Preoperative serum CA19-9 predicts postoperative pancreatic fistula in PDAC patients: retrospective analysis at a single institution.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a critical complication of pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). Recent papers reported that serum carbohydrate antigen (CA)19-9 levels predicted long-term prognosis. We investigated whether preoperative serum CA19-9 levels were associated with POPF in PDAC patients. METHODS: This cohort study was conducted at a single institution retrospectively. Clinicopathologic features were determined using medical records. RESULTS: Among of 196 consecutive patients who underwent pancreatectomy against PDAC, 180 patients whose CA19-9 levels were above the measurement sensitivity, were registered in this study. The patients consisted of 122 patients who underwent pancreaticoduodenectomy and 58 patients who underwent distal pancreatectomy. Several clinicopathological factors, including CA 19-9 level, as well as surgical factors were determined retrospectively based on the medical records. Patients with high CA19-9 levels had a significantly higher incidence of POPF than those with low levels (43.9 vs. 13.0%, P < 0.0001). The receiver operating characteristic curves calculated that the cutoff CA19-9 value to predict POPF was 428 U/mL. CA19-9, BMI, curability, and histology were statistically significant risk factors for POPF by univariate analysis. Multivariate analysis showed that CA19-9 and BMI levels were statistically significant independent risk factors for POPF. CA19-9 levels were correlated with both histology and curability. Disease free survival and overall survival of patients with higher levels of CA19-9 were significantly shorter than that of patients with lower levels of preoperative serum CA19-9. CONCLUSIONS: In patients undergoing pancreatectomy for PDAC, higher preoperative CA19-9 levels are a significant predictor for POPF.

Comprehensive Cancer Genomic Profiling of Liver Metastasis Led to the Unexpected Identification of Colorectal Cancer.

Comprehensive genomic profiling (CGP) of a metastatic liver tumor biopsy specimen suggested that the patient, who was initially diagnosed with cholangiocarcinoma, had colorectal cancer. The identification of both FBXW7 and APC mutations is deemed characteristic of colorectal cancer. Indeed, subsequent colonoscopy revealed sigmoid colon carcinoma that led to tumor resection followed by systemic chemotherapy. CGP is principally used to identify agents that might potentially benefit the patient. However, results must be interpreted carefully to ensure consistency with the initial diagnosis.

Diagnostic accuracy of preoperative adhesion mapping by ultrasonography for laparoscopic surgery in patients with past abdominal surgery with special reference to loose adhesion.

PURPOSE: Endoscopic surgery is widely accepted for both elective and emergent abdominal surgery. This study was performed to assess the accuracy of preoperative adhesion mapping by abdominal ultrasonography (US). METHODS: Intra-abdominal intestinal adhesions on the abdominal wall in 50 patients with a history of abdominal surgery were prospectively assessed by the visceral slide test with US before laparoscopic surgery from 2019 to 2022. Adhesion was assessed in six separate abdominal zones during US. Actual adhesion on the abdominal wall was confirmed during laparoscopic surgery. RESULTS: The sliding distances in upper right, upper central, upper left, lower right, lower central, and lower left zones in patients with versus without intestinal adhesion were 4.4 versus 1.4 cm (P = .004), 3.4 versus 2.5 cm, 4.3 versus 1.3 cm (P = .011), 3.1 versus 1.5 cm (P = .0014), 3.3 versus 1.1 cm (P = .013), and 3.4 versus 0.8 cm (P = .0061), respectively. Receiver operating characteristic analysis revealed the optimal value of sliding distance as 2.5 cm and the area under the curve as 0.86. The specificity of US assessment of adhesion was lower in the central zone than in lateral zones. Loose adhesion mostly seen around the scar was attributed to either filmy tissue or omental adhesion, leading to visceral sliding during US. CONCLUSION: This study revealed the reason for insufficient accuracy of preoperative US assessment of intestinal adhesion around the scar area because of loose adhesion. The upper lateral area might be optimal for first port insertion.

Advanced Cholangiocarcinoma With High Tumor Mutation Burden Achieving Complete Response to Immune Check Point Inhibitor.

