[A Case of Gastric Perforation Due to an Unresectable Advanced Gastric Cancer That Achieved pCR after Conversion Surgery following SOX plus T-mab Therapy].

This case pertains to a 72-year-old man who visited the emergency department with a complaint of upper abdominal pain. On examination, we suspected gastric perforation due to gastric cancer and decided to perform emergency surgery. We performed laparoscopic omentoplasty and collected #4d lymph nodes that were enlarged on CT. The pathological diagnosis was lymph node metastasis. Based on CT findings, we determined it was Bulky N. For initial management, we performed 3 preoperative chemotherapy(SOX therapy)courses and staging laparoscopy. On surgery, extensive disseminated nodules on the abdominal wall, stomach wall, and liver surface were found, and ascites cytology revealed positive findings. Therefore, we did not perform primary lesion resection. Although the disseminated nodule did not pathologically show tumor cells, CY1 was found, resulting to a diagnosis of unresectable gastric cancer. Since the tumor was HER2 3+, we initiated SOX/trastuzumab therapy. After 16 courses, staging laparoscopy was performed as the lymph nodes had shrunk significantly. The results showed no tumor cells in ascites and the disseminated nodules, and laparoscopic total gastrectomy was subsequently performed. Pathological findings showed no tumor cells in the primary lesion or lymph nodes; therefore, a diagnosis of pathological complete response was made. Currently, the patient is alive without recurrence for 6 months after surgery.

[A Case in Which the ICG Fluorography Was Useful for Detecting Minute Peritoneal Disseminations].

A 65-year-old man was emergently brought to our hospital because of rupture of 10 cm hepatocellular carcinoma(HCC) at left lobe in September 2019. He underwent selective transcatheter arterial embolization(TAE)for hemostasis. Enhanced computed tomography(CT)revealed one more 26 mm HCC at segment 8(S8)in addition to the ruptured HCC. Transcatheter arterial chemoembolization(TACE)was performed for both tumors. HCC at left lobe was resistant to TACE, hence we performed left hepatectomy. During the surgery we searched for peritoneal dissemination by using indocyanine green(ICG) fluorography and found 4 nodules with ICG accumulation in the omentum. All the nodules were pathologically diagnosed as peritoneal dissemination. We reported a case in which the ICG fluorography was very useful for detecting small peritoneal disseminations.

[A Case of Ileus Due to Colon Cancer with Non-Occlusive Mesenteric Ischemia].

Abdominal computed tomography(CT)revealed ileus due to sigmoid colon cancer in a 68-year-old man with abdominal pain, and endoscopic decompression using a transanal ileus tube was attempted. The blood test on the following day showed a marked increase in CRP 46.13mg/dL. Abdominal contrast CT was performed, and mesenteric ischemia was confirmed. Emergency surgery was performed on the same day. The ileum, and ascending, transverse, and descending colon appeared mottled and necrotic and were excised. A specialized diet started on the 5th postoperative day, and parenteral nutrition was used for a long period of time, due to the possibility of short bowel syndrome. The ileostomy and colostomy was closed 57 days after the operation. The patient finished parenteral nutrition on the 88th postoperative day without obvious nutritional absorption disorder and was discharged on the 94th postoperative day as oral intake only. We reported a case of ileus due to colon cancer with non-occlusive mesenteric ischemia(NOMI).

Low invasiveness of thoracoscopic esophagectomy in the prone position for esophageal cancer: a propensity score-matched comparison of operative approaches between thoracoscopic and open esophagectomy.

BACKGROUND: In this study, cytokine levels, outcome, and survival rates after esophagectomy for esophageal cancer were retrospectively investigated in a propensity score-matched comparison of operative approaches between the thoracoscopic esophagectomy (TE) in the prone position and open esophagectomy (OE). PATIENTS AND METHODS: Between 2005 and 2014, TE was performed on a group of 85 patients, which was compared with a group of 104 OE cases. Eventually, 65 paired cases were matched using propensity score matching. RESULTS: Although the TE group underwent a significantly longer operation time than the OE group (P < 0.001), the TE group exhibited less blood loss (P < 0.001) and had a shorter postoperative hospital stay (P = 0.038) than the OE group. The serum interleukin-6 levels on ICU admission (P < 0.001) and on POD 1 (P < 0.001) were significantly lower in the TE group. The interleukin-10 levels on ICU admission (P < 0.001), POD 1 (P = 0.016), and POD 3 (P < 0.001) were also significantly lower in the TE group. Pulmonary complication was significantly lower in the TE group (P = 0.043). The 5-year PFS rates in the TE and OE groups were 70.6 and 58.7% (P = 0.328), respectively, and OS rates were 64.9 and 50.2% (P = 0.101), respectively. CONCLUSION: TE compared to OE is a less invasive procedure with lower surgical stress and less pulmonary complication for the treatment of esophageal squamous cell carcinoma.

