The usefulness of laparoscopic surgery for inguinal endometriosis.

BACKGROUND: Inguinal endometriosis is a rare clinical disease with an unclear etiology and pathogenesis, and its diagnosis requires accurate medical history-taking and histological examination. However, surgical treatment for the condition has not yet been standardized. This report presents two cases of inguinal endometriosis. CASE PRESENTATION: The first patient was a 36-year-old woman who complained of pain and swelling in her right inguinal region. Physical examination revealed a soft, tender right inguinal mass. The size of the mass repeatedly increased and decreased during menstruation and did not show swelling with abdominal pressure. Magnetic resonance imaging showed a 3.5 × 2.5 cm mass with high intensity on T2-weighted imaging in the right inguinal canal, and no communication was found between the lesion site and the abdominal cavity. We diagnosed this case as inguinal endometriosis and managed it using an anterior approach and laparoscopic observation. The second patient was a 51-year-old woman who presented with an intermittently painful mass in her right inguinal region. The mass tended to increase in size, with worsening pain before menstruation. Abdominal computed tomography revealed a 2 × 2 cm cystic mass in the right inguinal region. We made a diagnosis of inguinal ectopic endometriosis and decided to operate via the totally extraperitoneal (TEP) method for excision plus transabdominal observation. The postoperative course in both cases was uneventful with no recurrence. CONCLUSIONS: Inguinal endometriosis is a rare entity that should be suspected in patients with cyclical symptoms of inguinal pain and swelling that correlate with their menstrual cycle, which might otherwise be attributed to inguinal hernia. It is crucial to make a preoperative diagnosis based on a careful medical review, physical examination, and imaging studies, and to make an appropriate surgical plan. Particularly, in the case of ectopic inguinal endometriosis involving the canal of Nuck, laparoscopic observation is useful for the intraoperative diagnosis of inguinal endometriosis to help rule out the involvement of other abdominal sites. However, it is important to select and modify the surgical technique to avoid rupturing the endometrisis mass and prevent postoperative recurrence.

Combined resection of the gastroduodenal artery without revascularization in distal pancreatectomy with en bloc celiac axis resection (extended DP-CAR) for pancreatic cancer: A case report.

INTRODUCTION: Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is performed to remove locally advanced pancreatic cancer (LAPC) that involves the celiac axis (CA), the common hepatic artery (CHA), or the root of the splenic artery (SpA). It is not usually applied to LAPC involving both the CA and the gastroduodenal artery (GDA) because transection of the GDA cannot assure hepatic perfusion. Preserving the replaced hepatic artery might allow combined resection of the GDA without revascularization. PRESENTATION OF CASE: A 78-year-old woman who was diagnosed with LAPC of the pancreatic head and body that invaded the GDA and proper hepatic artery, as well as the CA. The left hepatic artery (LHA) was solitarily branched from the left gastric artery (LGA), which was branched from proximal to the confluence of the CHA and the SpA. The root of the LGA was intact. We successfully performed DP-CAR with combined resection of the GDA, without revascularization, by preserving the LGA. DISCUSSION: This is the first English literature case of extended DP-CAR with preservation of the replaced LHA (r-LHA). Aberrant right and left hepatic arteries are common variations. Checking the arterial variations is very important when deciding the treatment strategy for LAPC, especially in cases that appear unresectable. CONCLUSION: Our case indicated that the r-LHA alone can supply the entire liver in extended DP-CAR. The resectability must be decided with close evaluations of the vessel variations and the tumor status.

Long-term disease-free survival of an undifferentiated pleomorphic sarcoma of the spleen: A case report and literature review.

INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) primarily occurs in the soft tissues of the extremities, trunk, and retroperitoneum. As the primary UPS of the spleen (splenic UPS) is extremely rare, to the best of our knowledge, only 19 cases have been reported in English literature. No cases of long-term survival without a local or distant recurrence have been reported. PATIENT CONCERNS: We report the case of a 37-year-old man who was referred to our hospital for a splenic tumor. He had no past medical or relevant familial history. On abdominal computed tomography (CT), a low attenuation solid mass and cystic component with mural calcifications were present at the lower pole of his spleen. The fluorodeoxyglucose-positron emission tomography (CT) indicated it as malignant tumor of the spleen. DIAGNOSES: The patient's provisional diagnosis was deduced to be angiosarcoma, which was the most common malignant tumor of the spleen. INTERVENTIONS: An elective laparoscopic splenectomy was performed, and the histology of the tumor was consistent with UPS (pT1, pN0, cM0, and AJCC8th). No adjuvant therapy was administered. OUTCOMES: Ten years have passed since the patient's splenectomy, and he continues to do well, without evidence of local or distant recurrence. LESSONS: To the best of our knowledge, this is the first case of long-term recurrence-free survival after surgical management of a splenic UPS. It is probable that radical splenectomy during the disease played the most important role in the patient's long-term survival. Understanding the characteristic findings of a splenic UPS in an abdominal CT may help to diagnose properly.

Recurrence of a congenital diaphragmatic hernia 57 years postoperatively: A case report and review of the literature.

RATIONALE: Postoperative recurrence of congenital diaphragmatic hernia (CDH) in adults is very rare. There is currently no precedent and no established treatment. We encountered a case of CDH which recurred 57 years, postoperatively. PATIENT CONCERNS: A 57-year-old man with dyspnea on exertion was referred to our hospital. He had undergone surgery at the same hospital for CDH when he was 46 days old. DIAGNOSIS AND INTERVENTIONS: Laboratory studies, except diagnostic imaging and spirometry, were otherwise within normal limits. He was diagnosed with recurrent CDH based on computed tomography and underwent laparoscopic surgery. OUTCOMES: His postoperative course was uneventful, and there was no recurrence on follow-up. LESSONS: We reported our encounter with a case of recurrent CDH, more than 50 years after the initial surgery. When managing diaphragmatic hernias, prompt surgical treatment, with consideration to prior surgical history for CDH, leads to satisfactory results.

Is Surgical Treatment Effective or Contraindicated in Patients with Colorectal Cancer Liver Metastases Exhibiting Extrahepatic Metastasis?

BACKGROUND: Surgical resection for patients with hepatic and extrahepatic colorectal metastases remains controversial. This study aimed to determine the efficacy of curative resection of distant extrahepatic metastatic lesions in patients with colorectal liver metastases (CRLM). METHODS: From 2007 to 2019, 377 patients with CRLM were treated; of these, 323 patients underwent hepatectomy, and 54 patients with extrahepatic metastases (EHM) had received only chemotherapy. Survival and recurrence were compared between patients with and without EHM. Variables potentially associated with survival were analyzed in univariate and multivariate analyses. RESULTS: Among patients who underwent hepatectomy, the median, 3-, and 5-year overall survival rates for patients with EHM (n = 60) were 32 months, 47%, and 28%, respectively, while those for patients without EHM (n = 263) were 115 months, 79%, and 66%, respectively (p < 0.001). Furthermore, outcomes were similar in R2 patients with EHM and those with unresectable tumors. However, outcomes were significantly better in the R0/1 group than in the R2 and unresectable groups (p < 0.001). Among patients with EHM, multivariate analysis revealed that higher clinical risk score, incomplete resection of all EHM, extrahepatic disease detected intraoperatively, and previous treatment with neoadjuvant chemotherapy were independently associated with worse survival. CONCLUSIONS: In patients with CRLM with EHM (liver + one organ), gross curative resection is necessary when surgical treatment is contemplated, and resection of liver metastases should be performed in patients with CRLM with smaller and fewer tumors (e.g., H1).

Surgical management of intraoperatively diagnosed portal annular pancreas: Two case reports.

