Minimally Invasive Surgery for Colorectal Cancer During the COVID-19 Pandemic in a Tertiary Medical Facility in Japan.

BACKGROUND/AIM: The coronavirus disease 2019 (COVID-19) pandemic has reduced hospital visits due to concerns regarding infection and also resulted in cancer screening delays. These changes may have had an impact on the progression of colorectal cancer (CRC). Therefore, the present study investigated the effects of the COVID-19 pandemic on minimally invasive surgery (MIS) for CRC using a correlation analysis of clinical outcomes before and during the COVID-19 pandemic. PATIENTS AND METHODS: The present study targeted CRC patients who underwent MIS between January 2018 and December 2019 (pre-COVID-19) and between April 2020 and March 2021 (COVID-19). A comparison analysis of clinical, surgical, and pathological findings between the pre-COVID-19 and COVID-19 groups was performed. RESULTS: Ninety-one patients underwent MIS for CRC pre-COVID-19 and 67 during COVID-19. The number of CRC cases detected by fecal occult blood tests was slightly higher in the pre-COVID-19 group than that in the COVID-19 group. Re-evaluations of laparoscopic videos revealed that the number of cases of surgical T4 CRC resected with the combined resection of the adjacent organs was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (16.4 vs. 4.4%, p=0.010). Furthermore, surgical times were significantly longer in the COVID-19 group than those in the pre-COVID-19 group (p<0.001). Pathological findings showed that the number of pT4 cases was significantly higher in the COVID-19 group than that in the pre-COVID-19 group (p=0.026). CONCLUSION: The number of T4 CRC cases was higher during than before the COVID-19 pandemic, with increases in the surgical difficulty of MIS.

Is pneumoperitoneum necessary for single-incision laparoscopy-assisted appendectomy for pediatric appendicitis?

INTRODUCTION: Several studies have reported the treatment of pediatric appendicitis with single-incision laparoscopy-assisted appendectomy using a muscle hook without pneumoperitoneum to lift the abdominal wall. However, very few studies have investigated the advantages of this procedure. We examined the utility of this procedure in our department. METHODS: This study included 33 children with appendicitis who underwent single-incision laparoscopy-assisted appendectomy at our hospital from April 2011 to March 2018. Patients were divided into two groups depending on whether they underwent the procedure with pneumoperitoneum: the no pneumoperitoneum group (n = 12) and the pneumoperitoneum group (n = 21). The clinicopathological factors and surgical costs were compared between the two groups. RESULTS: In the pneumoperitoneum group, the procedure was initiated in four patients by lifting the abdominal wall but was changed to include a pneumoperitoneum because of difficulty. There were no significant differences between the two groups with regard to age, sex, or pathological severity. CT revealed a significant difference in the distance from the appendicular root to the umbilicus between the groups. There was a significant difference in the operative duration, but not in estimated blood loss or length of postoperative hospital stay. Complications were observed in one patient in each group. There was a significant difference in cost between the two groups. CONCLUSIONS: Single-incision laparoscopy-assisted appendectomy without pneumoperitoneum is less expensive because certain supplies and CO2 are not required. Because there were no differences in the length of postoperative hospital stay or complications, this procedure may be safe in cases that are expected to be mild.

Early Neuropathy Related to Oxaliplatin Treatment in Advanced and Recurrent Colorectal Cancer.

BACKGROUND/AIM: Chemotherapy dose adjustments in colorectal cancer are usually based on body surface area (BSA). The goal of this study was to investigate patients with nutritional disorder who developed early peripheral neuropathy due to inappropriate dose adjustment of oxaliplatin. PATIENTS AND METHODS: The study subjects were 88 patients with advanced or recurrent colorectal cancer who underwent chemotherapy with oxaliplatin. The psoas muscle area (PMA) was used as a nutritional index. Mild (grades 0-1, MN group) and severe (grades 2-3, SN group) peripheral neuropathy was defined using neurotoxicity criteria of Debiopharm. RESULTS: Severe peripheral neuropathy developed in 29 patients (33.0%). The total oxaliplatin dose/PMA was significantly higher for the SN group (107.6±8.5 mg/cm2) and compared with the MN group (53.8±6.0 mg/cm2) in univariate (p<0.0001) and multivariate (p=0.012) analyses. CONCLUSION: In order to prevent peripheral neuropathy from chemotherapy for colorectal cancer, dose adjustment of oxaliplatin should be based on PMA, in addition to BSA.

