A Case of Tumor Lysis Syndrome during Palliative Radiotherapy for Breast Cancer Metastases.

Tumor lysis syndrome (TLS) is the rapid disintegration of a malignant tumor treated with anticancer drugs or radiation, causing electrolyte abnormalities such as elevated uric acid levels, elevated potassium and phosphorus levels, and decreased calcium levels. These abnormalities can lead to hypotension, renal dysfunction, consciousness disorders, and even death in some cases. The current patient was a 65-year-old woman who had breast cancer with local invasion, lung metastasis, and bone metastasis from the time of the initial disease onset. Despite the administration of various chemotherapy and hormone therapy regimens, the tumor increased gradually, and at 2 years and 5 months after the initial onset, pain and bleeding from metastatic infiltration of the cervical lymph nodes were noted. Therefore, radiotherapy was indicated for palliation of pain and bleeding caused by metastatic invasion of the cervical lymph nodes. Irradiation (30 Gy/10fr) was planned with a 3-field technique using 4MVX and 10MVX. Approximately 11 h after the initial irradiation, symptoms such as respiratory distress, tachycardia, and hypotension were observed. Blood tests revealed hyperuricemia and hyperkalemia, leading to a diagnosis of TLS. Dialysis and electrolyte correction were immediately initiated resulting in normalization of electrolytes and stabilization of the blood pressure. It is crucial to understand that TLS is relatively rare but can occur after radiation therapy or in solid tumors, and warrants a prompt response if suspected based on symptoms or blood findings.

Clinical impact of perirenal thickness on short- and long-term outcomes of gastric cancer after curative surgery.

Background: A variety of factors for short- and long-term outcomes have been reported after radical resection for gastric cancer (GC). Obesity and emaciation had been reported to be a cause of poor short- and long-term outcomes with gastrointestinal cancer. However, the indicators are still controversial. The purpose of this study was to evaluate the relationship between perirenal thickness (PT) and short- and long-term outcomes after radical surgery for GC. Methods: We analyzed the data of 364 patients with GC who underwent radical surgery. We evaluated the distance from the anterior margin of the quadratus lumborum muscle to the dorsal margin of the left renal pole using computed tomography (CT) as an indicator of PT. The association between PT and clinicopathological factors and short- and long-term outcomes was evaluated. Results: The PT data were divided into low, normal, and high groups by gender using the tertile value. We found that the PT low group was 121 patients, normal group was 121 patients, and high group was 122 patients. Multivariate analyses showed that the high PT group was an independent risk factor for a short-outcome after curative surgery in GC patients (odds ratio 2.163; 95% confidence interval [CI] 1.156-4.046; P = .016). And the low PT group was an independent risk factor for overall survival (hazard ratio 2.488; 95% CI 1.400-4.421; P = .0019) and relapse-free survival (hazard ratio 2.342; 95% CI 1.349-4.064; P = .0025) after curative surgery in GC patients. Conclusion: Perirenal thickness is a simple and useful factor for predicting short- and long-term outcomes after radical surgery for GC.

Pancreaticoduodenectomy at a Non-high-volume Center and Efforts to Perform Safe Surgery.

AIM: The aim of the current study was to investigate whether the artery-first approach (AFA) improved surgical outcomes of pancreaticoduodenectomy (PD) at our non-high-volume center. PATIENTS AND METHODS: We retrospectively reviewed data on 121 consecutive patients who underwent PD between January 2009 and December 2018. The perioperative data of 49 patients who underwent conventional PD (conventional group) and 72 patients who underwent PD via artery-first approach were analyzed and compared to assess the effectiveness of the AFA. RESULTS: Although no significant difference was observed between the two groups overall, in those with pancreatic cancer, the duration of surgery, intraoperative blood loss and transfusion rate in the AFA group (n=33) were significantly lower than those for the conventional group (n=11) (p=0.011, p=0.021 and p=0.038 respectively). CONCLUSION: AFA can be used to reduce the operative time, intraoperative blood loss, and transfusion rate in patients with pancreatic cancer.

Retroperitoneal fibrous tumor recurring as lung metastases after 10 years: a case report.

