[A Case of Advanced Gastric Cancer Treated with Conversion Surgery followed by Nivolumab Combination Chemotherapy].

The use of nivolumab as first-line therapy for unresectable advanced gastric cancer has now become a standard practice, and its efficacy has been established. This is the first report of a patient with advanced gastric cancer who underwent conversion surgery after first-line nivolumab combination chemotherapy. The patient was a 58-year-old woman. Her medical history included hypertension and dyslipidemia. She had advanced gastric cancer with extensive lymph node metastasis in the left supraclavicular fossa and around the abdominal aorta. After confirming the HER2-negative status and the PD-L1 CPS score to be ≥5, nivolumab was administered in combination with chemotherapy. After the treatment, she underwent a total gastrectomy with D2 dissection, combined splenectomy and pancreatic tail resection for adhesions, and para-aortic lymph node sampling as a conversion surgery. There was no obvious cancerous remnant in the resected specimen, and the pathological response was Grade 3. The patient was alive and recurrence-free at 4 months postoperatively.

[A Case of Primary Amelanotic Malignant Melanoma of the Esophagus, Wherein Pseudoprogression Was Suspected during Immune Checkpoint Inhibitor Treatment].

A 78-year-old man was admitted to our hospital with a diagnosis of esophageal cancer and gastric cancer. Gastroscopy showed a type 2 tumor located in the cardia from the lower esophagus, and a pathological examination showed malignant melanoma. Based on the physical examination and other imaging tests, the patient was diagnosed with primary amelanotic malignant melanoma of the esophagus, but the tumor was unresectable due to extensive lymph node metastasis. According to the guideline, immune checkpoint inhibitor(nivolumab)was used for treatment, but because the tumor progressed after 2 courses and the performance status of the patient worsened, aggressive treatment was ended. Six weeks after finishing treatment, computed tomography showed that the tumor had shrunk to some extent. The patient ultimately died from aspiration pneumonia 4 months after the first consultation. The patient was thought to have had an immune-related adverse event, with the tumor showing pseudoprogression.

[Recurrence-Free Survival after Repeated Resections for Metastatic Inguinal Tumor in Colorectal Mucinous Adenocarcinoma-A Case Report].

A 79-year-old male presented with right inguinal mass and right leg pain. Laparoscopic right hemicolectomy was performed for transverse colon cancer(type 1, muc, pSS, pN1a, pStage Ⅲa)3 years and 6 months ago. We resected the mass located in the spermatic cord and reconstructed it using the Direct Kugel Patch. Histopathological examination revealed mucinous carcinoma and was diagnosed as a metastatic lesion. Local recurrence was detected in the spermatic cord 1 year after resection, and radical inguinal orchiectomy was performed. Six months after the surgery performed for local recurrence, repeated recurrence was detected in the mesh used for reconstruction. Because this recurrence time was short, the patient opted for chemotherapy; however, this resulted in tumor growth, and surgery had to be scheduled. We performed extended resection of the abdominal wall and reconstruction using the fascia lata tensor muscle flap. Although intestinal obstruction, aspiration pneumonia, and skin flap necrosis were observed, the patient was discharged on the 85th postoperative day and remained alive without recurrence for 17 months. Mucinous carcinoma tends to cause local recurrence and requires adequate surgical margin resection. Extended excision should be considered in such cases of repeated local recurrence without distant metastases.

[A Case of Boderline Resectable Pancreatic Cancer Curatively Resected after Chemotherapy with Gemcitabine and Nab-Paclitaxel].