BACKGROUND/AIM: Genomic examination of tumor tissue has been clinically accepted, and the identification of actionable mutations for molecular-targeted therapy may provide substantial survival benefit for patients with advanced malignancies. CASE REPORT: A female patient in her 60s showed a stenosis of the afferent loop of the small intestine because of circumferential metastatic tumor 14 months after curative surgery for hilar cholangiocarcinoma. Chemotherapy with gemcitabine plus cisplatin was administered for 18 months. An oncopanel examination was performed during chemotherapy, and a high tumor mutation burden was revealed. At 38 months after surgery, a new recurrent tumor, 2.7 cm in size, was observed in the abdominal wall, which was histologically proven to be metastatic adenocarcinoma. Atezolizumab was administered. After three cycles of treatment, treatment was switched to pembrolizumab because of its acceptance by healthcare insurance. The recurrent tumors in the abdominal wall and small intestine disappeared 6 months after the administration of immune checkpoint inhibitor, and the patient has continued pembrolizumab, surviving for 76 months after surgery without any clinical evidence of tumor. CONCLUSION: Immune checkpoint blockade successfully prolonged the survival of a patient with advanced hilar cholangiocarcinoma with high tumor mutation burden, although the optimal number of mutations for such a successful response needs to be clarified.

Combined Neutrophil-to-Lymphocyte Ratio Score Is Associated With Chemotherapeutic Response and Predicts Prognosis in Patients With Advanced Pancreatic Cancer.

BACKGROUND/AIM: Neutrophil-to-lymphocyte ratio (NLR) is a prognostic indicator for several malignancies, including pancreatic cancer. We developed a novel combined NLR score (cNLRS) based on baseline NLR and change in NLR after chemotherapy (ΔNLR), and examined its prognostic value and role in chemotherapeutic response in patients with advanced pancreatic cancer. PATIENTS AND METHODS: This study retrospectively assessed 210 advanced pancreatic cancer patients receiving chemotherapy between 2010 and 2021. The cNLRS was developed and its association with chemotherapeutic response and prognosis was investigated. RESULTS: The cNLRS consisted of baseline NLR ≥2.5 and ΔNLR ≥0, both of which were remained as independent poor predictors of prognosis adjusting for other traditional clinicopathological features. A high cNLRS served as an independent prognostic factor of reduced overall survival. Of note, the cNLRS was significantly associated with disease control rate and treatment duration not only in 1st line treatment but also in 2nd line treatment. CONCLUSION: The cNLRS established as a useful prognostic biomarker might be associated with chemotherapeutic response and could predict survival in advanced patients with pancreatic ductal adenocarcinoma treated with chemotherapy.

Long-term survivor of giant pancreatic solid pseudopapillary neoplasm with splenic infiltration and lymph node metastasis.

A man in his 70s with a 10 cm abdominal mass in the tail of the pancreas was diagnosed with pancreatic tail cancer. Distal pancreatectomy with curative intent was performed. Since tumour invasion of the spleen and transverse colon was suspected, pancreatectomy with splenectomy, left adrenalectomy and partial transverse colectomy was performed. Pathological examination of the resected specimen showed a giant pancreatic tumour, and a diagnosis of locally invasive solid pseudopapillary neoplasm (SPN) of the pancreas was made. The patient achieved 8-year survival without any recurrences. We herein report a very rare case of a giant pancreatic SPN with splenic infiltration and lymph node metastasis that was cured by resection.

A case of accessory hepatic duct entering cystic duct successfully treated by laparoscopic cholecystectomy for cholecystolithiasis.

Although laparoscopic cholecystectomy is a well-established surgical procedure, an accessory hepatic duct (AcHD) entering the cystic duct is poorly understood. A 77-year-old woman with symptomatic cholecystlithiasis was referred to our hospital. Abdominal ultrasonography indicated several small stones in the gall bladder. Magnetic resonance cholangiopancreatography (MRCP) did not reveal an anomalous cystic duct. Dissecting the gall bladder bed at operation, AcHD entering the cystic duct was suspected. Intraoperative cholangiography revealed that B5 branch entered the cystic duct. We ligated the AcHD, and divided it. Laparoscopic cholecystectomy was completed, and the patient was discharged without any complication. A week after the operation, MRCP showed that ventral branch of B5 was dilated. The patient showed no symptom for more than a year. The present case exhibited extremely rare AcHD entering the cystic duct, which was hardly recognized before surgery. It is possible to recognize such anomalous variants with standard laparoscopic approach based on 2018 Tokyo Guidelines and with attention to the possibilities of AcHD entering the cystic duct.

