A Case of Gallbladder Metastasis of Malignant Melanoma.

In the clinical course of malignant melanoma, which can metastasize to multiple organs, gallbladder metastases are rarely detected. A 69-year-old man who underwent resection of a primary malignant melanoma was subsequently treated with nivolumab for lung metastases and achieved complete response. Seven years after surgery, multiple nodules were found in the gallbladder, and he underwent laparoscopic cholecystectomy. The postoperative diagnosis was metastases of malignant melanoma. He has been recurrence-free 8 months after surgery. If radical resection is possible, such surgery should be performed for gallbladder metastases found in patients with other controlled lesions of malignant melanoma.

Nutritional assessment and surgical outcomes in very elderly patients undergoing pancreaticoduodenectomy: a retrospective study.

PURPOSE: To evaluate and compare the nutritional factors and clinical outcomes of pancreaticoduodenectomy between elderly and non-elderly patients. METHODS: This retrospective study evaluated 122 consecutive patients who underwent pancreaticoduodenectomy from April 2008 to April 2020. Preoperative and postoperative nutritional factors (prognostic nutritional index), complication rates, and survival rates were compared between the elderly (≥ 80 years) and non-elderly (< 80 years) patient groups. Changes in nutrition markers were evaluated before surgery to 1 year after surgery. RESULTS: A total of 20 elderly patients (16.4%) and 102 non-elderly patients (83.6%) underwent pancreaticoduodenectomy. Elderly patients had a significantly lower preoperative prognostic nutritional index than did non-elderly patients. At 3 months postoperatively, elderly patients had a lower albumin level and prognostic nutritional index. The median length of hospital stay was significantly longer (39.9 vs. 27 days, P = 0.004), the rate of death due to other diseases was higher, and the overall survival rate was significantly lower (1-/3-/5 year overall survival rates: 78.1%/26.7%/13.3% vs. 87.1%/54.4%/46.7%; log-rank test, P = 0.003) in the elderly group than in the non-elderly group. CONCLUSIONS: The results suggest that careful patient selection and optimal perioperative care are necessary to determine whether pancreaticoduodenectomy is indicated for elderly patients.

Solitary Cardiac Metastasis of Hepatocellular Carcinoma.

Cardiac metastasis originating from hepatocellular carcinoma (HCC) is a rare condition with a poor prognosis. No therapeutic standards for cardiac metastasis originating from HCC have been established. At 19 months after a curative hepatectomy, a 64-year-old Japanese hepatitis B virus-positive male patient experienced solitary cardiac metastasis originating from HCC. The cardiac tumor was discovered in the right ventricle. The patient received three courses of radiotherapy and chemotherapy and survived > 3 years after the initial diagnosis of cardiac metastasis. His case demonstrates that radiotherapy combined with chemotherapy can be an effective treatment for cardiac metastasis.

The Late Phase/Early Phase Ratio of Pancreatic CT Values as a Novel Predictor of Pancreatic Fistula after Distal Pancreatectomy.

Post-operative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). In this retrospective study, we reviewed the data from patients who underwent DP between 2008 and 2019 in our institute to determine whether the late phase/early phase ratio (L/E ratio) by preoperative computed tomography (CT) scan in the pancreas could predict POPF occurrence after DP. We examined the relationship between preoperative or intraoperative factors and the occurrence of POPF after DP using statistical methods in 23 males and 21 females with a mean age of 73. The mean L/E ratio was significantly lower in the POPF group than the non-POPF group (p=0.035). The L/E ratio had moderate diagnostic accuracy, with a calculated optimal cutoff value of 0.77. In univariate analysis, a significant association was noted between POPF and stump thickness ≥ 16.9, body mass index ≥ 27.5, and L/E ratio ≤ 0.77. In the multivariate analysis, the L/E ratio (odds ratio, 5.96; p=0.036) was an independent risk factor for POPF. Our findings suggest that the pancreatic L/E ratio may predict the occurrence of POPF after DP. This measure may be useful in preoperative risk stratification, patient counseling, and perioperative patient management, improving clinical outcomes after DP.