Combination therapy containingnab -paclitaxel(nab-PTX)and gemcitabine(GEM)is widely administered for metastatic pancreatic cancer. Recently, this regimen is likely to be applied for treatment in patients with locally advanced disease or for neoadjuvant chemotherapy(NAC)in patients with borderline resectable(BR)pancreatic cancer. We report a case of BR pancreatic cancer in a patient who was eligible for comparison of the imaging findings with the microscopic findings of the resected specimen. A 72-year-old woman was admitted to our hospital with a complaint of jaundice. Enhanced CT showed a 35mm tumor at the head of the pancreas involvingthe portal vein and in contact with the superior mesenteric artery(SMA). After 4 courses of chemotherapy containinga combination of nab-PTX and GEM, the tumor reduced in size, but was still in contact with the portal vein and SMA on imaging. The level of tumor marker CA19-9 was remarkably reduced. Subtotal stomach-preservingpancreaticoduodenectomy with portal vein reconstruction was performed. Macroscopic findings of the cut surface of the resected specimen showed that a white nodule at the pancreas head involved the portal vein and was in contact with the close-cut margin from the SMA; however, microscopic findings revealed that tumor cells had disappeared in the plexus around the SMA. R0 resection was achieved. The histological treatment effect based on Evans' classification and TNM classification were GradeⅡ and pT3N1aM0(pStage ⅡB), respectively. There has been no recurrence 15 months after the surgery. Based on the abovementioned findings, chemotherapy containing a combination of nab-PTX and GEM can be an effective option of NAC for BR-A pancreatic cancer. Even if the tumor is in contact with the SMA on imaging, when the CA19- 9 level is markedly reduced, there is a possibility of achievingR0 surgery.

[Devised a New Preoperative Simulation Using (99m)Tc-GSA SPECT Quantitative Method for Liver Resection].

PURPOSE: We developed a new imaging method to assess liver function by analyzing the amount of liver asialo single photon emission computed tomography (SPECT) using technetium-99m diethylenetriamine pentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA) injection. A preoperative simulation using various regions of interest (ROIs) was performed, and the usefulness of the method for predicting the residual liver function was examined. METHODS: Ninety-three patients were enrolled who underwent both asialo scintigraphy and dynamic computed tomography (CT) scanning. The two-dimensional dynamic data were analyzed using the Patlak plot method to calculate Kup and perfusion index (PI). The PIi (the quantity of GSA in a reference slice) was calculated using the PI. The qualitative SPECT data were analyzed using the quantitative images and the PIi, and we calculated the amount of asialo uptake per unit, which we named asialo uptake index (AUI). Volume registration was done between the collected breath holding SPECT data and CT images. RESULTS: We were able to obtain AUI images and calculate the liver sparing ability by analyzing the two-dimensional data. The AUI and each of the liver counts (HH15, LHL15, LU15, and PI) were correlated, and we could perform the preoperative simulation using any ROI. CONCLUSION: Preoperative simulation for the outcome of hepatectomy could be done using our new method employing quantitative SPECT.

[A Case of Locally-Advanced Breast Cancer with Liver Metastasis, Treated with Mastectomy of the Primary Tumor after Chemotherapy].

The patient was a 39-year-old woman who was referred to our hospital with suspicion of locally-advanced breast cancer. After several tests, she received a diagnosis of cT4bN1M1 (liver), Stage Ⅳbreast cancer. The liver metastasis was located in S4, and was 1 cm in size. Core needle biopsy was performed on the breast tumor; the pathological diagnosis was invasive ductal carcinoma (scirrhous carcinoma), nuclear Grade (NG) 3, and HER2-positive. She received epirubicin plus cyclophosphamide (EC) followed by docetaxel (DOC) plus pertuzumab (PER) plus trastuzumab (HER). After chemotherapy, the liver metastasis and axillary lymph node metastases had disappeared on imaging findings, showing a complete response (CR), but the primary breast tumor remained, showing a partial response (PR). She underwent mastectomy and axillary lymph node dissection for local control. After surgery, no metastases including liver metastases were seen on CT. The patient is currently receiving tamoxifen and anti-HER2 therapy.

[A Case of Pathologically Complete Response of a Rectal Cancer after Preoperative Treatment with mFOLFOX6 and Radiation Therapy].