[A resected case of gastric regional lymph node metastasis from ascending colon cancer].

A 67-year-old man underwent right hemi-colectomy for ascending colon cancer in 2007. One year later, he was diagnosed as early gastric cancer, and endoscopic submucosal dissection was performed. Pathologically, cancer cells were detected on the vertical margin, so we conducted distal gastrectomy. A dissected lymph node around the hepatic artery was histologically proved to contain adenocarcinoma cells. The cancer cells were positive for CK20. Colon cancer cells were also positive for CK20 but gastric cancer cells were focally positive for CK20. This pattern of CK staining suggested the ascending colon cancer metastasized to a gastric regional lymph node.

[A resected case of locally invasive rectal cancer successfully treated with neoadjuvant capecitabine, oxaliplatin, bevacizumab and radiation therapy].

A 57-year-old man was admitted to our hospital with a complaint of perineal pain. He was diagnosed as advanced rectal cancer with an invasion of prostate, and we conducted neoadjuvant capecitabine, oxaliplatin, bevacizumab and radiation therapy. After chemoradiation therapy, the tumor regressed to an ulcerative lesion without invasion of the prostate. Abdominoperineal resection was then performed without radical resection. The tumor regressed to an ulcer and only a few cancer cells were detected in the submucosal layer pathologically.

Population pharmacokinetics and renal toxicity of cisplatin in cancer patients with renal dysfunction.

PURPOSE: The pharmacokinetics (PKs) of cisplatin have not been investigated in patients with renal dysfunction, characterized by creatinine clearance (Ccr) < 60 mL/min. In this study, we performed a population pharmacokinetic (PPK) analysis of unchanged cisplatin in patients with renal dysfunction. We investigated the effects of renal dysfunction on the PKs and nephrotoxicity of unchanged cisplatin. METHODS: We enrolled 23 patients with moderate renal dysfunction (Ccr calculated to be 30-60 mL/min using the Cockcroft-Gault formula) treated with cisplatin. PPK analysis was performed by nonlinear mixed effect modeling using NONMEM (Version 7.2). We evaluated gender, age, body surface area (BSA), weight, baseline Ccr, baseline serum creatinine (Scr), and baseline urea nitrogen as potential covariates. The final model was evaluated using bootstrap analysis. Renal toxicity was evaluated using Common Terminology Criteria for Adverse Events ver. 4.0. The frequency of severe renal dysfunction (Grade 3/4 Scr elevation) was measured in the population. RESULTS: A one-compartment model adequately described the unchanged cisplatin data. The population mean values for clearance (CLtot) and volume of distribution (Vd) were 19.1 L/h [coefficient of variation (CV) 19.4%] and 13.8 L (CV 41.0%), respectively. The final model identified BSA as a significant covariate for CLtot. There were no significant covariates for Vd. No patients suffered from severe nephrotoxicity to the point that hemodialysis was required. CONCLUSION: Moderate renal dysfunction does not affect the PKs of unchanged cisplatin. The increased serum concentration of cisplatin may not lead to increased toxicity in patients with renal dysfunction. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: UMIN000007091 (January 17, 2012).

Roles of Autophagy and Pancreatic Secretory Trypsin Inhibitor in Trypsinogen Activation in Acute Pancreatitis.

The focus of the review is on roles of autophagy and pancreatic secretory trypsin inhibitor (PSTI), an endogenous trypsin inhibitor, in trypsinogen activation in acute pancreatitis. Acute pancreatitis is a disease in which tissues in and around the pancreas are autodigested by pancreatic digestive enzymes. This reaction is triggered by the intrapancreatic activation of trypsinogen. Autophagy causes trypsinogen and cathepsin B, a trypsinogen activator, to colocalize within the autolysosomes. Consequently, if the resultant trypsin activity exceeds the inhibitory activity of PSTI, the pancreatic digestive enzymes are activated, and they cause autodigestion of the acinar cells. Thus, autophagy and PSTI play important roles in the development and suppression of acute pancreatitis, respectively.