RATIONALE: Portal annular pancreas (PAP) is a rare pancreatic anomaly characterized by portal vein encasement in the pancreatic parenchyma. Due to its rarity, PAP may often be missed on preoperative computed tomography (CT) review, and surgeons may face challenges in dealing with an unexpected intraoperative encounter with PAP. We documented 2 such intraoperatively diagnosed cases and illustrated their surgical management. PATIENTS CONCERNS: In case 1, a 70-year-old man was found to have a 15-mm mass in the pancreatic body and dilatation of the peripheral main pancreatic duct on enhanced CT. Case 2 involved a 46-year-old woman with a history of familial adenomatous polyposis, and rectal cancer with a mass in the duodenal papilla. DIAGNOSES: The patient in case 1 was diagnosed with resectable pancreatic cancer. In case 2, the patient was diagnosed with duodenal papillary carcinoma. INTERVENTIONS: In case 1, the patient underwent distal pancreatectomy with lymph node dissection. In case 2, the patient underwent pancreaticoduodenectomy. Intraoperatively, PAP was observed in both cases. In case 1, after the usual transection at the right border of the portal vein, an additional dissection was performed on the dorsal pancreas using a powered linear stapler. In case 2, an additional section was made in the pancreatic body caudal to the cricoid pancreatic junction so that the pancreatic cross-section was oriented in 1 plane. OUTCOMES: The patient in case 1 was discharged without complications. In case 2, although the patient had a grade-B pancreatic fistula (International Study Group of Pancreatic Fistula Classification), the patient recovered conservatively and was discharged without significant complications. In both cases, a retrospective review identified PAP in patients' preoperative CT images. LESSONS: Both cases required ingenuity during pancreatectomy. Awareness about PAP and its management will enable surgeons to prepare for unexpected encounters with the condition. Moreover, surgeons (especially pancreatic surgeons) should consider the possibility of PAP while managing pancreatic anomalies to make appropriate treatment decisions.

Overexpression of PD-1 on T cells promotes tolerance in cardiac transplantation via ICOS-dependent mechanisms.

The programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is a potent inhibitory pathway involved in immune regulation and is a potential therapeutic target in transplantation. In this study, we show that overexpression of PD-1 on T cells (PD-1 Tg) promotes allograft tolerance in a fully MHC-mismatched cardiac transplant model when combined with costimulation blockade with CTLA-4-Ig. PD-1 overexpression on T cells also protected against chronic rejection in a single MHC II-mismatched cardiac transplant model, whereas the overexpression still allowed the generation of an effective immune response against an influenza A virus. Notably, Tregs from PD-1 Tg mice were required for tolerance induction and presented greater ICOS expression than those from WT mice. The survival benefit of PD-1 Tg recipients required ICOS signaling and donor PD-L1 expression. These results indicate that modulation of PD-1 expression, in combination with a costimulation blockade, is a promising therapeutic target to promote transplant tolerance.

Esophago-bronchial fistula treated by the Over-The-Scope-Clipping (OTSC) system with argon beam electrocoagulation: A case report.

RATIONALE: An esophago-bronchial fistula is one of the rare postoperative complications of esophageal cancer. There are various medical treatments, including suturing, endoscopic clip, and fibrin glue. However, these treatments often lead to unsatisfactory results, causing physicians to opt for surgical alternatives. The Over-The-Scope-Clipping (OTSC) system offers an alternative method for fistula closure. It can capture a large amount of tissue and is able to compress the lesion until it has fully healed. However, data indicating the efficacy of OTSC for esophago-bronchial fistula are limited. PATIENT CONCERNS: A 64-year-old man presented with an esophago-bronchial fistula after surgery for esophageal cancer. We chose to use a stent as the first line of treatment, but the fistula did not close. DIAGNOSES: Intractable esophago-bronchial fistula associated with esophageal surgery. INTERVENTIONS AND OUTCOMES: On the 94th postoperative day, fistula closure with OTSC was performed, and no leakage of the contrast agent was observed during fluoroscopy. We also attempted to close the fistula by combining OTSC and argon plasma coagulation (APC) to burn off the scar tissue from around the fistula. The fistula gradually shrank after a total of 4 rounds of OTSC, and closure of the fistula was achieved on the 185th postoperative day. There were no adverse events during the treatment of this case. LESSONS: We demonstrate that OTSC is useful in the management of esophago-bronchial fistulas, and may become a standard procedure for the endoscopic treatment of esophago-bronchial fistulas, replacing the use of stents, clips, or glue.

Association Between Neoadjuvant Chemoradiotherapy and Intractable Serous Ascites After Pancreaticoduodenectomy for Pancreatic Cancer.