A 60-year-old man who had bloody stools after sigmoid colonoscopy was admitted to our hospital. A digital examination and sigmoid colonoscopy showed a type 2 circular tumor at location Rb with incomplete mobility and tumor hemorrhage, and the result of a biopsy was moderately differentiated adenocarcinoma (tub2). Computed tomography and magnetic resonance imaging suggested a possibility of invasion of the primary rectal tumor to the sacrum. The clinical stage was cT4bN0M0H0P0, cStage Ⅱ, which is generally not treatable by surgery. Sigmoid colostomy was performed, and a central venous port was implanted. After a preoperative treatment consisting of 3 courses of mFOLFOX6 and radiation therapy, the clinical stage changed to ycT2N0M0H0P0, ycStageⅠ. Super-low anterior resection and covering ileostomy were performed 46 days after the preoperative treatment. A pathological examination revealed no residual cancer cells in the primary lesion and lymph node (Grade 3, pCR). The patient has been disease-free for 4 years and 9 months after the operation.

[Clinical evaluation of eribulin mesylate for the treatment of metastatic breast cancer].

BACKGROUND: Eribulin mesylate, a novel non-taxane inhibitor of microtubule dynamics, results in a significant improvement in the overall survival of heavily pretreated patients with metastatic breast cancer(MBC). In the present study, we aimed to clarify the efficacy and safety of eribulin mesylate for the treatment of MBC. PATIENTS AND METHODS: We examined 18 patients with MBC who received eribulin mesylate in our hospital from October 2011 to May 2013. The patients were assessed for therapeutic response and adverse events with this treatment; in addition, these parameters were assessed in patients undergoing a combination treatment of eribulin mesylate and trastuzumab. RESULTS: The mean age of the patients in this study was 68.7 years(range, 60-85 years). All patients exhibited metastases to lymph nodes and distant sites. The mean number of prior regimens was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment administered was 7.2(range, 2- 17). The objective response rate and clinical benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the median progression-free survival was 6 months. The Grade 3/4 adverse events occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1 patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who received the combination treatment of trastuzumab and eribulin mesylate experienced no adverse events. CONCLUSIONS: eribulin mesylate appears to demonstrate an acceptable tumor response in patients with MBC, and it can be safely administered to elderly patients if myelosuppression is carefully managed.

[A case of adenosquamous carcinoma of the sigmoid colon with inferior mesenteric vein thrombosis].

A 63-year-old man who had been admitted to another institute with sepsis and renal failure was referred to our hospital after computed tomography (CT) findings showed thickening of the walls in the sigmoid colon and a defect in contrast enhancement in the portal and inferior mesenteric veins. Emergency sigmoid colon resection with D2 lymphadenectomy was performed after detection of perforation due to sigmoid colon cancer. The histopathological diagnosis was adenosquamous carcinoma, pSS, int, INF b, ly1, v0, pN2, pStage IIIband inferior mesenteric vein thrombosis. He was discharged on day 12, and we administered anticoagulant warfarin therapy.

[A case of sigmoid colon cancer with abdominal wall abscess].

A 63-year-old man was admitted for an abdominal mass. Computed tomography revealed an abscess (21 × 20 cm) in the abdominal wall and a tumor in the sigmoid colon. Thus, cancer of the sigmoid colon complicated by an abscess of the abdominal wall was diagnosed. The abscess was drained and transverse colostomy was performed with curative intent. After the intervention, chemotherapy (XELOX×3) was administered. Three months later, sigmoidectomy was performed and the stoma was closed. Macroscopic and microscopic examination of the resected specimen detected no remnants of cancer. In patients with advanced colon cancer and abdominal wall involvement, a two-stage operation and preoperative chemotherapy may be considered essential when curative resection is performed.

[Long-term survival of a patient with esophageal cancer with brain metastasis after multidisciplinary therapy - a case report].

