[A Case of Neuroendocrine Carcinoma Originating from the Papilla of Vater].

A woman in her late 70s with fatigue, nausea, and epigastric discomfort was found to have a tumor at the papilla of Vater through endoscopy. We performed subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. The immunohistological analysis showed positive staining for chromogranin A, synaptophysin, and CD56. The definitive diagnosis was neuroendocrine carcinoma of the papilla of Vater. Although the patient declined adjuvant chemotherapy, she had to start chemotherapy with carboplatin and etoposide because multiple liver metastases, lymph node metastasis, and peritoneal dissemination occurred 6 months after surgery. We performed 6 courses of chemotherapy. However, progressive disease(PD)was assessed, and she died of cancer 13 months after the surgery. The prognosis of the disease is poor when surgery alone is performed. Adjuvant chemotherapy, in addition to surgery, may be necessary.

The Impact of Tumor-associated Macrophages on Chemoresistance via Angiogenesis in Colorectal Cancer.

BACKGROUND/AIM: The tumor microenvironment plays an important role in tumor progression. Tumor-associated macrophages (TAMs) have been reported to promote proliferation, invasion, metastasis, angiogenesis, and immunosuppression. Furthermore, angiogenesis has been reported to induce chemoresistance due to the inefficient distribution of drugs to cancer cells. However, the impact of TAMs on chemoresistance via angiogenesis in colorectal cancer (CRC) remains unclear. The aim of the study was to evaluate the impact of TAMs on the chemotherapeutic outcome in CRC. PATIENTS AND METHODS: We enrolled 54 patients who underwent chemotherapy for unresectable metastatic CRC after resection of the primary tumor. We evaluated the density of TAMs and the degree of angiogenesis by immunohistochemistry and then explored the correlation between the density of TAMs and chemotherapeutic outcome. Furthermore, we assessed any correlation between the density of TAMs and that of neovascularity. RESULTS: The high-TAMs group had a significantly worse progression-free survival (p=0.0006) and a poorer response rate (p=0.0274) than the low-TAMs group. In addition, a positive correlation was observed between the density of TAMs and the degree of neovascularity (r=0.665, p=0.0004). CONCLUSION: TAMs were shown to promote chemoresistance via angiogenesis in CRC.

[Successful Experience of Negative Pressure Wound Therapy with Instillation and Dwelling(NPW Ti-d)for Patient with Wound Dehiscence Developed by Infection after Right-Hemicolectomy for Ascending Colon Cancer].

We report a case of infected and incised wound cured by negative pressure wound therapy with instillation and dwelling (NPWTi-d)after right hemicolectomy for ascending colon cancer. The patient was a 72-year-old male. An ascending colon cancer with abdominal wall invasion and enterocutaneous fistula was found. We performed the right hemicolectomy and debridement of abdominal wall for the patients. However, the leakage of ileum-transverse colon anastomosis was found on postoperative day 3. We performed the resection of anastomosis and ileostomy. Nevertheless, 2 days after second operation, the abdominal wall of debridement became open by infection, and the small intestine was exposed. As the surgical treatment and NPWT was thought to be difficult because of infection, we started NPWTi-d on day 4 after second operation. 25 day after starting NPWTi-d, benign granulation covered the small intestine. NPWTi-d may be useful for wound dehiscence after surgery in infectious conditions.

Inflammation Caused by Surgical Stress Has a Negative Impact on the Long-term Survival Outcomes in Patients With Colorectal Cancer.

BACKGROUND/AIM: Inflammation is known to promote the progression of cancer, and there is increasing evidence that inflammation caused by the antitumor response of the host and post-operative infectious complications worsens the prognosis for colorectal cancer. However, the impact of post-operative inflammation caused by surgical stress on long-term survival is unclear. PATIENTS AND METHODS: A total of 274 patients who underwent curative operation for stage II/III colorectal cancer were enrolled and assessed for the serum C-reactive protein (CRP) levels on postoperative day (POD) 1 and 7 and postoperative infectious complications. RESULTS: The high POD-1 CRP group had a significantly lower relapse-free and overall survival rate than the low POD-1 CRP group. Similarly, the high POD-7 CRP group had a significantly lower relapse-free and overall survival rate than the low POD-7 CRP group. Sub-group analysis limited to patients without postoperative infectious complications indicated that the high POD-7 CRP group tended to have a lower relapse-free survival rate and a significantly lower overall survival rate than the low POD-7 CRP group. CONCLUSION: Inflammation caused by postoperative infectious complications and by surgical stress worsens long-term survival outcomes after a curative operation for colorectal cancer.

Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer.

Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty-four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post-treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post-treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post-treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte-mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.

The feasibility and short-term clinical outcomes of single-incision laparoscopic surgery for patients with complex Crohn's disease.

PURPOSE: Single-incision laparoscopic surgery (SILS) offers excellent cosmetic results compared with conventional multi-port laparoscopic surgery. Recently, this technique has been applied to Crohn's disease (CD) with primary ileocolic strictures; however, the application of a laparoscopic approach for complex CD, which involves abscess formation, fistula formation, and recurrent CD, is controversial. The aim of this study was to investigate the safety and feasibility of SILS for patients with complex disease and to compare its clinical results in patients with complex disease vs. those with simple stricture disease. METHODS: Fifty patients who underwent SILS for CD were divided into two groups: those with complex disease (complex group, n = 25), and those with simple strictures (simple group, n = 25). The preoperative data and clinical outcomes were analyzed and compared between the groups. RESULTS: The operative time, blood loss and length of laparotomy incision were not significantly different between the groups. Although the rate of conversion and need for an additional port tended to be higher in the complex group, the rate of postoperative complications and length of hospital stay did not differ significantly between the groups. CONCLUSION: SILS may be feasible for carefully selected patients with complex CD.

[A Case of Rectal Gastrointestinal Stromal Tumor(GIST)with Long-Term Survival Treated with Multidisciplinary Therapy].

We report a case of gastrointestinal stromal tumor(GIST)with long-term survival treated by multidisciplinary therapy, including surgery and imatinib to prevent repeated recurrence. A 76-year-old woman visited our hospital with difficulty in defecation and bloody bowel discharge. She was diagnosed with rectal GIST and underwent transanal partial resection of the rectum. Local recurrence occurred 1 year after the operation, and the tumor was resected transanally. Hepatic metastasis occurred 8 months after the second operation. The patient was administered imatinib for 2 months, which caused the tumor to shrink, and extended left lobectomy was performed. Imatinib was administered for 2 years after hepatectomy. After another 2 years, metastasis to the liver and thoracic and lumbar vertebrae occurred. The recurrent tumors reverted to cystic lesions after 6 months of imatinib treatment. She has been alive without tumor progression during re-treatment with imatinib for 7 years(13 years after the first surgery).

The Prognostic Significance of the Tumor-infiltrating Programmed Cell Death-1+ to CD8+ Lymphocyte Ratio in Patients with Colorectal Cancer.

BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the antitumor immunity of the host and correlate with the therapeutic outcomes and survival. Nowadays TILs are attracting attention as new biomarkers of diseases such as colorectal cancer. TILs are classified into several subsets, among which CD8+ T cells directly attack cancer cells and play a central role in antitumor immunity. A high density of CD8+ TILs has been reported to correlate with a better clinical outcome. Programmed cell death-1 (PD-1) is recognized to be a surface marker for dysfunction of T lymphocytes. However, the prognostic significance of PD-1+ TILs remains unclear. The aim of this study was to evaluate the prognostic significance of the number of PD-1+ TILs and the tumor-infiltrating PD-1+ to CD8+ lymphocyte ratio (PD-1/CD8 ratio) in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 90 patients with stage II/III CRC who underwent curative surgery were enrolled in this study. Immunohistochemistry was used to assess the densities of PD-1+ TILs and CD8+ TILs. The PD-1/CD8 ratio was defined as the number of PD-1+ TILs divided by the number of CD8+ TILs. The optimum cut-off value for the number of PD-1+ TILs and the PD-1/CD8 ratio was determined via a receiver operating characteristic analysis. We then assessed the prognostic significance of the number of PD-1+ TILs and the PD-1/CD8 ratio. RESULTS: The relapse-free and overall survival rates were significantly worse in the high-PD-1/CD8 ratio group than in the low-PD-1/CD8 ratio group (relapse-free survival: p=0.0257, overall survival: p=0.0363), although the number of PD-1+ TILs showed no prognostic significance. CONCLUSION: The PD-1/CD8 ratio may, therefore, be a useful prognostic marker for stage II/III CRC. What is important for predicting the prognosis may be the PD-1/CD8 ratio rather than the absolute number of PD-1+ TILs.

The peripheral monocyte count is associated with the density of tumor-associated macrophages in the tumor microenvironment of colorectal cancer: a retrospective study.

