[A Case of Unresectable Advanced Lower Esophageal Adenocarcinoma That Achieved Pathological Complete Response after Conversion Surgery following Nivolumab plus SOX Therapy].

An 80-year-old woman presented with epigastric discomfort and dysphagia, underwent upper gastrointestinal endoscopy, and was diagnosed with type 2 advanced lower esophageal adenocarcinoma. Computed tomography data revealed that there was the lower esophageal tumor is T3, but a large carina lymph node invading the left bronchus. We diagnosed this patient unresectable cT4bN1M0, cStage ⅣA advanced esophageal adenocarcinoma, and we administered nivolumab plus S-1 plus oxaliplatin(SOX)therapy. After 3 courses of the therapy, imaging showed marked reduction in the size of primary tumor and carina lymph node. We diagnosed partial response(PR)and attempted conversion surgery. Video-assisted thoracoscopic esophagectomy with 2 fields lymphadenectomy was performed. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of primary tumor was determined to be Grade 3, with a pathological complete response(pCR). Currently, the patient is alive without recurrence for 1 year after surgery.

[A Case of Early Ascending Colon Cancer Complicated the Mesenteric Phlebosclerosis Who Underwent Laparoscopic Subtotal Colectomy].

A 71-year-old woman who have been taking Sanshishi for 50 years until the age of 70 for dermatitis underwent colonoscopy( CS)to reveal the reason of abdominal pain. CS showed ascending colon tumor(AT)with major axis 3 cm and suspicious of the mesenteric phlebosclerosis. Although endoscopic submucosal dissection(ESD)was performed for AT, colon perforation due to colonic wall fibrosis was occurred and ESD was suspended. Therefore, surgical resection was planned. Intraoperative observations by laparoscopy showed that the color of colon serosa from the cecum to the splenic flexure was grayish white and colonic wall thickening with lead tubular change was observed. From the descending colon to the sigmoid colon, wall thickening was mild, and Haustra was confirmed. Although the tumor location was in the ascending colon, laparoscopic subtotal colectomy and functional end-to-end anastomosis of ileum and sigmoid colon was performed for safe intestinal anastomosis. For treat of colon cancer complicated mesenteric phlebosclerosis(MP), endoscopic resection is considered difficult due to fibrosis and extended resection of the colon may be required to reduce the risk of anastomotic leakage. Herein, we report our case and details of past reported literatures.

Feasibility and Efficacy of Neoadjuvant Chemotherapy without Radiotherapy for Locally Advanced Rectal Cancer.

OBJECTIVES: This retrospective study explored the feasibility of neoadjuvant chemotherapy (NAC) without radiotherapy in patients with locally advanced rectal cancer (LARC). METHODS: Patients with clinical stage of T3-T4 and/or N-positive LARC patients were included. We retrospectively analyzed patients' NAC-related and perioperative outcomes. RESULTS: The study enrolled 30 patients. mFOLFOX6 or SOX plus cetuximab was administered to 12 patients with the wild-type RAS gene and FOLFOXIRI or SOXIRI to 18 patients with mutant-type RAS. The NAC completion rate was 90.0%. All patients underwent total mesorectal excision, and 29 patients underwent combined bilateral lateral lymph node dissection. The R0 operation rate was 90.0%. Although the postoperative complication rate was 40%, no complications were associated with NAC. The response rate of NAC and the proportion of histological anti-tumor effect grade ≥ 2 were 56.7% and 46.7%, respectively. CONCLUSIONS: NAC was considered to be a safe, feasible treatment option for LARC.

[Two Cases of Locally Advanced Lower Rectal Cancer with Pathological Complete Response after Cetuximab plus SOX as Neoadjuvant Chemotherapy].

