Integrated Endoscopic System Based on Optical Imaging and Hyperspectral Data Analysis for Colorectal Cancer Detection.

BACKGROUND/AIM: Two-dimensional hyperspectral data systems with enhanced area detection and diagnostic abilities are now available in gastrointestinal endoscopy for colorectal cancer. We evaluated a new hyperspectral system for diagnosis of colorectal cancer. PATIENTS AND METHODS: A resected-specimen spectrum observation module (stereoscopic macroscope, hyperspectral camera, and xenon lamp) was used to evaluate 21 resected colorectal cancer specimens (ex vivo experiment). A colonoscopy spectrum observation module (imaging fiberscope and hyperspectral camera) was used to perform 24 colonoscopic spectroscopy evaluations (in vivo experiment). RESULTS: An approximately 525-nm increase in spectral absorption occurred between normal mucosa and adenoma, with a tendency toward decreased absorption rates with aggravation of other tumor types. In vivo discrimination between tumorous and non-tumorous tissues showed 72.5% sensitivity and 82.1% specificity. CONCLUSION: This in vivo hyperspectral diagnostic system showed that reflectance spectra intensity may discriminate between normal and abnormal colonic mucosa.

Novel, high-definition 3-D endoscopy system with real-time compression communication system to aid diagnoses and treatment between hospitals in Thailand.

INTRODUCTION: Traditionally, laparoscopy has been based on 2-D imaging, which represents a considerable challenge. As a result, 3-D visualization technology has been proposed as a way to better facilitate laparoscopy. We compared the latest 3-D systems with high-end 2-D monitors to validate the usefulness of new systems for endoscopic diagnoses and treatment in Thailand. METHODS: We compared the abilities of our high-definition 3-D endoscopy system with real-time compression communication system with a conventional high-definition (2-D) endoscopy system by asking health-care staff to complete tasks. Participants answered questionnaires and whether procedures were easier using our system or the 2-D endoscopy system. RESULTS: Participants were significantly faster at suture insertion with our system (34.44 ± 15.91 s) than with the 2-D system (52.56 ± 37.51 s) (P < 0.01). Most surgeons thought that the 3-D system was good in terms of contrast, brightness, perception of the anteroposterior position of the needle, needle grasping, inserting the needle as planned, and needle adjustment during laparoscopic surgery. Several surgeons highlighted the usefulness of exposing and clipping the bile duct and gallbladder artery, as well as dissection from the liver bed during laparoscopic surgery. In an image-transfer experiment with RePure-L®, participants at Rajavithi Hospital could obtain reconstructed 3-D images that were non-inferior to conventional images from Chulalongkorn University Hospital (10 km away). CONCLUSION: These data suggest that our newly developed system could be of considerable benefit to the health-care system in Thailand. Transmission of moving endoscopic images from a center of excellence to a rural hospital could help in the diagnosis and treatment of various diseases.

Evaluation of techniques to prevent colorectal anastomotic leakage.

BACKGROUND: Anastomotic leakage is a major complication after anterior resection for rectal cancer. The double-stapling technique (DST) is the main method for creating a colorectal anastomosis. However, the rate of anastomotic leakage after DST remains high, and the technical risk factors have not been well established. MATERIALS AND METHODS: Five methods of colorectal anastomosis were performed on the porcine rectum and colon: single-stapled double-purse-string (SSDP), DST, side-to-side with a linear stapler (SS-L), side-to-side with a circular stapler (SS-C), and SS-C with hand-sewn reinforcement (n = 6 for each method). In each group, burst pressures were tested, paying special attention to the locations of the first disruptions. The anastomosis line, including staples, was embedded in polyester resin, and polished sections were examined histologically. RESULTS: Burst pressures were significantly higher in the SS-L and SS-C than those in the SSDP and DST groups (P < 0.001) and were higher in the SS-C with hand-sewn reinforcement than those in the SS-L and SS-C groups (P < 0.001). Remarkably, in the SSDP, DST, and SS-C groups, the first disruptions occurred on the staple line created by the circular stapler. CONCLUSIONS: The experimentally strongest colorectal anastomosis created with instruments currently in use was a SS-C. This anastomosis does not overlap staple lines and does not require a purse-string suture. Hand-sewn reinforcement was effective in increasing the anastomotic strength.