BACKGROUND: Inflammation is widely recognized to play an important role in cancer progression, and the peripheral monocyte count has been reported to correlate with the prognosis in patients with colorectal cancer. This is based on the hypothesis that the peripheral monocyte level and the density of tumor-associated macrophages (TAMs) in the cancer microenvironment correlate with each other. However, the influence of TAMs on the prognosis and the correlation between the peripheral monocyte count and the density of TAMs have not yet been elucidated. METHODS: A total of 168 patients with stage II/III colorectal cancer were enrolled in this study. Preoperative blood samples were obtained at the time of the diagnosis before surgery. The expression of TAMs in the cancer microenvironment was assessed by immunohistochemistry. RESULTS: The progression-free and overall survival rate were significantly worse in the high-TAMs group than in the low-TAMs group (p = 0.0012 and p = 0.0207, respectively). The peripheral monocyte count was significantly associated with the number of TAMs (correlation coefficients: 0.202, p = 0.047). CONCLUSIONS: The peripheral monocyte count was associated with the density of the TAMs, which created a microenvironment favorable for cancer development and were correlated with a poor prognosis. Therefore, the peripheral monocyte count is a useful prognostic marker reflecting the status of the tumor microenvironment.

[A Case of Laparoscopic Surgery Performed for Locally Advanced Rectal Cancer Suspected of Invasion to Prostate].

A-58-year-old man was admitted to other hospital with complaints of anal pain and bloody stools, diagnosed as rectal cancer with invasion to prostate, and performed sigmoid colostomy. After taking 6 courses of mFOLFOX6 as preoperative chemotherapy, he introduced our hospital for the purpose of operation. Preoperative evaluation of chemotherapy was PR, but infiltration of the prostate remained. Therefore, laparoscopic abdomino-perineal resection of rectum, prostatectomy and urethral reconstruction by urethral-bladder anastomosis were performed. Postoperative course was good and he was discharged on 10 days after surgery. Currently 2 years after surgery, he has no dysurea and relapse free survival. This procedure was considered to be a very useful technique in that a good operative field and reliable resection can be obtained.

[A Case of Small Intestinal Metastasis with Intussusception Due to Barium].

A 48-year-old man noticed nausea and took health examination. After chest X-ray and gastrointestinal barium study was underwent, he was referred to our hospital because of abnormal shadow in the chest X-ray. CT scan revealed about 4 cm tumor in the hilum of left lung and target sign in the small intestine. He was diagnosed with intussusception and emergency operation was performed. During the laparotomy, we found 2 intussusceptions in the small intestine and we performed manual reduction using Hutchinson's maneuver. We confirmed the mass in oral side of the intussusception site but we did not confirmed any tumor in anal of the intussusception. This suggests the intussusception was caused by barium. Finally 3 small intestine tumor was observed and we resected and reconstructed each of the tumor. Histopathological examination showed small intestinal metastasis from pleomorphic carcinoma of the lung.

Salvage surgery after chemotherapy with S-1 plus cisplatin for α-fetoprotein-producing gastric cancer with a portal vein tumor thrombus: a case report.

BACKGROUND: Patient with α-Fetoprotein (AFP)-producing gastric cancer usually has a short survival time due to frequent hepatic and lymph node metastases. Gastric cancer with portal vein tumor thrombus (PVTT) is rare and has an extremely poor prognosis. CASE PRESENTATION: A 63-year-old man was found to have a huge Type 3 gastric cancer with a PVTT and a highly elevated serum AFP level. Chemotherapy with S-1 plus cisplatin was given to this patient with unresectable gastric cancer for 4 months. The serum AFP level decreased from 6,160 ng/mL to 60.7 ng/mL with chemotherapy. Since the PVTT disappeared after the chemotherapy, the patient underwent total gastrectomy. Histological findings of the primary tumor after chemotherapy showed poorly differentiated adenocarcinoma without hepatoid cells and viable tumor cells remaining in less than 1/3 of the neoplastic area of mucosa and one lymph node. The cancerous cells were immunohistochemically stained by anti-AFP antibody. The patient has survived for 48 month without recurrence. CONCLUSIONS: AFP-producing gastric cancer with a PVTT has an extremely poor prognosis, but long-term survival was achieved for this dismal condition by salvage surgery after chemotherapy.

[Complete Response to Chemotherapy after Resection of Rectal Cancer with Virchow's Lymph Node Metastasis].

A 62-year-old woman was admitted to our hospital because of bloody stool. Colonoscopy revealed stenosis by a type 2 tumor of the recto-sigmoid colon. A biopsy specimen contained moderately differentiated adenocarcinoma. Thoraco-abdominal computed tomography (CT) showed liver metastasis (S7, 10 mm) and enlargement of Virchow's lymph node (17 mm) and several para-aortic lymph nodes (15 mm on average). Because of oozing from the tumor and severe stenosis of the recto-sigmoid colon, we performed laparoscopic-assisted high anterior resection of the primary lesion. After surgery, 3 courses of mFOLFOX6, 20 courses of mFOLFOX6 plus bevacizumab, and 5 courses of infusional 5-FU plus Leucovorin plus bevacizumab were administered. Thoraco-abdominal CT demonstrated complete response to the 1 year 2 months of chemotherapy. The patient has been alive without relapse for 2 years after surgery.