A 70-year-old woman was admitted for difficulty in swallowing. Esophageal cancer (MtLt, type 3, T4N3M0, cStage IVa) was diagnosed in May 2010. The cancer was unresectable, and chemoradiotherapy (CRT) with TS-1 was initiated in June 2010, and a partial response (PR) was observed. After CRT, TS-1 was continued, but a brain metastasis was detected owing to the development of right hemiplegia in April 2012. Craniotomy and tumorectomy were performed, and the right hemiplegia improved. Pathological examination of the brain tumor indicated squamous cell carcinoma. Because of a recurrence of brain metastasis, a gamma knife procedure was performed in May 2012. Subsequently, several recurrences of brain metastases were diagnosed, and a total of 7 gamma knife procedures were performed up to January 2014. Although systemic chemotherapy (5-fluorouracil and cisplatin [FP], 5 courses)was administered, the patient showed progressive lung metastases in February 2013. The chemotherapy regimen was changed from FP to docetaxel (TXT), but the lung metastases continued to progress up to June 2013. The patient died in March 2014. Patients with esophageal cancer and metastases to the brain have poor prognosis, but the present patient survived approximately 2 years after first diagnosis of metastases to the brain after multidisciplinary therapy.

A flexible-arm liver retractor that provides an optimal surgical field without postoperative liver dysfunction.

BACKGROUND/AIMS: It is important to retract the lateral liver segment during laparoscopic gastrectomy to achieve an optimal surgical field. Few retractors cause transient liver dysfunction after surgery; therefore, for an easier and safer procedure, we devised a new liver retractor and implemented a trial clinical application. METHODOLOGY: The novel liver retractor comprises a metallic, flexible arm retractor attached to the operating table and an air compressor which pneumatically moves and fixes the retractor. It was inserted directly into the abdominal cavity just below the xiphisternum to retract the left lobe of the liver anterosuperiorly, thereby exposing the hiatus. Blood samples were collected from the patients on days 1, 3, and 7 after surgery to assess the levels of the liver enzymes AST and ALT. RESULTS: During laparoscopic gastrectomy, no liver damage was observed macroscopically. The surgical fields obtained were optimal and efficient for laparoscopic surgery. Notably, it was possible to retract the liver as often as needed. Further, none of the patients developed postoperative liver dysfunction. CONCLUSIONS: The novel flexible-arm retractor provided an optimal surgical field without inducing liver dysfunction.

Surgical advantages of gastric SMTs by laparoscopy and endoscopy cooperative surgery.

BACKGROUND/AIMS: The treatment of gastric submucosal tumors (SMTs) is strictly surgical and enucleation of the tumor or wedge resection of the stomach is efficient to achieve R0 resection. Laparoscopic and endoscopic cooperative surgery (LECS) can be safely performed with adequate cutting lines. This study describes the initial 16 cases treated by LECS and evaluates the advantages by LECS for gastric SMTs retrospectively. METHODOLOGY: Sixteen patients with gastric SMT underwent LECS from June 2007 to December 2010, their surgical data, clinical characteristics and surgical specimens of SMTs were compared. The surgical specimens of 9 gastric SMTs treated by laparoscopic wedge resection (LWR) were compared as a control. RESULTS: The median (range) length of operation time, blood loss, hospital stay after surgery were minutes 172 (115- 220), <5mL (<5-115) and 10 days (6-17), respectively. The median (range) ratio of the longest diameter of the tumor divided by the longest diameter of the surgical specimen in LECS and LWR were 0.86 (0.625-1.0) and 0.69 (0.44-1.0), respectively (p=0.0189, Wilcoxon rank sum test). CONCLUSIONS: LECS minimizes the surgical specimen while still providing sufficient surgical margins to successfully cure gastric SMTs.

[A case of a patient with gastric cancer and liver metastasis -a long-term survival of 10 years].

We report a case of patient who is alive 10 years after total gastrectomy and partial liver resection for gastric cancer and liver metastasis, respectively. The patient is 69-year-old man who was examined in another hospital for nausea, tarry stool, and weight loss. Diagnosis by stomach fluoroscopy revealed gastric cancer and he was admitted to our hospital in September 2002. Computed tomography (CT) scan and ultrasonography (US) revealed liver metastasis in S7. Distant metastases were not detected. The patient underwent distal gastrectomy, transverse colon partial resection, and a hepatic partial resection in October 2002. Pathological findings showed SI, N1, and M1. Though adjuvant chemotherapy was given, a local recurrence was detected in the liver in February 2003. Hepatic arterial infusion (HAI) was started in April 2003. After 8 courses, HAI was discontinued because of hepatic artery obstruction. No additional distant metastases were found. Therefore, transdiaphragmatic radiofrequency ablation (RFA) was performed by thoracotomy. Currently, the patient is treatment free and remains alive after 10 years with no recurrence.