Endoscopic evaluation of clinical colorectal anastomotic leakage.

BACKGROUND: Anastomotic leakage (AL) is a major complication after anterior resection. However, its therapeutic strategies and technical risk factors have not been well established. Therefore, we endoscopically evaluated anastomotic regions after laparoscopic colorectal anastomosis using a double-stapling technique (DST) for determination of treatment and investigation of technical factors. METHODS: In total, 191 consecutive patients underwent laparoscopic anterior resection with a DST from September 2008-January 2013. Anastomotic regions were endoscopically evaluated in patients suspected to have AL after surgery. RESULTS: Anastomotic dehiscence was observed in 19 patients, and AL was diagnosed in 18 (9.3%). Of the 19 patients, 12 were treated by creation of an intestinal stoma and 7 were treated conservatively based on their clinical status and endoscopic findings. Twenty-three dehiscences were observed among 19 anastomotic regions; all 23 were observed on the circular stapler anastomosis lines. Of these 23 dehiscences, 13 (56.5%) were located at the point at which the anastomosis lines of the circular and linear staplers overlapped, and 10 (43.5%) were located on the circumferential aspect between the overlapping points. CONCLUSIONS: Endoscopic evaluation of anastomotic regions is safe and useful for the determination of therapeutic strategies. The DST anastomotic technique itself may be closely related to the development of AL.

Intraoperative visualization of cerebral oxygenation using hyperspectral image data: a two-dimensional mapping method.

PURPOSE: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is an important technique for cerebrovascular reconstruction. Intraoperative hemodynamic imaging is needed to perform cerebrovascular reconstruction safely and effectively. Optical intrinsic signal (OIS) imaging is commonly used for assessing cerebral hemodynamics in experimental studies, because it can provide high-resolution mapping images. However, OIS is not used clinically due to algorithm, instrumentation and spectral resolution limitations. We tested the feasibility of a hyperspectral camera (HSC) for assessment of cortical hemodynamics with spectral imaging of the cerebral cortex in rats and in vivo humans. METHODS: A hyperspectral camera (HSC) was tested in a rat model of cerebral ischemia (middle cerebral artery occlusion) and during human revascularization surgery (STA-MCA anastomosis). Changes in cortical oxygen saturation were derived from spectral imaging data (400-800 nm) collected by exposing the cortex to Xenon light. Reflected light was sampled using the HSC. The system was then tested intraoperatively during superficial temporal artery to middle cerebral artery anastomosis procedures. Comparison with single-photon emission computed tomography (SPECT) imaging data was done. RESULTS: During middle cerebral artery occlusion in rats, the HSC technique showed a significant decrease in cortical oxygen saturation in the ischemic hemisphere. In clinical cases, the cortical oxygen saturation was increased after STA-MCA anastomosis, which agreed with the SPECT imaging data. CONCLUSION: Continuous collection of imaging spectroscopic data is feasible and may provide reliable quantification of the hemodynamic responses in the brain. The HSC system may be useful for monitoring intraoperative changes in cortical surface hemodynamics during revascularization procedures in humans.

Analysis of hand motion differentiates expert and novice surgeons.

BACKGROUND: The number of operations performed by a surgeon may be an indicator of surgical skill. The hand motions made by a surgeon also reflect skill and level of expertise. We hypothesized that the hand motions of expert and novice surgeons differ significantly, regardless of whether they are familiar with specific tasks during an operation. METHODS: This study compared 11 expert surgeons, each of whom had performed >100 laparoscopic procedures, and 27 young surgeons, each of whom had performed <15 laparoscopic procedures. Each examinee performed a specific skill assessment task, in which instrument motion was monitored using magnetic tracking system. We analyzed the paths of the centers of gravity of the tips of the needle holders and the relative paths of the tips using two mathematical methods of detrended fluctuation analysis and unstable periodic orbit analysis. RESULTS: Detrended fluctuation analysis showed that the exponent in the function describing the initial scaling exponent (α1) differed significantly for experts and novices, being close to 1.0 and 1.5, respectively (P < 0.01). This indicated that the expert group had a greater long-range coherence with an intrinsic sequence and smooth continuity among a series of motions. Likewise, unstable periodic orbit analysis showed that the second period of unstable orbit was significantly longer for experts in comparison with novices (P < 0.01). This demonstrates mathematically that the hands of experts are more stable when performing laparoscopic procedures. CONCLUSIONS: Objective evaluation of hand motion during a simulated laparoscopic procedure showed a significant difference between experts and novices.