We have introduced neoadjuvant chemotherapy(NAC)for locally advanced lower rectal cancer(LARC)since 2014. We report 2 LARC cases in which a pathological complete response(pCR)was obtained by using cetuximab(Cmab)plus oxaliplatin plus S-1(SOX)for NAC. Case 1: A 68-year-old woman underwent 4 courses of Cmab plus SOX for Rb rectal cancer (well-differentiated adenocarcinoma, cStage Ⅲc: cT4b[vagina]N3M0). Lap posterior pelvic exenteration was performed. The pathological findings of the resected specimen revealed no carcinoma and we diagnosed it as pCR. As of 31 months after the operation, she is alive without recurrence. Case 2: A 72-year-old man underwent 4 courses of Cmab plus SOX for middle and lower rectal cancer(Rab, moderately differentiated tubular adenocarcinoma, cStage Ⅲc: cT3N3M0). After NAC, with the diagnosis of ycT3N0M0, laparoscopic-assisted(Lap)super-low anterior resection with bilateral lateral pelvic node dissection was performed. The pathological findings of the resected specimen revealed no carcinoma and we diagnosed it as pCR. As of 37 months after the operation, he is alive without recurrence. NAC with Cmab plus SOX may be an effective treatment for LARC.

[Laparoscopic Total Pelvic Exenteration of Locally Advanced Rectal Cancer Invading Urogenital Organs].

Application of laparoscopic surgery(Lap)for colorectal cancer has expanded, and laparoscopic total pelvic exenteration (TPE)of locally advanced rectal cancer(LARC)invading the urogenital organs has been introduced in some institutions. In our institute, we have performed Lap TPE and posterior-TPE(PPE)in a total of 6 LARC patients so far. Here, we report the surgical technique of Lap TPE, and the associated surgical and short-term outcomes. We performed Lap TPE and Lap PPE in 3 patients each. Operation time was approximately 562 min, and the blood loss was 310 mL on an average. No patient developed postoperative complications above Clavien-Dindo Grade Ⅲ. One patient exhibited recurrence in the liver and another in peritoneum in the Lap PPE group. No recurrence was observed in the Lap TPE group(median follow-up period: 24.5 months). Although Lap TPE and PPE are difficult to perform and time consuming, it is suggested that these procedures may help reduce the intraoperative bleeding volume and shorten the length of postoperative hospital stay compared to open TPE and PPE.

Short-term outcomes of laparoscopic lateral pelvic node dissection for advanced lower rectal cancer.

BACKGROUND: The laparoscopic magnified visual effects and evolution of the laparoscopic camera system have recently enabled us to observe details in the deep pelvic floor. Indications of laparoscopic surgery for colorectal cancer have been expanded, and laparoscopic (Lap) lateral pelvic node dissection (LLND) has been introduced in some institutions. We investigated the feasibility of Lap LLND in patients with locally advanced rectal cancer (LARC). METHODS: Lap LLND was performed in 38 patients diagnosed with cT3-4 or cN1-2 cancer during 2014-2018. We retrospectively analyzed their surgical and short-term outcomes. RESULTS: Laparoscopic surgery was performed in all patients. cStages II/III/IV were found in 6/31/1 patients, respectively. Among them, 25 patients underwent neoadjuvant chemotherapy without radiotherapy. Lap unilateral LLND was performed in 6 patients and Lap bilateral LLND was performed 32 patients. The number of harvested lymph nodes (LNs) were 4 in the unilateral group and 15 in the bilateral group. Operation time was 531 min, and blood loss was 105 ml. Oral intake has started on postoperative day (POD) 3, and pelvic drain was removed on POD 7. Hospital stay was 18.5 days. Seven patients developed a neurogenic bladder (all Clavien-Dindo grade (CD) II and all occured in the bilateral LLND group), one patient developed abdominal bleeding (CD IIIb) and one patient developed anastomotic leakage (CD IIIb). Pathological results revealed 2/5/16/14/1 patients with pStages 0/I/II/III/IV, respectively. Four patients had histopathologically verified lateral pelvic lymph node metastases. There were no local recurrences after curative surgery (median follow-up 24.2 months). CONCLUSION: Although the median follow-up period is relatively short and further follow-up is necessary, oncologically, especially in the point of local control rate, Lap LLND appears to have acceptable in the treatment of LARC without radiotherapy in experienced centers. Further investigations focusing on indications and the Lap LLND procedural technique are required.