BACKGROUND: Intractable serous (not chylous) ascites (IA) that infrequently develops early following pancreaticoduodenectomy (PD) for pancreatic cancer is a life-threatening problem. The relationship between neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer and the incidence of IA following PD has not been evaluated. This study aims to identify the risk factors associated with IA that develops early after PD for pancreatic cancer. METHODS: We retrospectively identified 94 patients who underwent PD for pancreatic cancer at the Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan, from April 2012 to March 2020. Data on 29 parameters were obtained from medical records. Univariate and multivariate analyses were conducted to identify independent risk factors. Levels of serum albumin were compared before and after NACRT to analyze its effect. Survival analysis was also conducted. RESULTS: Of the 92 patients included in this study, 8 (8.70%) were categorized into the IA group. Multivariate analysis identified NACRT [odds ratio (OR) 27, 95% confidence interval (CI) 1.87-394, p = 0.016)] and hypoalbuminemia (≤ 1.6 g/dl) just after the operation (OR 50, 95% CI 1.68-1516, p = 0.024) as risk factors. The level of serum albumin was significantly decreased following NACRT. The IA group had poorer prognosis than the control group. CONCLUSIONS: IA is a serious problem that aggravates patient's prognosis. Postoperative lymphatic leak might be a trigger of IA. NACRT was a major risk factor, followed by hypoalbuminemia caused by various reasons. These factors may act synergistically and cause IA.

Laparoscopic cholecystectomy for cholecystitis using direct gallbladder indocyanine green injection fluorescence cholangiography: A case report.

: Laparoscopic cholecystectomy is the treatment of choice for almost all biliary diseases. We present a novel technique using near-infrared fluorescence imaging for laparoscopic cholecystectomy. : A 78-year-old woman diagnosed with acute cholecystitis (Grade II) was scheduled for emergency laparoscopy according to Tokyo Guidelines 2018. We performed a direct percutaneous drainage of the gallbladder to grasp the gallbladder itself. Subsequently, indocyanine green was administered into the gallbladder through the same tube, and the cystic and common bile ducts could be easily detected. The postoperative course was good, and the patient was discharged in remission nine days after the surgery. : Real-time fluorescence cholangiography with indocyanine green is reliable for biliary anatomy visualization before the dissection of the Calot's triangle. Our method of indocyanine green injection into the same drainage catheter does not require pre-preparation and can be simultaneously performed with drainage intraoperatively. This surgical technique is simple, straightforward, and effective and can be useful in intraoperative decision-making, especially during laparoscopic cholecystectomy.

Is Postoperative Adjuvant Transcatheter Arterial Infusion Therapy Effective for Patients with Hepatocellular Carcinoma who Underwent Hepatectomy? A Prospective Randomized Controlled Trial.

BACKGROUND: The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone. METHODS: From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900). RESULTS: The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients. CONCLUSIONS: Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.

The usefulness of intraoperative neurological monitoring for esophageal cancer with double aortic arch; a case report.

BACKGROUND: Double aortic arch (DAA) is a congenital anomaly of the aorta. Esophageal cancer with DAA is rare, and consequently, the appropriate surgical approach has not been standardized. Herein, we report the utilization of intraoperative neurological monitoring (IONM) system to preserve the function of the recurrent laryngeal nerve. CASE PRESENTATION: A 79-year-old man with esophageal cancer was diagnosed with DAA incidentally. The descending aorta was located on the right side of the thoracic vertebrae. Safe dissection of the mediastinal lymph nodes was difficult using the right transthoracic approach because of the anatomical abnormalities. During surgery, we used cervical mediastinoscopy combined with the IONM system to preserve the bilateral recurrent laryngeal nerves. Severe complications, including recurrent nerve palsy, were not observed postoperatively. CONCLUSION: IONM may be useful for evaluation of the function of the recurrent laryngeal nerve, and it would be suitable for atypical cases of esophageal cancer.

Surgical treatment of gastric venous congestion in association with extended resection of pancreas: a case report.

