Primary Malignant Melanoma of the Esophagus Treated with Surgical Resection at an Early Stage.

Introduction: Primary malignant melanoma of the esophagus is a very rare disease with a poor prognosis. We herein report a patient with primary malignant melanoma of the esophagus who underwent surgical resection. Case Presentation: A 73-year-old female underwent an upper gastrointestinal endoscopy during follow-up for colonic diverticulitis. An endoscopic examination and constructed radiography revealed a slightly elevated black pigmented lesion in the upper esophagus and a black pigmented area in the esophagogastric junction. Through a preoperative endoscopic biopsy, she was diagnosed with malignant melanoma of the esophagus. We performed thoracoscopy-assisted and laparoscopy-assisted subtotal esophagectomy with lymphadenectomy. The surgical specimens were subjected to immunohistochemical analysis, resulting in a diagnosis of malignant melanoma. The tumor cells were positive for Melan-A and HMB-45 diffusely, supporting that diagnosis. We performed surgical resection in a case of primary malignant melanoma of the esophagus, and the patient has remained disease free for 2 years since the surgery. Conclusion: Early diagnosis and radical resection may be essential for long-term survival in patients with malignant melanoma of the esophagus.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

Adrenocortical carcinoma mimicking hepatocellular carcinoma: A case report.

INTRODUCTION AND IMPORTANCE: Adrenocortical carcinoma (ACC) is a relatively rare tumor arising in the adrenal cortex. Its imaging and histopathologic findings are not well known to be similar to those of hepatocellular carcinoma (HCC). We report here a case of ACC with hepatic resection in the preoperative diagnosis of HCC. CASE PRESENTATION: A 46-year-old woman was noted to have a tumor 45 mm in size in the segment 7 of the liver on CT during a medical checkup. The tumor had consistent imaging findings as HCC on Ultrasound, CT, and MRI examinations, and the result of the liver tumor biopsy was a diagnosis of intermediate differentiated HCC. We considered the tumor to be HCC and performed a posterior segmentectomy with combined resection of the right adrenal gland, which had adhesions suspected to direct invasion. The pathology of the resected specimen confirmed the diagnosis of ACC with direct invasion into the liver. CLINICAL DISCUSSION: ACC may show a contrast pattern similar to that of HCC on imaging, and histopathology may show atypical cells with eosinophilic sporulation, similar to that of HCC. Our case serves to alert physicians that ACC should be considered a differential diagnosis in patients with suspected HCC in the posterior segment. CONCLUSION: Tumors suspected of HCC in the dorsal posterior segment of the liver should be considered as possible ACC.

Risk Factors of Complications from Central Bisectionectomy (H458) for Hepatocellular Carcinoma: A Multi-Institutional Single-Arm Analysis.

BACKGROUND: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). METHODS: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. RESULTS: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. CONCLUSIONS: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB.

Impact of S-1 adjuvant chemotherapy longer than 6 months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data.

BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. METHODS: In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days. RESULTS: The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. CONCLUSIONS: The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.

Application of laparoscopic distal pancreatectomy for normal anatomy after hiatal hernia repair: A case report.

We describe a case of pancreatic tumor associated with a giant type IV hiatal hernia that had prolapsed into the posterior mediastinum. Hiatal hernia repair should be performed first because it enables laparoscopic distal pancreatectomy to be performed in the normal anatomical position.

Hepatocellular carcinoma with situs inversus totalis treated by caudate lobectomy: A case report.

INTRODUCTION: Situs inversus totalis (SIT) is a congenital anatomical variant in which organs and vasculature are positioned in a mirror-image relationship to the normal condition. Therefore, the surgical procedures need to be carefully planned with these factors in mind. CASE PRESENTATION: A 57-year-old man with SIT was diagnosed with a hepatocellular carcinoma (HCC) and was planned for caudate lobectomy. As preoperative preparation, 3D reconstructed images were created based on the contrast-enhanced CT images, and careful simulations were performed on the vascular anomalies and location of the tumor. There was a replaced left hepatic artery forming a common trunk with a left gastric artery. In addition, using media player software, a previous caudate lobectomy video was played in right and left inverted mode to simulate the abdominal surgical field image in SIT. The operative time was 285 min, and the blood loss was 440 ml. The preoperative careful simulation allowed us to proceed with the surgery without significant discomfort. CONCLUSION: Even in the case of hepatocellular carcinoma with SIT, hepatectomy for hepatocellular carcinoma can be safely performed by careful preoperative simulations.

