[Experience of Using Immune Checkpoint Inhibitors and Chemotherapy in the Upper Gastrointestinal Tract at Our Hospital].

We investigated the gastric and esophageal cancer cases treated with immune checkpoint inhibitors and chemotherapy at our hospital. Out of 17 gastric cancer cases, 9 were treated with nivolumab(Nivo)plus S-1/oxaliplatin(SOX), 5 with Nivo plus 5-fluorouracil/Leucovorin/oxaliplatin(FOLFOX), and 3 with Nivo plus capecitabine/oxaliplatin(CapeOX), yielding a response rate of 35.3%. We also treated 3 cases of esophageal cancer. Two of these were treated with Nivo plus cisplatin/5- fluorouracil(CF)and 1 case with pembrolizumab(Pembro)plus CF, with a response rate of 33.3%. The incidence of Grade 3 or higher adverse events was 29.4% in gastric cancer and 33.3% in esophageal cancer, and no serious immune-related adverse events were observed. Further case accumulation and long-term studies are required to evaluate efficacy and adverse events in clinical practice.

Impact of Sarcopenic Obesity on Severe Postoperative Complications in Patients with Gastric Cancer Undergoing Gastrectomy.

INTRODUCTION: Several studies have indicated that sarcopenia affects the short- and long-term outcomes of cancer patients, including those with gastric cancer. In recent years, sarcopenic obesity and its effects have been reported in cancer patients. This study aimed to evaluate the impact of sarcopenic obesity on postoperative complications in patients with gastric cancer undergoing gastrectomy. METHODS: This single-center, retrospective study included 155 patients who underwent curative gastrectomy for gastric cancer from January 2015 to July 2021. Sarcopenia was defined by the psoas muscle index (<6.36 cm2/m2 in men and <3.92 cm2/m2 in women), which measures the iliopsoas muscle area at the lumbar L3 level using computed tomography. Obesity was defined by body mass index (≥25). Patients with both sarcopenia and obesity were defined as the sarcopenic obesity group and others as the non-sarcopenic obesity group. Severe postoperative complications were defined as Clavien-Dindo classification grade IIIa or higher. RESULTS: Of the 155 patients, 26 (16.8%) had sarcopenic obesity. The incidence of severe postoperative complications was significantly higher in the sarcopenic obesity group (30.8% vs. 10.9%; p = 0.014). Multivariate analysis indicated that sarcopenic obesity was an independent risk factor for severe postoperative complications (odds ratio, 3.950; 95% confidence interval, 1.390-11.200; p = 0.010). CONCLUSION: Sarcopenic obesity is an independent risk factor for severe postoperative complications.

Transanal minimally invasive surgery for rectal neuroendocrine tumors.

BACKGROUND: There is no literature that mainly searched for rectal neuroendocrine tumor (rNET) using transanal minimal invasive surgery (TAMIS). We report our clinical experiences of TAMIS for rectal neuroendocrine tumors to evaluate the feasibility and safety. METHODS: Between December 2010 and March 2020, the 25 consecutive patients with rectal neoplasma underwent the TAMIS procedure performed by single laparoscopic surgeon at the two hospitals. Of these, ten patients with rectal neuroendocrine tumors were reviewed retrospectively. The full-thickness excision down to the outer fatty tissues was completed using TAMIS technique. Clinicopathological findings, perioperative and postoperative complications were recorded. RESULTS: TAMIS for small rNET was successfully completed in all cases. There were seven cases with a tumor size of less than 10 mm, and three cases with a tumor size between 10 and 15 mm. Six patients underwent the primary tumor excision; the remaining four patients underwent resection for the scar after endoscopic procedure. The median surgical duration was 80.5 (53-124) minutes and the median blood loss was 1 (1-12) ml. All removed tumors in the 6 primary excisions were diagnosed as neuroendocrine tumor G1. The margins of specimens were completely free in all cases. Among the four patients after endoscopic procedure, all had no histological evidence of residual tumor. The median length of hospital stay was 7 days postoperatively. There was no post-operative mortality or severe complication. The median length of observation was 54 months. No recurrence, no local or distant metastasis and no mortality of all patients were observed. CONCLUSIONS: TAMIS is safety and feasible procedure for small rNET. Further experience and clinical trials are needed to fully define the advantages, disadvantages, and indications of TAMIS for rNET.

Comparison of Short-Term Outcomes Between Hand-assisted Laparoscopic Distal Gastrectomy and Laparoscopy-assisted Distal Gastrectomy in Gastric Cancer.

