[Three Cases of Conversion Surgery for Unresectable Advanced Gallbladder Cancer with Distant Metastasis Treated with Gemcitabine plus CDDP].

All three patients were female, one in her 50s, and the other two in their 60s. The one in her 50s had liver metastasis and the other two had unresectable advanced cholecystic carcinomas with peritoneal dissemination. All three received 8-12 courses of gemcitabine plus CDDP(GC). After GC, all three were deemed to be candidates for R0 resection and underwent resection of two central liver segments. In addition, the second patient required an extrahepatic cholangiectomy; an extended cholecystectomy, plus an extrahepatic cholangiectomy, plus a complete omental resection; and the third needed an extended cholecystectomy, plus an extrahepatic cholangiectomy with a partial transverse colon resection, plus a partial duodenectomy. The pathologic response to chemotherapy was moderate in the patient with liver metastases, mild in the one who underwent the omental resection, and moderate in the patient who had the partial resection of the digestive tract. All three patients continued with postoperative chemotherapy. The patient with liver metastases and the one with the partial gastrointestinal tract resection have survived without recurrence for 52 months and 43 months, respectively, after the initial treatment. The patient with the omental resection has survived 44 months after the initial treatment with recurrent peritoneal dissemination and is continuing chemotherapy as an outpatient. Although further study is needed to accumulate more cases, the results suggest the usefulness of multidisciplinary treatment including conversion surgery in cases such as these.

[A Case of Stage â £ Gastric Cancer Treated with Conversion Surgery after Chemotherapy].

A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric stenosis. Although open gastrectomy was planned the gastric cancer was unresectable due to pancreatic invasion and peritoneal dissemination. Cytology with abdominal lavage was CY0. She underwent gastrojejunostomy. She was treated by 19 courses of chemotherapy with SOX therapy for 2 years. The tumor reduced, and she underwent distal gastrectomy as conversion surgery. Pathological findings were por2>muc>tub2>tub1, ypT2(ypMP), INF c, int, Ly1a, V0, pPM0, pDM0, pN0(0/43), ypStage ⅠB, R0, Grade 2b. Adjuvant chemotherapy(S-1 and docetaxel)was administered after conversion surgery. She is alive without recurrence for 1 year and 6 months after gastrectomy. We report a case of Stage Ⅳ gastric cancer treated with conversion surgery after chemotherapy.

[Gallbladder Cancer with Multiple Liver Metastases Completely Responding to Gemcitabile plus Cisplatin Chemotherapy-A Case Report].

A 59-year-old man was diagnosed with cholecystolithiasis and cholecystitis and underwent cholecystectomy. The pathological findings were moderately differentiated adenocarcinoma(pT2)in the gallbladder fundus. Sixteen days after surgery, he visited our hospital due to jaundice. Abdominal enhanced CT and EOB-MRI revealed multiple liver metastases and lymph node metastases in the hepatoduodenal ligament that we deemed to be unresectable. A metallic stent was inserted for bile duct obstruction, and he underwent chemotherapy with gemcitabine plus cisplatin(GC). After 12 courses of GC, the metastatic lesions disappeared, and the patient showed complete response. FDG-PET/CT showed FDG uptake in the hepatoduodenal ligament and we subsequently decided to perform surgery. He underwent resection of the extrahepatic bile duct and regional lymphadenectomy. The pathological findings revealed no residual carcinomas in the bile duct or lymph nodes. We are continuing chemotherapy at present, and the patient is alive with no signs of recurrence at 1 year and 3 months following the diagnosis of multiple liver metastases.

[A Case of Liver Recurrence of Choriocarcinoma and AFP-Producing Carcinoma of the Stomach Showing a Complete Histological Response after Chemotherapy].

A 65-year-old man was hospitalized for gastric cancer. Abdominal computed tomography detected lower gastric cancer and invasion of the liver. Initial laboratory data showed high levels of serum AFP(2,688.6 ng/mL). He underwent distal gastrectomy with left lobectomy of the liver and cholecystectomy. Histology confirmed that the tumor consisted of 2 components: primary gastric choriocarcinoma and AFP-producing carcinoma. The pathological staging was pT4b(liver), N3aM0, Stage ⅢC. After surgery, AFP levels decreased to within the normal limits. Adjuvant chemotherapy(S-1)was administered for 1 year after the operation. Fourteen months later, PET-CT and EOB-MRI detected liver recurrence. He was treated with weekly paclitaxel(PTX)chemotherapy for the liver recurrence. After 12 courses, the tumor had disappeared. The patient was continuously treated with weekly PTX and is doing well without recurrence 24 months after the resection of the liver tumor. Co-existence of primary gastric choriocarcinoma and AFP-producing carcinoma is very rare. We report a case of liver recurrence of choriocarcinoma and AFP-producing carcinoma of the stomach showing a complete histological response after chemotherapy.

