Robotic vs. laparoscopic distal gastrectomy for gastric cancer: A propensity score-matched retrospective comparative study at a single institution.

BACKGROUND: Although robotic surgery is becoming more widespread worldwide, it is still in its infancy. This study aimed to confirm the safety and feasibility of the induction of robotic-assisted gastric surgery at a local hospital. METHODS: For five years, between 2016 and 2020, 42 laparoscopic and 71 robotic distal gastrectomies were performed at the same institution. Patients diagnosed with gastric cancer were retrieved from the database. Propensity score matching was performed based on covariates such as Age, Sex, BMI, the American Society of Anesthesiologists Physical Status, Tumor Location, pT, and pN. Clinicopathological characteristics, surgical performance, postoperative outcomes, and pathological data were retrospectively collected and compared by the Chi-square test, the Fisher's exact test, the Student's t-test, and the Mann-Whitney U test. RESULTS: Billroth II reconstruction was often selected for the robotic group more than the laparoscopic group (59.4% and 15.6%, respectively). In addition, the number of lymph nodes harvested after D2 dissection tended to be more significant in the robotic group than in the laparoscopic group (52.1 ± 7.6 and 29.1 ± 3.7, respectively; p = 0.00934). The mean operative time was 271.4 ± 10.5 min for the robotic group and 220.8 ± 12.3 min for the laparoscopic group (p = 0.00005). There were no differences in short-term clinical outcomes between the two groups. CONCLUSIONS: Although a single-center, small comparative study, the results showed that the robotic surgery group was not inferior to the laparoscopic group in feasibility and safety. Moreover, robotic surgery enables harvesting a higher number of lymph nodes, which may be more advantageous than laparoscopic surgery. This study also showed that as the surgeon gains experience with robotic surgery, its operative time becomes significantly shorter.

A case of recurrent epiphrenic esophageal diverticulum treated with lower esophagogastric resection and interstitial jejunal reconstruction.

The patient is a 60-year-old female with a history of multiple times of recurrences of an esophageal diverticulum. She was referred for a diagnosis of persistent dysphagia and vomiting. Balloon dilation did not improve the symptoms; thus, she was referred for surgery. Esophageal fluoroscopy revealed a 5 cm diverticulum. There was no significant change in the size before and after dilation. Gastrointestinal endoscopy revealed a diverticulum in the lower esophagus, with a residue accumulation. The esophagus directly below the diverticulum was narrowed. The patient was diagnosed with recurrent lower esophageal diverticulum and underwent surgery. The operative findings showed poor coloration of the gastric fundus surrounding operated before by Nissen's method, so the patient underwent lower esophagogastric resection and interstitial jejunal reconstruction. The postoperative course was uneventful and discharged on the 19th day. She is 6 years postoperatively and gained six kg compared to her preoperative weight. She has remained in excellent health.

Metachronous triple cancers of the stomach, duodenum and rectum in a patient with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by the presence of at least 100 adenomatous polyps in the colon and rectum. The risk of upper gastrointestinal tumors is relatively high in patients with FAP, but a case of triple cancers has not been reported in the literature. We herein report a case of metachronous triple cancers of the stomach, duodenum and rectum in a patient with FAP.

A case report of anaplastic carcinoma with osteoclast-like giant cells arising in the pancreatic body.

The patient is a 58-year-old woman. She was referred to our hospital following a computed tomography scan that revealed a 2-cm tumor-like lesion in the pancreatic body. Endoscopic ultrasound fine-needle aspiration examination revealed a suspected undifferentiated carcinoma with pleomorphic type. The patient was diagnosed with anaplastic carcinoma of the pancreas (ACP) and underwent distal pancreatectomy with lymph nodes dissection. The resected body and tail of the pancreas had a nodular tumor measuring 30 mm in diameter. Histologically, the main lesion of the tumor showed well-differentiated adenocarcinoma, and diffuse proliferation of atypical short spindle cells and round cells accompanied by multinucleated giant cells aggregation was observed around the tubular structure; hence, it was diagnosed with ACP. The postoperative course was uneventful, and the patient was discharged 14 days after the operation. It has already been about 5 years since the surgery, and although the tumor has recurred, the patient is still alive and undergoing chemotherapy.

A case of post-operative stenosis caused by colonic ischemia after low anterior resection for rectal cancer, followed by delayed colo-anal anastomosis.

Cases of delayed colo-anal anastomosis (DCAA) are currently reported instead of the colo-anal anastomosis with a protective loop ileostomy for rectal cancer. Post-operative colonic ischemia is considered as one of the serious complications of colorectal resection. Although indication of DCAA should be carefully selected, we experienced a case of post-operative stenosis caused by colonic ischemia after low anterior resection for rectal cancer, followed by this procedure.

