Prognostic value of preoperative carcinoembryonic antigen and D-dimer concentrations in patients undergoing curative resection for colorectal cancer.

PURPOSE: Carcinoembryonic antigen (CEA) has limited value as a standalone predictor of the survival in patients with colorectal cancer (CRC). D-dimer (DD) is a predictor of the survival in patients with metastatic CRC. We aimed to predict the prognosis in patients undergoing curative resection for the treatment of CRC by integrating the evaluation of preoperative CEA and DD concentrations with the pathological classification for stage grouping (pStage). METHODS: The study enrolled 304 patients between 2007 and 2012. The Combination of DD and CEA Score (CDCS) awarded 1 point each for a CEA concentration of > 5.0 ng/ml and DD concentration of > 1.0 µg/ml. Patients were classified according to the total points: CDCS 2, increased DD and CEA concentrations; CDCS 1, increased concentration of either DD or CEA; CDCS 0, normal concentrations. RESULTS: The overall survival (OS) and relapse-free survival (RFS) were significantly lower in patients with CDCS 2 than in those with CDCS 1 or 0. The pStage and CDCS were not independent prognostic predictors of the OS but were predictors of the RFS. The C-index value of the combination of the pStage and CDCS was better than that of either alone for the OS and RFS. CONCLUSION: The combination of the pStage and CDCS accurately predicts relapse in patients with CRC.

[Two Cases of Stevens-Johnson Syndrome after Nivolumab Therapy for Gastric Cancer].

Case 1: A 51-year-old man with advanced gastric cancer and peritoneal metastasis was referred to our hospital. He received fourth-line chemotherapy with nivolumab, but it became PD. Next, he received S-1 plus docetaxel therapy as fifth- line therapy. After 2 courses of S-1 plus docetaxel, erythema and blisters appeared on his limbs, with erosions of the oral mucosa and penis. We diagnosed Stevens-Johnson syndrome(SJS)based on the clinical and pathological findings. He received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue the chemotherapy because of the SJS. Case 2: A 75-year-old woman with recurrence of peritoneally disseminated gastric cancer received third-line chemotherapy with nivolumab. After 1 course of nivolumab, erythema appeared on her body and limbs, with erosion of the lips and oral mucosa. We diagnosed SJS based on the clinical findings. She received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue chemotherapy because of the SJS. It should be noted that the onset of serious irAEs, such as SJS, might make continuous chemotherapy difficult.

[Outcome of Repeated Surgical Resections of Hepatic and Pulmonary Metastases from Colorectal Cancer].

Previous reports have demonstrated that repeated surgical resections of resectable hepatic and pulmonary metastases from colorectal cancer contribute to a better prognosis. We retrospectively assessed the outcomes of 19 patients with colorectal cancer who underwent repeated resections of hepatic and pulmonary metastases between February 2007 and February 2017. The median observation period was 69.9 months, and 26 liver and 27 lung resections were performed. The cumulative 5-year survival rates after resection of the last metastasis was 75.1% and the median disease-free survival after resection of the last metastasis was 34.7 months. Although 7 patients showed recurrence and 4 patients died, 7 patients exhibited long-term survival. Univariate analysis revealed that simultaneous liver and lung metastases were significantly predictor of poor prognosis(p=0.039). Progress of the patients in the present study were comparable to those in previous reports. Therefore, we propose that repeated surgical resection of hepatic and pulmonary metastasis from colorectal cancer could improve patient prognosis. Further studies should examine to identify more accurate prognostic factor with large series.

[Effect on Prognosis of Immune-Related Adverse Events after Nivolumab Treatment in Gastric Cancer].

BACKGROUND: The clinical efficacy of nivolumab has been shown as a third-line treatment for advanced gastric cancer; however, nivolumab sometimes causes immune-related adverse events(irAEs). We retrospectively examined the clinical features and influence on treatment in cases of irAEs after nivolumab treatment. METHOD: We retrospectively examined 43 patients who received nivolumab treatment at our institution between October 2017 and December 2019. RESULT: The incidence of irAEs was 23.2%(10/43), and Grade 3 or higher irAEs included interstitial pneumonia, hypoadrenalism, Stevens- Johnson syndrome(SJS), and type 1 diabetes. Three patients showed long-term disease control after irAE onset. Meanwhile, SJS prevented patients from continuing treatment for gastric cancer. DISCUSSION: Nivolumab is effective in some patients with gastric cancer, while irAEs made subsequent treatment difficult. Trifluridine/tipiracil or irinotecan are also known to be effective as therapeutic drugs after third-line treatment for gastric cancer in addition to nivolumab; therefore, the choice of the third-line drug and management of irAEs owing to individual cases are considered desirable. CONCLUSION: Long-term efficacy is expected with nivolumab, but it may be necessary to recognize that the onset of serious irAEs might make subsequent treatment difficult.