[A Case of Recurrent Gastric Cancer with Durable Complete Response after Short-Term Nivolumab Therapy].

We report the case of a patient with recurrent gastric cancer that showed a complete response(CR)after short-term nivolumab administration. A 76-year-old woman was diagnosed with unresectable advanced gastric cancer(T4b, N+, M0, cStage ⅣA). The patient was administered 7 courses of SOX. Since the primary lesion was reduced significantly after the chemotherapy, radical gastrectomy was performed. Although postoperative adjuvant chemotherapy with weekly nab-PTX was performed, cancer recurrence occurred in the abdominal cavity, and another surgery was performed. However, complete resection was difficult to achieve. Postoperatively, chemotherapy was continued; however, CEA levels increased, and thus RAM+PTX was administered as second-line treatment. Stable disease was maintained for a while; however, disease progression occurred eventually. Thus, RAM+PTX was discontinued after 8 courses, and nivolumab was administered as the third-line treatment. However, due to the rapid deterioration of renal function, nivolumab could not be continued after 3 courses. After nivolumab discontinuation, CEA levels normalized and the image showed CR. Approximately 1.5 years have passed since then, with no report of recurrence without any treatment. Although nivolumab has been shown to be useful as a third-line treatment for unresectable advanced/recurrent gastric cancer, there are few reports demonstrating CR and none showing maintenance of CR after short-term nivolumab administration. Moreover, the rationale of continuing nivolumab is unclear once clinical CR is achieved. Our experience shows the feasibility of discontinuation of short-term nivolumab if CR is achieved.

[A Case of Intraperitoneal Bleeding Due to Vitamin K Deficiency after Laparoscopic Total Pelvic Exenteration for Advanced Rectal Cancer].

A 70-year-old man underwent a colonoscopy and enhanced CT for scrutiny of his anemia. These examinations revealed rectal cancer(cT4b[rectal mesenteric infiltration], N3M0, cStage Ⅲc). We introduced neoadjuvant chemotherapy(NAC) (cetuximab plus oxaliplatin plus S-1, 4 courses)for this patient and diagnosed ycStage Ⅲc(ycT4bN3M0)after the therapy. We performed laparoscopic total pelvic exenteration with bilateral pelvic lymph node dissection. Cefmetazole was administered as a preventive antibiotic in the perioperative period(intraoperatively to postoperative day 3). On postoperative day 4, intra-abdominal heavy bleeding occurred. Blood examination revealed remarkable coagulation disorder with parameters such as APTT 58.9 sec, PT-INR 3.33, and a remarkably high PIVKA- / Ⅱ score of 11,754 mAU/mL. Based on these findings, the patient was diagnosed with complicated vitamin K(VK)deficiency. The coagulation disorders improved following the administration of VK. VK is a fat-soluble vitamin, and the main absorption pathways are dietary, intestinal bacterial production, and recycling in the VK metabolic cycle. In our case, it was considered that the causes of VK deficiency were a marked decrease in VK intake, impairment of the VK metabolic cycle due to taking antibiotics with a N-methyl-thiotetrazole group, and deficiency of VK accompanying suppression of the intestinal flora by antibiotics. We should also consider VK deficiency when patients are diagnosed with postoperative bleeding.

Active Hexose Correlated Compound Has Protective Effects in Ischemia-Reperfusion Injury of the Rat Small Intestine.