BACKGROUND: Total pancreatectomy is performed for chronic pancreatitis, tumors involving the entire pancreas or remnant pancreas after pancreatectomy. Gastric venous congestion and bleeding may be associated with total pancreatectomy. We report the case of a patient who underwent left gastric vein to splenic vein bypass to relieve gastric venous congestion during total pancreatectomy for remnant pancreatic cancer. CASE PRESENTATION: A 60-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy for cancer of the pancreatic head. A follow-up computed tomography revealed a low-density tumor of the remnant pancreas. The pathological diagnosis was adenocarcinoma on endoscopic ultrasound-fine needle aspiration. Total resection of the remnant pancreas was performed for the tumor 3 years after the initial surgery. We ligated the splenic vein at the point of distal side of the left gastric vein confluent. Immediately, the vein congestion around the stomach was confirmed. We found the stenosis of the confluent between the left gastric vein and splenic vein. We subsequently anastomosed the left gastric vein and splenic vein, following which the gastric venous congestion was relieved. CONCLUSION: In cases wherein all the drainage veins from the stomach are removed, an anastomosis between the left gastric vein and splenic vein can be effectively used to prevent gastric venous congestion and bleeding after total pancreatectomy.

Initial pulmonary metastasis after pancreatectomy for pancreatic ductal adenocarcinoma.

Patients who undergo pancreatectomy for pancreatic ductal adenocarcinoma (PDA) develop relatively early recurrence, but pulmonary metastasis from PDA is rare. Between January 2008 and December 2016, a total of 120 consecutive patients underwent pancreatectomy for primary PDA at Osaka Medical College Hospital. Among these, 13 patients developed pulmonary metastasis and 6 patients underwent pulmonary metastasectomy. Among these patients, the median disease-free survival following initial pancreatic surgery was 26.1 months, and the median overall survival (OS) interval was 39 months. On the other hand, seven patients did not undergo pulmonary resection. The median OS interval of these patients was 33 months. The 1-, 3-, and 5-year OS rates were 100%, 80%, and 60%, respectively, for patients who underwent pulmonary metastasectomy and 100.0%, 42.8%, and 0%, respectively, for those who did not undergo the procedure. Our experience has shown that surgical resection may lengthen the survival time of patients who tolerate surgery.

Duodenal obstruction due to chronic pancreatitis of the pancreas tail treated by surgical intervention: A case report.

RATIONALE: Duodenal obstruction (DO) sometimes induces the groove pancreatitis. However, the case of DO due to chronic pancreatitis in pancreas tail (CPPT) is extremely rare. Therefore, the managements of DO caused by CPPT have not been established yet. PATIENT CONCERNS: A 68-year-old man, who was under the treatment of chronic pancreatitis, presented to our hospital with nausea and abdominal pain. He was diagnosed as DO caused by CPPT. The Conservative treatment, including the nasogastric aspiration and intravenous infusion under the absence of food, was performed. The drainage fluid from naso-gastric tube had been more than 2000 ml per a day although continuing treatment for 14 days. Hence, we decided that the conservative therapy was failed and the surgical intervention was required. DIAGNOSIS: Computed tomography showed gastroduodenal expansion due to stenosis at the horizontal portion of the duodenum with increasing pancreatic pseudocyst. The contrast radiography of the duodenum showed severe stenosis around Treitz ligament. His pre-surgical diagnosis was DO due to CPPT through exclusion of other etiologies for DO such as annular pancreas, SMA syndrome, duodenal diaphragm and Crohn disease. INTERVENTION: Spleen preserving distal pancreatectomy (Warshaw operation) was performed with gastrojejunostomy. During surgery, marked redness and thickness of the mesenteric serosa around Treiz ligament were observed. His surgical findings were supported our preoperative prediction. OUTCOMES: The patient was successfully treated and discharged uneventfully after postoperative day 14. At the 9 months follow-up visit, the patient is still doing well without any symptoms. CONCLUSION: Combination of gastrojejunostomy and Warshaw operation is one of the ideal surgical procedures for patients of DO due to CPPT.

Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms.

