4 patients (4 lesions, 0.25%). A diagnosis of delayed perforation requires prompt action, including surgical intervention when required.

Chemoradiotherapy for patients with recurrent lymph-node metastasis or local recurrence of gastric cancer after curative gastrectomy.

OBJECTIVES: Whether chemoradiotherapy (CRT) is clinically beneficial for the management of postoperative recurrence of advanced gastric cancer remains unclear. We retrospectively studied treatment outcomes in patients who had unresectable localized recurrence after surgery for advanced gastric cancer and evaluated the safety and efficacy of CRT. METHODS: The study group comprised 21 patients who received concurrent CRT for unresectable localized recurrence after undergoing R0 resection for stage II/III advanced gastric cancer. Localized recurrence was defined as a few or limited recurrent lesions. RESULTS: The recurrence pattern was anastomotic recurrence in 7 patients, abdominal lymph-node recurrence in 12, and anastomotic recurrence plus abdominal lymph-node recurrence in 2. The median total dose of radiotherapy was 48.6 Gy (range 39.6-56.0), and the CRT completion rate was 100 % (21 of 21 patients). CRT-related grade 3 or higher toxicity comprised neutropenia in 33.3 % of patients and anorexia in 9.5 %. The response rate was 61.9 % (complete response 38.1 %, partial response 23.8 %). The median overall survival was 35.0 months. CONCLUSIONS: We conclude that CRT may become one treatment strategy for the management of unresectable localized recurrence after curative resection of advanced gastric cancer.

Survival outcome of Borrmann type IV gastric cancer potentially improved by multimodality treatment.

BACKGROUND: Type IV macroscopic gastric cancer has the poorest prognosis of all gastric cancer types. Although progress of multidisciplinary treatments is outstanding, the current survival outcome of such therapies is obscure. PATIENTS AND METHODS: Among 5,172 patients with gastric cancer between 1971 and 2013, 287 cases of type IV were identified (5%). We divided time period into early (1971-2004) and late periods (2005-2013), and compared their prognosis. Multivariate Cox proportional hazards model was applied to the univariate prognostic factors, and identified independent prognostic factors and long-term survivors. RESULTS: Five-year overall survival (OS) was 13% and 31% in the early and late periods, respectively (p=0.0010). Univariate prognostic factors were age, pathological tumor depth of invasion (pT), pathological lymph node metastasis (pN), peritoneal dissemination (P), intra-peritoneal cytology test (CY), and margin status. Multivariate analysis determined independent prognostic factors to be treatment period (p=0.0001), pT (p=0.0024) and P (p=0.035). Survival outcomes were stratified by combination of pT and P in both periods, where OS was improved in the late period. Long-term survivors often underwent long-term postoperative chemotherapy with S-1. CONCLUSION: Long-term postoperative S-1 chemotherapy may improve survival outcome of patients with type IV gastric cancer, and their prognosis is predicted by pT and P status.

Comparison of site-specific gene expression levels in primary tumors and synchronous lymph node metastases in advanced gastric cancer.

BACKGROUND: Many malignant tumors consist of heterogeneous subpopulations of cells. This heterogeneity is associated with genetic characteristics. However, it remains unclear whether gene expression levels differ among specific sites of tumors in gastric cancer. METHODS: We studied differences in gene expression levels among specific sites of primary tumors and synchronous lymph node metastases, using formalin-fixed, paraffin-embedded specimens resected surgically from 48 patients with previously untreated advanced gastric cancer. Specimens were obtained by laser-captured microdissection from five regions: (1) nonneoplastic mucosa, (2) surface layer (mucosa) of the primary tumor (surface sections), (3) middle layer (submucosa) of the primary tumor (middle sections), (4) the deepest layer of the primary tumor (muscularis propria or deeper) at the site of deepest invasion (deep sections), and (5) level 1 synchronous lymph node metastasis (lymph node metastases). Expression levels of the following target genes were determined by quantitative real-time polymerase chain reaction: thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF1α). RESULTS: TP, DPD, EGFR, and HIF1α gene expression levels were significantly higher in deep sections than in surface sections. TP, EGFR, VEGF, and HIF1α gene expression levels were significantly higher in lymph node metastases than in surface sections. TP, DPD, EGFR, VEGF, and HIF1α gene expression levels were positively correlated with the specific samples harvested from the tumors. CONCLUSIONS: Our results show that the expression levels of some genes in tumor cells can change in specific sites of tumors and can become higher in association with tumor progression.

Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2).