BACKGROUND: Ischemia-reperfusion (IR) injury of the small intestine is a serious problem in abdominal aortic aneurysm surgery or small intestine transplantation. Active hexose correlated compound (AHCC) is a popular anti-inflammatory drug in complementary and alternative medicine. The aim of this study was to examine whether pretreatment with AHCC reduces intestinal IR injury. METHODS: Rats were given a normal diet (IR group) or normal diet supplemented with 2% AHCC (IR + AHCC group) ad libitum for 10 d. After 1 d of fasting, the superior mesenteric artery was occluded by clipping for 45 min. Intestinal and blood samples were collected for 1-6 h after reperfusion. The messenger RNA (mRNA) and protein levels of inflammatory factors were analyzed. RESULTS: The IR + AHCC group had reduced mucosal abrasion and significantly increased mucosal thickness of the intestinal tissues 6 h after reperfusion, compared with the IR group. AHCC decreased mRNA expression of inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant 1 and interleukin 6 in the mucosa of the small intestine. AHCC also decreased expression of iNOS protein. Serum levels of cytokine-induced neutrophil chemoattractant 1 and tumor necrosis factor α were decreased in the IR + AHCC group compared with the IR group. Electrophoretic mobility shift assay of mucosal nuclear extracts revealed that AHCC inhibited the activation of nuclear factor kappa B. AHCC also inhibited the expression of iNOS antisense transcript, which stabilizes iNOS mRNA. CONCLUSIONS: Our findings suggest that AHCC reduces expression of inflammatory mediators, in part, by inhibiting nuclear factor kappa B activation. AHCC may have anti-inflammatory effect in patients with intestinal IR injury.

Peritoneal dissemination of ascending colon cancer demonstrating relapse-free survival for 40 months with panitumumab monotherapy: A case report.

INTRODUCTION: The prognosis of metastatic colorectal cancer (mCRC) patients receiving multiple cytotoxic agents and targeted therapies (CATT) has improved, but a complete cure by CATT is still very rare. PRESENTATION OF CASE: We report the successful treatment of ascending colon cancer complicated by peritoneal disseminations (PDs) with panitumumab (Pmab) plus mFOLFOX6 therapy. A 67-year-old male patient was diagnosed with clinical stage IV cancer of the ascending colon with PDs, and underwent ileostomy. Eighteen courses of Pmab plus mFOLFOX6 caused remarkable tumor shrinkage and the disappearance of PDs on ECT. Laparotomy revealed tumor shrinkage and scarring at the PD sites. We performed right hemicolectomy, subtotal omentectomy, and ileostomy closure as curability B surgery. Seven months later, new PDs were detected by ECT so we resumed Pmab plus mFOLFOX6 therapy. After nine courses of treatment, the target lesion had completely disappeared. After a total of 20 courses, we changed to Pmab monotherapy as maintenance therapy because there was no recurrence. Forty months after the initiation of Pmab monotherapy, there has been no oncologic progression. DISCUSSION: Pmab plus mFOLFOX6 treatment resulted in a complete response for PDs, which is extremely rare for CATT. CONCLUSION: We consider that Pmab therapy should be introduced for the treatment of mCRC complicated by PDs.

Laparoscopic management for spontaneous jejunal perforation caused by nonspecific ulcer: A case report.

INTRODUCTION: Nonspecific small bowel ulcers are rare and there have been limited reports. We applied laparoscopic surgery successfully for the perforation caused by this disease of jejunum. PRESENTATION OF CASE: A 70-year-old man visited to our hospital with complaint of abdominal pain and fever. He was diagnosed abdominal peritonitis with findings of intraperitoneal gas and fluid. Emergency laparoscopic surgery was performed. A perforation 5mm in diameter was recognized in jejunum opposite side of mesentery. Partial resection of jejunum with end-to-end anastomosis and peritoneal lavage were performed. Pathologically, an ulcer was recognized around the blowout perforation without specific inflammation. He was discharged uneventfully 12days after surgery. CONCLUSION: Laparoscopic surgery has diagnostic and therapeutic advantages because of its lower invasion with a good operation view, and in case of the small bowel, it is easy to shift extra-corporeal maneuver.

Laparoscopic surgery for colon cancer with intestinal malrotation in adults: Two case reports and review of literatures in Japan.