BACKGROUND: Transplantation is the treatment of choice for many patients with end-stage organ disease. Despite advances in immunosuppression, long-term outcomes remain suboptimal, hampered by drug toxicity and immune-mediated injury, the leading cause of late graft loss. The development of therapies that promote regulation while suppressing effector immunity is imperative to improve graft survival and minimize conventional immunosuppression. Notch signaling is a highly conserved pathway pivotal to T-cell differentiation and function, rendering it a target of interest in efforts to manipulate T cell-mediated immunity. METHODS: We investigated the pattern of Notch-1 expression in effector and regulatory T cells (Tregs) in both murine and human recipients of a solid-organ transplant. Using a selective human anti-Notch-1 antibody (aNotch-1), we examined the effect of Notch-1 receptor inhibition in full major histocompatibility complex-mismatch murine cardiac and lung transplant models, and in a humanized skin transplant model. On the basis of our findings, we further used a genetic approach to investigate the effect of selective Notch-1 inhibition in Tregs. RESULTS: We observed an increased proportion of Tregs expressing surface and intracellular (activated) Notch-1 in comparison with conventional T cells, both in mice with transplants and in the peripheral blood of patients with transplants. In the murine cardiac transplant model, peritransplant administration of aNotch-1 (days 0, 2, 4, 6, 8, and 10) significantly prolonged allograft survival in comparison with immunoglobulin G-treated controls. Similarly, aNotch-1 treatment improved both histological and functional outcomes in the murine lung transplant model. The use of aNotch-1 resulted in a reduced proportion of both splenic and intragraft conventional T cells, while increasing the proportion of Tregs. Furthermore, Tregs isolated from aNotch-1-treated mice showed enhanced suppressive function on a per-cell basis, confirmed with selective Notch-1 deletion in Tregs (Foxp3EGFPCreNotch1fl/fl). Notch-1 blockade inhibited the mammalian target of rapamycin pathway and increased the phosphorylation of STAT5 (signal transducer and activator of transcription 5) in murine Tregs. Notch-1low Tregs isolated from human peripheral blood exhibited more potent suppressive capacity than Notch-1high Tregs. Last, the combination of aNotch-1 with costimulation blockade induced long-term tolerance in a cardiac transplant model, and this tolerance was dependent on CTLA-4 (cytotoxic T-lymphocyte-associated antigen-4) signaling. CONCLUSIONS: Our data reveal a promising, clinically relevant approach for immune modulation in transplantation by selectively targeting Notch-1.

Lymphocyte-to-Monocyte Ratio and Prognostic Nutritional Index Predict Poor Prognosis in Patients on Chemotherapy for Unresectable Pancreatic Cancer.

BACKGROUND/AIM: Recently, several systemic inflammation-based scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), modified Glasgow prognostic score (GPS), and prognostic nutritional index (PNI), have been proposed as prognostic factors for several cancers. In this study, we aimed to determine the influence of systemic inflammation-based scores and nutrition status on the outcome in patients receiving chemotherapy for unresectable pancreatic cancer. PATIENTS AND METHODS: A total of 93 consecutive patients who underwent chemotherapy for unresectable pancreatic cancer at Osaka Medical College Hospital, Takatsuki, Japan, between January 2008 and December 2014 were eligible for this study. The outcomes assessment included one- and two-year overall survival (OS) rates, according to changes in LMR and PNI prior to, and following chemotherapy. RESULTS: LMR<3.4 (OR=5.02, 95%CI=1.559-19.85, p=0.005) and PNI<43 (OR=3.53, 95%CI=1.057-14.21, p=0.03) independently predicted a poor outcome in patients receiving chemotherapy for unresectable pancreatic cancer using multivariate analysis. According to changes in LMR and PNI prior to, and following chemotherapy, compared to patients who maintained LMR≥3.4, patients whose LMR decreased from ≥3.4 to <3.4 had significantly lower OS rates (p<0.001). Similarly, compared to patients who maintained PNI≥43, patients whose PNI deteriorated had significantly lower OS rates (56.2% versus 25.8% at one year, and 12.5% versus 0% at two years; p=0.003). CONCLUSION: LMR<3.4 and PNI<43 are identified as independent predictors of poor outcome in patients receiving chemotherapy for unresectable pancreatic cancer. LMR and PNI may help clinicians identify patients at high risk for poor prognosis.

Computational modeling of pancreatic cancer patients receiving FOLFIRINOX and gemcitabine-based therapies identifies optimum intervention strategies.

Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questions remain as to the timing and sequence of therapies and the role of radiotherapy for unresectable PDAC. Here we developed a computational analysis platform to investigate the dynamics of growth, metastasis and treatment response to FFX, gemcitabine (GEM), and GEM+nab-paclitaxel. Our approach was informed using data of 1,089 patients treated at the Massachusetts General Hospital and validated using an independent cohort from Osaka Medical College. Our framework establishes a logistic growth pattern of PDAC and defines the Local Advancement Index (LAI), which determines the eventual primary tumor size and predicts the number of metastases. We found that a smaller LAI leads to a larger metastatic burden. Furthermore, our analyses ascertain that i) radiotherapy after induction chemotherapy improves survival in cases receiving induction FFX or with larger LAI, ii) neoadjuvant chemotherapy improves survival in cases with resectable PDAC, and iii) temporary cessations of chemotherapies do not impact overall survival, which supports the feasibility of treatment holidays for patients with FFX-associated adverse effects. Our findings inform clinical decision-making for PDAC patients and allow for the rational design of clinical strategies using FFX, GEM, GEM+nab-paclitaxel, neoadjuvant chemotherapy, and radiation.

Is neoadjuvant chemotherapy appropriate for patients with resectable liver metastases from colorectal cancer?

PURPOSE: Neoadjuvant chemotherapy (NAC) for resectable liver metastasis from colorectal cancer (CRLM) is used widely, but its efficacy lacks clear evidence. This study aimed to clarify its worth and develop appropriate treatment strategies for CRLM. METHODS: We analyzed, retrospectively, the clinicopathological factors and outcomes of 137 patients treated for resectable CRLM between 2006 and 2015, with upfront surgery (NAC- group; n = 117) or initial NAC treatment (NAC+ group; n = 20). RESULTS: The time to surgical failure (TSF) and overall survival (OS) after initial treatment were significantly worse in the NAC+ group than in the NAC- group (P = 0.002 and P = 0.032, respectively). At hepatectomy, the NAC+ group had a lower median prognostic nutrition index (PNI), higher rates of a positive Glasgow Prognostic Score (P = 0.002) and more perioperative blood transfusions (P = 0.027) than the NAC- group. Moreover, the serum albumin (P = 0.006), PNI (P ≤ 0.001) and lymphocyte-to-monocyte ratio (P ≤ 0.001) were significantly decreased and the GPS positive rate was increased from 15 to 35% in the NAC+ group. The OS rates did not differ significantly according to the NAC response (5-year OS rates-CR/PR 67%, SD 60%, PD 38%). CONCLUSIONS: Patients with resectable CRLM should undergo upfront hepatectomy because NAC did not improve OS after initial treatment in these patients.

A Concealed "Natural Orifice": Umbilicus Anatomy for Minimally Invasive Surgery.

INTRODUCTION: A recent development in minimally invasive surgery (MIS) is single-port surgery, where a single large multiport trocar is placed in the umbilicus. All medical schools require that students complete an anatomy course as part of the medical curriculum. However, there is limited instruction regarding the detailed parts of the "umbilicus." In several famous anatomy atlases, the umbilicus is not dissected at all and is merely represented as a button. Until now, the true nature of the umbilicus has not been anatomically demonstrated. METHODS: Five cadavers were obtained from the Osaka Medical College medical student anatomy class. The umbilicus was dissected in the anatomy laboratory, to demonstrate all the layers. A detailed dissection was performed, focusing on the exact center of the umbilicus, in order to ascertain whether there exists a "natural orifice" or a fascial defect. RESULTS: In all cadavers, a small defect of fascia was identified just below the center of the umbilicus. Yellow fatty tissue was present just below the skin in the exact center of the umbilicus. A probe placed exactly in the middle of this defect passes easily through into the abdominal cavity. CONCLUSIONS: With the widespread use of MIS, umbilical incision is commonly used to reduce pain and improve cosmetic results. This study consistently revealed a natural defect of fascia in the center of the umbilicus. Therefore, the umbilicus can be called a concealed "natural orifice." It is important to recognize and utilize this defect effectively to minimize unnecessary tissue trauma during MIS.