Significance of metacognitive skills in laparoscopic surgery assessed by essential task simulation.

BACKGROUND: Metacognition is the knowledge about one's own methods of perceiving, remembering, thinking, and acting. This study determined the significance of metacognitive skills in laparoscopic surgery with the aim of applying the findings in a laparoscopic surgery training program. MATERIAL AND METHODS: Eighteen medical students with no experience in laparoscopic surgery (novice group) and eight expert surgeons who had each performed >100 laparoscopic surgeries (expert group) were enrolled. The examinees in each group performed an evaluation task using a virtual reality simulator and answered questions about the task. RESULTS: The longest performance times, longest path lengths, and most frequent tissue damage occurred at 135° in the novice group and at 180° in the expert group. The greatest recognition of task difficulties, impatience, and irritation occurred at 135° in the novice group and at 180° in the expert group. There were statistically significant correlation coefficients between the instrument path length and task difficulty (metacognition) at 135° (R = 0.74, p = 0.03) and 180° (R = 0.79, p = 0.02) in the expert group, but there were no significant correlations in the novice group. CONCLUSION: We elucidated the significance of metacognitive skills in laparoscopic surgery. A training program should include recognition feedback systems.

Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan.

PURPOSES: This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy. METHODS: The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing. RESULTS: A detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3-4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018). CONCLUSIONS: The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.

Contribution of BubR1 to oxidative stress-induced aneuploidy in p53-deficient cells.

DNA aneuploidy is observed in various human tumors and is associated with the abnormal expression of spindle assembly checkpoint (SAC) proteins. Oxidative stress (OS) causes DNA damage and chromosome instability that may lead to carcinogenesis. OS is also suggested to contribute to an increase in aneuploid cells. However, it is not clear how OS is involved in the regulation of SAC and contributes to carcinogenesis associated with aneuploidy. Here we show that an oxidant (KBrO3) activated the p53 signaling pathway and suppressed the expression of SAC factors, BubR1, and Mad2, in human diploid fibroblast MRC5 cells. This suppression was dependent on functional p53 and reactive oxygen species. In p53 knockdown cells, KBrO3 did not suppress BubR1 and Mad2 expression and increased both binucleated cells and cells with >4N DNA content. BubR1 and not Mad2 downregulation suppressed KBrO3-induced binucleated cells and cells with >4N DNA content in p53 knockdown cells, suggesting that BubR1 contributes to enhanced polyploidization by a mechanism other than its SAC function. In analysis of 182 gastric cancer specimens, we found that BubR1 expression was significantly high when p53 was positively stained, which indicates loss of p53 function (P = 0.0019). Moreover, positive staining of p53 and high expression of BubR1 in tumors were significantly correlated with DNA aneuploidy (P = 0.0065). These observations suggest that p53 deficiency may lead to the failure of BubR1 downregulation by OS and that p53 deficiency and BubR1 accumulation could contribute to gastric carcinogenesis associated with aneuploidy.

Advances in esophageal surgery in elderly patients with thoracic esophageal cancer.

AIM: To justify esophagectomy for elderly patients. PATIENTS AND METHODS: A total of 1,002 patients with thoracic esophageal cancer who underwent esophagectomy were divided into three groups: I (≤ 74 years old, n=898); II (75-79 years, n=81); and III (≥ 80 years, n=23). Historical changes were compared between the first surgical period (1964-1989) and the second period (1990-2011). RESULTS: The morbidity rates were 40%, 41% and 26% in the respective groups. Pulmonary complications decreased historically in groups II and III (36% to 15% and 43% to 0%, respectively). The mortality was higher in the older groups (4.8%, 8.6% and 13.0%, respectively); however, there was a marked historical decrease in groups II (18.2% to 5.1%) and III (28.6% to 6.3%). The 5-year survival improved from 5% to 35% in group II and from 0% to 17% in group III. CONCLUSION: The outcomes of esophagectomy for elderly patients have markedly improved, with acceptable mortality even in octogenarians.