[Three Cases of Obstructive Left-Sided Colon Cancer Resected by Laparoscopic Surgery].

We report 3 cases of obstructive left-sided colon cancer that could be treated with laparoscopic resection.Case 1: A 25- year-old man was given a diagnosis of colonic obstruction due to transverse colon cancer.Twenty -four days after decompression by a nasointestinal tube, we performed a laparoscopic partial colectomy.Case 2: A 75-year-old woman was given a diagnosis of colonic obstruction due to sigmoid colon.Forty -nine days after decompression by a laparoscopic transverse colostomy, we performed a laparoscopic sigmoidectomy.Case 3: A 48-year-old man was given a diagnosis of colonic obstruction due to sigmoid colon cancer.Twenty -two days after decompression by colonic stent, we performed a laparoscopic sigmoidectomy.In these 3 cases, decompression was sufficient when resecting the primary lesions, and the operations could be completed laparoscopically.Elective radical surgery was possible by resolution of oncologic emergency state.

Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer.

Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin-eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four-point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin-eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune-enhancing effect. As such, the immune-related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.

miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.

Novel Indications for Surgical Resection of Metachronous Lung Metastases From Pancreatic Cancer After Curative Resection.

Few reports exist regarding surgical resection of metachronous lung metastases (MLM) from pancreatic ductal adenocarcinoma (PDA) after curative resection. To elucidate the indications for surgical resection of MLM and long-term survival, we analyzed Japanese case reports of MLM from PDA. Between 1983 and 2014, 17 Japanese case reports concerning surgical resection of MLM from PDA were published. We determined long-term survival in 16 patients (considering the published data of 15 patients and 1 of our own) by using a questionnaire survey and analyzing the relationships between background factors and long-term survival. In 16 patients with long-term survival, 4 patients were still alive without recurrence. The remaining 12 patients died of disease after recurrence. The median survival after the initial lobectomy was 37 months and the 3- and 5-year survival for all patients after lobectomy was 50% and 41%, respectively. Fourteen patients had a disease-free interval after initial resection of the primary pancreatic tumor of >20 months. These patients had a longer median survival period after lobectomy (46 vs. 25.5 mo, P=0.19). Seven patients had MLM of <16 mm. These patients had a statistically longer overall survival after lobectomy (83 vs. 16 mo, P=0.04). Three of 4 patients with primary stage I tumors were still alive without recurrence. We found that the conventional criteria for surgical resection of MLM from PDA (first disease-free interval of >20 mo with no other metastatic lesions) were appropriate. In addition, it is possible that MLM of <16 mm or primary stage I tumors are novel criteria.

[A Difficult Diagnostic Case of Pancreatic Acinar Cell Carcinoma].

The patient was a 46-year-old woman with left lower abdominal pain.Abdominal dynamic CT revealed a 40 mm, gradually- enhanced pancreatic head mass.The interior of the tumor was heterogeneous and partly low in density.Endoscopic ultrasonography showed a well-defined and heterogeneous tumor with an echoic area in the pancreatic head.Therefore, the cystic lesion with solid components was suspected to be a solid pseudopapillary neoplasm(SPN), considering the age of the patient.Subtotal stomach-preserving pancreaticoduodenectomy was performed.The postoperative course was uneventful, and she was discharged on the 13th day after surgery.Postoperative pathology confirmed a diagnosis of pancreatic acinar cell carcinoma.SPNs often show an image very similar to pancreatic acinar cell carcinoma and it is difficult to distinguish between the two only by imaging findings.Due to the divergence between clinical findings such as age and image findings, it was difficult to confirm a diagnosis of pancreatic acinar cell carcinoma in this case.

[A Case of Conversion Surgery for Unresectable Colorectal Liver Metastases, Following Effective Combined Chemotherapy with Molecular Targeting Agents].

A 50-year-old man with complaints of epigastralgia, pyrexia, and malaise was diagnosed with sigmoid colon cancer, descending colon cancer, and unresectable colorectal liver metastases. Because the prognosticator was liver metastases, he went through chemotherapy(biweekly CapeOX plus cetuximab)as soon as possible. After 6 courses of this regimen, multiple liver metastases were markedly reduced in size(partial response[PR]), resulting in conversion therapy with complete resection. Recently, some reports showed that patients who had R0 resection after conversion chemotherapy could expect favorable long-term prognosis. It is important to select the appropriate first-line chemotherapy and the timing of the conversion resection.