Prognostic Impact of Relative Dose Intensity of Adjuvant Chemotherapy With S-1 on Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Although adjuvant chemotherapy (AC) with S-1 is currently the standard treatment for pancreatic ductal adenocarcinoma (PDAC) in Japan, the associations between its relative dose intensity (RDI) and survival outcomes remain unclear. PATIENTS AND METHODS: We reviewed 310 patients with PDAC who had undergone pancreatectomy from January 2014 to June 2020 at three institutions. Of these, patients who had received adjuvant S-1 monotherapy were analyzed. Patients who had died or developed recurrences within 6 months, or received neoadjuvant chemotherapy, were excluded from the analyses. Possible predictors of overall survival (OS), including RDI, were analyzed using Cox regression. The cutoff value for RDI was determined by receiver operating characteristic analysis. RESULTS: Ninety-four patients with a median age of 69 years (range=39-84 years) were analyzed. In the high-RDI group (RDI≥72.3%, n=74), the OS rates were 98.5% and 80.8% at 1 and 3 years, respectively, whereas in the low-RDI group (RDI <72.3%, n=20) they were 88.9% and 51.6%, respectively (p=0.001). By multivariate analysis, lymph node metastasis [hazard ratio (HR)=3.06; p=0.020], low RDI (HR=2.95; p=0.020), and time interval from surgery to initiation of AC > 51 days (HR=2.50; p=0.046) were independently associated with inferior OS. The combination of the latter two factors clearly stratified both OS and recurrence-free survival (p<0.001 and p=0.017, respectively). CONCLUSION: Early initiation and maintenance of RDI of S-1 monotherapy after pancreatectomy may improve the OS of PDAC patients.

Validity of a model using routinely collected data for identifying infections following gastric, colon, and liver cancer surgeries.

PURPOSE: Validating outcome measures is a prerequisite for using administrative databases for comparative effectiveness research. Although the Japanese Diagnosis Procedure Combination database is widely used in surgical studies, the outcome measure for postsurgical infection has not been validated. We developed a model to identify postsurgical infections using the routinely collected Diagnosis Procedure Combination data. METHODS: We retrospectively identified inpatients who underwent surgery for gastric, colon, or liver cancer between April 2016 and March 2018 at four hospitals. Chart reviews were conducted to identify postsurgical infections. We used bootstrap analysis with backwards variable elimination to select independent variables from routinely collected diagnosis and procedure data. Selected variables were used to create a score predicting the chart review-identified infections, and the performance of the score was tested. RESULTS: Among the 746 eligible patients, 96 patients (13%) had postoperative infections. Three variables were identified as predictors: diagnosis of infectious disease recorded as a complication arising after admission, addition of an intravenous antibiotic, and bacterial microscopy or culture. The prediction model had a C-statistic of 0.885 and pseudo-R2 of 0.358. A cut-off of one point of the score showed a sensitivity of 92% and specificity of 72%, and a cut-off of two points showed a sensitivity of 75% and specificity of 91%. CONCLUSIONS: Our model using routinely collected administrative data accurately identified postoperative infections. Further external validation would lead to the application of the model for research using administrative databases.

Evaluation of Preoperative Magnetic Resonance Cholangiopancreatography in Acute Cholecystitis to Predict Technical Difficulties in Laparoscopic Cholecystectomy.

Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive imaging technique that provides high-quality visualization of the biliary tree, including the gallbladder. This study aimed to evaluate the useful-ness of preoperative MRCP for acute cholecystitis in predicting technical difficulties during laparoscopic chole-cystectomy (LC). A total of 168 patients who underwent LC with preoperative MRCP were enrolled in this study. Patients were divided into two groups according to preoperative MRCP findings: the visualized group (n = 126), in which the entire gallbladder could be visualized; and the non-visualized group (n = 42), in which the entire gallbladder could not be visualized. The perioperative characteristics and postoperative complica-tions of the two groups were retrospectively analyzed. Operation time was longer in the non-visualized group (median 101.5 vs. 143.5 min; p < 0.001). The non-visualized group had significantly more intraoperative blood loss than the visualized group (median 5 vs. 10 g; p = 0.05). The rate of conversion to open cholecystectomy was significantly higher in the non-visualized group (1.6 vs. 9.5%; p = 0.03). In conclusion, patients in the non- visualized group showed higher difficulty in performance of LC. Our MRCP-based classification is a simple and effective means of predicting difficulties in performing LC for acute cholecystitis.

Carcinosarcoma of the Thoracic Esophagus That Presented as Focal Ulcerative Lesion.

Esophageal carcinosarcoma is a rare malignant tumor composed of both carcinomatous and sarcomatous elements. We report a case of esophageal carcinosarcoma in a 56-year-old woman with dysphagia. Esophageal ulcerative tumors were detected by endoscopy and resected by thoracoscopic esophagectomy. Carcinosarcoma was confirmed by the presence of both carcinomatous and sarcomatous tumor components. On immunohistochemistry, the sarcomatous area was positive for keratin staining, while the sarcomatous area was positive for vimentin staining. The tumor reportedly had a better prognosis than SCC of the esophagus, especially in terms of survival rate. The patient's disease was classified as ypT3N0M0, ypStage II. No definitive diagnosis was made preoperatively. We report this case along with a review of the literature.

Increased Expression of the lncRNA NRON Along With NFATc1/PIM-1 in Labial Salivary Glands of Sjögren's Syndrome Patients.

The aim of our study was to analyze the expressions of nuclear factor of activated T cells (NFAT)-related substances including long noncoding RNA NRON which participates in pathophysiology of Sjögren's syndrome (SS), and to assess the histologic findings in individuals with SS. In this study, the expressions of NRON, NFATc1, CD3/CD4, and proviral integration site for Moloney murine leukemia virus (PIM)-1 were examined by in situ hybridization, immunohistochemical analysis, and immunofluorescence in labial salivary glands (LSGs) obtained from 16 patients with SS and five controls. The microcell count method has been applied to calculate the NFATc1-positive area/infiltrating cell area in LSGs, and we compared those results to the infiltrating cell area, focus score, serum immunoglobulin G, and the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index. The NRON expression in the nuclei of cell-infiltration lesions of the SS patients were prominent. The NFATc1 expression was strong in the cytoplasm of infiltrating mononuclear cells and weak in ducts of both SS and controls. In SS, the NFATc1-positive area/infiltrating cell area was positively correlated with the infiltrating cell area and focus score. CD3/CD4 was expressed in infiltrating mononuclear cells, and PIM-1 colocalized with NFATc1 in the cytoplasm. These results suggest NRON along with NFATc1/PIM-1 in SS LSGs might participate in SS pathophysiology.

Pretreatment Absolute Lymphocyte Count and Neutrophil-to-lymphocyte Ratio Are Prognostic Factors for Stage III Breast Cancer.

BACKGROUND/AIM: Stage III breast cancer comprises a broad spectrum of disease, including the extent of supraclavicular/internal mammary lymph node metastasis. In this study, we evaluated the usefulness of the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of patients with stage III breast cancer. PATIENTS AND METHODS: Seventy-five patients with stage III breast cancer who underwent surgery were included. We compared their clinicopathological factors according to the presence or not of supraclavicular/internal mammary lymph node metastasis, and pretreatment ALC or NLR. RESULTS: Patients with metastasis of the studied lymph nodes had a poorer prognosis in comparison to those without metastasis. In patients without these types of lymph node metastasis, both the ALC and NLR were predictive factors for relapse-free and overall survival. Among these patients, those with a low ALC or high NLR had recurrence-free and overall survival comparable to those of patients with supraclavicular/internal mammary lymph node metastasis. CONCLUSION: Pretreatment ALC and NLR were prognostic factors for patients with stage III breast cancer.

A case of cystic duct syndrome.

In the diagnosis of gallbladder induced pain without gallstones, drip-infusion cholangiographic computed tomography, and endoscopic retrograde cholangiography are useful in differentiating cystic duct syndrome.

