The usefulness of the endoscopic surgical skill qualification system in laparoscopic right hemicolectomy: a single-center, retrospective analysis with propensity score matching.

PURPOSE: Recently, a new certification system called the Endoscopic Surgical Skill Qualification System (ESSQS) has been launched in Japan to improve surgical safety. This study aimed to determine whether ESSQS-qualified surgeons affect the short- and long-term outcomes of laparoscopic right hemicolectomy. METHODS: A total of 187 colon cancer patients who underwent laparoscopic right hemicolectomy at Kindai University Hospital between January 2016 and December 2020 were enrolled. These patients were divided into two groups based on surgeries performed by ESSQS-qualified surgeons (QS group) and non-ESSQS-qualified surgeons (NQS group). The short- and long-term outcomes were compared between the two groups before and after propensity score matching (PSM). RESULTS: After PSM, 43 patients from each group were included in the matched cohort. In the short-term outcomes, the total operative time was significantly longer in the NQS group than in the QS group (229 vs. 174 min, p < 0.0001). However, there were no significant differences in the two groups regarding blood loss (0 vs. 0 ml, p = 0.7126), conversion (0.0% vs. 7.0%, p = 0.0779), Clavien-Dindo ≥ 2 complications (9.3% vs. 7.0%, p = 0.6933), mortality (2.3% vs. 0.0%, p = 0.3145), and postoperative hospital stay (9 vs. 9 days, p = 0.5357). In the long-term outcomes, there were no significant differences between the two groups in the 3-year overall survival (86.6% vs. 83.0%, p = 0.8361) and recurrence-free survival (61.7% vs. 72.0%, p = 0.3394). CONCLUSION: Laparoscopic right hemicolectomy performed by ESSQS-qualified surgeons contributed to shorter operative time. Under the supervision of ESSQS-qualified surgeons, almost equivalent safety and oncological outcomes are expected even in surgeries performed by non-ESSQS-qualified surgeons.

Endoscopic submucosal dissection with reinforcement using a laparoscopic approach for a duodenal cavernous hemangioma.

Video 1Endoscopic submucosal dissection with reinforcement using a laparoscopic approach (duodenal-laparoscopic and endoscopic coordinated surgery with endoscopic submucosal dissection) for a duodenal cavernous hemangioma. The mucosal defect was reinforced with laparoscopic seromuscular sutures after duodenal endoscopic submucosal dissection was performed.

Effectiveness of negative pressure wound therapy with instillation and dwelling after stoma closure: a retrospective and propensity score matching analysis.

The use of temporary diverting stoma has become more common in low colorectal anastomosis to reduce anastomotic complications. Surgical site infection (SSI) at the stoma closure site has been one of the most frequent postoperative complications. The aim of this study was to compare the short-term outcomes between conventional primary suture closure and negative pressure wound therapy with instillation and dwelling (NPWTi-d) therapy following purse-string suturing, using propensity score matching analysis. We retrospectively evaluated the medical records of 107 patients who underwent stoma closure between January 2016 and October 2020. The primary outcome was the proportion of SSI. The secondary outcome was the day of postoperative length of stay. Propensity score matching with one-to-one match was performed for reducing treatment selection bias. Of a total of 107 patients, 67 patients had been treated with conventional primary closure and 40 with NPWTi-d therapy. The propensity score matching derived 37 pairs. The respective SSI proportions were 0% and 16.2% in the groups with NPWTi-d and primary closure (P = 0.025). The respective median days of postoperative hospital stay were 9.0 and 10.0 in the groups with NPWTi-d and primary closure (P = 0.453). NPWTi-d therapy with purse-string suturing was effective in reducing SSI after stoma closure.

Laparoscopic complete mesocolic excision with central vascular ligation for splenic flexure colon cancer: short- and long-term outcomes.