Laparoscopic splenectomy for polysplenia with splenic torsion: a case report.

BACKGROUND: Polysplenia refers to the presence of two or more equal-sized spleens. Very rarely, one of the multiple spleens may develop torsion and infarction. CASE PRESENTATION: A 21-year-old woman presented with left upper quadrant pain, the cause of which could not be diagnosed. She returned to our hospital, 2 days later, without any pain improvement. Enhanced computed tomography showed splenic infarction and polysplenia. Initially, we could not identify the cause of the infarction and started conservative therapy, which did not result in any improvement. Hence, we performed a splenectomy, after securing informed consent. Because the patient was a young woman, we opted for a laparoscopic approach. During surgery, we identified the cause of the infarction as spleen pedicle torsion; the infarcted spleen was excised using an automated suturing device. We completed the laparoscopic surgery without converting it to an open laparotomy, and the patient was discharged 4 days later. This was a rare case of polysplenia with splenic torsion. CONCLUSION: Laparoscopic splenectomy is minimally invasive and has cosmetic advantages. Thus, this approach may be considered as a treatment option for this condition.

[Metastatic breast cancer with microangiopathic hemolytic anemia successfully treated by using eribulin].

A 48-year-old woman was diagnosed with metastatic breast carcinoma and multiple bone metastases as well as a brain metastasis in 2004. Multiple bone metastases and brain metastases were also diagnosed in 2005, 2006, and 2010, but she remained stable with the use of chemotherapy and hormonal therapy for about 8 years. In 2013, severe anemia occurred, and the patient was diagnosed with microangiopathic hemolytic anemia (MHA). She was treated with eribulin(1.4 mg/m²), and recovered successfully after treatment. Approximately 8 months have elapsed after initiating the therapy, and there has been no recurrence. MHA associated with breast cancer is very rare, and is regarded as a disease with a poor prognosis. However, eribulin could be a valid treatment for prolonging the survival of patients with MHA associated with breast cancer.

Regeneration of peritoneum using amniotic membrane to prevent postoperative adhesions.

BACKGROUND/AIMS: Adhesions following intraperitoneal surgery are frequent causes of small bowel obstruction. Attempts to prevent postoperative adhesions have mostly proven disappointing clinically. Currently used by ophthalmologists in ocular surface disorders, amniotic membrane transplantation can reduce inflammation and promote re-epithelization. We used amniotic membrane for facilitating peritoneal regeneration and prevention of adhesions with surgical trauma. METHODOLOGY: 20 rats were randomized in equal number into treatment or control groups. Seven days after operation, the incidence and severity of adhesions were evaluated. Histologic and immunohistochemical analyses were examined at 1, 4, 10 weeks after operation. RESULTS: While severe adhesions were observed after 1 week between the cecum and surrounding organs in the control group, adhesion formation was significantly reduced in the amniotic membrane group. Histologic examination demonstrated that free-floating myofibroblasts in the peritoneal cavity attached to surfaces of amniotic membrane grafts to form a layered structure. Free-floating mesothelial cells were incorporated into the regenerating mesothelium on the myofibroblast layer in 4 weeks, while implanted amniotic membrane grafts were absorbed by 10 weeks. In the amniotic membrane group the cecum appeared nearly normal. CONCLUSIONS: Amniotic membrane grafts reduced intraperitoneal adhesions after surgical trauma, were well absorbed, and served as a substrate for regenerating mesothelium.

Laparoscope-assisted superlow anterior resection combined with inter sphincteric rectal dissection for very low advanced rectal cancers combined with preoperative chemotherapy.