Aberrant common hepatic artery from the left gastric artery and with no connection to the gastroduodenal artery: Risky vascular anomaly in gastrectomy.

Knowledge of anatomical variations of the celiac axis is important in upper abdominal surgery. Aberrant common hepatic artery originating from the left gastric artery without connecting the gastroduodenal artery is extremely rare. Preoperative vascular anatomy assessment using reconstructions of CT images may be useful for safe surgical procedure.

Immunotherapeutic advances in gastric cancer.

Advanced gastric cancers are responsible for overwhelming human suffering and death. Despite the development of combination chemotherapies, the survival rates of patients with gastric cancer remain unsatisfactory. Given the growing evidence of the benefits of immunotherapy as an alternative treatment for other cancers such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and refractory Hodgkin's lymphoma, researchers have begun to explore its application in the treatment of gastric cancer. Three types of immunotherapy have shown promising effects against gastric cancer: immune checkpoint inhibitors, chimeric antigen rector (CAR)-T cells, and tumor vaccines. Clinical trials have used either immuno-oncology monotherapies or combination immuno-chemotherapies to improve the overall survival times and objective response rates of patients with gastric cancer. We review the clinical efficacy of immunotherapy including checkpoint inhibitors, CAR­T, and tumor vaccines, in the treatment of gastric cancer. Based on initial evidence, we believe that immunotherapy could positively impact the natural history and improve the outcomes of a subgroup of patients with gastric cancer.

Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy.

INTRODUCTION: Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. METHODS: Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. RESULTS: Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. CONCLUSIONS: Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs.

Prevention of well-leg compartment syndrome following lengthy medical operations in the lithotomy position.

PURPOSE: Compartment syndrome that occurs after lengthy surgery in the lithotomy position is known as well-leg compartment syndrome. It has serious consequences for patients, including amyotrophic renal failure, limb loss, and sometimes even death. This study aimed to identify effective preventive measures against well-leg compartment syndrome using a retrospective cohort study of 1,951 patients (985 and 966 in the prevention and control groups, respectively). MATERIAL AND METHODS: The following preventive interventions were analyzed: (1) changing from the lithotomy position to the open-leg position, (2) removing lower leg pressure caused by the lithotomy position, (3) limiting leg elevation based on the height of the right atrium, (4) horizontally repositioning the operating table every 3 hours, and (5) decompressing the contact area of the lower leg in the lithotomy position during operation. RESULTS: Eight cases of well-leg compartment syndrome occurred in the control group, whereas no well-leg compartment syndrome occurred in the prevention group. CONCLUSION: These findings suggest that the five interventions assessed can prevent the development of well-leg compartment syndrome.

Serum kynurenine levels are a novel biomarker to predict the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: We examined serum kynurenine levels in patients with chronic hepatitis C virus infection, and the relationship between serum kynurenine and prognosis in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C. METHODS: We retrospectively analyzed 604 patients with HCC diagnosed between January 1999 and December 2015, and 288 patients without HCC who were seen at the National Hospital Organization Nagasaki Medical Center between October 2014 and November 2017. The association between serum kynurenine and prognosis was evaluated using the Cox's proportional hazards regression analysis. RESULTS: Patients with HCC had significantly higher values of serum kynurenine than patients without HCC (median: 557.1 vs. 464.2 ng/mL, p<0.001). Five-year survival rates of HCC patients with serum kynurenine ≥900 (n = 65), 600-899 (n = 194), and <600 ng/mL (n = 345) were 30.6%, 47.4%, and 61.4%, respectively (p = 0.001, log-rank test). Multivariate analysis identified serum kynurenine as an independent predictor for prognosis of HCC patients. The hazard ratio of serum kynurenine ≥900, and 600-899 compared with serum kynurenine <600 ng/mL were 1.91 (p<0.001) and 1.37 (p = 0.015), respectively. CONCLUSIONS: A high level of serum kynurenine correlated with poor prognosis of HCC. Serum kynurenine levels may be a novel biomarker to predict the prognosis of patients with HCC. The development of drugs that inhibit kynurenine production is expected to help improve the prognosis of patients with HCC.