BACKGROUND: Complete mesocolic excision (CME) with central vascular ligation (CVL) for colon cancer is an essential procedure for improved oncologic outcomes after surgery. Laparoscopic surgery for splenic flexure colon cancer was recently adopted due to a greater understanding of surgical anatomy and improvements in surgical techniques and innovative surgical devices. METHODS: We retrospectively analyzed the data of patients with splenic flexure colon cancer who underwent laparoscopic CME with CVL at our institution between January 2005 and December 2017. RESULTS: Forty-five patients (4.8%) were enrolled in this study. Laparoscopic CME with CVL was successfully performed in all patients. The median operative time was 178 min, and the median estimated blood loss was 20 g. Perioperative complications developed in 6 patients (13.3%). The median postoperative hospital stay was 9 days. According to the pathological report, the median number of harvested lymph nodes was 15, and lymph node metastasis developed in 14 patients (31.1%). No metastasis was observed at the root of the middle colic artery or the inferior mesenteric artery. The median follow-up period was 49 months. The cumulative 5-year overall survival and disease-free survival rates were 85.9% and 84.7%, respectively. The cancer-specific survival rate in stage I-III patients was 92.7%. Recurrence was observed in 5 patients (11.1%), including three patients with peritoneal dissemination and two patients with distant metastasis. CONCLUSIONS: Laparoscopic CME with CVL for splenic flexure colon cancer appears to be oncologically safe and feasible based on the short- and long-term outcomes in our study. However, it is careful to introduce this procedure to necessitate the anatomical understandings and surgeon's skill. The appropriate indications must be established with more case registries because our experience is limited.

Hybrid method using laparoscopy and Lichtenstein's technique for incarcerated inguinal hernia in a patient with liver cirrhosis and severe varicose veins: A case report.

INTRODUCTION: Cirrhosis is a significant determinant of postoperative morbidity and mortality. Patients with severe liver cirrhosis are substantially contraindicated for surgical treatment of inguinal hernia because of the substantial recurrence rate and high postoperative morbidity and mortality. However, hernia with incarceration and strangulation, which could become life-threatening, should be repaired urgently even for patients with severe liver cirrhosis. No clear surgical guidelines have been established regarding the treatment strategy for inguinal hernia in patients with cirrhosis. PRESENTATION OF CASE: A 62-year-old man with a history of chronic C-type liver cirrhosis (Child-Pugh classification C) and hepatocellular carcinoma was referred to us for surgical treatment of an irreducible right inguinal hernia. An abdominal computed tomography (CT) scan revealed that the small intestine had herniated into the scrotum and severe abdominal wall varicose veins due to liver cirrhosis. We performed a hybrid method that combines examination laparoscopy and Lichtenstein's technique to observe the abdominal cavity and to avoid the risks due to severe varicosis of the inferior epigastric vein. DISCUSSION: There have been some reports of inguinal hernia with cirrhosis and ascites, but no reports of incarcerated inguinal hernia with abdominal wall varicose veins. In the present case, we chose a laparoscopic approach to observe the abdominal cavity to confirm intestinal necrosis. Hybrid surgery using laparoscopy and Lichtenstein's technique for incarcerated inguinal hernia could be performed safely. CONCLUSION: Hybrid surgery using laparoscopy and Lichtenstein's technique may be an effective method for patients with incarcerated inguinal hernia with end-stage cirrhosis and severe abdominal varicosis.

The technique for less infectious and earlier healing of stoma closure wound: negative pressure wound therapy with instillation and dwelling followed by primary closure.

BACKGROUND: Temporary stomas have been widely used to avoid the risk of complications such as anastomotic leakage after colorectal resection. Stoma closure is relatively easy; however, postoperative surgical site infection (SSI) may be a problem. Various methods have been used to reduce the incidence of SSI. We aimed to evaluate a new technique for stoma wound closure. METHODS: We enrolled patients who underwent stoma closure at our hospital between September 2019 and May 2020. We selected patients who lived far from our hospital and had difficulty visiting the hospital regularly and who agreed to undergo this surgical technique. We used negative pressure wound therapy with instillation and dwelling (NPWTi-d) and delayed primary closure for these patients. RESULTS: Four patients underwent NPWTi-d and delayed primary closure without the occurrence of SSI. The median postoperative hospital stay was 9 days (range: 7-14 days), and the median number of days to confirmation of epithelialization was 11.5 days (range: 10-16 days). CONCLUSION: The combined use of NPWTi-d and delayed primary closure for the stoma wound was very effective. This method may be a valuable new technique for wound management after stoma closure.

Visualization of lymphatic flow in laparoscopic colon cancer surgery using indocyanine green fluorescence imaging.

Intraoperative visualization of lymphatic flow could guide surgeons performing laparoscopic colon cancer surgery on the extent of intestinal resection required. The purpose of this study was to investigate indocyanine green fluorescence imaging for intraoperative detection of lymphatic flow and nodes in such patients. All patients undergoing elective laparoscopic surgery for colorectal cancer from October 2016 to July 2017 were included in this study. Indocyanine green was injected submucosally around the tumors via a colonoscope and lymphatic flow assessed with a laparoscopic near-infrared camera system intraoperatively. Lymphatic flow was visualized perioperatively in 43 of 57 patients (75.4%). The rate of visualized lymphatic flow was significantly higher in patients with a lower clinical stage than in those with a higher clinical stage (p = 0.0103). Among the 14 patients in whom lymphatic flow was not visualized, 10 (71.4%) had cStage III or IV cancer. Our results indicate the potential role of intraoperative navigation in colon cancer surgery in early-stage colon cancers. This method allows the surgeon to clearly identify lymphatic flow during surgery and allows the determination and individualization of the lymph node dissection range.

Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer.

The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy. The primary objective of the study was to compare relapse-free survival (RFS) in patients with HLA-A*2402 vs. those without HLA-A*2402. Secondary objectives included comparisons between the two groups regarding overall survival, safety, tolerability and peptide-specific activities of cytotoxic T lymphocytes (CTLs) as measured by the ELISPOT assay. Between December 2009 and December 2014, a total of 46 patients were enrolled to the present study. Three-year RFS was not significantly different between HLA-A*2402 matched and unmatched groups [67.8 vs. 73.6%, respectively; hazard ratio (HR)=1.254, 95% confidence interval (CI): 0.48-4.63; P=0.706]. Three-year RFS was significantly better in patients with positive CTL responses in the HLA-A*2402 matched group compared with those without (85.7 and 33.3%, respectively; HR=0.159, 95% CI: 0.023-0.697; P=0.011). In conclusion, vaccination-induced immune responses combined with UFT/LV were positively associated with survival benefit in patients with HLA-A*2402-positive stage III CRC. Further study is required to clarify whether vaccination-induced immune responses shortly following the initiation of therapy can predict the therapeutic effect and help develop a promising therapeutic strategy for patients with stage III CRC.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion. After the disclosure of HLA, 28 patients were in the HLA-A*2402-matched and 16 were in the unmatched group. In the HLA-matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA-unmatched group, 10 CTL responses were positive and 2 negative. In the HLA-matched group, 3-year relapse-free survival (RFS) was significantly better in the positive CTL subgroup than in the negative-response subgroup. Patients with negative vaccination-induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA-unmatched group, the positive CTL response subgroup showed an equally good 3-year RFS as in the HLA-matched group. In conclusion, vaccination-induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC.

[A Case of Cecal Cancer Associated with Dermatomyositis].

We report a relatively rare case of cecal cancer with dermatomyositis. An 81-year-old man was diagnosed with dermatomyositis associated with the symptoms of eruption, limb muscle weakness, and difficulty swallowing. Colonoscopy revealed a type 2 tumor in the cecum. The patient underwent laparoscopic ileocecal resection. Although it was impossible for the patient to stand before the surgery, he could stand 10 days after the surgery and walk without assistance 14 days after the surgery. In addition, the eruption disappeared, and the preoperatively high creatine kinase(CK)value normalized. Dermatomyositis with malignant tumor has been reported to be associated with poor prognosis. Symptoms related to dermatomyositis may be improved by the resection of the associated tumor. Therefore, it is important to treat the malignant tumor when the patient's condition permits.

[A Case of Local Resection for Rectal GIST Following Neoadjuvant Imatinib Mesylate Treatment].

A 67-year-old woman presented with bloody stools and constipation. A rectal digital examination revealed a smooth and elastic hard tumor in the posterior wall of the rectum. We diagnosed the tumor as rectal GIST measuring 5 cm in diameter. Because the patient desired anal preservation, neoadjuvant imatinib mesylate(IM)(400mg/day)treatment was administered. Although the diameter of the tumor reduced to 2 cm in the third week of administration, the patient experienced erythema-type drug eruption(Grade 3). We discontinued the IM treatment and initiated steroid therapy. After the eruption had disappeared, IM treatment was resumed, initially with half doses. Local transanal resection was performed 36days after the neoadjuvant IM treatment. Currently, the indication and the administration period of IM for preoperative treatment is not clear. It may be necessary to accumulate cases to evaluate neoadjuvant IM therapy.

Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinomas.

BACKGROUND: Although colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high-grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low-grade mucinous adenocarcinoma (low-MC) and high-grade mucinous adenocarcinoma (high-MC). METHODS: Patients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low-MC and high-MC were investigated with next-generation sequencing. RESULTS: A total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high-MC. Patients with MC had significantly shorter disease-free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low-MC patients and high-MC patients were compared, those with high-MC had significantly shorter DFS and OS periods than those with low-MC. Multivariate analyses revealed that high-MC was significantly associated with both shorter DFS and shorter OS, but low-MC was not. A genome analysis revealed that low-MC had a considerably larger number of mutations than high-MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low-MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high-MC. CONCLUSIONS: High-MC is an independent prognostic factor in CRC (but low-MC is not), and it is genetically different from other CRCs, including low-MC. Both the clinicopathological differences and the genetic differences suggest that low-MC and high-MC should be distinguished in clinical settings.