[Two Cases of Laparoscopic Simultaneous Resection for Synchronous Liver Metastasis of Colon Cancer].

We report 2 cases of laparoscopic simultaneous resection for synchronous liver metastasis of colon cancer. Case 1: A 76- year-old woman was diagnosed with advanced cecum cancer(type 3)with synchronous liver metastasis(segment 5: 23mm), Laparoscopic ileocecal resection and partial liver resection were performed for 414 minutes, with 20 mL of blood loss. The patient was discharged 11 days after the operation. Case 2: A 78-year-old woman was diagnosed with advanced sigmoid colon cancer(type 2)with synchronous liver metastasis(segment 2: 70mm). Laparoscopic sigmoidectomy and extrahepatic resection were performed for 382 minutes, with 10 mL of blood loss. Portal vein thrombus(umbilicus)was recognized but relieved with warfarin. The patient was discharged 15 days after the operation. Simultaneous laparoscopic colon and hepatectomy for synchronous liver metastasis of colorectal cancer can be safely performed for selected indications.

[A Case of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern].

A 56-year-old man with HCV infection was referred to our hospital for further evaluation and treatment of hepatic tumor. Abdominal enhanced computed tomography demonstrated an S8 hepatic tumor, about 15mm in maximal diameter. The tumor showed enhancement on the arterial phase and washout on equilibrium phase. EOB-MRI scan also showed the hepatic tumor with enhancement in the early phase and washout in the delayed phase. Liver function was normal. Serum AFP and PIVKA- II were normal and CEA and CA19-9 were elevated. However, no other tumor was detected by the colonoscopy, esophagogastroduodenoscopy and PET-CT. Under the diagnosis of HCC, partial hepatectomy was performed. Histologically, the tumor was composed of neoplastic glands with irregularly dilated lumen of adenocarcinoma, resembling ductal plate malformation(DPM). And Von Meyenburg complexes and foci of ordinary intrahepatic cholangiocarcinoma(ICC)were also found. ICC with this histologic features reported as a new subtype of ICCs.

Prediction of the efficacy of immunotherapy by measuring the integrity of cell-free DNA in plasma in colorectal cancer.

We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA-A*2402-restricted CTL in combination with oxaliplatin-containing chemotherapy (FXV study) as first-line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five-peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell-free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small-sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi-quantitative real-time PCR. Progression-free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA-A*2402-matched group, patients with a low plasma cfDNA integrity value had significantly better progression-free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA-A*2402-unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer.

Calreticulin is highly expressed in pancreatic cancer stem-like cells.

Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). A P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2-D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in the CRThigh /CD44v9low population was much higher than that in the CRTlow /CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.

Risk Factors and Managements of Bile Leakage After Hepatectomy.

BACKGROUND: The purpose of this study was to retrospectively determine the risk factors and evaluate the management of bile leakage. METHODS: Three hundred and thirty-four patients who underwent hepatectomy for Child classification grade A liver disease, without biliary reconstruction and laparoscopic procedures, between 2003 and 2013 were included. Risk factors were identified using multivariate analysis. RESULTS: Bile leakage was observed in 30 (9.0%) patients. Multivariate analysis demonstrated that type of hepatectomy (segmentectomy 1, medial sectionectomy, anterior sectionectomy, or central bisectionectomy) and operating time was independent risk factors for bile leakage. Among 30 patients with confirmed bile leakage, central type leakage that was in communication with the biliary tree occurred in 23 (76.7%) patients and peripheral type, which was not in communication with the biliary tree, in 7 (23.3%) patients. Ten patients were treated with only drainage. Endoscopic or percutaneous transhepatic procedures were performed in 15 cases with central type leakage. Ablation treatment using ethanol or minocycline was mainly performed for peripheral type leakage. Four cases with central type leakage had strictures of the right hepatic duct. Two of them were treated with ablation treatment, portal vein embolization, or fistulojejunostomy. Median duration from diagnosis to end of therapy was 77 days (11-323) in central type and 44 days (6-123) in peripheral type leakage, respectively. CONCLUSIONS: Complex hepatectomy and operating time are independent risk factors for postoperative bile leakage. Biliary exploration should be performed as soon as possible after diagnosis, because most bile leakage is the central type. Central type of bile leakage is sometimes refractory to therapy, needing various treatments and requiring a long time for recovery.

[A Case of Ascending Colon Cancer with Extensive Abdominal Wall Abscess].

