[Eight mm Port-Site Hernia Following Robot-Assisted Abdominoperineal Resection for Rectal Cancer-A Case Report].

A 70s woman with a history of asthma and dyslipidemia underwent a robot-assisted abdominoperineal resection for rectal cancer. The ports were placed as per the method of Shizuoka Cancer Center and no intraoperative complications were observed. The colostomy was constructed in the left lower abdomen by the retroperitoneal route. The 12-mm port part was closed in 2 layers, the fascia and dermis, and the 8-mm port part was closed only in the dermis. The postoperative course was good; however, the patient vomited 10 days after surgery. Abdominal computed tomography revealed an incarcerated small intestine in the 8-mm port of the left abdomen, and it was diagnosed as port-site hernia incarceration. Emergency laparotomy hernia repair was performed on the day. A part of the 8-mm port was incised to 30-mm and the fascia dilatation to 30-mm was observed. The color tone of the incarcerated small intestine was good. Only adhesion peeling was performed, the small intestine was returned, and the fascia was closed. The postoperative course was uneventful and the patient was discharged 17 days after the second surgery. At the 1 year postoperative follow-up, recurrence of hernia or rectal cancer was not observed.

A case of intraductal papillary neoplasm of the bile duct accompanied by intraductal papillary mucinous neoplasm of the pancreas and hepatocellular carcinoma.

A 73-year-old man with mixed-type intraductal papillary mucinous neoplasm of the pancreas body was followed up for 14 years. Based on imaging findings, the intraductal papillary mucinous neoplasm of the pancreas met the high-risk stigmata, and new hepatic masses were suspected to be intraductal papillary neoplasms of the bile duct. With a diagnosis of intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct, the patient had undergone left lateral hepatectomy and distal pancreatectomy. Based on pathology, the pancreatic specimen was diagnosed as a high-grade intraductal papillary mucinous neoplasm of the pancreas, and the hepatic specimen was diagnosed as an intraductal papillary neoplasm of the bile duct and hepatocellular carcinoma. The intraductal papillary neoplasms of the bile duct and hepatocellular carcinoma were adjacent to each other. Fifteen months after surgery, recurrence in the remnant pancreas was detected. The patient had undergone residual total pancreatectomy, with no recurrence thirty months after the second resection. This case demonstrates that second surgery for metachronous high-risk lesions in the remnant pancreas of patients with intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct may also be considered to improve survival.

[A Case of Complete Resection Using the Liver-First Approach after Systemic Chemotherapy in a Patient with Synchronous Colorectal Liver and Lung Metastases].

Conversion surgery for patients with initially unresectable colorectal liver metastases is increasingly being performed because of effective systemic chemotherapy. Additionally, many studies have reported the benefit of the liver-first approach for advanced liver metastasis. We report a case of an initially unresectable advanced colon cancer with multiple liver and lung metastases that was successfully treated with the liver-first approach following chemotherapy. The patient was a 36-year- old woman who was diagnosed with advanced rectal cancer, cT4aN2aM1b, cStage Ⅳb. After a temporary transverse colostomy, she was administered systemic chemotherapy for 9 months. The primary tumor and liver metastases showed partial response while the lung metastases showed complete response. Since it was considered that liver metastases were the main prognostic factors, we performed a right hemihepatectomy plus S3 partial hepatectomy, followed by laparoscopic high anterior resection. A partial pneumonectomy was also performed because of the regrowth of the lung metastases, and we succeeded in complete resection. The liver-first approach was a beneficial treatment option for this patient with unresectable colorectal liver metastases.

CD244+ polymorphonuclear myeloid­derived suppressor cells reflect the status of peritoneal dissemination in a colon cancer mouse model.