Transanal intersphincteric resection (ISR) has been increasingly used as a surgical treatment for extremely low rectal cancer. We hypothesized that high quality less invasive surgery could be achieved if ISR and laparoscopic surgery were combined. The patient was a 46-year-old male with advanced rectal cancer on the lower rectum adjacent to the dentate line. The patient refused abdomino-perineal resection (APR), so we performed laparoscope-assisted ISR after preoperative chemotherapy. Previous dissection of this patient facilitated the muscle layer-oriented curative dissection, and more importantly, made the subsequent laparoscopic rectal excision effortless. This patient showed favorable recovery including postoperative anal function with no complications or recurrent disease. This procedure is feasible and has favorable short-term results for the radical treatment of very low rectal disease, while preserving anal function. This operative procedure may be appropriate for locally advanced rectal cancers to avoid a permanent colostomy.

[Case of laparoscopic cholecystectomy for a double gallbladder].

A case of a double gallbladder, a congenital anomaly of biliary system is reported in a 71-year-old woman presenting with right hypochondrial pain. After a confirmed diagnosis of double gallbladder with gallstones was made by MRCP or ERCP, both gallbladders were removed laparoscopically. Double gallbladder is rare anatomic malformation of the biliary tract with only 88 cases, including ours, reported in the Japanese literature. Detailed preoperative investigations are required for an accurate preoperative diagnosis especially when considering laparoscopic removal to avoid inadvertent damage to biliary ductal system.

Event ontology: a pathway-centric ontology for biological processes.

Event ontology is a new biomedical ontology developed to annotate pathway components in a pathway database. It organizes the concepts and terms of sub-pathways, pathways, biological phenomena, experimental conditions, medications, and external stimuli appearing in biological pathways (e.g. signal transduction, disease-, metabolic-, molecular interaction-, genetic interaction pathways, etc.). Concepts in the Event ontology are extracted manually from scientific literature. Each term has links to external databases such as Gene Ontology, Reactome, KEGG, BioCyc, and PubMed.

Monoclonal antibody conjugated to gadolinium as a contrast agent for magnetic resonance imaging of human rectal carcinoma.

BACKGROUND AND OBJECTIVES: Local disease is the most frequent recurrence pattern of rectal carcinoma, and its prognosis is not good. One reason for the poor prognosis is the difficulty of making the diagnosis at an early stage. To detect local recurrence as early as possible, we produced the monoclonal antibody, A7-gadolinium (Mab A7-Gd), conjugate as a contrast agent for magnetic resonance imaging to distinguish between carcinoma and normal tissue. METHODS: We examined the in vitro immunoreactivity of Mab A7 coupled to Gd by chelate, and stability of Mab A7-EDTA-Gd in human serum. Its in vivo distribution in nude mice with human colorectal carcinoma was also examined. RESULTS: Mab A7-Gd retained binding activities that were nearly identical to intact Mab A7. Mab A7-Gd was stable in human serum. More radiolabeled Mab A7-Gd accumulated in the tumor than normal mouse IgG-Gd. Both Mab A7-Gd and normal mouse IgG-Gd disappeared from blood linearly over time. Accumulation levels in normal tissues decreased linearly over time but were lower than those in tumors. CONCLUSIONS: Mab A7 conjugated to gadolinium selectively accumulated in the tumor. Our results suggest that it is potentially suitable as a contrast agent for MR imaging to detect local rectal carcinoma recurrence.

[A long-term survival case with multiple liver metastases from duodenal gastrointestinal stromal tumor that was drastically reduced by the treatment with imatinib].

Constitutive activation of c-kit receptor tyrosine kinase is a critical factor in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate (IM), a selective tyrosine kinase inhibitor, has been shown in clinical studies to work against such tumors. But there is little information on whether a combination of IM and surgical treatment can prolong survival in a case of unresectable multiple liver metastases. We report a case of postoperative recurrence of gastrointestinal stromal tumor (GIST) treated by the tyrosine kinase inhibitor IM and surgical treatment. Therefore, we discuss some important implications. This 37-year-old Japanese man underwent a pancreaticoduodenectomy for GIST of the duodenum in January 2003. The postoperative course was good at first, but 3 months after the initial operation, MRI showed multiple liver metastases. The patient was treated with 400 mg of IM once daily with only weak liver dysfunction as a side effect. The initial response to treatment of CR continued for 18 months. Currently, IM is the first-line therapy for non-resectable GISTs. As the mechanisms of recurrence and resistance to imatinib in GIST remain unclear, they should be intensively performed in the sight of both clinical and molecular biological viewpoints. Further examination in more cases of recurrent GIST is also necessary to estimate the effectiveness of treatment with IM.