A case of right hepatic duct entering cystic duct successfully treated by laparoscopic subtotal cholecystectomy through preoperatively placed biliary stent.

BACKGROUND: Laparoscopic cholecystectomy is a well-established surgical procedure and is one of the most commonly performed gastroenterological surgeries. Therefore, strategy for the management of rare anomalous cystic ducts should be determined. CASE PRESENTATION: A 56-year-old woman was admitted to our hospital owing to upper abdominal pain and diagnosed with acute cholecystitis. Magnetic resonance cholangiopancreatography suspected that several small stones in gallbladder and the right hepatic duct drained into the cystic duct. Endoscopic retrograde cholangiopancreatography confirmed the cystic duct anomaly, and an endoscopic nasobiliary drainage catheter (ENBD) was placed at the right hepatic duct preoperatively. Intraoperative cholangiography with ENBD confirmed the place of division in the gallbladder, and laparoscopic subtotal cholecystectomy was safely performed. CONCLUSIONS: The present case exhibited rare right hepatic duct anomaly draining into the cystic duct, which might have caused biliary tract disorientation and bile duct injury (BDI) intraoperatively. Any surgical technique without awareness of this anomaly preoperatively might insufficiently prevent BDI, and preoperative ENBD would facilitate safe and successful surgery.

Increase in the serum bile acid level predicts the effective hypertrophy of the nonembolized hepatic lobe after right portal vein embolization.

BACKGROUND: The purpose of the present study was to investigate the clinical association between serum bile acid level changes and liver hypertrophy in portal vein embolization (PVE). METHODS: In 31 patients, the serum total bile acid level was prospectively measured before and 1, 3, 5, 7, and 14 days after right PVE. Computed tomographic volumetry was performed before and 25.0 +/- 3.6 days after PVE. RESULTS: Portal vein embolization induced the liver hypertrophy with a median increase in the left lobe volume (ILV) of 165 cm(3) and a median percentage ILV (%ILV) of 29%. Compared with the pretreatment level, the serum bile acid levels significantly increased on day 3 and day 14 after PVE (p = 0.017 and p = 0.003, respectively). In patients with greater hypertrophy after PVE (ILV > 165 cm(3) and %ILV > 30%), the increases in the bile acid level on day 3 were larger than that in those with lesser hypertrophy (p = 0.008 and p = 0.002, respectively). The increase on day 3 positively correlated with the ILV and %ILV (p = 0.003 and p = 0.004, respectively). The serum bile acid levels on day 3, 5, and 7 after PVE increased in patients with %ILV > 30% but not in those with %ILV < or = 30%. CONCLUSIONS: Portal vein embolization increases the serum bile acid level in patients with effective liver hypertrophy in the nonembolized lobe. The increase on day 3 is a useful predictor of effective hypertrophy of the nonembolized lobe. Thus, bile acid signaling may be important for liver regeneration post-PVE.

Farnesyltransferase inhibitor, manumycin a, prevents atherosclerosis development and reduces oxidative stress in apolipoprotein E-deficient mice.

OBJECTIVE: Statins are presumed to exert their antiatherogenic effects in part via lipid-lowering-independent mechanisms. Inhibition of protein farnesylation and/or geranylgeranylation by statins has been postulated to contribute to the lipid-lowering-independent effects. However, a role for protein farnesylation in atherogenesis has not yet been studied. Therefore, we examined the effects of farnesyltransferase inhibitor, manumycin A, on the development of atherosclerosis in apolipoprotein E (apoE)-deficient mice fed a high-fat diet. METHODS AND RESULTS: Manumycin A treatment for 22 weeks decreased Ras activity, and reduced fatty streak lesion size at the aortic sinus to 43% of that in vehicle-treated apoE-deficient mice (P<0.05), while plasma total cholesterol was unaltered. Moreover, manumycin A reduced alpha-smooth muscle actin-positive area to 29% of that in vehicle-treated apoE-deficient mice (P<0.01). The prevention of atherogenesis by manumycin A was accompanied by amelioration of oxidative stress, as judged by reduced ex vivo superoxide production and nitrotyrosine immunoreactivity. CONCLUSIONS: These results indicate that the inhibition of farnesyltransferase prevents the development of mature atherosclerosis with concomitant alleviation of oxidative stress in apoE-deficient mice. The present data highlight farnesyltransferase as a potential molecular target for preventive and/or therapeutic intervention against atherosclerosis.