Hand-assisted laparoscopic surgery is considered to provide the benefits of laparoscopic surgery in various diseases. However, limited information is available regarding the feasibility of hand-assisted laparoscopic distal gastrectomy (HALDG)-a subset of hand-assisted laparoscopic surgery-as a gastric cancer treatment. This study aimed to evaluate the usefulness of HALDG compared with laparoscopy-assisted distal gastrectomy (LADG). Consecutive patients who underwent HALDG (n=58) or LADG (n=90) for stage I gastric cancer between 2005 and 2016 were eligible. Operative time was significantly shorter and blood loss was significantly higher in HALDG than in LADG (P<0.001, both). Postoperative aminotransferase levels were significantly lower in HALDG than in LADG (P<0.001). There was no significant difference in perioperative complications, a number of analgesics, postoperative C-reactive protein levels, and 3-year relapse-free and overall survival rates between the groups. This study suggests that HALDG is a safe and feasible approach and could become an effective option for stage I gastric cancer treatment.

Laparoscopic repair of Morgagni hernia with composite mesh in an elderly woman: Report of a case.

A 78-year-old woman was admitted to another hospital with vomiting. Chest X-ray showed an abnormal shadow in the lower right lung field, and CT indicated a Morgagni hernia containing the stomach and transverse colon. The patient was transferred to our hospital and underwent laparoscopic surgery. After the hernia contents were repositioned into the abdominal cavity, we repaired the hernia orifice with a prosthetic mesh to achieve a tension-free repair. There were no complications after the surgery, and there has been no recurrence. The patient has remained free of clinical symptoms since 10 months after the surgery. Laparoscopic repair with a prosthetic mesh for Morgagni hernia is a simple and safety procedure for elderly patients.

Evaluation of three types of platforms in single-incision laparoscopic surgery for performing transanal endoscopic microsurgery (SILSTEM).

BACKGROUND/AIMS: Transanal endoscopic microsurgery using a platform for single-incision laparoscopic surgery (SILSTEM) is safe for excising rectal lesions. We tested three types of platforms. METHODOLOGY: Nine patients underwent SILSTEM by one surgeon. Tumors located 5­15 cm from the anal verge were eligible. After measuring their dimensions, length, and trocar channels, the platforms tested were the SILSTM port (SP), EZTM access (EA), and GelPOINTTM Path (GP). Clinicopathology, intraoperative parameters, and postoperative outcomes were recorded. RESULTS: Six men and three women (median age 63 years) underwent SILSTEM using platform SP in three patients, EA in four, GP in two. Median operation time was 128 min (range 71­313). Median blood loss was 3 ml (range 1­71). Pathology confirmed adenocarcinoma in five patients, adenoma in three, and carcinoid in one. Patients were discharged within 2­13 days postoperatively. There was no postoperative fecal incontinence or soiling. Overall median follow-up was 13.3 months (range 1.3­27.2). There were no recurrences. CONCLUSION: SILSTEM can effectively resect rectal tumors using any of three platforms. Large prospective trials are needed to define the advantages, disadvantages, and indications for each platform and to draw conclusions regarding operation time, anorectal function, and costs.

[A case of rectal cancer with sacrum metastasis treated with S-1 leading to a complete response].

The patient is a 47-year-old female. She had undergone abdominoperineal resection for rectal cancer at 39 years of age. Two years and 9 months after surgery, she was diagnosed with a vagina invasion. Radiation therapy and chemotherapy (UFT/ LV) were performed. After 4 courses of UFT/LV, a complete response (CR) was noted. Four years and 3 months after surgery, she was diagnosed with a sacrum metastasis. Chemotherapy with S-1 was performed. After 2 courses of S-1, a CR was noted. There has been no recurrence sign to date.

Detection of aberrations of ubiquitin-conjugating enzyme E2C gene (UBE2C) in advanced colon cancer with liver metastases by DNA microarray and two-color FISH.

Using DNA microarrays, the expression profiles of 1,700 genes in the primary tumor, liver metastases and paired normal tissue obtained from nine patients with advanced colorectal cancer was studied. Twenty genes were upregulated and only one gene was downregulated in the primary tumors. In the liver metastases, 39 genes were upregulated and only three genes were downregulated. There was no significant difference in gene expression between the primary tumors and the liver metastases. The most highly overexpressed gene in both the primary tumors and the liver metastases was the ubiquitin-conjugating enzyme E2C gene (UBE2C), located at 20q13.1. Additionally, two-color FISH analysis using probes for the region 20q13.1 and the chromosome 20 centromere revealed that amplification at 20q13.1 had occurred in 5 of 10 (50%) colon cancers. Comparison between the levels of gene expression and FISH results revealed that UBE2C expression is significantly changed by amplification at 20q13.1, suggesting genomic amplification as one mechanism of increased UBE2C expression. Our results showing aberrations in levels of gene expression and locus copy number of UBE2C suggest that this gene may play an important role in tumor progression leading to advanced colon cancer with liver metastasis.