[Total Pelvic Exenteration and Perineal Reconstruction with a Gracilis Myocutaneous Flap for Local Recurrence of Rectal Cancer].

The case involved a female in her 70s. Six years prior, she had undergone an abdominoperineal rectal resection for rectal cancer. Local recurrence was observed during follow-up so preoperative chemoradiotherapy was performed to shrink the tumor, followed by a total pelvic exenteration, bilateral ureterocutaneous fistula, and perineal reconstruction with a gracilis myocutaneous flap. She was discharged from hospital 39 days following surgery with no major complications. We herein report on a case of a good postoperative course due to surgery including a total pelvic exenteration and perineal reconstruction with a gracilis myocutaneous flap for postoperative local recurrence.

[Simultaneous Distal Gastrectomy, Distal Pancreatectomy, and Splenectomy Based on Remnant Gastric Blood-Flow Evaluation with Intraoperative ICG Fluorescence].

The splenic artery and vein are important to the remnant stomach after distal gastrectomy(DG). Hence, total gastrectomy is recommended when performing gastrectomy and distal pancreatectomy(DP)with splenectomy(S). In the present case, a man in his 70s was diagnosed with early gastric cancer. Abdominal CT detected a dilated main pancreatic duct. Chronic pancreatitis was suspected, but malignancy could not be completely ruled out. Thus, DG with Roux-en-Y reconstruction and DP with S were performed simultaneously. The remnant gastric blood flow was evaluated with intraoperative indocyanine green(ICG)fluorography and the blood flow was confirmed. Finally, the remnant stomach was preserved. The postoperative course was uneventful, except for the occurrence of anastomosis edema. This result suggests that ICG fluorescence is useful to evaluate remnant gastric blood flow and that it may be possible to perform DG and DP with S simultaneously depending on the case.

[A Case of Gastric Cancer with Continued Progression-Free Survival Even after Total Gastrectomy and Nivolumab Therapy].

This is a first report of gastrectomy after nivolumab immunotherapy. We describe a case in an elderly woman with gastric cancer diagnosed with cT4bN3M1(LYM), cStage ⅣB disease. Although she was administered 2 courses of SOX chemotherapy as the primary treatment, she could not continue the treatment to due to bone marrowsuppression. The second-line treatment was weekly PTX therapy, but she experienced Grade 3 neutropenia and thrombocytopenia in the first course and could not continue treatment. Nivolumab as the next treatment was effective but was discontinued for suspected druginduced pneumonia. During that time, tumor hemorrhage occurred and we performed total gastrectomy. Postoperatively, nivolumab chemotherapy was resumed. There were no adverse events and the patient has had a continued partial response for 30 courses. Gastrectomy was necessary in this case, allowing observation of the pathological findings of this highly effective case.

[Microsatellite Instability in Gastric Cancer].

INTRODUCTION: Pembrolizumab and nivolumab are anti-programmed death receptor-1(PD-1)antibodies. The use of pembrolizumab for unresectable or metastatic cancer with microsatellite instability-high(MSI-High)has been recently approved. However, there were few clinical reports on MSI in gastric cancer. MATERIALS AND METHODS: We examined the clinicopathological features and MSI for 37 patients who underwent chemotherapy for unresectable gastric cancer in January 2019. RESULTS: MSI-High was observed in 3 patients(8.1%). Among the MSI-High patients, there was a tendency towards older age, female sex, undifferentiated type, distal-located lesions and lymphatic vessel invasions, but the differences were not significant. Eleven patients underwent chemotherapy with nivolumab, 4 of them had partial response(PR). Three out of the 4 patients (75%)were MSI-High. CONCLUSIONS: These results suggested that anti-PD-1 antibody could be effective as a secondary treatment for unresectable or metastatic gastric cancer among MSI-High patients.

[A Case of Duodenal Invasive Advanced Gastric Cancer in Which the Primary Tumor Achieved pCR, but Viable Cancer Cells Remained in Lymph Node No.13 after Neoadjuvant Chemotherapy].