BACKGROUND: Solitary fibrous tumor (SFT) is a relatively rare mesenchymal tumor that mainly affects adults. Its prognosis is good after curative resection, but distant recurrences after 10 years or longer have been reported. Recurrent SFT usually arises as a local lesion; distant metastasis is rarely reported. Here, we report lung metastases that recurred a decade after excising a retroperitoneal primary SFT. CASE PRESENTATION: A 44-year-old woman had an SFT resected from her right retroperitoneum at our hospital. Ten years later, at age 54, she underwent a lung resection after CT showed three suspected metastases in her left lung. All three were histologically diagnosed as lung metastases from the retroperitoneal SFT. However, whereas the primary SFT had 1-2 mitotic cells/10 high power fields (HPF), the metastatic lesion increased malignancy, at 50/10 HPF. CONCLUSION: Patients who have had resected SFTs should be carefully followed up, as malignancy may change in distant metastasis, as in this case.

A case of repeat hepatectomy for liver metastasis from solid pseudopapillary neoplasm of the pancreas: a case report.

BACKGROUND: Solid pseudopapillary neoplasm of the pancreas is a rare tumor in young women, metastasizing in only 5-15% of cases, and most commonly to the liver. Although treatment guidelines have not been established, surgical resection is usually performed. We report a rare case of repeat hepatectomy for liver metastases after distal pancreatectomy with solid pseudopapillary neoplasm. CASE PRESENTATION: The patient was a 71-year-old woman who underwent distal pancreatectomy for solid pseudopapillary neoplasm, and liver metastasis occurred 4 years after the first surgery. Partial liver resection was performed for four liver metastases, and histopathological examination revealed a diagnosis of liver metastasis from solid pseudopapillary neoplasm. However, 18 months later, liver metastases were detected again; three tumors were identified, and partial resection was performed, which has provided 18 months' recurrence-free survival. CONCLUSIONS: Long-term prognosis can be expected following R0 resection for resectable liver metastasis from solid pseudopapillary neoplasm.

A rare anastomosis between the root of common hepatic artery and proper hepatic artery: implications for pancreaticoduodenectomy.

BACKGROUND: Hepatic artery anomalies are often observed, and the variations are wide-ranging. We herein report a case of pancreatic cancer involving the common hepatic artery (CHA) that was successfully treated with pancreaticoduodenectomy (PD) without arterial reconstruction, thanks to anastomosis between the root of CHA and proper hepatic artery (PHA), which is a very rare anastomotic site. CASE PRESENTATION: A 78-year-old woman was referred to our department for the examination of a tumor in the pancreatic head. Contrast-enhanced computed tomography (CT) revealed a low-density tumor of 40 mm in diameter located in the pancreatic head. The involvement of the common hepatic artery (CHA), the root of the gastroduodenal artery (GDA), and portal vein was noted. Although such cases would usually require PD with arterial reconstruction of the CHA, it was thought that the hepatic arterial flow would be preserved by the anastomotic site between the root of the CHA and the PHA, even if the CHA was dissected without arterial reconstruction. PD with dissection of the CHA and PHA was safely completed without arterial reconstruction, and sufficient hepatic arterial flow was preserved through the anastomotic site between the CHA and PHA. CONCLUSION: We presented an extremely rare case of an anastomosis between the CHA and PHA in a patient with pancreatic cancer involving the CHA. Thanks to this anastomosis, surgical resection was successfully performed with sufficient hepatic arterial flow without arterial reconstruction.

A Case of 15-Year Recurrence-free Survival After Microwave Coagulation Therapy for Liver Metastasis from Gastric Cancer.

A 70-year-old man with a growing liver tumor had undergone subtotal gastrectomy with pancreaticoduodenectomy for gastric cancer (T4b P0 H0 N1, Stage IIIB) 30 months before admission to our hospital. Enhanced computed tomography revealed two hypervascular nodules in segments 4 and 8. After histological diagnosis of small liver metastases from gastric cancer in segment 8, the patient underwent open microwave coagulation therapy (MCT) for the tumor (diameter: 30 mm) in segment 4. MCT was performed by using 1.5-cm and 3-cm monopolar needle electrodes with 22 times of puncture under the condition of 100 W × 60 sec. Liver abscess developed at the MCT site; however, it was decreased with percutaneous drainage. The patient is alive, without tumor recurrence even after 15 years since the MCT. This successful case proves that appropriate MCT is a promising treatment for patients with gastric liver metastases.