[Utility of dopa decarboxylase as a novel marker for the detection of peritoneal micro-metastases of gastric cancer with realtime RT-PCR].

We have examined the utility of DDC as a novel marker for the detection of peritoneal micrometastases of gastric cancer. DDC mRNA in the peritoneal wash from 114 gastric cancer patients was quantified for a comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently labeled probe to predict peritoneal recurrence. The cut-off value was set at the upper limit of the quantitative value for non-cancer patients, and those above this cut-off value constituted the micrometastasis (MM+) group. Thirteen of 15 cases with peritoneal dissemination were MM+DDC (87% sensitivity), and one of 48 t1 cases was MM+ (98% specificity). DDC levels in peritoneal washes from patients with synchronous peritoneal metastases were more than 50 times higher than in those from patients without metastasis (p<0.01). For 15 cases of peritoneal dissemination (seven cases were cytologically positive), DDC was positive in 13 cases (87% sensitivity), but CEA failed to detect micrometastases in four cases (73% sensitivity), indicating that DDC is in some cases superior to CEA for the detection of peritoneal micrometastases of gastric cancer in terms of sensitivity as well as specificity, especially for poorly differentiated adenocarcinomas. Combination of CEA and DDC improved the accuracy of diagnosis up to 93%. These results suggest that DDC is potentially a novel marker for peritoneal dissemination of gastric cancer and that quantitative RT-PCR of DDC is reliable and efficient for the selection of patients for adjuvant intraperitoneal chemotherapy to prevent peritoneal recurrence.

Management of postoperative follow-up and surgical treatment for Krukenberg tumor from colorectal cancers.

BACKGROUND/AIMS: The purpose of this retrospective study was to evaluate the clinical presentation as well as surgical intervention for ovarian metastasis from colorectal cancers identified during postoperative follow-up. METHODOLOGY: Nine cases of ovarian metastasis were observed among 452 female patients with colon cancers between 1990 and 2000. Initial symptoms were pain (67%), pelvic mass (50%), vaginal bleeding (33%), and uterine bleeding (17%). On pathological evaluation, six cases (67%) were found to be moderately differentiated, and three (33%) well differentiated adenocarcinomas. RESULTS: Early diagnosis is very difficult. The growth of metastatic ovarian tumors are slow in elder patients, its growth is rapid in younger patients, and frequently diagnosed as huge ovarian tumors. In some cases, as cystic ovarian lesions they were identified in their early stage but could not be diagnosed as ovarian metastases, later curative operation could not be performed. The consulting gynecologist could not reach the correct diagnosis. Regular postoperative pelvic CT or MRI should be helpful for diagnosis. Although serum CEA levels did not increase in most cases, tumor markers CA125 and SLX were elevated in several cases, and thus may be useful for the detection of ovarian metastases. Surgical treatment consisted of bilateral and unilateral salpingo-oophorectomy or pelvic exenteration and additional hysterectomy for one patient because of association with cervical cancer. The median survival time after the primary operation was 20.8 months, ranging from 3 to 96 months. Peritoneal dissemination and bone metastases were frequently observed as recurrence after these operations. Two cases (non-synchronous solitary metastasis or direct involvement, located in the pelvis) survived more than 5 years (85 and 96 months, respectively), and both patients were treated with pelvic exenteration. CONCLUSIONS: This suggests that in general most cases with ovarian metastasis have a poor prognosis and that radical operation such as pelvic exenteration can improve survival only in cases of recurrent solitary ovarian metastasis or local extended disease, i.e. when the lesion is located only in the pelvis.

Relationships between oxygen and glucose metabolism in human liver tumours: positron emission tomography using (15)O and (18)F-deoxyglucose.