[A Case of Multiple Lymph Node Metastases Treated with Nivolumab after an Adrenalectomy for Solitary Adrenal Metastasis of Gastric Cancer after a Gastrectomy].

A 69-year-old man was hospitalized for gastric cancer. He underwent total gastrectomy with distal pancreatectomy, splenectomy, and cholecystectomy. Pathological staging was pT3N3aM0 and Stage ⅢB. Adjuvant chemotherapy(S-1)was administered postoperatively. Ten months later, left adrenal metastasis was detected on computed tomography(CT)scans. He was then treated with 4 courses of chemotherapy with SOX therapy and 2 courses of PTX plus RAM therapy for the left adrenal metastasis. However, the tumor size increased. He underwent adrenalectomy with left nephrectomy and partial resection of the transverse colon for the solitary adrenal metastasis. His pathological diagnosis was metastatic carcinoma of the left adrenal gland and lymph nodes, which invaded the left renal vein and originated from gastric carcinoma. Three months after the adrenalectomy, CT scans identified paraaortic, porta hepatis, and left supraclavicular lymph node metastases. The patient was continuously treated with nivolumab, for 20 courses, and is doing well with good PS. Adrenalectomy for solitary adrenal metastasis of gastric cancer very rarely occurs. We report a case of multiple lymph node metastases treated with nivolumab after an adrenalectomy for solitary adrenal metastasis of gastric cancer after a gastrectomy.

[Successful Treatment of Necrotizing Fasciitis Due to Ascending Colon Cancer-A Case Report].

A 70-year-old woman was brought to our hospital by ambulance because of severe groin pain on the right side. Computed tomography scan revealed a tumor in the ascending colon, intraperitoneal abscess spread to the subcutaneous tissues, and a large amount of pneumoderma. She was diagnosed with necrotizing fasciitis caused by penetration of ascending colon cancer and underwent lavage and drainage, right hemicolectomy, end ileostomy, and debridement of necrotic tissues on emergency. Postoperatively, she underwent debridement and irrigation at the bedside every day, but the necrotizing tissues spread. Debridement under general anesthesia was repeated on postoperative day 8. On postoperative day 20, negative pressure wound therapy(NPWT)was initiated to manage the exudates and wound condition, and healthy granulation tissues formed gradually. After 4 weeks, she underwent split-thickness skin graft implantation. The postoperative course was uneventful, and she was discharged from the hospital. She is currently on chemotherapy and has been alive for 1 year and 3 months after the first operation.

Living donor liver transplantation in a pediatric patient with preexisting yolk sac tumor.

There is ongoing discussion regarding the indications and timing of LT for patients with a preexisting extrahepatic malignancy. We herein report a pediatric case that underwent LDLT after therapy for YST. The patient, a 13-year-old female with biliary atresia, had undergone portoenterostomy at 2 months of age. She developed a left ovarian tumor with a high serum alpha-fetoprotein concentration at 10 years of age. She underwent left oophorectomy and was diagnosed with ovarian YST (Stage I). After surgery, hepatopulmonary syndrome progressed gradually. She was examined carefully and exhibited no findings to suggest the recurrence of YST. We decided to perform LDLT at 3 years and 6 months of age after the surgery for YST. The patient is currently alive and doing well without recurrence of YST at approximately 2 years after transplantation. There is no significant difference between the recurrence rate of preexisting extrahepatic malignancy and the incidence of de novo malignancy if specific cases are selected. The indications and period from surgery for preexisting extrahepatic malignancy to LT should thus be determined according to the type and stage of cancer.

[Cystic Duct Cancer with Postoperative Liver Metastasis That Achieved Complete Response after Gemcitabine Treatment - A Case Report].

A 72-year-old woman was diagnosed with gallbladder cancer and underwent extended cholecystectomy and extrahepatic bile duct resection. The pathological findings were CGnBdGb, circ, nodular infiltrating type, 20×10 mm, tub2, pT3b, int, INF c, ly1, v1, ne3, pN0, pDM0, pHM0, pEM0, pPV0, pA0, R0, Stage III A. Because the main localization was in the cystic duct, we diagnosed this as cystic duct cancer. Seven months after surgery, follow-up computed tomography scan revealed a metastatic region in segment 7 of the liver. She underwent chemotherapy with gemcitabine(GEM). After 3 courses of GEM, the metastatic lesion became obscure. After 8 courses, the metastatic lesion disappeared, and the patient showed complete response. We discontinued chemotherapy after 21courses of GEM, and the patient is alive with no signs of recurrence 4 years and 4 months after surgery.