Combined radical retropubic prostatectomy and abdominoperineal excision of the rectum for locally invasive rectal cancer as a less invasive surgery: report of a case.

The optimal therapy for carcinoma of the rectum with invasion of the prostate gland has not been established. For a patient who has rectal carcinoma invading into the prostate and seminal vesicles and not invading into any other pelvic viscera, we performed combined radical retropubic prostatectomy and abdominoperineal excision of the rectum with reconstruction of the urinary tract by anastomosis of the ureter to the bladder. En bloc excision yielded negative surgical margins. After the operation, the patient had an infection of the abdominal wound and leakage of the anastomosis of the urethra to the bladder. These complications were treated conservatively and improved without becoming critical. The patient now has satisfactory postoperative function of voiding. This technique obviates the need for urinary diversion or urinary reconstruction such as the neobladder in the case of total pelvic exenteration. We consider this procedure is of benefit for improving the quality of life of patients with rectal cancer invading into the prostate.

Internal hernia after laparoscopic right hemicolectomy, report of a case.

Mesenteric defects are often not closed in laparoscopic colectomy. We herein report a case of an internal hernia projecting through a mesenteric defect following laparoscopy-assisted right hemicolectomy. A 74-year-old woman was hospitalized for the surgical treatment of double colon cancer. Preoperative colonoscopy demonstrated the presence of ascending colon and transverse colon cancers. A laparoscopic-assisted right hemicolectomy was performed. The mesenteric defect resulting from the colectomy was not closed. Three months after the surgery, the patient developed a bowel obstruction. Under a diagnosis of strangulated bowel obstruction, we performed a laparotomy, and found a necrotic small bowel, which had passed into the bursa omentalis through the mesenteric defect. We removed the necrotic small bowel and closed the mesenteric defect by suturing. The patient's postoperative course was uneventful. An internal hernia projecting through a mesenteric defect following laparoscopy-assisted right hemicolectomy developed a severe strangulated bowel obstruction.

Hand-assisted laparoscopic spleen-preserving distal pancreatectomy combined with laparoscopic distal gastrectomy for the treatment of pancreatic neuroendocrine tumor with early gastric cancer: Report of a case.

INTRODUCTION: In a distal pancreatectomy combined with a distal gastrectomy, the splenic artery and vein must be conserved. However, it is not easy in pure laparoscopic surgery. We performed a hand-assisted laparoscopic spleen-preserving distal pancreatectomy (HALS-SPDP) combined with a laparoscopic distal gastrectomy (LDG) for the treatment of a pancreatic neuroendocrine tumor (NET) with early gastric cancer. PRESENTATION OF CASE: A 67-year-old male was hospitalized with no complaint. He was diagnosed with a pancreatic tail tumor (1.5cm in diameter) and early gastric cancer. He had undergone an endoscopic submucosal dissection (ESD). The pathohistology of the dissected tissue demonstrated that the histology was moderately differentiated adenocarcinoma, and the depth of the gastric cancer was pT1b2 (submucosal layer ∼1000µm). First, a pancreatectomy was performed extracorporeally under direct vision after detaching the spleen and the distal pancreas from the retroperitoneum under a hand-assisted laparoscopy. After the distal pancreatectomy, an LDG with a D1 lymphadenectomy was performed intracorporeally. The postoperative course was not eventful. Six months after surgery, an enhanced computed tomography (CT) scan revealed the patency of the splenic artery. CONCLUSION: An HALS-SPDP combined with an LDG is beneficial and safe for the patients who have a pancreatic benign or low-grade malignant tumor and gastric cancer.

Significance of lymphadenectomy with splenectomy in radical surgery for advanced (pT3/pT4) remnant gastric cancer.