A woman approximately 70-years-old with duodenal invasive advanced gastric cancer was referred to our hospital. Meta- stasis to lymph node(LN)No.13 was suspected based on FDG/PET-CT. For better curability, we selected neoadjuvant chemotherapy( NAC)with S-1 plus oxaliplatin(SOX therapy). After 3 courses of SOX, distal gastrectomy with D2(+No.13) lymphadenectomy was performed. Upon pathological evaluation, no viable cancer cells were found in the primary tumor, but viable cancer cells were identified in LN No.6 and 13. LN No.13 was defined as M1 according to the current Japanese classification of gastric carcinoma. On the other hand, the 2014 Japanese gastric cancer treatment guidelines(ver. 4)mentioned that D2(+No.13)lymphadenectomy may be an option in potentially curative gastrectomy for tumors invading the duodenum. This case suggests that No.13 lymphadenectomy is necessary as a curative operation for duodenal invasive advanced gastric cancer, even if the primary tumor has achieved pCR after NAC.

[Clinical Outcome of Hepatectomy of Liver Metastasis of Duodenal Ampullary Cancer].

We evaluated the clinical outcome and assessed the indication of hepatectomy for liver metastasis of duodenal ampullary cancer. We analyzed 42 cases of duodenal ampullary cancer and 4 patients who underwent hepatectomy for liver metastasis. Eleven(50%)of 22 cases with recurrence of duodenal ampullary cancer had liver metastasis. Four cases were solitary and 7 cases were multiple. Four patients underwent hepatectomy didn't had other organ metastasis. Three of 4 cases with solitary liver metastases and one of 7 cases with multiple metastasis underwent hepatectomy. One of 3 cases of solitary liver metastasis died of lung and bone metastases without liver recurrence 2 years and 8 months after hepatectomy. Other 2 cases are long surviving without recurrence 8 years and 8 months and 4 years and 9 months after hepatectomy respectively. One case of multiple liver metastases died of early liver recurrence 10 months after hepatectomy. The indication of hepatectomy for liver metastasis was restrictive. However the prognosis of patients with solitary liver metastasis was relatively favorable. Therefore hepatectomy could be indicated for solitary liver metastasis of duodenal ampullary cancer.

[A Case of Anaplastic Carcinoma Spindle Cell Type of the Pancreas].

Anaplastic carcinoma spindle cell type is an extremely rare disease and its prognosis is very poor. We herein report a case of anaplastic carcinoma spindle cell type of the pancreas. A 50-year-old man complaining of epigastralgia was found to have a pancreatic body-tail tumor by abdominal US and CT studies. Abdominal CT showed an irregular poorly-enhanced 33mm tumor containing a cystic component. ERCP revealed the main pancreatic duct was cut off at the tumor. Cytology of the pancreatic fluids did not indicate malignancy. A pancreatic tumor with a cystic component similar to pancreatic neoplasms containing cystic degeneration or a mass-forming pancreatitis concomitant with pancreatic pseudocyst was suspected. Therefore, we performed distal pancreatectomy. Histological findings showed the center of the tumor was severely necrotized and oval or spindle dysplastic cells proliferated around the peripheral area. According to the immunohistological staining pattern, the patient was diagnosed as having anaplastic carcinoma spindle cell type. He was administered oral S-1 for 6 months and is now recurrence-free, surviving for 15 months after pancreatectomy. Reports of long-term survival cases that also demonstrated R0 resection should be indicated in the treatment of anaplastic carcinoma spindle cell type despite the poor prognosis.

[A Case of Mixed Hepatocellular and Primary Hepatic Neuroendocrine Carcinomas with Remnant Liver Recurrence and Rapid Exacerbation].

The patient was a 77-year-old man with a 4.0 cm hepatictumor in hepaticsegment 4. Plain computed tomography(CT) showed the tumor with low density. On dynamicexamination, the tumor showed heterogeneous enhancement during the arterial phase. Magneticresonanc e imaging showed the tumor as a low intensity area in the hepatobiliary phase in hepatic segments 4, 6, and 8. A month later, CT showed an enlarged tumor in segment 4 measuring 7.0 cm. We diagnosed the tumor as primary liver cancer and suspected it to be hepatocellular carcinoma(HCC)preoperatively. We performed extended medial segmentectomy and partial hepatectomy of segment 6. The histopathological diagnosis was mixed HCC and primary hepatic neuroendocrine carcinoma(PHNEC). Three months after hepatectomy, the patient died of multiple intrahepatic recurrences. In most of the reported cases of mixed HCC and PHNEC, only the PHNEC component has been detected in the biopsy of the metastatic lesions. This fact might suggest that PHNEC has a higher proliferative activity and malignant potential than HCC. Standard treatment for mixed HCC and PHNEC is unclear; therefore, development of multidisciplinary treatment strategies combining surgical treatment and systemic chemotherapy is required.