Preoperative predictive factors of pancreatic fistula after pancreaticoduodenectomy: usefulness of the CONUT score.

PURPOSE: Postoperative pancreatic fistula (POPF) is the most important factor affecting morbidity and mortality after pancreaticoduodenectomy (PD). Patients with a high controlling nutritional status (CONUT) score, which is used to assess nutritional status, are expected to have high morbidity rates. This study aimed to determine the usefulness of the CONUT score. METHODS: Data from 97 consecutive cases of PD performed in the Department of Surgery of Iwakuni Clinical Center, from April 2008 to May 2018, were included. Preoperative patient data, including sex, age, and hypertension, and postoperative complication data were collected to analyze pancreatic fistula occurrence. RESULTS: Of the 97 patients, 2 9 patients (29.8%) were diagnosed with POPF ≥ B, with 26 cases (26.8%) classified as grade B and 3 (3.1%) as grade C. The mortality rate was 2.1% (2 of 97). In the univariate analysis, a significant association was observed between POPF and the following factors: body mass index (BMI) ≥ 22 kg/m2, high CONUT score, nonpancreatic carcinoma, and CT attenuation values. In multivariate analysis, BMI ≥ 22 kg/m2 (odds ratio [OR], 6.16; P < 0.001), high CONUT score (OR, 3.77; P = 0.009), nonpancreatic carcinoma (OR, 5.72; P = 0.009), and CT attenuation values (late/early ratio) in the pancreas (OR, 9.07; P = 0.006) were independent risk factors for POPF. CONCLUSION: Patients with a high CONUT score are at high risk of POPF. Further study correlating preoperative nutritional intervention with risk of POPF is necessary.

Preoperative C-Reactive Protein/Albumin Ratio as a Predictive Factor for Gallbladder Carcinoma.

BACKGROUND/AIM: The C-reactive protein (CRP) to albumin ratio (CAR) is associated with outcomes in patients with sepsis. We aimed to evaluate the significance of preoperative CAR in therapeutic outcomes after gallbladder carcinoma (GBC) resection. PATIENTS AND METHODS: Fifty-three patients who underwent surgical resection for GBC between January 2008 and September 2019 were enrolled. We retrospectively investigated the relation between preoperative CAR and overall and disease-free survival. RESULTS: The optimal cut-off CAR was 0.07. Multivariate analysis showed that i) R1 or R2 resection (p=0.033), ii) advanced tumor stage (p=0.047), iii) CAR≥0.07 (p=0.011), and iv) postoperative complications (p=0.028) were significant independent predictors of overall survival; moreover, higher carbohydrate antigen levels (p=0.036) and R1 or R2 resection (p<0.001) were significant independent predictors of disease-free survival. CONCLUSION: Preoperative CAR may be a significant independent predictor of long-term outcomes after GBC resection.

Preoperative Nutritional Assessment Using the Controlling Nutritional Status Score to Predict Pancreatic Fistula After Pancreaticoduodenectomy.

Backgound: This study aimed to determine the usefulness of the Controlling Nutritional Status (CONUT) scorescore for predicting postoperative pancreatic fistula (POPF). PATIENTS AND METHODS: Data from 108 consecutive pancreaticoduodenectomy cases performed at the Surgery Department of Iwakuni Clinical Center, from April 2008 to May 2018, were included. Preoperative patient data and postoperative complication data were collected. RESULTS: Of the 108 patients (male=65; female=43; mean age=70 years), 41 (37.9%) had indication for pancreaticoduodenectomy due to pancreatic carcinoma. Grade B or higher POPF was diagnosed in 32 patients (29.6%). In the multivariate analysis, body mass index ≥22 kg/m2 [odds ratio (OR)=5.24; p=0.005], CONUT score ≥4 (OR=3.28; p=0.042), non-pancreatic carcinoma (OR=47.17; p=0.001), and a low computed tomographic contrast attenuation value (late/early ratio) (OR=4.39; p=0.029) were independent risk factors for POPF. CONCLUSION: Patients with high CONUT score are at high risk for POPF. Preoperative nutritional intervention such as immunonutrition might help reduce the POPF risk in these patients.