Inter- and intra-tumor profiling of multi-regional colon cancer and metastasis.

Intra- and inter-tumor heterogeneity may hinder personalized molecular-target treatment that depends on the somatic mutation profiles. We performed mutation profiling of formalin-fixed paraffin embedded tumors of multi-regional colon cancer and characterized the consequences of intra- and inter-tumor heterogeneity and metastasis using targeted re-sequencing. We performed targeted re-sequencing on multiple spatially separated samples obtained from multi-regional primary colon carcinoma and associated metastatic sites in two patients using next-generation sequencing. In Patient 1 with four primary tumors (P1-1, P1-2, P1-3, and P1-4) and one liver metastasis (H1), mutually exclusive pattern of mutations was observed in four primary tumors. Mutations in primary tumors were identified in three regions; KARS (G13D) and APC (R876*) in P1-2, TP53 (A161S) in P1-3, and KRAS (G12D), PIK3CA (Q546R), and ERBB4 (T272A) in P1-4. Similar combinatorial mutations were observed between P1-4 and H1. The ERBB4 (T272A) mutation observed in P1-4, however, disappeared in H1. In Patient 2 with two primary tumors (P2-1 and P2-2) and one liver metastasis (H2), mutually exclusive pattern of mutations were observed in two primary tumors. We identified mutations; KRAS (G12V), SMAD4 (N129K, R445*, and G508D), TP53 (R175H), and FGFR3 (R805W) in P2-1, and NRAS (Q61K) and FBXW7 (R425C) in P2-2. Similar combinatorial mutations were observed between P2-1 and H2. The SMAD4 (N129K and G508D) mutations observed in P2-1, however, were nor detected in H2. These results suggested that different clones existed in primary tumors and metastatic tumor in Patient 1 and 2 likely originated from P1-4 and P2-1, respectively. In conclusion, we detected the muti-clonalities between intra- and inter-tumors based on mutational profiling in multi-regional colon cancer using next-generation sequencing. Primary region from which metastasis originated could be speculated by mutation profile. Characterization of inter- and inter-tumor heterogeneity can lead to underestimation of the tumor genomics landscape and treatment strategy of personal medicine.

[Clinical trial of a seven-peptide vaccine and tegafur-uracil/leucovorin as combination therapy for advanced colorectal cancer].

We conducted a clinical trial of a seven-peptide vaccine in combination with tegafur-uracil/Leucovorin for advanced colorectal cancer. These antigenic peptides were derived from 5 proteins identified as cancer-testis antigens(ring finger protein 43 [RNF43], translocase of outer mitochondrial membrane 34[TOMM34], maternal embryonic leucine zipper kinase[MELK], forkhead box M1[FOXM1], and holliday junction recognition protein[HJURP])and 2 vascular endothelial growth factor receptors(VEGFR1 and VEGFR2). Thirty patients with advanced colorectal cancer were enrolled. We found that 25 patients had Grade 1 injection-site redness/induration and 1 patient had Grade 3 anaphylaxis. Tumor imaging revealed that 3 patients had a partial response (PR), 15 had stable disease(SD)and 12 had progressive disease(PD). This trial showed that treatment with the seven-peptide vaccine and UFT/LV was well tolerated and feasible for advanced colorectal cancer.

[Treatment outcome of peptide vaccination for advanced colorectal cancer].

Complementary DNA( cDNA) microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen (HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different cancer-testis antigens, ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34( TOMM34). We conducted a clinical trial of colorectal cancer-specific peptide( RNF43, TOMM34) vaccines with uracil/tegafur( UFT)+Leucovorin( LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any serious adverse events. There were long-term survivors in the group showing cytotoxic T lymphocyte (CTL) responses against both RNF43 and TOMM34, as well as in the group showing CTL responses against either RNF43 or TOMM34. A new study has been planned to obtain more immunological responses. We started a clinical trial of vaccines against multiple peptides (RNF43, TOMM34, forkhead box protein M1 [FOXM1], maternal embryonic leucine zipper kinase [MELK], holliday junction recognition protein[HJURP], vascular endothelial growth factor receptor 1[VEGFR1], and VEGFR2) for the treatment of advanced or recurrent colorectal cancer.

[A case whose lung metastasis was detected and resected eleven years after resection of primary colon cancer].