Despite the recent development of chemotherapeutic agents, the prognosis of colorectal cancer (CRC) patients with peritoneal dissemination (PD) remains poor. The tumor immune microenvironment (TIME) has drawn attention as a key contributing factor of tumor progression. Of TIME components, myeloid­derived suppressor cells (MDSCs) are considered to play a responsible role in the immunosuppressive characteristics of the TIME. MDSCs are classified into two major subsets: Monocytic MDSCs (M­MDSCs) and polymorphonuclear MDSCs (PMN­MDSCs). Therefore, we hypothesize that MDSCs would play important roles in the PD­relevant TIME and PD progression. To address this hypothesis, we established PD mouse models. As the PD nodules consisted scarcely of immune cells, we focused on the peritoneal cavity, but not PD nodule, to evaluate the PD­relevant TIME. As a result, intraperitoneal PMN­MDSCs were found to be substantially increased in association with PD progression. Based on these results, we phenotypically and functionally verified the usefulness of CD244 for identifying PMN­MDSCs. In addition, the concentrations of interleukin (IL)­6 and granulocyte­colony stimulating factor (G­CSF) were significantly increased in the peritoneal cavity, both of which were produced by the tumors and thought to contribute to the increases in the PMN­MDSCs. In vivo depletion of the PMN­MDSCs by anti­Ly6G monoclonal antibody (mAb) significantly inhibited the PD progression and reverted CD4+ and CD8+ T cells in the peritoneal cavity and the peripheral blood. Collectively, these results suggest that the targeted therapy for PMN­MDSCs would provide not only new therapeutic value but also a novel strategy to synergize with T­cell­based immunotherapy for CRC­derived PD.

Laparoscopic vs open surgery for colorectal cancer patients with high American Society of Anesthesiologists classes.

INTRODUCTION: Laparoscopic surgery has become popular for colorectal cancer treatment in recent years. However, its success rate even among high-risk patients remains debatable. The present study aims to compare the short- and long-term outcomes between laparoscopic and open surgeries in the American Society of Anesthesiologists (ASA) classes 3 and 4 patients with colorectal cancer. METHODS: This was a single-center, retrospective, cohort study performed at a university hospital, with 78 patients suffering from colorectal cancer who underwent surgery in ASA classes 3 and 4 as respondents. Patient and tumor characteristics, operative outcomes, and prognoses were factors compared between the open and laparoscopic groups. RESULTS: Compared with the open group, laparoscopic group had longer operation time (median 287.5 vs 204.5 minutes, P = .001), less operative blood loss (median 40 vs 240 mL, P = .020), and fewer postoperative complications (24% vs 55%, P = .011). In addition, operative approach (open vs laparoscopic) served as an independent factor for the occurrence of postoperative complications [HR = 3.963 (1.344-12.269), P = .013]. In terms of overall survival and recurrence-free survival (P = .171 and .087, respectively), no significant difference was found between the two groups. CONCLUSION: Laparoscopic surgery is thus associated with more favorable short-time outcomes and could be adopted as treatment even for colorectal cancer ASA class 3 and 4 patients.

Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8+ Tumor-infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP). PATIENTS AND METHODS: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8+ tumor-infiltrating lymphocytes (TILs) in pretreatment biopsy specimens-versus-surgical specimens after resection. We determined the prognostic significance of these factors. RESULTS: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8+ TIL density was significantly increased after neoadjuvant treatment. However, PD-L1 expression on TCs or ICs, and CD8+ TIL density, was not significantly associated with patient survival in ESCC patients. CONCLUSION: NAC-FP induced PD-L1 expression on ICs and CD8+ TILs in ESCC patients. This finding suggests that PD-1/PD-L1 blockade could be combined with NAC-FP to treat ESCC patients.

Laparoscopic transabdominal preperitoneal approach for giant inguinal hernias.

BACKGROUND: Many surgical techniques have been developed to treat inguinal hernia. In recent years, the laparoscopic transabdominal preperitoneal (TAPP) approach has been widely performed to repair inguinal hernia. Giant inguinal hernia (GIH) is an extremely rare disease that is a challenge for general surgeons. GIH appears when patients neglect the treatment for many years and it is defined as an inguinal hernia that extends below the midpoint of inner thigh in standing position. According to previous publications, the Lichtenstein tension-free hernioplasty is recommended to repair GIH. In this article, we describe consecutive four cases of GIH repaired via the TAPP approach. METHODS: From April 2015 to March 2017, 200 patients underwent hernioplasty against inguinal hernia at our hospital. Inguinal hernias were treated via the TAPP approach in principle. We performed hernioplasty via the TAPP approach in all 4 patients (2%) who met the definition of Type 1 GIH. Demographic information, maximum diameter of hernia sac, hernia orifice size, and surgical data were obtained. RESULTS: The mean operative time was 135 min. No intraoperative complications were encountered. All patients could walk from postoperative day 1 and were discharged home early, but they all had scrotal seromas. Three patients did not need puncture or drainage, but one of them required puncture. All seromas disappeared within 6 months. There was no recurrence in the 8- to 24-month follow-up. CONCLUSION: The TAPP approach is a feasible, safe therapeutic option that may reduce wound size and pain following surgical treatment of Type 1 GIH.

Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment.