[A Rare Case of Abdominal Malignant Triton Tumor].

A 60-year-old woman presented at our hospital with abdominal pain and vomiting.Three abdominal tumors were detected, and she was referred to our department for surgery.She underwent an enterectomy including 2 of the tumors.The third tumor could not be resected because it had invaded the superior mesenteric artery(SMA)and superior mesenteric vein(SMV). Based on positive immunohistochemistry results for S-100 protein and desmin, nerve sheath differentiation with rhabdomyoblastic differentiation was confirmed, and she was diagnosed with a malignant triton tumor(MTT).She received postoperative chemotherapy with adriamycin and dacarbazine.However, she died 7 months after surgery, with multiple peritoneal metastases.MTT is a subtype of malignant peripheral nerve sheath tumor and is very rare.MTT has a poor prognosis with a high tendency of local recurrence and early metastasis.The most common treatment strategy is radical resection followed by postoperative chemoradiotherapy.When preoperative diagnosis is possible, radical resection with clear margins should be performed.

Baseline disease is a more important predictor of intestinal necrosis than CT findings in patients with acute mesenteric ischemia.

OBJECTIVE: Acute mesenteric ischemia (AMI) is a potentially fatal vascular emergency, and several computed tomographic (CT) findings have been introduced to determine the presence of intestinal ischemia or necrosis, although the most useful finding is unknown. METHODS: We retrospectively analyzed data of 43 consecutive patients with AMI who were treated during the period from 2006 to 2015. Study patients included both superior mesenteric artery dissection (n = 29) and thrombosis (SMAT, n = 14). Epidemiological data, CT findings, and the primary end point defined as the composite of intestinal ischemia or necrosis based on surgical finding and in-hospital mortality were investigated. The classification and regression tree was used to assess determinants of the primary end point, and area under the curve of receiver operating characteristics was used to evaluate discriminating accuracy. RESULTS: In total, the primary end point occurred in 27.9% (0.0% in superior mesenteric artery dissection and 85.7% in SMAT). Classification and regression tree demonstrated that the baseline disease was the only and strong determinant of the primary outcome (P< .001), which was also confirmed by the highest area under the curve of 0.968 (95% confidence interval, 0.924-1.000). CONCLUSIONS: The baseline disease rather than CT findings is the most important determinant of the primary end point. In patients with AMI, SMAT should undergo exploratory surgery and subsequent surgical treatment without delay.

[A Case of Malignant Obstruction of the Colon Due to Peritoneal Dissemination of Gastric Carcinoma Treated with Colon Stenting and Colectomy after Chemotherapy].

A man in his 60s underwent gastrectomy to treat gastric carcinoma. Approximately 2.5 years after the surgery, he was admitted to the hospital because of abdominal pain. He was diagnosed with obstruction of the transverse colon due to a colon tumor. A stent was placed to treat the obstruction and avoid oncologic emergency. Biopsy results and imaging showed that the patient did not have colon cancer, but his previous gastric cancer had disseminated peritoneally. Chemotherapy was selected as treatment for recurrent gastric cancer. After chemotherapy, the patient underwent colectomy with removal of the stent. His postoperative course was good, and he was discharged from hospital without complications. The patient received additional chemotherapy. We encountered a case of colon obstruction due to peritoneal dissemination of gastric cancer that was successfully treated using a metallic colorectal stent. Colon stenting for malignant bowel obstruction is useful to avoid oncologic emergencies. However, there is no evidence at this time that long-term placement of a stent is safe. The decision to remove or retain the stent should be made upon carefully considering the condition of the patient and progression of the disease.

[A Case of Locally Advanced Pancreatic Cancer Showing R0 Resection after Resection of the Portal Vein Following Preoperative Chemoradiotherapy].

We report a case of pancreatic cancer showing R0 resection after resection of the portal vein(PV)following preoperative chemoradiotherapy. A 71-year-old woman was admitted to our hospital with back pain. We diagnosed the patient with pancreatic cancer using computed tomography scan and fine-needle aspiration biopsy. Because the tumor directly invaded the PV, we diagnosed it as a borderline resectable locally advanced pancreatic cancer. Radiation therapy(40 Gy/20 Fr)was administered with S-1 monotherapy(120 mg/body/day on days 1-5 and days 8-12). After the treatment, the main tumor was stable without distant metastasis. Therefore, we performed pancreaticoduodenectomy with resection of the PV. Pathological examination confirmed negative margin status. The patient was healthy and showed no sign of recurrence eight months after surgery.