Recombinant soluble thrombomodulin for postoperative disseminated intravascular coagulation.

BACKGROUND: Thrombomodulin is a thrombin receptor on the endothelial cell surface that plays an important role in the regulation of intravascular coagulation. The purpose of this study was to evaluate the efficacy and safety of treatment with recombinant human soluble thrombomodulin (rhTM) for patients with septic-disseminated intravascular coagulation (DIC) associated with gastroenterological surgery. MATERIALS AND METHODS: From April 2011-September 2013, 201 patients with DIC associated with gastroenterological surgery were treated in 16 institutions in Kumamoto, Japan. The patients were diagnosed according to the Japanese Association for Acute Medicine DIC scoring system. The clinical course, mortality rate at 28 d, and adverse events were evaluated retrospectively. RESULTS: Forty-five patients were excluded because they did not meet the Japanese Association for Acute Medicine DIC criteria or had an insufficient duration of drug administration. Thus, 156 patients were analyzed. Of these patients, 107 received rhTM at the discretion of the attending surgeon and 49 did not. The most common reason for surgery in both groups was peritonitis due to perforation of the colon. Within 7 d, the platelet count, prothrombin time-international normalized ratio, DIC score, neutrophil count, and C-reactive protein level significantly improved in the rhTM group compared with those in the control. Treatment with rhTM was significantly associated with reduced inhospital mortality at 28 d. The incidence of adverse events did not differ between the two groups. CONCLUSIONS: Therapy with rhTM may be associated with reduced inhospital mortality in patients with septic DIC associated with gastroenterological surgery without increasing adverse events.

Mucinous cystic neoplasm of the pancreas activated during pregnancy.

The characteristic histological feature of pancreatic mucinous cystic neoplasm (MCN) is ovarian-like stroma (OS) underlying the epithelium and existence of estrogen receptors and progesterone receptors in the nucleus of OS. We experienced a case of pancreatic MCN which was activated during pregnancy and confirmed the existence of estrogen receptors and progesterone receptors. In cases with potential factors for malignancy, surgical resection of MCN may be needed during pregnancy. On the other hand, in cases without these, as female sex hormones may have an influence on the behavior of pancreatic MCN during pregnancy, the timing of surgery should be decided on a case-by-case basis, taking into consideration the status of the malignancy, the stage of the pregnancy, and the condition of the mother and fetus.

[A case report of primary adenocarcinoma of the small intestine with peritoneal dissemination treated with multidisciplinary therapy].

A 55-year-old woman consulted our hospital complaining of abdominal distention and vomiting. She was diagnosed with a malignant tumor in the small intestine and an ovarian tumor with an upper gastro-intestinal series based on a computerized tomography(CT)examination. Intra-operative findings showed that the primary tumor was located in the proximal jejunum, 10 cm on the anal side from Treitz's ligament. There were no liver metastases, but the tumor had spread into the peritoneal cavity(light ovary). The jejunum and light ovary were therefore resected. Pathological diagnosis of the resected specimen revealed adenocarcinoma with lymph node metastases(T4N1M1, UICC StageIV). The patient received systemic chemotherapy with oral S-1. A recurrent lesion on the right ovary was detected 6 months after surgery. The patient subsequently underwent resection of the right ovary. For lung metastases and recurrent peritoneal dissemination, combination chemotherapy with XELOX or FOLFIRI, along with capecitabine plus bevacizumab, and cetuximab, was administered. The patient died 33 months after the first surgery. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed at an advanced stage because there are very few characteristic symptoms. This case may be an important case for the development of a standard chemotherapy regimen for advanced and recurrent adenocarcinoma of the small intestine.

Tumor compression-induced portal obstruction and selective transarterial chemoembolization increase functional liver volume in the unobstructed area, facilitating successful resection of a large HCC.