[A Case of Disseminated Peritoneal Leiomyomatosis with Several Recurrences].

A 60's woman had undergone abdominal total hysterectomy due to uterine leiomyoma 17 years previously. She underwent resection of multiple intra-abdominal tumors 9 years previously, and was diagnosed with disseminated peritoneal leiomyomatosis. Because of several recurrences, she was referred to our hospital and treated with GnRH agonist therapy. However, the tumors enlarged gradually and she underwent further resection for multiple intra-abdominal tumors. After surgery, we performed several operations. This is an extremely rare disease and we present this case with a discussion of the literature.

FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma.

UNLABELLED: The response rate to sorafenib in hepatocellular carcinoma (HCC) is relatively low (0.7%-3%), however, rapid and drastic tumor regression is occasionally observed. The molecular backgrounds and clinico-pathological features of these responders remain largely unclear. We analyzed the clinical and molecular backgrounds of 13 responders to sorafenib with significant tumor shrinkage in a retrospective study. A comparative genomic hybridization analysis using one frozen HCC sample from a responder demonstrated that the 11q13 region, a rare amplicon in HCC including the loci for FGF3 and FGF4, was highly amplified. A real-time polymerase chain reaction-based copy number assay revealed that FGF3/FGF4 amplification was observed in three of the 10 HCC samples from responders in which DNA was evaluable, whereas amplification was not observed in 38 patients with stable or progressive disease (P = 0.006). Fluorescence in situ hybridization analysis confirmed FGF3 amplification. In addition, the clinico-pathological features showed that multiple lung metastases (5/13, P = 0.006) and a poorly differentiated histological type (5/13, P = 0.13) were frequently observed in responders. A growth inhibitory assay showed that only one FGF3/FGF4-amplified and three FGFR2-amplified cancer cell lines exhibited hypersensitivity to sorafenib in vitro. Finally, an in vivo study revealed that treatment with a low dose of sorafenib was partially effective for stably and exogenously expressed FGF4 tumors, while being less effective in tumors expressing EGFP or FGF3. CONCLUSION: FGF3/FGF4 amplification was observed in around 2% of HCCs. Although the sample size was relatively small, FGF3/FGF4 amplification, a poorly differentiated histological type, and multiple lung metastases were frequently observed in responders to sorafenib. Our findings may provide a novel insight into the molecular background of HCC and sorafenib responders, warranting further prospective biomarker studies.

Evaluation of the usefulness of the indocyanine green clearance test for chemotherapy-associated liver injury in patients with colorectal cancer liver metastasis.

BACKGROUND: The indocyanine green (ICG) clearance test is reported to be useful for the preoperative evaluation of hepatic functional reserve. However, the ICG clearance test has not been sufficiently investigated in patients with colorectal liver metastasis after chemotherapy. The aim of the present study was to evaluate whether the ICG clearance test is a useful parameter for the preoperative detection of chemotherapy-associated liver injury. METHODS: Ninety-four patients undergoing liver resection for colorectal liver metastasis after chemotherapy were studied. The medical records for each case were retrospectively reviewed. They underwent pathological assessment to clarify the degree of histopathological liver injury of the nontumoral liver parenchyma. In addition, the correlation between the pathological score and the ICG retention rate at 15 min (ICG-R15) was analyzed. RESULTS: Sinusoidal injury was observed in the 31 of 94 patients. Steatohepatitis was observed in the 40 of 94 patients. There was no strong correlation between the preoperative ICG-R15 value and the sinusoidal pathological score (r = 0.117, P = 0.261). There was no strong correlation between the ICG-R15 and the nonalcoholic fatty liver disease activity score (r = 0.215, P = 0.037). CONCLUSIONS: It was difficult to predict the degree of chemotherapy-associated liver injury by the preoperative ICG-R15 value. It is necessary to estimate the hepatic functional reserve based on a combination of several clinical indicators without relying on the ICG test, in order to perform a safe radical liver resection.

[A case of metastatic liver tumor arising from gastric cancer resected after second-line chemotherapy].