PURPOSE: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. METHODS AND MATERIALS: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m(2)) and cisplatin (40 mg/m(2)) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m(2)/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. RESULTS: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). CONCLUSIONS: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.

Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial).

PURPOSE: We compared biweekly irinotecan plus cisplatin (BIRIP) with irinotecan alone as the second-line chemotherapy (SLC) for advanced gastric cancer (AGC). METHODS: Patients with metastatic or recurrent gastric cancer refractory to S-1-based first-line chemotherapy were randomly assigned to receive BIRIP (irinotecan 60mg/m(2) plus cisplatin 30mg/m(2), every 2weeks) or irinotecan alone (irinotecan 150mg/m(2), every 2weeks). The primary end-point was to show the superiority of BIRIP to irinotecan in terms of progression free survival (PFS). RESULTS: 130 patients were enrolled. PFS was significantly longer in the BIRIP group (3.8months [95% confidence interval (CI) 3.0-4.7]) than in the irinotecan group (2.8months [2.1-3.3]; hazard ratio 0.68, 95% CI 0.47-0.98; P=0.0398). Median overall survival was 10.7months in the BIRIP group and 10.1months in the irinotecan group (HR 1.00, 95% CI 0.69-1.44, P=0.9823). The objective response rate was 22% in the BIRIP group and 16% in the irinotecan group (P=0.4975). However, the disease control rate was significantly better in the BIRIP group (75%) than in the irinotecan group (54%, P=0.0162). The incidences of grade 3 or worse adverse events did not differ between the two groups. Any grade elevation of serum creatinine was more common in the BIRIP group (25% versus 8%, P=0.009), but any grade diarrhoea (17% versus 42%, P=0.002) was more common in the irinotecan group. CONCLUSION: BIRIP significantly prolonged PFS as compared with irinotecan alone and was tolerated as SLC, but did not demonstrate the survival benefit in this trial.

Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a retrospective comparison with conventional endoscopic resection in a single center.

BACKGROUND: Few studies have compared the outcomes of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in patients with early gastric cancer. METHODS: We studied 780 lesions for which endoscopic treatment was indicated according to the Japanese Gastric Cancer Association (JGCA) criteria or the extended National Cancer Center (NCC) criteria from April 1995 to December 2007. A total of 359 lesions were treated by endoscopic aspiration mucosectomy (EAM) between April 1995 and March 2003 (EAM group), and 421 lesions were treated by ESD between April 2003 and December 2007 (ESD group). Long-term outcomes (local recurrence rate, overall survival) were compared between the groups. RESULTS: The median follow-up was 73 months in the EAM group and 65 months in the ESD group. Overall, the local recurrence rate was significantly lower in the ESD group (0.2 %, 1/421) than in the EAM group (4.2 %, 15/359) (p < 0.05). For lesions meeting the JGCA criteria, the local recurrence rate was 2.9 % in the EAM group and 0 % in the ESD group (p < 0.05). For lesions meeting the NCC criteria, the local recurrence rate was 12.5 % in the EAM group and 0.6 % in the ESD group (p < 0.05). There was no significant difference between the groups in overall survival. CONCLUSIONS: On long-term follow-up, ESD was associated with a lower rate of local recurrence than EAM for lesions that met the JGCA or the NCC criteria. From the point of view of radical curability, ESD can be recommended for the management of lesions that meet either set of criteria.

A phase II study of endoscopic submucosal dissection for superficial esophageal neoplasms (KDOG 0901).

BACKGROUND: Most previous studies of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms were retrospective; prospective studies are scant. OBJECTIVE: To prospectively assess the efficacy and safety of ESD for superficial esophageal neoplasms. DESIGN: Phase II study. SETTING: University hospital. PATIENTS: Fifty-two patients (median age 68 years; 48 men) who had a histologic diagnosis of superficial esophageal cancer without metastasis on CT or high-grade intraepithelial neoplasia (HGIN) were enrolled from April 2009 through November 2011. INTERVENTION: ESD was used to treat 56 lesions. All procedures were done by 4 endoscopists who each had previously performed ESD in more than 100 patients with gastric tumors. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the R0 resection rate, and secondary endpoints were the safety and the rate of accurately diagnosing tumor depth on endoscopic examination. RESULTS: The median treatment time was 69 minutes (24-168 minutes). The histopathologic diagnosis was squamous cell carcinoma in 49 lesions, HGIN in 5, and tubular adenocarcinoma in 2. The en bloc resection rate and R0 resection rate were 100% and 94.6%, respectively. The rates of adverse events during ESD and after ESD were 22.2% and 53.8%, respectively, but most events were mild. One patient (1.9%) had mediastinal emphysema without perforation. The rate of accurately diagnosing tumor depth on endoscopic examination was 76.8%. LIMITATIONS: Single-center, nonrandomized study. CONCLUSION: Our study showed that ESD was an effective and relatively safe treatment for superficial esophageal neoplasms. ESD may be a useful treatment option for superficial esophageal neoplasms in hospitals with endoscopists who are experts in performing ESD for gastric tumors. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000002047.).