The classification of anatomic variations in the perigastric vessels by dual-phase CT to reduce intraoperative bleeding during laparoscopic gastrectomy.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) is a less invasive alternative compared with an open procedure. However, it is difficult to obtain a full-view image and to estimate the three-dimensional (3D) relationships between organs during laparoscopic procedures. Determining the vascular anatomy by 3D CT imaging has been shown to play a critical role in reducing the risks associated with laparoscopic gastric cancer surgery. The purpose of this study was to evaluate the clinical anatomic variations and to estimate its positive contribution in obtaining less intraoperative bleeding. METHODS: Scanning was performed using a 64-row MDCT scanner. Three-dimensional CT images in the arterial and portal phase were reconstructed and fused together using the volume-rendering technique. The intraoperative bleeding findings were compared between two periods. RESULTS: The anatomic variations of the celiac trunk were divided into six types. There were 159 patients with Adachi's type I, type II=8, type III=1, type IV=1, type V=2, type VI=3, and other=1. The inflows of the left gastric coronary vein (LCV) were divided into three types. The LCV flowed into the portal vein (PV) in 79 patients, into the splenic vein (SpV) in 65, and into the junction of these two veins in 27. The splenic artery was divided into flat type and curved type, and 65 cases (37%) showed the flat type. Intraoperative bleeding was significantly less between 2007 and 2008, in which the operations were performed without first making a 3D anatomy study, than in 2009, in which 3D anatomy studies were made and analyzed before surgery in all patients. CONCLUSIONS: Dual-phase 3D CT is a useful and essential modality to visualize the precise anatomy around the stomach. As a result, by comparing 3D CT images with our classifications, it is believed that any surgeons may reduce the degree of intraoperative blood loss.

Low peritoneal and systemic inflammatory response after laparoscopy-assisted gastrectomy compared to open gastrectomy.

BACKGROUND/AIMS: Peritoneal immune response as well as systemic response was objectively evaluated in laparoscopy-assisted distal gastrectomy (LADG) compared to open distal gastrectomy (ODG). METHODOLOGY: A total of 42 patients with gastric cancer were enrolled, with 23 undergoing LADG and 19 ODG. We evaluated the levels of IL-6 in peritoneal drain fluid, serum C-reactive protein (CRP), white blood cells (WBC), and the postoperative presence of systemic inflammatory response syndrome (SIRS). RESULTS: The serum CRP level was significantly higher in the ODG group than in the LADG group (p=0.007) on postoperative day (POD) 1. WBC counts showed no statistically significant difference between the two groups (p=0.105). The rate of cases exhibiting SIRS was significantly higher in the ODG group than in the LADG group (p<0.001). The IL-6 level of drain fluid was significantly higher in the ODG group than the LADG group (p<0.01) on POD1. Although weak correlation between IL-6 on POD1 and blood loss (R=0.38, p=0.0154) was observed, no significant correlation between IL-6 and operation time was noted. CONCLUSIONS: LADG seems to be a lesser traumatic approach for the treatment of gastric cancer.

Survival predictors of patients with primary duodenal adenocarcinoma.

This single-institution experience retrospectively reviewed the outcomes in 21 patients with primary duodenal adenocarcinoma. Twelve patients underwent curative surgery, and 9 patients underwent palliative surgery at the Chiba University Hospital. The maximum follow-up period was 8650 days. All pathologic specimens from endoscopic biopsy and surgical specimens were reviewed and categorized. Twelve (57.1%) patients underwent curative surgery (R0): 4 pancreaticoduodenectomies (PD), 4 pylorus-preserving PDs (PpPD), 2 local resections of the duodenum and 2 endoscopic mucosal resections (EMR). Palliative surgery was performed for 9 patients (42.9%) following gastro-intestinal bypass. The median cause-specific survival times were 1784 days (range 160-8650 days) in the curative surgery group and 261 days (range 27-857 days) in the palliative surgery group (P = 0.0003, log-rank test). The resectability of primary duodenal adenocarcinoma was associated with a smaller tumor size, a lower degree of tumor depth invasiveness, and less spread to the lymph nodes and distant organs.