A 51-year-old woman was seen in our hospital because an ascending colon tumor with extensive abdominal wall abscess was detected on computed tomography(CT). On the same day, we performed open drainage and laparoscopic assisted ileocolostomy. Postoperative day 35, we performed right hemicolectomy with abdominal wall resection and closure of the colostomy as a radical surgery. After surgery, we started(negative pressure wound therapy: NPWT)to the surgical wound site; hence, the abdominal wall defect could be healed without a musculocutaneous flap. Laparoscopic assisted open drainage, a two-stage operation, and NPWT are useful in a case of colon cancer with abdominal wall abscess.

[Long-Term Survival of a Patient with Recurrent Duodenal GIST Treated with Various Molecular Targeted Drugs and TAE - A Case Report].

The patient was 66-year-old woman with anemia. A 6 cm GIST was diagnosed in the fourth portion of the duodenum using abdominal CT. Duodenal-jejunal segmental resection was performed for the GIST. Four years after surgery, multiple liver metastatic recurrences ofGIST were diagnosed using abdominal CT. The metastatic tumor was treated with imatinib, but the treatment caused adverse events such as leukocytopenia(Grade 2)and anemia(Grade 3). The treatment continued for 41 months while reduced or discontinued during the administration period. Sunitinib was administered, but the treatment caused a reduced platelet count(Grade 3), anemia(Grade 2), and melena(Grade 3). The treatment continued for 12 months while reduced or discontinued during the administration period. Regorafenib was administered and continued for 9 months. Thereafter, trancecatheter arterial embolization(TAE)was performed 5 times. The patient is alive 8 years and 3 months after recurrence.

[Unresectable Stage IV Sigmoid Colon Cancer with Extended Resection for Primary Tumor - A Case Report].

A 65-year-old woman who was diagnosed with unresectable Stage IV sigmoid colon cancer underwent transverse colostomy with double orifices. Although KRAS gene mutation was observed, we could not administer bevacizumab because of the risk of bleeding from the primary tumor and peritumoral abscess. We started bi-weekly XELOX therapy but bloody bowel discharge continued. We planned extended resection of the primary tumor in order to control the bleeding and perforation. Sigmoidectomy, partial resection of the left ureter and small intestine, partial hysterectomy, bilateral salpingo-oophorectomy, and umbilical tumor resection were performed and the patient was discharged on the 10th day after surgery. After surgery, bloody bowel discharge disappeared and bevacizumab was administered in the 55th day. Extended resection for a primary tumor may contribute to bleeding control and broaden treatment options.

[Two Cases of Primary Hepatic Mucosa-Associated Lymphoid Tissue(MALT) Lymphoma].

Case 1: A 57-year-old woman with chronic hepatitis related to the hepatitis B virus was found to have a liver tumor on ultrasonography(US). Computed tomography(CT), magnetic resonance imaging(MRI), and angiography revealed 2 tumors in the liver. The patient underwent right anterior sectorectomy, and histopathologic analysis revealed mucosa-associated lymphoid tissue(MALT)lymphoma. Thirty months later, recurrence was confirmed using liver biopsy. CR was confirmed after radiation and chemotherapy, and the patient has survived. Case 2: A 71-year-old woman came to our hospital for rheumatism treatment. US, CT, and MRI revealed a tumor in the left lateral segment of the liver. The patient underwent laparoscopic partial liver resection and histopathologic analysis revealed MALT lymphoma. The patient has survived.

[A Case of Borderline Resectable Pancreatic Cancer Responding to Preoperative GEM plus Nab-PTX Combination Chemotherapy].

We report a case of borderline resectable(BR)pancreatic cancer, which was eligible for R0 resection following preoperative chemotherapy with GEM plus nab-PTX. A 77-year-old woman presented with brown urine and clay-colored stool. After further examination, she was diagnosed with obstructive jaundice due to pancreatic head cancer. Because the tumor was in contact with the region attached to the SMA nerve plexus, she was also diagnosed with BR-A pancreatic cancer. After 6 courses of preoperative GEM plus nab-PTX combination chemotherapy, she underwent subtotal stomach-preservingpancreaticoduodenectomy with SMV resection and right semicircular SMA nerve plexus dissection. In the histopathological diagnosis, malignant cells were observed at low levels in both the pancreatic parenchyma and duodenal mucosa. There were no findings of residual malignant cells in the wall of the SMV or in the nerve plexus around the SMA. Since the final diagnosis was pT3,(DU+), pN0, cM0, fStage III , we concluded that the R0 resection as complete. Histological therapeutic evaluation with the Evans classification concluded that the disease was Grade III . GEM plus nab-PTX combination chemotherapy could be considered for preoperative chemotherapy, which may allow R0 resection for BR pancreatic cancer.