INTRODUCTION: Intestinal malrotation is a congenital anomaly, and its occurrence in adults is rare. Colon cancer with intestinal malrotation is far more rare. We herein report two cases of colon cancer with intestinal malrotation treated with laparoscopic surgery and reviewed the literatures in Japan. PRESENTATION OF CASES: Case 1 involved a 78-year-old man. Abdominal enhanced computed tomography (CT) showed that the tumor was located in the sigmoid colon. Intraoperatively, the cecum and ascending colon were located along the midline and the small intestine occupied the right side of the abdomen. The tumor was located in the cecum, and the patient was diagnosed with cecal cancer with intestinal malrotation. We performed laparoscopy-assisted ileocecal resection. Case 2 involved a 81-year-old man. Colonoscopy revealed a laterally spreading tumor in the cecum. Intraoperatively, the position of the small intestine and the ascending colon was similar to case 1, and Ladd's band was found in front of the duodenum. Thus, we diagnosed the patient with a laterally spreading cecal tumor with intestinal malrotation and performed laparoscopy-assisted ileocecal resection. DISCUSSION: A review of the literature revealed 49 cases of colon cancer with intestinal malrotation and laparoscopic surgery performed at 30.6%. If laparoscopic mesenteric excision for colon cancer with intestinal malrotation is unsafe because of the abnormalities of the artery, mesenteric excision should be performed outside the body. CONCLUSION: If the intestinal malrotation is diagnosed preoperatively, 3D-CT angiography should be used to reveal the vascular anatomic anomalies for safe performance of laparoscopic surgery.

Elental® amino acid component has protective effects on primary cultured hepatocytes and a rat model of acute liver injury.

Amino acids can exert protective effects on the liver either when administered as a medication or following an operation. In this study, we examined the protective effects of amino acids on the liver using in vitro and in vivo models by studying their influence on the induction of inducible nitric oxide synthase (iNOS) and nitric oxide production as a liver injury marker in cultured hepatocytes and liver-protective effects in d-galactosamine and lipopolysaccharide (GalN/LPS)-treated rats, respectively. Primary cultured rat hepatocytes were treated with interleukin (IL)-1ß in the presence or absence of Elental® amino acid component (EleAA; 17 amino acids). Rats were pretreated with either EleAA or a diet containing selected amino acids followed by GalN/LPS injection. Survival rate and mRNA expression were analyzed. EleAA inhibited iNOS induction through reduction of mRNA synthesis and stability in cultured hepatocytes, indicating prevention of liver injury, but did not show a liver-protective effect in GalN/LPS rats. Among EleAA, Lys, Trp, His, and Arg (4AA) markedly decreased nitric oxide production and inhibited nuclear factor-κB (NF-κB) activation. In GalN/LPS rats, 4AA (3% of each amino acid in diet) increased survival rate by 50% and decreased mRNA expression of iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 in the liver. 4AA reduced NF-κB activation induced by GalN/LPS. 4AA inhibited the expression of inflammatory mediators, in part through inhibition of NF-κB activation in cultured hepatocytes and GalN/LPS-treated rats. The results suggest that EleAA has therapeutic potential for organ injuries including liver.

Efficacy and safety of thromboembolism prophylaxis with fondaparinux in Japanese colorectal cancer patients undergoing laparoscopic surgery: A phase II study.

PURPOSE: We aimed to assess the safety and efficacy of fondaparinux (FPNX) for patients undergoing laparoscopic colorectal surgery (LAC). METHODS: Patients scheduled for LAC received once-daily subcutaneous injections of FPNX 1.5-2.5 mg for 4-8 days. The primary endpoint was the incidence of bleeding events. The secondary endpoint was the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE). RESULTS: Among 128 patients evaluable for efficacy, 119 patients were administered FPNX. Nine patients were excluded owing to intraoperative events, including conversion to open surgery among others. Thirteen patients discontinued treatment owing to anastomotic bleeding (n = 5), anastomotic leakage (n = 3), bleeding at drain insertion site (n = 2), subcutaneous bleeding (n = 1), drug-induced rash (n = 1), and sepsis (n = 1). Among the FPNX discontinuations, there were eight cases of bleeding (6.7%), and two cases of major bleeding (1.7%). In multivariate analysis, operative time >300 min was identified as a risk factor for bleeding events (p = 0.001) secondary to FPNX. The incidence rate of DVT was 2.5% (3/119 cases); these patients were asymptomatic. CONCLUSION: There were no cases of PE. It is necessary to establish strict criteria for VTE prophylaxis with FPNX after LAC for Japanese patients considering the incidence of bleeding events.