BACKGROUND: Recently, investigators have measured glucose utilization in liver tumours using F-deoxyglucose positron emission tomography (FDG PET) in order to characterize tumours and predict therapeutic effects. However, the detectability of liver tumours by this method remains unclear. In addition, no study has examined the association between oxygen and glucose metabolism in liver tumours using PET. AIM: To evaluate these associations in human liver tumours in vivo using O and FDG. METHODS: Thirteen patients with liver tumours were studied: six with hepatocellular carcinoma (HCC), one with cholangiocarcinoma (CCC) and six with metastatic colon cancer (MET). We measured regional tumour blood flow (Ft), regional oxygen extraction fraction (OEF) and regional metabolic rate of oxygen (MRO2) using O PET. Using FDG PET, we determined a standardized uptake value (SUV) for liver tumours as an index of glucose metabolism. RESULTS: The mean values (mean+/-SE) for Ft, OEF, MRO2 and SUV were 42.5+/-7.0 ml x (100 g) x min, 43.4+/-4.9%, 2.57+/-0.39 ml x (100g) x min and 4.01+/-0.36, respectively. SUV for MET (4.44+/-0.48) was higher than that for HCC (3.52+/-0.59), and the blood flow in MET [31.4+/-4.1 ml x (100 g) x min] was lower than that in HCC [57.1+/-12.4 ml x (100 g) x min]. Significant negative correlations were noted between MRO2 and SUV (r=-0.741, P=0.004), and between Ft and SUV (r=-0.713, P=0.006). No correlation was apparent between Ft and OEF (r=-0.348, P=0.24), or between OEF and SUV (r=-0.023, P=0.94). CONCLUSION: O and FDG PET showed a significant negative correlation between MRO2 and SUV in human liver tumours. In addition, MRO2 depends on Ft rather than on OEF.

FREX: a query interface for biological processes with hierarchical and recursive structures.

An intelligent system for signal transduction pathways and other higher order functional knowledge is presented. Molecular mechanisms of biological processes are typically represented as diagrams ("pathways") that have a graph-analogical network structure. However, due to the diversity of topics that pathways cover, their constituent biological entities are highly diverse and range from metal ion to protein to biological processes in general. In addition, the kinds of interactions that connect biological entities are likewise diverse. Consequently, current knowledge about pathways is highly heterogeneous both in the sense of the types of constituents and the granularity of descriptions. To cope with this problem, the proposed system adopts a recursive and hierarchical representation model that enables the annotation and query of pathways or sub-pathways of arbitral granularity. By combining the use of this hierarchical structure and biological ontologies, literature-based information regarding biological mechanisms becomes accessible by computer.

The molecule role ontology: an ontology for annotation of signal transduction pathway molecules in the scientific literature.

In general, it is not easy to specify a single sequence identity for each molecule name that appears in a pathway in the scientific literature. A molecule name may stand for concepts of various granularities, from concrete objects such as H-Ras and ERK1 to abstract concepts or categories such as Ras and MAPK. Typically, the relations among molecule names derive a hierarchical structure; without a proper way to handle this knowledge, it becomes ever more difficult to develop a reliable pathway database. This paper describes an ontology that is designed to annotate molecules in the scientific literature on signal transduction pathways.

[Screening of novel biomarkers for the detection of intraperitoneally disseminated cancer cells using human cDNA microarray].

In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumor (SNU-1) and that of other cell lines established from the metastasis to the peritoneal cavity (KATO-III, SNU-5, SNU-719, MKN45P, HS39). The application of a high-density cDNA microarray method made it possible to analyze the expression of approximately 21,168 genes. Our examinations of KATO-III, SNU-5, SNU-719, MKN45P, and HS39 showed that several genes were up-regulated in addition to expression of sequence tags (ESTs). The analysis revealed altered up-regulation of CD44 (cell adhesion), CEA, 14-3-3, Ubiquitin A and several kinds of ESTs in gastric cancer cells from malignant ascites. We then analyzed these gastric cancer cell lines with Northern blots and observed preferential up-regulation of these selected genes in cells prone to peritoneal dissemination. RT-PCR confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination promise to provide new insights into the study of human gastric cancer peritoneal dissemination.