Safety of Surgical Treatment for Elderly Patients with Gallbladder Carcinoma.

Gallbladder carcinoma (GBC) is a common malignancy with a poor prognosis. With the average life expectancy increasing globally, the incidence of GBC is predicted to increase as well. We investigated the safety and feasibility of surgical treatment for elderly patients with GBC. We retrospectively compared clinical pathological data and treatment outcomes in 45 consecutive GBC patients (23 patients ≥ 75 years [elderly group] and 22 patients < 75 years [younger group]) who underwent curative resection at the Iwakuni Center from January 2008 to December 2017. The proportion of preoperative comorbidities and anticoagulant use was significantly higher in the elderly group. The American Society of Anesthesiologists score was higher in the elderly versus the younger group, and the elderly group had significantly shorter operation times. Reduced activities of daily living was more common in the elderly versus younger group. The percentage of radical resection and overall 3-year survival (66.6% younger vs. 64.4% elderly) were similar between the groups. Controlling Nutritional Status (CONUT) score ≥ 3 and R0 resection were identified as prognostic factors for overall survival rate among all patients. After careful patient selection.

Pancreatic Ductal Adenocarcinoma in Remnant Pancreas after Pancreaticoduodenectomy for Acinar Cell Carcinoma: A Case Report.

We report a case of a pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas of a 78-year-old man after pancreaticoduodenectomy for acinar cell carcinoma, a relatively rare pancreatic neoplasm. After diagnosis of pancreatic carcinoma, subtotal stomach-preserving pancreaticoduodenectomy was performed. The pathological diagnosis was acinar cell carcinoma of the pancreas (disease stage IA, pT1, pN0, M0), without regional lymph node invasion. Cancer antigen 19-9 levels gradually increased during the 22 months after surgery, and computed tomography showed two solid tumors, 1.1 and 2.1 cm in diameter, at the site of the remnant pancreas. Endoscopic ultrasound fine-needle aspiration revealed pancreatic ductal adenocarcinoma. The tumor cells were not immunoreactive for trypsin. Both tumors were diagnosed as PDAC of the remnant pancreas. The patient declined curative resection, and chemoradiotherapy was started as alternative treatment. The patient died 28 months after surgery. Because this is an extremely rare case, additional cases and studies are needed in order to clarify its pathogenesis.

Preoperative Risk Factors for Conversion of Laparoscopic Cholecystectomy to Open Cholecystectomy and the Usefulness of the 2013 Tokyo Guidelines.

To identify predictive factors for conversion from laparoscopic cholecystectomy (LC) to open cholecystectomy performed for mixed indications as an acute or elective procedure. We retrospectively analyzed the data of 236 consecutive cases of LC performed in our department between January 2012 and January 2015, and evaluated preoperative risk factors for conversion and the usefulness of the 2013 Tokyo guidelines (TG2013) for diagnosing acute cholecystitis. The conversion rate in our series was 8% (19/236 cases). The following independent predictive factors of conversion were identified (p≤0.04): previous upper abdominal surgery (odds ratio (OR), 14.6), pericholecystic fluid (OR, 10.04), acute cholecystitis (OR, 7.81), and emergent LC (OR, 15.8). Specifically for patients with acute cholecystitis defined using the 2013 Tokyo guidelines, use of an antiplatelet or anticoagulant drug for cardiovascular disease (p=0.043), previous upper abdominal surgery (p<0.031) and a resident as operator (p=0.041) were predictive factors. The risk factors for conversion identified herein could help to predict the difficulty of the procedure and could be used by surgeons to better inform patients regarding the risks for conversion. The TG2013 can be an effective tool for diagnosing acute cholecystitis to make informed clinical decisions regarding the optimal procedure for a patient.