A 62-year-old man with hepatitis B was admitted for treatment of a large hepatocellular carcinoma. The right portal vein was completely obstructed by tumor compression. Although we initially planned a right trisectionectomy as curative hepatectomy, the percentage of future remnant liver volume (%RLV) and the percentage of functional liver volume (%RFLV) were 31.2% and 41.3%, respectively. Because %RFLV showed marginal tolerability for curative hepatectomy and %RLV was very low, we opted for transarterial chemoembolization of segment IV and the right lobe containing the tumor as an approach to selectively reduce liver volume and abolish liver function. One month later, %RLV and %RFLV had dramatically increased to 46.6% and 67.2%, resulting in curative hepatectomy. Our results suggest that tumor compression-induced portal obstruction and selective transarterial chemoembolization increase %RFLV much more than %RLV. This may represent a useful approach in preoperative management in patients with large hepatocellular carcinomas to improve %RFLV for hepatic resection.

Choledochal cyst during pregnancy: case report and literature review of treatment.

Choledochal cysts are uncommon conditions, usually diagnosed during childhood, but rarely during pregnancy. Choledochal cysts during pregnancy carry several risks, including development of biliary tract cancer and peritonitis due to rupture of dilated cysts induced by pregnancy itself. We present here a case of choledochal cyst during pregnancy, and discuss appropriate treatments for choledochal cysts first presenting during pregnancy. A 25-year-old primigravida at 15 weeks' gestation was admitted to our hospital with abdominal pain. Magnetic resonance cholangiopancreatography diagnosed a type 1 choledochal cyst without a mass lesion. A healthy baby arrived without complication at 38 weeks' gestation. The patient underwent cholecystectomy and choledochal cyst excision. The postoperative course was uneventful with discharge on day 8. Pathological examination diagnosed no malignant feature. Surgery may be performed after delivery for choledochal cysts first presenting during pregnancy, and monitoring with magnetic resonance imaging, blood tests, and ultrasonography is necessary during observation.

Glasgow Prognostic Score as a useful prognostic factor after hepatectomy for hepatocellular carcinoma.

BACKGROUND: Several previous studies have revealed that the Glasgow Prognostic Score (GPS) is a clinically useful scoring system to predict the prognosis of patients with various kinds of advanced cancers. However, there have been few reports on the relationship between the GPS and prognosis after hepatectomy for hepatocellular carcinoma (HCC). Therefore, we performed an analysis of the relationship between the GPS and prognosis after hepatectomy for HCC. METHODS: Between January 2005 and December 2009, 352 HCC patients underwent hepatectomy at Kumamoto University Hospital. Nineteen clinicopathologic factors were analyzed, using univariate and multivariate analyses. RESULTS: Univariate analysis showed that significant risk factors for poor survival included serum albumin level (<3.5 g/dL), tumor size (>35 mm), presence of ascites, portal vein invasion, operation time (>400 min), blood loss (>360 mL), requirement for blood transfusion, and GPS. Multivariate analysis revealed that tumor size [hazard ratio (HR) 3.355; p = 0.003], operation time (HR 2.634; p = 0.006), portal vein invasion (HR 2.419; p = 0.009), and GPS (HR 3.796; p < 0.001) were independent factors for poor prognosis. CONCLUSION: The GPS was demonstrated to be a statistically significant prognostic factor after hepatectomy for HCC.

Cutaneous metastases secondary to pancreatic cancer.

AIM: To evaluate prognoses after cutaneous metastases, derived from pancreatic cancer. METHODS: We treated two patients with cutaneous metastases from pancreatic cancer. We reviewed 40 reported patients in addition to our cases and analyzed clinical features of cutaneous metastases from pancreatic cancer. RESULTS: The median survival time (MST) was 5 mo after diagnoses of cutaneous metastases. The cumulative 2-year survival rate was 3.5%. The most frequent site of cutaneous metastases was the umbilicus. The MST of patients who were treated with chemotherapy or chemoradiotherapy (CRT) was 6.5 mo, which was statistically longer in comparison to patients without treatment. Prognoses of cutaneous metastases are similar to other metastatic sites from pancreatic cancer. Receiving chemotherapy or CRT was the only prognostic factor of cutaneous metastases from pancreatic cancer. CONCLUSION: The prognoses of cutaneous metastases are similar to other metastatic pancreatic cancers. Receiving chemotherapy or CRT was the only prognostic factor of cutaneous metastases from pancreatic cancer.