Robot-assisted excision of rectal duplication cysts: A case report.

Rectal duplication cysts are extremely rare and account for only 4% of all gastrointestinal duplication cysts. They may become challenging for removal in the case of a large tumor in a narrow pelvis. Herein, we report a case of rectal duplication cysts excision via robotic-assisted laparoscopic surgery and its utility.

A case of emergency pancreatoduodenectomy for bleeding from the duodenal mucosa due to arteriovenous malformation of the pancreatic head.

A rare case of bleeding from the duodenal mucosa due to arteriovenous malformation of the pancreatic head is reported. Caution needs to be observed, then excision may be necessary since noninvasive treatment such as coil embolization is not enough for complete hemostasis when patient suddenly decompensates.

RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment With Anti-EGFR Antibodies in Patients With Metastatic Colorectal Cancer.

PURPOSE: Several trials have evaluated the efficacy of rechallenge treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS: We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS: Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION: RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC.

Behavioural Response Alteration in Caenorhabditis elegans to Urine After Surgical Removal of Cancer: Nematode-NOSE (N-NOSE) for Postoperative Evaluation.

The technique used for cancer monitoring is essential for effective cancer therapy. Currently, several methods such as diagnostic imaging and biochemical markers have been used for cancer monitoring, but these are invasive and show low sensitivity. A previous study reported that Caenorhabditis elegans sensitively discriminated patients with cancer from healthy subjects, based on the smell of a urine sample. However, whether C. elegans olfaction can detect the removal of cancerous tumours remains unknown. This study was conducted to examine C. elegans olfactory behaviour to urine samples collected from 78 patients before and after surgery. The diagnostic ability of the technique termed Nematode-NOSE (N-NOSE) was evaluated by receiver operating characteristic (ROC) analysis. The ROC curve of N-NOSE was higher than those of classic tumour markers. Furthermore, we examined the change in C. elegans olfactory behaviour following exposure to preoperative and postoperative samples. The results suggest that a reduction in attraction indicates the removal of the cancerous tumour. This study may lead to the development of a noninvasive and highly sensitive tool for evaluating postoperative cancer patients.

Correction to: S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102).

In the original publication, in Abstract, the sentence that reads as, "Oral S-1 at a dose of 80 mg/m2 was…………. drug-free interval" should read as, "Oral S-1 at a dose of 40 mg/m2 was administered twice daily for 2 weeks, followed by a 1-week drug-free interval.

A small pancreatic hamartoma with an obstruction of the main pancreatic duct and avid FDG uptake mimicking a malignant pancreatic tumor: a systematic case review.

BACKGROUND: Pancreatic hamartomas are extremely rare and may be misdiagnosed as malignant tumors. We report herein a case of a small, solid-type pancreatic hamartoma. CASE PRESENTATION: A 72-year-old female was incidentally detected pancreatic lesion by ultrasonography. Computed tomography and magnetic resonance imaging revealed a 2.0-cm solid lesion. The main pancreatic duct (MPD) was obstructed by the lesion in the head of the pancreas, and the upstream MPD was dilated. 18F-fluorodeoxyglucose (FDG) accumulated avidly in the lesion and increased in FDG intensity from the early to the delayed images. The histopathological studies confirmed the diagnosis of pancreatic hamartoma. Immunohistochemically, the cell membrane of the accessory glands and ducts showed homogeneous expression of glucose transporter type I and hexokinase II. CONCLUSION: Pancreatic hamartomas causing dilatation of the MPD are extremely rare, and this appears to be the first case of a hamartoma to take up FDG avidly. It was a rare occurrence and should be noted that pancreatic hamartomas can cause an obstruction of the MPD and show avid FDG uptake, thereby mimicking malignant pancreatic tumors.

A pilot study for texture analysis of 18F-FDG and 18F-FLT-PET/CT to predict tumor recurrence of patients with colorectal cancer who received surgery.