Metachronous colorectal carcinoma with massive submucosal invasion detected by annual surveillance in a Lynch syndrome patient: a case report.

BACKGROUND: Lynch syndrome is the most common form of hereditary colorectal carcinoma. It is characterized by the presence of germline mutations in DNA mismatch repair genes. Mutation carriers have a lifetime risk of developing colorectal carcinoma of approximately 80%. Current treatment guidelines recommend periodic surveillance for colorectal carcinoma in patients with Lynch syndrome. However, the optimal interval between colonoscopies has not yet been determined. CASE PRESENTATION: We describe a 54-year-old man with Lynch syndrome who was undergoing annual colonoscopy surveillance for the development of colorectal carcinoma. At 54, 57, 59, and 60 years old, a colonoscopy showed high-grade dysplasia and adenoma. Therefore, endoscopic mucosal resection was performed. At 61 years old, a colonoscopy showed metachronous colorectal carcinoma with massive submucosal invasion. He subsequently underwent laparotomy for colorectal carcinoma. CONCLUSIONS: Annual surveillance using colonoscopy can detect colorectal carcinoma at an early stage, leading to reduced mortality. However, some patients might require a laparotomy, as was the case here. More frequent colonoscopic surveillance might be necessary to avoid surgery for colorectal carcinoma in Lynch syndrome patients with multiple risk factors for interval cancer.

Synchronous coexistence of liver metastases from cecal leiomyosarcoma and rectal adenocarcinoma: A case report.

Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both intestinal leiomyosarcoma and adenocarcinoma. The patient described in this report successfully underwent resection of both primary lesions and liver metastases in combination with chemotherapy. As for the leiomyosarcoma, the primary cecal lesion was revealed more than three years after the patient's first visit. Peritoneal, lymph-node, and lung recurrences were observed afterward, and thus surgeries on those regions were performed. Pathologically, the peritoneal and lung recurrences comprised leiomyosarcoma and the lymph-node recurrence was diagnosed as adenocarcinoma. Despite newly discovered multiple lung recurrences and regional lymph-node metastases, the patient lived a normal life for 73 mo after the initial operation based on multidisciplinary therapy. He ultimately died of liver failure due to invasive lymph-node recurrence from the rectal adenocarcinoma, in addition to multiple lung recurrences from the leiomyosarcoma. Hepatic recurrence did not occur in this patient's case, which appears to be one reason for his long-term survival.

Evaluation of surgical treatment for incidental gallbladder carcinoma diagnosed during or after laparoscopic cholecystectomy: single center results.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the accepted standard management for benign gallbladder disease. LC rarely results in a diagnosis of incidental gallbladder carcinoma (IGBC). The aim of our study was to report our experience with IGBC diagnosed during or following LC. METHODS: Between January 2008 and January 2015, 352 patients underwent LC at Iwakuni Clinical Center. Among these patients, 8 (2.3%) were diagnosed with IGBC. We evaluated their characteristics, surgical related variables, histopathological findings and surgical outcomes. RESULTS: Patient median age was 71 (range 49-88) years, and 3 out of 8 were female. All patients with IGBC were Japanese. The grade of cancer was as follows: pT1a (3 cases), pT2 (4 cases) and pT3 (1 case). Two patients with pT2 disease underwent radical surgery. The median follow-up time of these patients was 24 (range 11-80) months. All patients are still alive and two of three patients who refused radical surgery have developed recurrence (liver metastases and recurrence in the peritoneum). CONCLUSIONS: Although the number of cases was small, the results of this study further support the suggestion that gallbladder carcinoma may be curable if diagnosed as IGBC at an early stage. If the cancer has reached an advanced stage, radical surgery should be performed.