Clinical application of oligonucleotide probe array for full-length gene sequencing of TP53 in colon cancer.

OBJECTIVE: TP53 mutations are the most frequent genetic alterations in colon cancer. We studied whether the recently developed oligonucleotide microarray technique, GeneChip p53 assay, can be applied to sensitive detection of TP53 gene mutations in surgical specimens from colon cancer patients. METHODS: TP53 gene mutations in exons 2-11 in 20 colon cancers and the corresponding histopathologically normal mucosa at the surgical margins were assessed by GeneChip p53 assay, and the results were further evaluated by direct sequencing of the involved exon or by mutant-allele-specific amplification (MASA). The expression of TP53 protein was also evaluated immunohistochemically and the result was compared with the gene alteration. RESULTS: The GeneChip p53 assay detected TP53 mutations in 65% of primary cancers; 61% of the mutations were within the evolutionarily conserved regions, and 46% of the mutations were within the zinc-binding domains (regions of loop 2 and loop 3). Direct sequencing confirmed these mutations. Immunohistochemical examination detected TP53 protein overexpression in 47% of primary cancers, but this protein did not accumulate with all types of TP53 mutations. In addition, the GeneChip assay detected a mutation identical to that in the primary tumor in 2 samples from the surgical margins, and MASA confirmed both mutations, implying the presence of occult cancer cells. CONCLUSION: The GeneChip p53 assay is sufficiently sensitive to detect TP53 mutations in surgical specimens from colon cancers and may be applicable to screening examination in clinical laboratories as a routine procedure.

Up-regulation of vitamin D3 up-regulated protein 1 gene in response to 5-fluorouracil in colon carcinoma SW620.

Despite the wide use of 5-fluorouracil (5-FU) for colon cancer, the genes regulating its cytotoxic effect are poorly understood. We used a high-density oligonucleotide microarray representing approximately 7000 genes to determine changes in gene expression caused by 5-FU treatment in the colon cancer cell line, SW620. The microarray showed that the most strongly up-regulated gene by 5-FU was vitamin D3 up-regulated protein 1 (VDUP1), an interesting stress response gene, which was originally reported as a vitamin D3 inducible gene in HL-60. TaqMan RT-PCR assay confirmed that VDUP1 gene expression was significantly increased after 24 h of 5-FU treatment compared with untreated control (p<0.01). Moreover, the expression of vitamin D3 receptor, thymidylate synthase (TS), and E2F1 did not change within 24 h of 5-FU treatment, suggesting a different gene-regulatory pathway from that of VDUP1. Recent studies have gradually clarified the potential role of VDUP1 via interaction with TRX in an anti-tumor effect. Therefore, VDUP1 not only may be induced by stress response as a result of 5-FU cytotoxicity, but may also play a key role in 5-FU cytotoxicity in colon cancers. Our experiment using a microarray and TaqMan RT-PCR assay, together with previous reports, provides new insight into a potential mechanism of 5-FU cytotoxicity.

Vitamin D3 up-regulated protein 1 (VDUP1) expression in gastrointestinal cancer and its relation to stage of disease.

Decreased expression of VDUP1, which is an interesting stress response gene, has been shown in rat mammary tumors and has been discussed in relation to the development of the tumor. However, VDUP1 expression in clinical specimens of human cancer remains unclear. We employed TaqMan RT-PCR assay to investigate VDUP1 expression in surgical specimens of primary tumors and their adjacent normal tissues from gastrointestinal cancer patients, 40 with colorectal and 12 with gastric cancers. TaqMan RT-PCR assay showed that VDUP1 expression in colorectal and gastric cancers was significantly lower than that in their adjacent normal tissues (p < 0.0001 and p < 0.001, respectively). In addition, we found that VDUP1 expression was associated with clinical stage in colorectal cancer (p < 0.01). VDUP1 expression in stage II patients was significantly higher than that in stage III (p < 0.05) and in stage IV patients (p < 0.01). These results suggest a possible role of VDUP1 in the pathogenesis of gastrointestinal cancer, as well as its clinical significance.