[Laparoscopic repair of incarcerated diaphragmatic hernia as a late complication of laparoscopic right hepatectomy: a case report].

Incarcerated diaphragmatic hernia after laparoscopic right hepatectomy is very rare. An 81-year-old man underwent laparoscopic right hepatectomy for giant hepatic hemangioma. Twenty months after the surgery, he began to complain of nausea and abdominal pain and was brought to our hospital. Chest X-ray showed an abdominal gas shadow above the right diaphragm and computed tomography showed herniation of the colon into the right thoracic cavity. We diagnosed ileus due to incarcerated diaphragmatic hernia and performed emergency operation under laparoscopic surgery. After successfully reducing the prolapsed colon back to the abdominal cavity, the diaphragmatic hernia orifice was repaired. Incarcerated diaphragmatic hernia sometimes causes the fatal state. Clinicians must therefore consider such findings a late complication of laparoscopic hepatectomy.

Rigid and flexible endoscopic rendezvous in spatium peritonealis may be an effective tactic for laparoscopic megasplenectomy: significant implications for pure natural orifice translumenal endoscopic surgery.

BACKGROUND: We recently experienced 10 patients with cirrhosis who underwent laparoscopic splenectomy. A portion of these patients underwent dissection with a flexible endoscope in the peritoneal cavity. This pilot study mainly focused on the technical aspects and immediate results. METHODS: From November 2009 to September 2010, 10 patients with cirrhosis and hypersplenism were entered into this pilot study. They were indicated to undergo laparoscopic splenectomy to treat portal hypertension and to facilitate initiation and completion of either interferon therapy for liver cirrhosis or anticancer therapy for hepatocellular carcinoma. To dissect the upper end of the gastrosplenic ligament and the marginal region between the left diaphragm and upper pole of the spleen, a flexible single-channel endoscope was introduced into the peritoneal cavity simultaneously with the use of a rigid laparoscope. Dissection with the flexible endoscope in the peritoneal cavity was performed using an insulation-tipped electrosurgical knife through the channel of the flexible endoscope. RESULTS: The flexible endoscope offered a magnified operative view, a water-jet lens cleaner, and a powerful lavage and suction capability. The upper end of the gastrosplenic ligament and the marginal region between the left diaphragm and upper pole of the spleen were easily seen, and dissection of these critical regions was smoothly conducted with articulation of the tip of the flexible endoscope, even in patients with splenomegaly. No patient experienced major intraoperative complications or required conversion to open surgery. CONCLUSIONS: Dissection with a flexible endoscope in the peritoneal cavity may be an effective tactic for laparoscopic megasplenectomy, and significant implications for pure natural orifice translumenal endoscopic surgery have been raised. Although future randomized controlled prospective studies are needed to confirm these findings, surgeons might find this to be a typical example of an appropriate strategy for high-risk patients.

Laparoscopic resection for gastrointestinal stromal tumors in the stomach.

PURPOSE: Gastrointestinal stromal tumors (GISTs) should be surgically resected, even those smaller than 5 cm in size, which is the threshold of clinical malignancy for submucosal tumors (SMTs) in the gastrointestinal tract. This study reviewed the use of laparoscopic surgery for gastric partial resection of GISTs or SMTs that were suspected to be GISTs. METHODS: Eighteen patients underwent laparoscopic partial resection of the stomach for GISTs or SMTs. The tumor location was confirmed by intraluminal endoscopy. One-half of the circumference around the tumor was dissected, and the tumor was turned toward the abdominal cavity. The nonresected part of the tumor and the edge of the incision line was lifted up using forceps, and the incision line was closed using laparoscopic stapling devices. RESULTS: Two cases were diagnosed as GIST by endoscopic biopsy. Six patients underwent endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) examinations, which diagnosed five GISTs. There were 18 tumors smaller than 5 cm, including 10 GISTs, 4 leiomyomas, 3 schwannomas, and one heterotopic pancreas. CONCLUSIONS: Endoscopic ultrasound-guided FNAB is recommended for definite preoperative diagnosis of histopathologically unknown SMTs to determine the indications for surgery. The laparoscopic approach with the assistance of endoscopy is useful for improving the curability, with minimal invasiveness for the partial resection of GISTs.