A man in his 60s was diagnosed with gastric cancer and underwent distal gastrectomy and D2 lymph node dissection. The histological diagnosis was adenocarcinoma (T3, N1, StageIIB). He was treated with S-1 as adjuvant chemotherapy for 1 year. One year and 2 months after gastrectomy, a computed tomography (CT) scan revealed liver metastasis (S8, 38 mm). The patient was diagnosed with liver metastasis(refractory to S-1), and administered combination chemotherapy with irinotecan and cisplatin. After 4 courses of treatment, a CT scan detected a progressive liver tumor (55 mm). Combination chemotherapy with docetaxel and S-1 was selected as second-line chemotherapy. After 6 courses of treatment, the tumor size reduced to 40 mm in diameter, and no other metastasis was detected. Nine months after the diagnosis of liver metastasis, partial resection of the liver (S8) was performed. A pathological diagnosis of metastatic adenocarcinoma was determined, and the pathological therapeutic effect was rated as Grade 1b. Combination chemotherapy with docetaxel and S-1 was found to be effective, and was thus administrated after the operation. There have been no signs of recurrence for 6 months after the operation. Surgery with perioperative chemotherapy can be an effective treatment for liver metastasis from gastric cancer.

[A case of surgical resection of a combined hepatocellular and cholangiocarcinoma after transarterial chemoembolization].

A 48-year-old woman was admitted to our hospital for the treatment of a liver tumor (diameter, 10 cm), which was detected by abdominal contrast-enhanced computed tomography. The tumor occupied mainly the left medial segment and caudate lobe, invaded the left and right hepatic arteries, and obstructed the left portal vein. The tumor was diagnosed as an unresectable intrahepatic cholangiocarcinoma, and chemotherapy (a combination of gemcitabine and S-1) was initiated. Because the tumor continued to grow despite the chemotherapy, we performed transarterial chemoembolization(TACE)as a second-line treatment, which successfully reduced tumor size to 7 cm. Thereafter, surgical resection was performed. Histopathological examination indicated the presence of intrahepatic cholangiocarcinoma, which formed the main component, combined with hepatocellular carcinoma. This tumor was diagnosed as a combined hepatocellular and cholangiocarcinoma. Although adjuvant chemotherapy was not administered because of prolonged pancytopenia, currently, at 5 years after the operation, the patient is alive and has not experienced any recurrence.

[Study of unresectable pancreatic cancer - successful resections after gemcitabine-based chemotherapy].

Pancreatic ductal adenocarcinoma( PDAC) is an extremely malignant tumor and carries a poor prognosis. Therefore, PDAC should be treated with multiple modalities. Chemotherapy has proven effective in some cases of unresectable (UR) PDAC, and there are published reports of cases in which curative surgery could be performed after chemotherapy. We examined the cases from January 2010 through November 2012 in which initially UR PDAC could be treated surgically after chemotherapy. Whether or not each cancer was resectable was evaluated according to the National Comprehensive Cancer Network (NCCN) guidelines. We performed surgery in 7 of the 25 patients initially diagnosed as UR during this period. The cancer proved inoperable in 2 of these 7 patients: 1 patient with peritoneal dissemination and 1 with locally advanced tumor. Some reports have suggested that resection after chemotherapy for UR pancreatic cancer improved the prognosis in patients relative to those in whom surgery was not attempted. From our experience, we believe that it very important for patients undergoing chemotherapy for UR pancreatic cancer to consider surgical treatment.

[A case of unresectable biliary tract cancer with liver metastasis that exhibited an effective response to chemotherapy].

Surgical resection is the only curative treatment for biliary tract cancer; however, it is only feasible if the cancer is detected at an early stage. Since early diagnoses are difficult, most patients are diagnosed when the cancer is at an unresectable, advanced stage. Current treatments for unresectable cases include radiotherapy and chemotherapy, although it remains difficult to achieve long-term survival. We herein present our experience with a case of unresectable biliary tract cancer that exhibited an effective response to chemotherapy with gemcitabine plus cisplatin (GEM+CDDP). The patient was a 76- year-old man with biliary tract cancer( T2N1M0, cStage III). Multiple liver metastases were detected during laparotomy. We judged the tumor to be unresectable and placed a biliary tract metallic stent. After surgery, we initiated chemotherapy with GEM+CDDP. No liver metastases were visualized on computed tomography (CT) after 5 courses of chemotherapy. We considered surgical resection; however, the patient chose to continue chemotherapy. Currently, the patient is alive and well without any recurrence of liver metastasis, 26 months after surgery.

ß-Catenin-activated inflammatory hepatocellular adenoma with pigmentation and atypical features: a case report.

Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of ß-catenin-activated inflammatory hepatocellular adenoma with malignant transformation. A 50-year-old man with a suspected liver tumor, based on abdominal ultrasonography findings, was referred to our hospital. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a liver tumor in S2 which was enhanced in the arterial phase to the delayed phase. Based on diagnostic imaging findings, hepatocellular adenoma or focal nodular hyperplasia was suspected. We considered the possibility of malignant potential because of the enlargement of the lesion. Thus, we performed a laparoscopic hepatectomy. Histological examination showed pigment deposition in the hepatocytes, which was determined to be lipofuscin. Mild nuclear swelling and atypia in the tumor area indicated nodular growth. Based on the histological and immunohistochemical findings, the diagnosis was ꞵ-catenin-activated inflammatory hepatocellular adenoma with atypical features. The imaging features of hepatocellular adenoma and focal nodular hyperplasia are similar, but if the tumor tends to grow, surgical treatment should be performed because of the possibility of malignant hepatocellular adenoma.

Introduction of a simulation model for choledocho- and pancreaticojejunostomy.

Pancreaticoduodenectomy includes choledochojejunostomy and pancreaticojejunostomy, which require hand-sewn anastomoses. Educational simulation models for choledochojejunostomy and pancreaticojejunostomy have not been designed. We introduce a simulation model for choledochojejunostomy and pancreaticojejunostomy created with a skin closure pad and a vascular model. A wound closure pad and a vein model (4 mm diameter) were used as a stump model of the pancreas. Pancreaticojejunostomy was simulated with a stump model of the pancreas and a double layer bowel model; these models were stabilized in an end-to-side fashion on a magnetic board using magnetic clips. In addition, vein (6 or 8 mm diameter) and bowel models were used to simulate choledochojejunostomy. Pancreatic and hepatobiliary surgery are relatively rare, particularly in a community hospital although surgical residents wish to practice these procedures. Our simulator enables surgeons and surgical residents to practice choledocho- and pancreaticojejunostomy through open or laparoscopic approaches.

Conversion surgery following gemcitabine plus cisplatin therapy for initially unresectable gallbladder cancer with peritoneal carcinomatosis: a case report.

BACKGROUND: Conversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer. CASE PRESENTATION: A 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis. She underwent gemcitabine plus cisplatin therapy for 9 months. Extended cholecystectomy, resection of the extrahepatic bile duct with regional lymph node dissection, and total omentectomy were then performed as conversion surgery. The patient has survived without recurrence for 19 months postoperatively (31 months after the initial diagnosis) while continuing chemotherapy. CONCLUSIONS: This case suggests that conversion surgery for advanced gallbladder cancer is effective and may be curative for locally advanced disease and distant metastasis such as peritoneal carcinomatosis.

CT-based deep learning enables early postoperative recurrence prediction for intrahepatic cholangiocarcinoma.

Preoperatively accurate evaluation of risk for early postoperative recurrence contributes to maximizing the therapeutic success for intrahepatic cholangiocarcinoma (iCCA) patients. This study aimed to investigate the potential of deep learning (DL) algorithms for predicting postoperative early recurrence through the use of preoperative images. We collected the dataset, including preoperative plain computed tomography (CT) images, from 41 patients undergoing curative surgery for iCCA at multiple institutions. We built a CT patch-based predictive model using a residual convolutional neural network and used fivefold cross-validation. The prediction accuracy of the model was analyzed. We defined early recurrence as recurrence within a year after surgical resection. Of the 41 patients, early recurrence was observed in 20 (48.8%). A total of 71,081 patches were extracted from the entire segmented tumor area of each patient. The average accuracy of the ResNet model for predicting early recurrence was 98.2% for the training dataset. In the validation dataset, the average sensitivity, specificity, and accuracy were 97.8%, 94.0%, and 96.5%, respectively. Furthermore, the area under the receiver operating characteristic curve was 0.994. Our CT-based DL model exhibited high predictive performance in projecting postoperative early recurrence, proposing a novel insight into iCCA management.

Usefulness of in-phase and out-of-phase magnetic resonance imaging for the detection of pancreatic lymphoepithelial cyst.

Lymphoepithelial cyst (LEC) of the pancreas is a rare benign lesion that may mimic cystic neoplasms. Diagnosis of pancreatic LEC has been depended on the elevation of serum carbohydrate antigen 19-9 (CA 19-9), biopsy of the cyst by endoscopic ultrasonography (EUS) and several abdominal imaging techniques including magnetic resonance imaging (MRI). However, it is very difficult to diagnose LEC of the pancreas preoperatively and excessive surgery has been done in spite of its benign nature. We herein report a case of pancreatic LEC which was preoperatively diagnosed by using in-phase and out-of-phase MRI and was successfully nucleated.