BACKGROUND: To date, the optimal surgical strategy for remnant gastric cancer has not been determined. The purpose of this study was to clarify the significance of lymphadenectomy with splenectomy in remnant gastric cancer surgery. METHODS: This retrospective cohort study was conducted at the Kumamoto Regional Medical Center. The primary endpoint was overall survival after surgery. We retrospectively analyzed the clinicopathologic features, surgical treatments, and long-term prognosis of remnant gastric cancer patients treated with total gastrectomy. RESULTS: A total of 80 patients with gastric cancer in the remnant stomach after distal gastrectomy and who underwent total gastrectomy were enrolled in the study. Splenectomy was performed in 38 patients. Lymph node metastasis in the splenic hilum was not observed in the patients with pT1/pT2 tumors, whereas nodal metastasis at the splenic hilum was detected in 30.4% of the patients with pT3/pT4 tumors. The survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy, although there was no difference in the patients with pT1/pT2 tumors. Among the patients classified as R0, the survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy. CONCLUSION: Lymphadenectomy with splenectomy in radical surgery is beneficial for patients with advanced (pT3/pT4) remnant gastric cancer.

Pancreatectomy using the no-touch isolation technique followed by extensive intraoperative peritoneal lavage to prevent cancer cell dissemination: a pilot study.

CONTEXT: In pancreatic cancer, even for patients who have undergone curative resection (R0), survival analysis has revealed a poor survival rate due to cancer recurrence. Because the operation itself might have caused the dissemination of these cancer cells, the no-touch isolation technique and extensive intraoperative peritoneal lavage may be a potential operative procedure for improving the outcome. PATIENTS: Eight patients treated by the no-touch isolation technique were compared with 10 patients treated using conventional techniques. MAIN OUTCOME MEASURES: Cancer cell detection rates in the portal venous blood, frequency of recurrence, and survival rate. We also analyzed the lymphatic fluid squeezed from the resected cancerous pancreatic tissue. RESULTS: In 5 out of 10 cases (50%) in the conventional procedure group, CEA mRNA was identified in the portal blood after tumor manipulation, while only 1 out of 8 cases (13%) in the no-touch isolation technique group was positive for portal CEA mRNA. All lymphatic fluid samples squeezed from the resected cancerous pancreatic tissue were positive (8/8) for CEA mRNA. The recurrence rate was 90% (9/10) in the conventional procedure group, and 38% (3/8) in the no-touch isolation technique group (P=0.043). In the conventional procedure group, hepatic metastasis, local recurrence, peritoneal dissemination, and extraabdominal recurrence were identified in 6 (60%), 4 (40%), 4 (40%), and 2 patients (20%), respectively. On the other hand, among the no-touch isolation technique group, recurrence was identified in 1 (13%), 1 (13%), 0 (0%), and 1 patient (13%), respectively. There was no peritoneal dissemination along with the decreased hepatic recurrence rate. Mean (+/-SEM) survival time was 21.2+/-5.8 months for the conventional procedure group and 41.5+/-5.6 months for the no-touch isolation technique group (P=0.018). The 3-year survival rate was 12.5+/-11.5% for the conventional procedure group and 75.0+/-21.7% for the no-touch isolation technique group. CONCLUSION: This study presented the potential of cancer dissemination during the intraoperative manipulation of tumors and its contribution to cancer recurrence, as well as the significance of the no-touch isolation technique and extensive intraoperative peritoneal lavage for pancreatic cancer surgery.

[Concept of SIRS and severe acute pancreatitis].

Acute pancreatitis is a potentially fatal disease, the severity of which ranges from a mild edematous form to a severe necrotizing form. Most patients develop systemic inflammatory response syndrome (SIRS), which is induced by proinflammatory cytokines. The cytokine production can be induced by activation of Toll-like receptor. The breakdown products of the pancreatic and peripancreatic tissues by proteases might be the agonists. Cytokines are supposed to be produced as a biological defense system. However, cytokines may often evoke organ failure and/or immunosuppressive state, if they would be produced excessively. To express this complicated pathologic condition, Ogawa proposed a concept of LISIS(local inflammation-induced systemic immunosuppression syndrome). We have to pay attention to such aspects in the management of this disease.