Clinical significance of salvage esophagectomy for remnant or recurrent cancer following definitive chemoradiotherapy.

BACKGROUND: The purpose of this study was to clarify the effect of preoperative chemoradiotherapy (CRT) for esophageal cancer on the postoperative course, and to determine the clinical significance of salvage esophagectomy after definitive CRT. METHODS: Based on their preoperative treatment, 477 patients with esophageal cancer were classified into three groups: 253 patients who received surgery alone (Group I), 197 who received planned CRT (30-45 Gy, Group II), and 27 who received a salvage esophagectomy (radiation ≥60 Gy, Group III). RESULTS: Postoperative complications developed in 25, 40, and 59% of the patients in Groups I, II, and III, respectively, with pulmonary complications developing in 10, 15, and 30%, and anastomotic leakage developing in 13, 23, and 37%, respectively. Mortality rates were 2.4, 2.0, and 7.4%, respectively. Multivariate analysis revealed preoperative therapy to be an independent factor associated with postoperative risks: the odds ratios (ORs) of Groups II and III compared to Group I were 1.8 and 4.0 for pulmonary complications, while they were 1.9 and 2.8, respectively, for anastomotic leakage. No critical complications developed in the 14 patients who received salvage surgery performed with strict surgical indications after 2005. The survival of Group III was not significantly different from that of Groups I and II. Most patients who received an R1/R2 resection after definitive CRT died within 2 years after salvage surgery. CONCLUSIONS: Preoperative CRT is associated with postoperative complications especially in patients with R2 resection, while long-term survival can be achieved after R0 resections. Salvage surgery should be considered for carefully selected patients in whom R0 resection can be achieved.

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention.

Both cigarette smoking and alcohol drinking are well-established risk factors for esophageal squamous cell carcinoma (ESCC), and the relationship of dose to cancer risk has already been described. Furthermore, the synergistic effect of these two factors has been reported. Our case-control study revealed the odds ratio of ESCC to be 50.1 for those who were both heavy smokers and heavy drinkers in comparison to people who neither drank nor smoked. In patients with ESCC, head and neck cancers as well as dysplastic lesions are frequently observed. Heavy smoking and heavy drinking are closely related to such multicentric carcinogenesis events in the upper aerodigestive tract (UADT), including the esophagus and head andneck region. Polymorphisms in acetaldehyde dehydrogenase 2 (ALDH2) are reported to be a key event in deciding individual susceptibility to UADT cancer. Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers. For the early detection of the disease, effective follow up using endoscopy with Lugol staining or narrow band imaging endoscopy is strongly recommended for high-risk populations, such as smokers, heavy drinkers, people with experience of flushing after the drinking of alcohol, and patients with UADT cancer.

Skills assessment using a virtual reality simulator, LapSim, after training to develop fundamental skills for endoscopic surgery.

Education and training to maintain medical safety are very important within clinical settings. We have established a training center for endoscopic surgery and we regularly hold a unique training course, which focuses on the development of fundamental skills. One hundred and ninety-four surgeons who participated in our training course were divided into four groups according to their experience in performing laparoscopic procedures. Group 1: 0-19 laparoscopic procedures (n=44). Group 2: 20-49 laparoscopic procedures (n=53). Group 3: 50-99 laparoscopic procedures (n=46). Group 4: more than 100 laparoscopic procedures (n=55). All subjects underwent evaluation for "Lifting & Grasping" using a virtual reality (VR) simulator, LapSim, before and after the training course. The mean efficiency score, time to completion and tissue damage after training were significantly improved after the training as compared with before training. Before training, subjects with greater experience had better scores. However, the only significant difference in the score was between the low experience group and greatest experience group. After training, the score increased in all groups compared with that before training, and there was no significant difference between groups. This study demonstrates the feasibility of using a VR simulator to assess fundamental skills for endoscopic surgery after training. We found that the scores for the task were associated with the level of experience of the surgeons.