[Assessment of Endoscopic Resection and Partial Duodenectomy for Duodenal Mucosal Tumor].

INTRODUCTION: The risk of perforation following endoscopic resection is high. We analyzed the outcome of partial duodenectomy and discussed the therapeutic strategy for duodenal mucosal tumor(DMT). PATIENTS AND METHODS: We analyzed 19 cases who have undergone endoscopic resection, and 11 cases who have undergone partial duodenectomy for DMT in our institute since 2007. We divided them into the first period(ESD actively indicated)and late period(ESD carefully indicated according to the alteration of indication of ESD for DMT in 2013)groups. RESULTS: In the first period, all 17 cases initially underwent endoscopic resection and 4 cases were complicated by perforation. On the other hand, in the late period, 6 of 12 cases initially underwent endoscopic resection and 1 case was complicated by perforation. Emergent partial duodenectomy was performed with additional resection in the perforation cases. There were no complications associated with surgery, and all 29 cases achieved curative resection, based on the histology results. CONCLUSION: We can safely indicate endoscopic resection for DMT with surgical back-up and cooperation with the endoscopic internal department.

[Two Cases of Locally Recurrent Rectal Cancer after Intersphincteric Resection That Were Controlled with a Combination of Chemoradiotherapy and Abdominoperineal Resection].

We report 2 cases of locally recurrent rectal cancer after intersphincteric resection(ISR)that were controlled with a combination of chemoradiotherapy and abdominoperineal resection(APR). In Case 1, we performed preoperative chemoradiotherapy( TS-1 plus RT 45 Gy)and APR for the local recurrence of ISR. On pathology, viable neoplastic cells were noted. In Case 2, we performed preoperative chemotherapy(Bmab plus mFOLFOX6)and APR for the local recurrence of ISR. On pathology, no viable neoplastic cells were noted. However, a local recurrence developed again 3 months later. Therefore, we performed chemoradiotherapy(TS-1 plus RT 53 Gy). The 2 patients survived without recurrence until now. Their pathology tissues and clinical courses showed that control of local recurrence with only chemoradiotherapy or surgical resection was likely to be difficult. We might be able to improve the prognosis of patients with a combination of chemoradiotherapy and surgical resection.

[A Long-Surviving Case of Unresectable Gall Bladder Carcinoma Treated with Gemcitabine-Based Chemotherapy].

We report a 5-year surviving patient with unresectable gall bladder carcinoma treated with gemcitabine(GEM)-based chemotherapy. A 64-year-old man was diagnosed with unresectable gall bladder carcinoma with peritoneal dissemination based on laparotomy findings. Two months later, he started to receive GEM chemotherapy. Twelve months after surgery, the patient chose to suspend GEM treatment. One year and 10 months later, multiple lung metastases appeared and GEM was restarted in combination with UFT. Although the primary lesion and lung metastases gradually progressed, the patient maintained a good quality of life. After 3 years and 2 months, chemotherapy was changed to GEM plus S-1 because of progressive disease. Five years and 2 months after surgery, his condition was complicated by a secondary pneumothorax, and the patient received home oxygen therapy. Five years and 8 months after surgery he died of respiratory distress caused by the progression of lung metastases. Even in the case of unresectable advanced gall bladder carcinoma, effective chemotherapy could improve quality of life and prolong survival.

[Report of a Case of Long-Term Survival with Mulitidisciplinary Therapy for a Patient with Multiple Liver Metastases from Rectal Cancer].

Multidisciplinary therapy is necessary to prevent recurrence of advanced rectal cancer and advanced cancer with metastases. Here we report a case of long-term survival of a patient with advanced rectal cancer with multiple liver metastases. An 80's woman had previously undergone both Hartmann's operation and a partial hepatectomy for advanced rectal cancer with multiple liver metastases. A year after chemotherapy, a CT scan revealed multiple liver metastases. Thus, we performed partial liver resection. After another round of chemotherapy, a CT scan revealed lung metastases and local recurrence of the rectal cancer; therefore, we performed partial lung resection and a Miles operation. These procedures were conducted 4 years after her first operation. The following year, PET-CT revealed a mediastinum lymph node metastasis; consequently, we performed radiation therapy. New lung metastases and local recurrences of rectal cancer were identified after the radiation therapy; thus, we resumed the therapy, including a molecular targeting drug. Although the patient is in a tumor-bearing state, she is still alive 10 years after her first operation.