Role of perfusion CT in assessing tumor blood flow and malignancy level of gastric cancer.

BACKGROUND/AIMS: Intratumoral hemodynamics or tumor perfusion is useful in understanding the pathological background of the cancer. A parameter for a non-invasive, preoperative assessment of tumor perfusion has yet to be developed. METHODS: The study included 50 patients who underwent surgery for gastric cancer. Perfusion computed tomography (P-CT) was performed using a 16-row multidetector CT, and tumor blood flow (ml/min/100 g tissue) values were measured. We compared blood flow with histopathological characteristics and evaluated its correlation with microvessel density and tumor stromal density and calculated the ratio of vessels and stromal tissue. RESULTS: There was a significant decrease in blood flow in advanced tumor depth, peritoneal dissemination and undifferentiated subtypes. Cases with Lauren's diffuse type carcinoma were found to have decreased blood flow compared to the mixed or intestinal type. As for the stromal structure, despite the lack of correlation with microvessel density, blood flow significantly decreased with increased stromal density. CONCLUSIONS: Decreased blood flow value acquired from P-CT may reflect a progressive state of gastric cancer. The pathological background for this relation involves the tumor stroma. Tumor perfusion decreased as the stage and malignant character of the tumor advanced, and therefore P-CT could be a better strategy to estimate the malignancy level of cancer.

[A case of long-term survival after resection for postoperative solitary adrenal metastasis from esophageal adenocarcinoma].

A 71-year-old man presented with chief complains of hoarseness and dysphagia. He was diagnosed to have an advanced esophageal adenocarcinoma in the middle thoracic esophagus for which chemoradiation therapy was started. Partial response was observed and he was referred to our hospital thereafter. After detailed examination, he underwent a subtotal esophagectomy followed by two-field lymphadenectomy in May 2001. Histopathological examination revealed a complete response. Ten months later, hematological examination showed a high serum CEA level and CT scan disclosed mediastinal lymph node recurrences. He received a course of systemic chemotherapy so called FP therapy and five months later, a course of combination chemotherapy with 700 mg/m2 5-FU on days 1-5 and 70 mg/m2 nedaplatin on day 1 was administered. Because the high serum CEA level sustained afterward, FDG-PET was undertaken in March 2003. The right adrenal gland showed an intense abnormal FDG uptake and CT scan detected a low density mass in the area. Since no metastases could be identified in other sites, right adrenalectomy was performed. Pathological finding was poorly-differentiated tubular adenocarcinoma. Five years and eleven months after adrenalectomy, he died of pneumonia with no signs of recurrence. Surgical resection may contribute to improving the prognosis of solitary adrenal metastasis of esophageal cancer without the other noncurative factors.

[Regional treatment of esophageal liver metastasis by intra-arterial low-dose 5-FU therapy].

The prognosis of esophageal liver metastasis remains poor because of the high incidence of synchronous metastasis in other area and insufficient response to systemic chemotherapy. We assessed loco-regional anticancer potential of intra-arterial 5-FU chemotherapy for esophageal liver metastasis aimed at combination with systemic chemotherapy, radiotherapy and ablation therapy as a multidisciplinary treatment. Six patients of esophageal cancer with liver metastasis and without extra-hepatic metastasis were enrolled. Intra-aortic chemotherapy consisted of 5-FU (250 mg/body) in a one-shot infusion or a continuous infusion for 7 days with 2-week intervals until failure. The responses of liver metastasis were 2 cases of CR, 3 of PR and 1 of SD. The response rate and the local control rate were 83% and 100%, respectively. The maximum time to progression was 53 months. Grade 3/4 toxicity was not observed. Two cases had catheter failure and the treatment was interrupted. Liver metastases were controlled well until death in all cases except one. Low-dose intra-aortic 5-FU chemotherapy provided a good regional response and a combination with systemic chemotherapy may prolong survival for the patients of liver metastasis of esophageal cancer.