Spontaneous rupture of a hepatic angiomyolipoma: Report of a case.

A 70-year-old female experienced sudden onset of back pain on the right side and was admitted to our hospital in December 2010. Abdominal computed tomography revealed an S7 hepatic mass measuring 7 cm in diameter accompanied by a subcapsular hematoma. Emergency angiography confirmed the diagnosis of a ruptured hepatic mass, and hemostasis was carried out by embolization of A8 and A7 of the liver. A right hepatic lobectomy was carried out 39 days following transarterial embolization. Although almost all aspects of the tumor were necrotic, residual tumor cells stained positive for HMB-45, and negative for α-SMA, S-100, CD 34, c-kit, CAM 5.2, and hepatocytes. The MIB-1 index was 2 %. Pathological diagnosis was hepatic angiomyolipoma (HAML). The patient has shown no signs of recurrence at 42 months following surgery. Here, we report on this case of spontaneous HAML rupture and discuss therapeutic strategies for HAML and ruptured hepatic tumors.

Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells.

The p16 tumor suppressor gene is frequently inactivated in human cancer tissues and cell lines. We previously reported that wild-type p16 expression from an adenovirus vector (Adv/p16) induced p53-dependent apoptotic cell death in non-small cell lung cancer (NSCLC) cell lines. Here we show the potential mechanism of apoptosis induced by Adv/p16 infection. Infection of human NSCLC cell line A549, which carries the wild-type p53 gene, with Adv/p16 resulted in activation of caspase-3, accompanied by the cleavage of its substrate poly (ADP-ribose) polymerase (PARP), on day 3 of infection. The retinoblastoma (Rb) cell cycle regulator protein was also cleaved after activation of caspase-3; when the levels of Rb significantly diminished, apoptosis began. When A549 cells were pretreated with the caspase-inhibitory peptide N-acetyl-asp-Glu-Val-Asp-CHO (aldehyde) (Ac-DEVD-CHO), Adv/p16-mediated apoptosis and Rb cleavage were greatly inhibited. Furthermore, MDM2, a negative regulator of p53 expression was upregulated 3 days after Adv/p16 infection, and MDM2 was subsequently cleaved by caspase-3; MDM2 cleavage was inhibited by Ac-DEVD-CHO treatment. These data implied that cleavage of Rb, in addition to activation of caspase-3, represented a mechanism by which Adv/p16 induced apoptotic cell death in human NSCLC cells. Our results support the clinical relevance of Adv/p16 as a treatment for p16-null human NSCLC that express wild-type p53.

p53 inhibits adriamycin-induced down-regulation of cyclin D1 expression in human cancer cells.

The tumor suppressor p53 gene product is an essential component of the cytotoxic pathway triggered by DNA-damaging stimuli such as chemotherapeutic agents and ionizing radiation. We previously demonstrated that adenovirus-mediated wild-type p53 gene transfer could enhance the cytotoxic actions of chemotherapeutic drugs both in vitro and in vivo; however, the molecular mechanism of this chemosensitization is still unclear. Cyclin D1 is a major regulator of the progression of cells into the proliferative stage of the cell cycle. Here we show that infection with an adenovirus vector expressing the wild-type p53 gene (Ad-p53) caused an increase in cyclin D1 protein levels in human colorectal cancer cell lines DLD-1 and SW620; treatment with the anti-cancer drug adriamycin, however, down-regulated their cyclin D1 protein expression in a dose-dependent manner. The suppression of cyclin D1 expression following adriamycin treatment could be blocked by simultaneous Ad-p53 infection. Furthermore, DLD-1 and SW620 cells transfected with the cyclin D1 expression construct displayed increased sensitivity to adriamycin compared to that of the vector-transfected control. Our results suggest that ectopic wild-type p53 gene transfer results in increased cyclin D1 expression and, consequently, sensitizes human colorectal cancer cells to chemotherapeutic agents.