Double-endoscope endoscopic submucosal dissection for the treatment of early gastric cancer accompanied by an ulcer scar (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) for early gastric cancer accompanied by an ulcer scar remains challenging. Several counter-traction techniques have been attempted to facilitate ESD, but a standard procedure remains to be established. OBJECTIVE: To evaluate the efficacy and safety of double-endoscope ESD by using a single light source in patients with early gastric cancer accompanied by an ulcer scar. DESIGN: Single center, retrospective study. SETTING: Kitasato University East Hospital. PATIENTS: A total of 30 early gastric cancers with ulcer scars were treated by double-endoscope ESD in 30 patients from October 2008 through May 2012. INTERVENTION: Double-endoscope ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, complete resection rate, treatment time, and adverse events. RESULTS: The use of two endoscopes for ESD provided a good field of vision and allowed counter-traction to be applied to the lesion, clearly facilitating submucosal dissection. Because only a single light source was used, the working space of the endoscope room was not compromised. Moreover, it was unnecessary to prepare another light source or to coordinate image filing. The en bloc resection rate and complete resection rate were 100% and 90%, respectively, and the median treatment time was 80 minutes. As compared with historical control data obtained before the introduction of double-endoscope ESD, the rate of cutting into the specimen was significantly lower (7% vs 35%; P = .01). No serious adverse events occurred during the procedure. Postoperatively, however, 3 patients (10%) had delayed hemorrhage, and 1 (3.3%) had a delayed perforation. LIMITATIONS: Single-center, nonrandomized study. CONCLUSION: Our experience indicates that our procedure for double-endoscope ESD is useful and feasible in patients with early gastric cancer accompanied by an ulcer scar.

Surveillance after endoscopic mucosal resection or endoscopic submucosal dissection for esophageal squamous cell carcinoma.

The objectives of surveillance after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma are: (i) early detection and treatment of recurrence; and (ii) early detection and treatment of metachronous esophageal squamous cell carcinoma and second primary cancers. Protocols for follow up after EMR or ESD for esophageal squamous cell carcinoma should be based on the risks of lymph node metastasis and distant metastasis as assessed on the basis of tumor staging at initial treatment. Early detection of recurrence or metachronous carcinomas often allows curative or less invasive treatment. Particular attention should be paid to the development of metachronous esophageal squamous cell carcinomas and second primary cancers (in particular, head and neck cancer and gastric cancer because of their high incidence).

Recommended sedation and intraprocedural monitoring for gastric endoscopic submucosal dissection.

Endoscopic submucosal dissection is associated with a longer treatment time and a higher risk of patient discomfort than conventional procedures. Adequate, safe sedation is therefore essential. Sedation can cause adverse effects such as hypoxemia and hypotension, requiring continuous intraoperative and postoperative monitoring of blood pressure, use of the electrocardiogram, and arterial blood oxygen saturation by pulse oximetry. A physician and a nurse solely responsible for sedating and monitoring the patient should be present during treatment.A combination of benzodiazepines and analgesics are generally used for sedation, but new sedatives such as propofol and dexmedetomidine hydrochloride are expected to be useful agents. Endoscopists should become more familiar with sedatives, analgesics, and emergency procedures in the future.

DOG1 is useful for diagnosis of KIT-negative gastrointestinal stromal tumor of stomach.

Approximately 80%-95% of gastrointestinal stromal tumors (GISTs) show positive staining for KIT, while the other 5%-20% show negative staining. If the tumor is negative for KIT, but is positive for CD34, a histological diagnosis is possible. However, if the tumor is negative for KIT, CD34, S-100, and SMA, a definitive diagnosis is often challenging. Recently, Discovered on GIST-1 (DOG1) has received considerable attention as a useful molecule for the diagnosis of GIST. DOG1, a membrane channel protein, is known to be overexpressed in GIST. Because the sensitivity and specificity of DOG1 are higher than those of KIT, positive staining for DOG1 has been reported, even in KIT-negative GISTs. KIT-negative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically. We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia. Our findings suggest that immunohistochemical staining for DOG1, in addition to gene analysis, is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.