A first reported case of metastatic anorectal amelanotic melanoma with a marked response to anti-PD-1 antibody nivolumab: A case report.

INTRODUCTION: Anorectal amelanotic melanoma (AAMM) is a rare disease with poor prognosis. A standard treatment strategy for AAMM has not been established. PRESENTATION OF CASE: We report a case of successful treatment of AAMM with nivolumab. A 67-year-old man was referred for colonoscopy which revealed type I tumor in the rectum. AAMM was diagnosed with immunostaining histopathological biopsy findings. Enhanced computed tomography (ECT) revealed the rectal tumor without distant organ metastasis. We performed laparoscopy-assisted abdominoperineal resection. ECT at three months after surgery revealed liver metastases and right ischial bone metastasis. Although we had started dacarbazine monotherapy, black spots that were suspicious of skin metastases had appeared on systemic skin. Therefore, we started nivolumab therapy. ECT at 3 months after initiation of nivolumab showed shrinkage of liver metastasis. We have continued strict follow-up every 2 months and checked no oncologic progression at 17 months after initiation of nivolumab. DISCUSSION: The anti-PD-1 antibody have improved prognosis of malignant melanoma. However, there are no reports of nivolumab for treatment of AAMM. CONCLUSIONS: Our patient is the first reported case of AAMM treated with nivolumab. We consider that nivolumab will be effective for non-cutaneous malignant melanoma.

Outcomes of neoadjuvant chemoradiotherapy in Japanese locally advanced rectal carcinoma patients.

BACKGROUND: We investigated the efficacy and prognosis of neoadjuvant chemoradiotherapy (NACRT) for Japanese locally advanced rectal carcinoma patients. METHODS: Fifty-seven patients diagnosed with cT3-4 or any cT/cN+ disease using enhanced computed tomography or magnetic resonance imaging from 2002 to 2014 were enrolled. The male/female ratio was 42/15, and the median age was 67 years. Ra/Rb/Rb-P/P was expressed by 6/35/14/2 patients. Histological tumor types were tub1/tub2/por/muc in 22/30/4/1 patients. For NACRT, radiotherapy doses were 40-50.4 Gy chemotherapy consisted of 5'-DFUR, capecitabine, or S1. RESULTS: All 57 patients received curative surgical treatment. The anal preservation rate was 65.0%. The ypStage of 0/I/II/IIIa/IIIb was 7/10/25/11/4 cases. The histological antitumor effect (HATE) was ≥grade (G) 2 and G3 in 31 (54.4%) and 7 (12.3%) cases, respectively. Postoperative complications occurred in 17 patients and exceeded GIII (Clavien-Dindo classification) in four patients. Recurrence was observed in 19 patients; the primary local recurrence rate was 5.3%. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 64.8 and 95.5%, respectively; the 5-year RFS and OS rates were 60.2 and 61.0%, respectively. In multivariate analysis, ypN+ was a high-risk factor for distant organ recurrence. As predictive factors regarding the efficacy of NACRT, a neutrophil concentration <70% and a neutrophil/lymphocyte ratio <3.0 in peripheral blood prior to treatment indicated that NACRT would be significantly more effective. CONCLUSIONS: NACRT was effective in reducing local recurrence but did not suppress distant organ recurrence in Japanese locally advanced rectal carcinoma patients. A further investigation of an extension of the NACRT regimen is required.