Evaluation of mass-forming intrahepatic cholangiocarcinoma with viral hepatitis.

BACKGROUND/AIMS: The correlation between the mass-forming type of intrahepatic cholangiocarcinoma (ICC) and the infection of the hepatitis B virus and hepatitis C virus are poorly understood. In this study, the clinical features of 34 patients with the mass-forming type ICC were reviewed to evaluate prognostic determinants. METHODOLOGY: Between January 1997 and December 2007, 34 patients underwent surgical resection for the mass-forming type of ICC in Kumamoto University Hospital. The significance of 14 clinicopathological factors consisting of age, gender, CA19-9 levels, CEA levels, size, intrahepatic metastases, portal vein invasion, bile duct invasion, histological differentiation, lymph node involvement, type B or C hepatitis, lymph node dissection, Sirius Red score of the tumor and platelet count in peripheral blood were analyzed, with regard to prognostic aspect. RESULTS: Univariate analysis showed that significant risk factors for poor survival included age =65 years, CEA levels =1.6ng/mL and pathological lymph node involvement. Multivariate analysis revealed that age, CEA levels and lymph node involvement were independent and significant poor prognostic factors. CONCLUSIONS: It was concluded that age, CEA levels and lymph node involvement were significantly poor prognostic factors. However, the infection with type B or C hepatitis was not a prognostic factor of the mass forming type ICC.

Portal vein embolization can prevent intrahepatic metastases to non-embolized liver.

BACKGROUND/AIMS: To determine the efficacy of portal vein embolization (PVE) against unresectable hepatocellular carcinoma (HCC). METHODOLOGY: We conducted a comparative study using 17 patients with HCC determined to be unresectable and who received a combination of PVE and transarterial chemoembolization (TACE) (PVE group) and 22 HCC patients with tumors in the unilateral lobe, which were treated only with repeated TACE (TACE group) from January 2000 to December 2008. RESULTS: There were no significant differences in background factors except for gender between the two groups. The cumulative intrahepatic recurrence rates in the non-portal-embolized area (in the contralateral lobe for the TACE group) at 1 year and 3 years was 41.1% and 58.8% in the PVE group and 77.3% and 81.8% in the TACE group, respectively. The former was significantly lower (p<0.05). The cumulative overall survival rate at 1 year, 3 and 5 years was 88.2%, 38.2% and 38.2% in the PVE group, and 68.1%, 22.7% and 8.5% in the TACE group, respectively. The former was significantly higher (p<0.05). CONCLUSIONS: Although in patients with unresectable HCC, when HCC is localized in the portal-embolized area, PVE combined with TACE can prevent intrahepatic metastasis to the non-portal-embolized area and improve overall survival.

Liver hanging maneuver decreases blood loss and operative time in a right-side hepatectomy.

BACKGROUND/AIMS: To clarify the clinical benefits of the maneuver in right-side hepatectomy. METHODOLOGY: Eighty-one patients with liver tumor (54 hepatocellular carcinoma, 17 metastatic liver tumor and 10 other tumors) treated with a right-side hepatectomy were prospectively analyzed. The patients were divided into the following three groups: a conventional approach (group A, n=21); liver dissection under the hanging maneuver after liver mobilization (group B, n=19) and liver dissection under the hanging maneuver prior to liver mobilization (group C, n=41). RESULTS: The liver hanging maneuver was safely performed in all the patients in groups B and C. Tumor size had a significantly positive correlation with the amount of intraoperative blood loss (R=0.52, p<0.05) in group A only. The patients in groups B and C had a significantly lower intraoperative use of blood loss (both p<0.01), operation time (p<0.05 and p<0.01) and the frequency of blood product (both p<0.05), in comparison to group A, respectively. The postoperative morbidity and the mortality rates were similar in the three groups. CONCLUSIONS: Liver hanging maneuver is a safe procedure, which can decrease intraoperative blood loss and administration of blood product in right-side hepatectomy.

NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells.