Argon plasma coagulation for superficial esophageal squamous-cell carcinoma in high-risk patients.

AIM: To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients. METHODS: We studied 17 patients (15 men and 2 women, 21 lesions) with SESC in whom endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and open surgery were contraindicated from March 1999 through February 2009. None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g., liver cirrhosis, cerebral infarction, or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy. After conventional endoscopy, an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins. The lesion was then ablated by APC. We retrospectively studied the treatment time, number of APC sessions per site, complications, presence or absence of recurrence, and time to recurrence. RESULTS: The median duration of follow-up was 36 mo (range: 6-120 mo). All of the tumors were macroscopically classified as superficial and slightly depressed type (0-IIc). The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2. The median treatment time was 15 min (range: 10-36 min). The median number of treatment sessions per site was 2 (range: 1-4). The median hospital stay was 14 d (range: 5-68 d). Among the 17 patients (21 lesions), 2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence. There were no treatment-related complications, such as bleeding or perforation. CONCLUSION: APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease, as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy.

Risk of superficial squamous cell carcinoma developing in the head and neck region in patients with esophageal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Multicentric squamous dysplasia in the esophagus can be visualized by Lugol chromoendoscopy as multiple Lugol-voiding lesions (LVLs). Narrow-band imaging combined with magnifying endoscopy (NBI-ME) facilitates the detection of superficial squamous cell carcinoma within the head and neck region (HNSCC). We investigated risk factors for superficial HNSCC in patients with esophageal squamous cell carcinoma (ESCC). STUDY DESIGN: Case-control study. METHODS: We studied 71 patients with synchronous or former ESCC. All patients underwent screening of the head and neck by NBI-ME and Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Genetic polymorphisms of aldehyde dehydrogenase type 2 (ALDH2) were identified by the sequence-specific primer polymerase chain reaction. Clinical factors related to superficial HNSCC were analyzed. RESULTS: All patients with superficial HNSCC were drinkers. On univariate analysis, multiple LVLs (odds ratio [OR], 56.92; 95% confidence interval [CI] 6.93-467.38; P < .001), ALDH2-2 allele (OR, 14.48; 95% CI, 1.8-116.56; P = .01), current smoker (OR, 4.25; 95% CI, 1.44-12.57; P = .009), and smoking index ≥ 1,000 (OR, 3.45; 95% CI, 1.19-9.99; P = .02) were associated with superficial HNSCC. On multivariate analysis, multiple LVLs (OR, 61.12; 95% CI, 5.4-691.64; P = .001), ALDH2-2 allele (OR, 16.19; 95% CI, 1.15-228.06; P = .04), and current smoker (OR, 8.02; 95% CI, 1.09-59.22; P = .04) were associated with superficial HNSCC. CONCLUSIONS: Patients with ESCC, particularly drinkers, current smokers, and those with the ALDH2-2 allele and multiple LVLs, have an increased risk of superficial HNSCC.

A multicenter phase II study of combined chemotherapy with docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer (KDOG 0601).

PURPOSE: We conducted a phase II study to evaluate the efficacy and safety of a triplet regimen of docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer. METHODS: Docetaxel (40 mg/m(2)) and cisplatin (70 or 60 mg/m(2)) were given on day 1 of a 28-day cycle. S-1 (40 mg/m(2)) was given twice daily on days 1-14. Treatment with this regimen was continued for a maximum of 6 cycles. Subsequently, patients with no disease progression received a combination of docetaxel and S-1. RESULTS: Fifty-nine patients were enrolled. The median number of administered cycles was 8 (range, 1-25). Because some patients had serious myelosuppression and renal dysfunction with 70 mg/m(2) of cisplatin, dose of cisplatin was reduced to 60 mg/m(2) after 19 patients had been treated. Common severe toxic effects of grade 3 or 4 were leukocytopenia (44%), neutropenia (72%), anemia (15%), and febrile neutropenia (14%). The overall response rate of this group was 81% (95% confidence interval (CI), 71-91%). The median overall survival and progression-free survival were 18.5 (95% CI, 15.6-21.5) and 8.7 (95% CI, 6.7-10.7) months, respectively. CONCLUSIONS: Triplet of docetaxel, cisplatin, and S-1 is a well-tolerated and highly active regimen for advanced or recurrent gastric cancer. A 60 mg/m(2) of cisplatin is as effective as 70 mg/m(2) of cisplatin.