PURPOSE: This retrospective study was done to examine whether the heterogeneity in primary tumor F-18-fluorodeoxyglucose (18F-FDG) and 18F-3'-fluoro-3'-deoxythymidine (18F-FLT) distribution can predict prognosis of patients with colorectal cancer who received surgery. METHODS: The enrolled 32 patients with colorectal cancer underwent both 18F-FDG- and 18F-FLT-PET/CT studies before surgery. Clinicopathological factors, stage, SUVmax, SUVmean, metabolic tumor volume (SUV ≥ 2.5), total lesion glycolysis, total lesion proliferation and seven texture heterogeneity parameters (coefficient of variation, local parameters: entropy, homogeneity, and dissimilarity; and regional parameters: intensity variability [IV], size-zone variability [SZV], and zone percentage [ZP]) were obtained. Progression free survival (PFS) was calculated by the Kaplan-Meier method. Prognostic significance was assessed by Cox proportional hazards analysis. RESULTS: Eight patients had eventually come to progression, and 24 patients were alive without progression during clinical follow-up [mean follow-up PFS; 55.9 months (range, 1-72)]. High stage (p = 0.004), high 18F-FDG-IV (p = 0.015), high 18F-FDG-SZV (p = 0.013) and high 18F-FLT-entropy (p = 0.015) were significant in predicting poor 5-year PFS. Other parameters did not predict the disease outcome. At bivariate analysis, disease event hazards ratios for 18F-FDG-IV and 18F-FDG-SZV remained significant when adjusted for stage and 18F-FLT-entropy (18F-FDG-IV; p = 0.004 [adjusted for stage], 0.007 [adjusted for 18F-FLT-entropy]; 18F-FDG-SZV; p = 0.028 [adjusted for stage], 0.040 [adjusted for 18F-FLT-entropy]). CONCLUSION: 18F-FDG PET heterogeneity parameters, IV and SZV, have a potential to be strong prognostic factors to predict PFS of patients with surgically resected colorectal cancer and are more useful than 18F-FLT-PET/CT heterogeneity parameters.

S-1 and irinotecan plus bevacizumab as second-line chemotherapy for patients with oxaliplatin-refractory metastatic colorectal cancer: a multicenter phase II study in Japan (KSCC1102).

BACKGROUND: Combination chemotherapy with S-1 and irinotecan is one of the standard treatments for metastatic colorectal cancer (mCRC) in Japan. However, there are few alternative practical second-line therapies. We conducted a phase II trial to evaluate the efficacy and safety of the combination of S-1 and irinotecan plus bevacizumab as a second-line treatment for oxaliplatin-refractory mCRC. METHODS: Patients with mCRC who were previously treated with oxaliplatin-containing regimens were enrolled. Oral S-1 at a dose of 40 mg/m(2) was administered twice daily for 2 weeks, followed by a 1-week drug-free interval. Irinotecan at a dose of 150 mg/m(2) and bevacizumab at a dose of 7.5 mg/kg were administered on day 1. The primary endpoint was progression-free survival (PFS). RESULTS: Thirty-seven patients were enrolled, and 34 and 36 patients were assessed for response and safety, respectively. The overall response rate was 20.6 % (95 % confidence interval [CI] 8.7-37.9), and the disease control rate was 76.5 % (95 % CI 58.8-89.3). The median PFS was 5.6 months (95 % CI 3.8-7.0). The median overall survival was 16.4 months (95 % CI 8.1-20.0). The most common grade 3/4 adverse events included neutropenia (25.0 %), anorexia (22.2 %), anemia (16.7 %), and fatigue/malaise (16.7 %). The most common grade 3/4 adverse event of special interest for bevacizumab was hypertension (30.6 %). One treatment-related death caused by gastrointestinal bleeding occurred. CONCLUSIONS: The findings suggest that the combination of S-1 and irinotecan plus bevacizumab is effective and tolerable as second-line chemotherapy for patients with oxaliplatin-refractory mCRC.

Angiopoietin-like protein 2 as a potential biomarker for colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Disease progression leads to its spread to other organs, such as the liver, and is associated with higher mortality rates. Early CRC detection is therefore crucial for maximizing the chances of complete cure. The measurement of serum-based tumor biomarkers has shown great potential for the detection of CRC. In this study, we investigated the feasibility of using angiopoietin-like protein 2 (ANGPTL2) as a candidate biomarker for CRC. We first investigated ANGPTL2 expression in 7 CRC cell lines, among which Colo320, NCC-CoCK-115P, Caco-2 and Colo205 exhibited comparatively high ANGPTL2 expression. The serum levels of ANGPTL2 in CRC patients (3.45±1.30 ng/ml) were higher compared with those in healthy controls (2.74±0.64 ng/ml) (P<0.05). A receiver operating characteristic analysis demonstrated that the diagnostic performance of ANGPTL2 was marginally lower compared with that of the established biomarker C-reactive protein, but higher compared with that of carbohydrate antigen 19-9. These results suggested that the simultaneous measurement of ANGPTL2, along with previously established serum biomarkers, may increase the likelihood of early detection of CRC.