In July 1999, a 79-year-old man underwent sigmoidectomy and D3 lymphadectomy for sigmoid colon cancer (ss, n(-), stage II, cur A). In September 2000, hepatectomy of right lobe and cholecystectomy were performed for his liver metastasis. Every three to six months follow-up had been kept since adjuvant chemotherapy (200 mg/day of 5-FU per os for two years) completed. Eleven years and two months after sigmoidectomy (in September 2010), a chest X-ray examination detected a small nodule in upper area of his right lung, which was diagnosed as either primary lung cancer or metastatic lung tumor followed by chest CT scan and PET-CT examination. In November 2010, laparoscopy-assisted partial resection of his right lung was performed. Histochemical examination of the resected lung tumor resulted cytokeratin 7(-), cytokeratin 20(+) and TTF-1(-), confirming its final diagnosis as lung metastasis from sigmoid colon cancer. He has been alive for six months without any recurrence since resection of his lung metastasis. It was a very rare case to have more than ten-year interval between colon cancer resection and detection of its lung metastasis. However, when we diagnosed the patient with lung tumor, who had undergone a colorectal resection, we should consider if he had a lung metastasis from colorectal cancer.

[A case of gastric cancer with liver metastasis had a good reaction to S-1/CDDP chemotherapy after S-1 chemotherapy was ineffective].

A woman in her sixties underwent total gastrectomy for gastric cancer. The pathological diagnosis was pT3, pN3, sH0, pCY0, sP0, sM0, fStage IV. Chemotherapy with S-1 was used after surgical treatment. Because a CT scan after three courses chemotherapy showed the paraaortic lymph nodes swelling, combination chemotherapy with S-1 and docetaxel was used as a second-line chemotherapy. When the CT scan after 8 courses of this combination chemotherapy revealed multiple liver metastases, the chemotherapy was changed to CPT-11 monotherapy and paclitaxel monotherapy as the third-and fourth-line chemotherapy, respectively. In spite of those chemotherapies, the metastatic disease progressed, and therefore, combination chemotherapy with S-1 and CDDP was used as the fifth-line chemotherapy. After 6 courses of this treatment, serum CEA and CA19-9 levels dropped into the normal range. Multiple liver metastases were markedly reduced, and were considered as a partial response(PR). The patient is still alive, maintaining the effect of PR for 17 months without any adverse effects except appetite loss and vomiting of grade 2.

[The effects of gastrojejunostomy for patients with advanced gastric cancer accompanied by peritoneal dissemination].

UNLABELLED: We evaluated the efficacy of gastrojejunostomy for advanced gastric cancer patients with peritoneal dissemination. PATIENTS AND METHODS: We evaluated the clinical outcome of 11 patients (average age 73.5 years for 8 men) who received gastrojejunostomy for gastric outlet obstruction caused by advanced gastric cancer with peritoneal dissemination between October 2003 and December 2008. We performed stomach-partitioning gastrojejunistomy with tube jejunostomy. RESULTS: Three patients with performance status 3 and severe peritoneal dissemination deteriorated during the early postoperative days and were transferred to terminal care. These three patients died after 23, 26 and 60 days. The other 8 patients were discharged from hospital between 10 and 35 days postoperatively (median hospital stay 16 days) and received chemotherapy with S-1 on an outpatient basis. All patients died within one year except the one who showed a partial response to chemotherapy and lived for 40 months (MST: 8 months in all patients). DISCUSSION: It seemed that there was little adaptation to gastrogejunostomy as palliation surgery for patients with poor performance status (PS 3) and severe peritoneal dissemination.

[Successful treatment of advanced esophageal cancer with lymph node metastases by docetaxel, cisplatin and 5-FU followed by salvage lymphadenectomy--a case report].

We present a case of advanced esophageal cancer with multiple lymph node metastases successfully treated by combination therapy of docetaxel, cisplatin and 5-FU (DCF) followed by salvage lymphadenectomy. The patient was a 60-year-old female with the diagnosis of squamous cell carcinoma of the middle thoracic esophagus. The clinical stage diagnosis was cT2N4M0, cStage IVa. Systemic chemotherapy with DCF was started as the initial treatment. The changes noted on endoscopy and CT scan in the primary lesion and lymph nodes after two cycles of DCF were judged as complete response (CR). However, recurrence was diagnosed in the left cervical lymph nodes based on FDG uptake on FDG-PET. Salvage cervical lymphadenectomy was performed. Thereafter, the patient again achieved CR after the second administration of DCF for upper mediastinal lymph node recurrence. At present, she is still alive three years after the first visit. Combination therapy of DCF and salvage lymphadenectomy is potentially effective for advanced esophageal cancer with lymph node metastases.