[A case of a villous tumor of the rectum with electrolyte depletion syndrome].

We report a case of a villous tumor of the rectum with electrolyte depletion syndrome (EDS). A 76-year-old woman developed general fatigue, and on investigation, we found a large laterally spreading tumor of the rectum using bowel enema and colon fiber. Pathologically, the biopsy specimen was graded Group 4. We intended to perform a laparoscopy-assisted low anterior resection in the patient. However, the operation was interrupted by a short-run type of ventricular premature contraction (VPC) due to EDS-induced hypokalemia. After treating the hypokalemia, low anterior resection or laparotomy was performed. The tumor was 19 × 13 cm in size and occupied the circumference of the rectum. Histological examination revealed well differentiated tubular adenocarcinomas with tubulovillous adenoma. Pathological staging was pTis, pN0, M0, stage 0 according to the Japanese Classification of Colorectal Carcinoma (8th edition). It is now 6 months after the operation and hypokalemia has not recurred in the patient.

[A case of laparoscopic surgery for a rectal carcinoid after ALTA therapy for an internal hemorrhoid].

We report a case of laparoscopic surgery for a rectal carcinoid after aluminum potassium and tannic acid (ALTA) therapy for an internal hemorrhoid. A 66-year-old man was admitted to our hospital because of bleeding during defecation. He was diagnosed via anoscopy with Goligher grade II internal hemorrhoids. Examination via colonoscopy revealed 2 yellowish submucosal tumors in the lower rectum that were 5mm and 10mm in diameter. A rectal carcinoid tumor was diagnosed based on histopathology. Abdominal computed tomography demonstrated no metastases to the liver or lymph nodes. First, we performed ALTA therapy for the internal hemorrhoids. Two weeks later, we performed laparoscopic-assisted low anterior resection (D2) for the rectal carcinoid. The patient was discharged without complications and has not experienced recurrence during the 2 years of follow-up care.

[A case of obstruction due to right-sided colon cancer in which good quality of life was achieved after colonic stenting].

We report a case of a 60-year-old woman with abdominal distension who was treated with self-expandable metal stent (SEMS) placement in the proximal transverse colon. She was found to have severe bowel obstruction due to advanced transverse colon cancer on plain computed tomography (CT) and colonoscopy. We performed colonic stenting safely, and the symptom promptly improved. Defecation and flatus were observed on the same day of stenting, and the patient was able to start drinking and eating on the next day. Enhanced abdominal CT revealed multiple liver metastasis, peritoneal dissemination, ascites, and cystic ovarian tumor. After treatment with 1 course of 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6), the patient was discharged on day 14 after admission. The rapidly enlarging ovarian tumors and primary colonic lesion with SEMS were surgically removed after treatment with mFOLFOX6 for 4 months in an outpatient basis. The patient has been alive with a good quality of life (QOL) and being treated with bevacizumab plus mFOLFOX6/Leucovorin, 5-fluorouracil, and irinotecan( FOLFIRI) for 6 months. SEMS placement could be safe and effective for the treatment of obstruction of the right colon, and could maintain a good QOL in patients.

Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer.

BACKGROUND: The combination of gemcitabine (GEM) and S-1, an oral 5-fluorouracil (5-FU) derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. METHODS: Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK) study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. RESULTS: The maximum concentration (Cmax), the area under the curve from the drug administration to the infinite time (AUCinf), and the elimination half-life (T1/2) of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax) were not significantly different between S-1 administration with and without GEM. CONCLUSION: There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

[A case of liver metastasis of mixed acinar-endocrine carcinoma treated with various loco-regional cancer therapies].

Mixed acinar-endocrine carcinoma of pancreas is a very rare tumor. We report a 60s female patient with pancreatic mixed acinar-endocrine carcinoma and liver metastasis. The patient admitted for further examination of pancreatic head mass. Computed tomography scan of abdomen showed a large tumor in pancreatic head and liver tumor. Angiography revealed a presence of embolism in portal vein. We conducted a pylorus-preserved pancreatoduodenectomy with resection of the portal vein on the diagnosis of acinar cell carcinoma by fine needle aspiration biopsy. Pathological examination showed a mixed acinar-endocrine carcinoma. Following the operation, the liver metastasis was controlled with various loco-regional cancer therapies.