Nitric oxide (NO) shows tumoricidal activity. We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway, but upregulates the MEK/ERK pathway downstream of growth factor signaling. We hypothesized that NO donor and MEK inhibitor in combination synergistically inhibit the viability of cancer cells compared to either NO donor or MEK inhibitor alone. We determined the effects of S-nitrosoglutathione (GSNO, NO-donor) and U0126 (MEK inhibitor) on insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) signaling, proliferation and invasion in cancer cell lines. GSNO inhibits phosphorylation of IGF-I receptor (IGF-IR), EGF receptor (EGFR) and Akt, but upregulates ERK1/2 phosphorylation in MIAPaCa-2 and HCT-116 cells after stimulation by IGF-I and EGF. On the other hand, U0126 inhibits phosphorylation of ERK1/2, but upregulates phosphorylation of IGF-IR and EGFR in MIAPaCa-2 and HCT-116 cells. The combination of GSNO and U0126 downregulates phosphorylation of IGF-IR, EGFR, Akt and ERK1/2 after stimulation by IGF-I and EGF. GSNO as well as U0126, inhibits the proliferation of MIAPaCa-2, HCT-116, Panc-1, MCF-7, HT-29 and AGS cells in a dose-dependent manner. GSNO and U0126 in combination synergistically inhibit proliferation and invasion of cancer cells. These results indicate that the combined treatment of NO donor and MEK inhibitor may be promising in cancer therapy.

Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas: loss of microRNA-101 promotes overexpression of histone methyltransferase EZH2.

BACKGROUND: The mechanisms of IPMN carcinogenesis are as yet unclear. This study aimed to determine whether expression of EZH2 promotes neoplastic progression of IPMN and PDCA, and to elucidate regulation of EZH2 expression by miR-101. METHODS: EZH2 mRNA and protein expression were investigated in 8 human pancreatic cancer cell lines by PCR and western blotting. Pre-miR-101 and anti-miR-101 were transfected into pancreatic cancer cells to elucidate EZH2 regulation by miR-101. To evaluate whether EZH2 modulates malignant progression of IPMN, EZH2 expression in IPMN was examined by immunohistochemistry. Next, we collected malignant and benign cells from FFPE samples of IPMNs using laser capture microdissection and extracted the RNA. miR-101 expression in IPMN was assessed using real-time PCR. RESULTS: All pancreatic cancer cell lines expressed EZH2 mRNA and protein. The induction of miR-101 by transfection of pre-miR-101 in MIA PaCa-2 was closely related to a reduction in EZH2 protein production compared with control, whereas there was little difference in the expression of EZH2 mRNA. Anti-miR-101 transfected pancreatic cancer cells showed an increase in EZH2 protein, while the level of EZH2 mRNA was not elevated. Immunohistochemistry revealed that the expression of EZH2 was significantly higher in malignant than benign IPMN. Expression of miR-101 was significantly lower in malignant IPMN than benign IPMN. CONCLUSIONS: MiR-101 targets EZH2 at the posttranscriptional level, and loss of miR-101 could be a trigger for the adenomacarcinoma sequence of IPMN by upregulation of EZH2. This study suggests miR-101-EZH2 blockade as a potential therapeutic target in IPMN carcinogenesis.

[The possible role of sorafenib as a part of the multimodal treatment for hepatocellular carcinoma].

The role of sorafenib is unclear in multimodal treatment for hepatocellular carcinoma (HCC). We analyzed patients who underwent multimodal treatment including surgical operation for advanced HCC after administration of sorafenib. A 79- year-old man underwent extended right hepatectomy for Stage III huge HCC. Three years later, multiple recurrences observed in the liver, and an extrahepatic tumor was diagnosed. Peritoneal seeding was suspected, thus we decided to start a sorafenib administration. After 11 months, new intrahepatic lesions were detected, but extrahepatic tumor was unchanged. We considered the extrahepatic tumor was solitary and resectable, and new lesions in the liver were still treatable, then we attempted a surgical treatment with partial hepatectomy and ablation therapy. The tumor was successfully resected, and residual viable tumors were treated by radiofrequency ablation. The patient remains alive without recurrence at 7 months. We could perform a surgical treatment for another 2 patients with sorafenib treatment. These results suggested that there are cases of advance HCC in which multimodality treatment including surgical treatment can be achieved after sorafenib administration.