Initial report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japanese patients.

BACKGROUND: A prospective feasibility study was planned to clarify the proportion of compliance and adverse events in the administration of capecitabine as adjuvant chemotherapy for colon cancer in Japanese patients. METHODS: We aimed initially to register 92 cases of R0 stage III colon cancer. Capecitabine (2,500 mg/m(2)/day) was given orally on days 1-14 every 3 weeks for 8 cycles. The proportion of treatments completed as planned was selected as the primary endpoint. RESULTS: Ninety-seven cases were registered and treated between September 2008 and August 2009. The proportion of treatments completed in the full analysis set was 64/97 [66.0%; 95% confidence interval (CI), 55.7-75.3%] and in the per protocol set was 64/91 (70.3%; 95% CI, 59.8-79.5%). Adverse events which led to treatment discontinuation included hand-foot syndrome (HFS) (7), haematotoxicity (5) and increased hepatic damage (4). The proportions of patients with major grade 3/4 adverse events were HFS 22.7%, neutropenia 7.2%, diarrhoea 2.1%, and increased bilirubin 0.0%. CONCLUSIONS: This collaborative multi-facility study, the first of its kind in Japan, presented results of a safety confirmation experiment on capecitabine as adjuvant chemotherapy for stage III colon cancer. The results suggest that capecitabine may be administered safely to Japanese patients.

Clinicopathological significance of BMP7 expression in esophageal squamous cell carcinoma.

BACKGROUND: Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor-ß (TGF-ß) superfamily of growth factors. Recent studies have shown that the influence of the expression of BMP7 was altered in several tumors. The purpose of the current study was to examine the expression of BMP7 in esophageal squamous cell carcinoma and to clarify the clinical impact of BMP7 expression in esophageal squamous cell carcinoma (ESCC). METHODS: A total of 180 patients with ESCC who underwent surgical resection from 1991 to 2004 were eligible for this study. The expression of BMP7 in esophageal tumor tissues was examined immunohistochemically. RESULTS: BMP7 expression was found in the cytoplasm of cancer cells. BMP7 positivity was observed in 61.7% of tumors. The BMP7-positive group had deeper progression, more advanced stages, and greater venous invasion than those without BMP7 expression (p < 0.001, p < 0.005, and p < 0.0005, respectively). In addition, expression of BMP7 correlated with poorer prognosis (p < 0.0005). Multivariate analysis showed that BMP7 expression status was an independent prognostic factor (p < 0.05). CONCLUSIONS: Patients with expression of BMP7 in ESCC had high malignant potential. BMP7 could be a useful prognostic marker for patients with ESCC.

Mesothelin expression correlates with prolonged patient survival in gastric cancer.

PURPOSE: Mesothelin expression is found in normal mesothelium, and cancerous mesothelin has been recently reported in ovarian and pancreas cancer. The clinicopathological implications of mesothelin expression have been discussed with respect to antitumor immunological mechanisms. However, there is no information on mesothelin expression in gastric cancer. The purpose of the current study is to identify the clinical significance of mesothelin in gastric cancer. EXPERIMENTAL DESIGN: A total of 212 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were enrolled in this study. Mesothelin was detected immunohistochemically and visualized by ABC method. Intensity of cancerous mesothelin was divided into two categories (0-50%: negative group and 51-100%: positive group). RESULTS: Mesothelin expression was detected in the cellular membrane. In accordance with the previous evaluation, patients were divided into two groups [mesothelin-positive group: 124 (59%) and mesothelin-negative group: 88 (41%)]. The mesothelin-positive group had significantly more nodal involvement and significantly deeper tumor invasion than the mesothelin-negative group (P < 0.05). However, by analysis confined to the 117 advanced gastric cancer patients, the 5-year survival rate of the mesothelin-positive group was 55%, which was significantly better than that of the mesothelin-negative group. Multivariate analysis revealed that mesothelin expression is one of the independent prognostic factors of gastric cancer. CONCLUSION: Cancerous mesothelin expression in gastric cancer may be a useful tool to predict patient survival.

Prognostic impact of CD168 expression in gastric cancer.

BACKGROUND: Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear. METHODS: We examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma. RESULTS: Cancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01). CONCLUSION: Our results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid.

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as second-line treatment for advanced colorectal cancer: a Japanese experience.

PURPOSE: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer. METHODS: A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment. RESULTS: Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%-35.0%). The median PFS was 5.6 months (95% CI, 4.1-7.0 months) and the median OS was 19.6 months (95% CI, 11.4-24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable. CONCLUSION: The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.