In tumor immunity, invariant natural killer T (iNKT) cells play a pivotal role as a link between the innate and adaptive immune systems. With a precisely regulated activation mechanism, iNKT cells have the ability to respond quickly to antigenic stimulation and rapidly produce cytokines and chemokines, and subsequently an effective antitumor immune response. The development of iNKT cell-targeted active immunotherapy enables, not only an antitumor immune response through innate and acquired immunity, but also the conversion of an immunosuppressive into an immunogenic microenvironment. This review is focused on the activation mechanism and the role of iNKT cells after therapeutic active immunization. The therapeutic strategy targeting iNKT cells is expected to be applied to clinical practice in combination with surgery and chemotherapy.

Immunosuppression Induced by Perioperative Peritonitis Promotes Lung Metastasis.

BACKGROUND/AIM: Perioperative intra-abdominal infection has been reported as a risk factor for metastasis. The aim of this study was to investigate the mechanism by which peritonitis induces immunosuppression in the lung, which in turn promotes lung metastasis. MATERIALS AND METHODS: C57BL/6 mice were intravenously administered B16F10 melanoma cells to induce lung metastasis and subsequently subjected to cecal ligation and puncture (CLP) to induce peritonitis or sham surgery. The number of lung metastatic nodules was evaluated. Cell fractions in lungs and serum cytokines after CLP were investigated. RESULTS: CLP mice showed an increased number of lung metastases compared to sham-treated mice. The fraction and number of natural killer (NK) cells in lungs of CLP mice were significantly reduced in early post-CLP phase. Myeloid-derived suppressor cells (MDSCs) in lungs were significantly decreased in CLP mice. Serum IL-6 and TNF levels were significantly elevated in CLP mice. CONCLUSION: Peritonitis promoted lung metastasis in a murine model, which may be attributable to the impact of NK cells and MDSCs in the lungs.

Frequency of Myeloid-derived Suppressor Cells in the Peripheral Blood Reflects the Status of Tumor Recurrence.

BACKGROUND: Malignant tumors inhibit antitumor immune responses, which are driven by T-regulatory cells or myeloid-derived suppressor cells (MDSCs). Since MDSCs are involved in invasion, migration, and metastasis of tumor cells, we hypothesized that MDSCs are also involved in tumor recurrence after surgical resection. MATERIALS AND METHODS: C57BL/6 mice were subcutaneously inoculated with B16F10 melanoma cells in the right flank. In some experiments, established tumors were surgically resected. Peripheral blood was drawn over time, and immune cells and cytokines were evaluated using flow cytometry. RESULTS: MDSCs and relevant pro-inflammatory cytokines increased in the peripheral blood of tumor-bearing mice. Moreover, the frequency of MDSCs rapidly increased in mice with tumor recurrence. CONCLUSION: The frequency of MDSCs in the peripheral blood of tumor-bearing mice reflects the status of tumor progression as well as tumor recurrence. Continuous monitoring of MDSCs in the peripheral blood might be a useful indicator of tumor recurrence.

[A case of erythema multiforme induced by regorafenib therapy for metastatic colon cancer].

A 47-year-old woman underwent colectomy for advanced colon cancer and thereafter received regorafenib therapy as fourth-line chemotherapy. On treatment day 12, the patient developed erythema multiforme (EM) induced by the regorafenib therapy. Immediately after regorafenib was withdrawn, the patient was treated with oral bepotastine and steroid ointment, which relieved the EM without progressing to Stevens-Johnson syndrome (SJS). Regorafenib is used for third- or fourth-line chemotherapy. Progression of regorafenib-induced EM to SJS may cause critical dysfunction among patients. Before administering regorafenib therapy, the patient should be made aware of this potential adverse effect and be advised to withdraw the treatment and visit the hospital immediately if symptoms of EM are observed.

[Pathological complete response in a large gastric GIST that became resectable after neoadjuvant chemotherapy with imatinib mesylate].

We report a case of a large gastric gastrointestinal stromal tumor (GIST), which became resectable and achieved pathological complete response after neoadjuvant chemotherapy with imatinib mesylate. A 59-year-old man presented with left hypochondrial pain. Abdominal computed tomography (CT) revealed gastric GIST invading the spleen and the diaphragm. Administration of imatinib mesylate was initiated as neoadjuvant chemotherapy. Six months after neoadjuvant chemotherapy with imatinib mesylate, abdominal CT revealed a reduction in tumor size. We judged the tumor resectable and performed partial gastrectomy and splenectomy. Histologically, number of myofibroblasts increased, but no viable tumor cells were observed. Pathological complete response was obtained.