[Surgical Outcomes and Clinicopathological Analysis of Laparoscopic Distal Pancreatectomy].

SUBJECTS: We first reviewed surgical outcomes and pathological findings of 32 patients(laparoscopic group: LDP n=11, open group: ODP n=21)who underwent distal pancreatectomy for pancreatic cancer from January 2018 to October 2022. Then we reviewed long-term outcomes, and recurrence type for 20 patients(LDP: n=5, ODP: n=15)from January 2018 to February 2021. RESULTS: LDP group had significantly longer operation time and less blood loss. There was no difference in length of hospital stay, postoperative complications, number of dissected lymph nodes, positive lymph node metastasis rate, and adjuvant chemotherapy rate. Because of high rate of pancreatic stump closure by hand sewing in ODP, postoperative pancreatic fistula rate was higher in ODP than in LDP. The 2-year relapse-free survival rate was 60% in LDP, 33% in ODP, and the 2-year overall survival rate was 60% in LDP, 71% in ODP, and there were no significant differences. As for the type of recurrence, in LDP group, 2 cases of distant metastases and no local recurrence was observed, and in ODP group, 6 cases each of local recurrences and distant metastases were observed. CONCLUSION: LDP was not inferior to ODP in short and long- term outcomes, safety, curability, and local control ability.

High expression of Krüppel-like factor 5 is associated with poor prognosis in patients with colorectal cancer.

Krüppel-like factor 5 (KLF5) plays an oncogenic role and has diverse functions in cancer cells. However, correlation between KLF5 and clinical outcome has not been determined in patients with colorectal cancer and colorectal liver metastasis. Herein, we analyzed 65 patients with colorectal cancer who developed colorectal liver metastasis. Clinical effects were assessed through immunohistochemical analysis of primary colorectal cancer lesions and metastatic liver lesions. High expression of KLF5 in these tissues correlated with the presence of vascular invasion, elevated serum carbohydrate antigen 19-9 levels, large diameters of metastatic liver tumors, and poor prognosis following surgery. Multivariate analyses revealed that high expression of KLF5 was an independent prognostic factor. Increased expression of KLF5 in both colorectal cancer primaries and colorectal liver metastasis was significantly associated with shorter overall survival time and time to surgical failure. Krüppel-like factor 5 expression positively correlated with Ki-67 and c-Myc expression in colorectal cancer tissues. In vitro experiments with colon cancer cell lines showed that siRNA knockdown of KLF5 inhibited cell proliferation. Western blot analyses revealed that knockdown of KLF5 expression reduced cyclin D1 and c-Myc expression. It also impaired the stem cell-like properties of cancer cells in tumorsphere formation assays. Furthermore, anoikis assay indicated that KLF5 contributed to anoikis resistance. High KLF5 expression is associated with poor prognosis in patients with colorectal cancer and liver metastasis by promoting cell proliferation and cancer stem cell-like properties.

Long-term outcomes and significance of preoperative lymphocyte-to-monocyte ratio as a prognostic indicator in patients with invasive pancreatic neoplasms after repeat pancreatectomy.

BACKGROUND: Invasive pancreatic neoplasms have a high propensity for recurrence even after curative resection. Recently, patients who underwent pancreatectomy have an opportunity of undergoing secondary pancreatic resection, so-called "repeat pancreatectomy" to achieve curative operation and prolong their survival. We evaluated the long-term clinical outcomes and identified the prognostic factors, including systemic inflammation markers and the lymphocyte-to-monocyte ratio (LMR) of patients who underwent repeat pancreatectomy for invasive pancreatic tumors. METHODS: Twenty-eight consecutive patients with invasive pancreatic neoplasms (22 pancreatic ductal adenocarcinomas, 2 pancreatic acinar cell carcinomas, and 4 invasive intra-papillary mucinous carcinomas) with isolated local recurrence only in the remnant pancreas were analyzed retrospectively. To identify factors for the selection of optimal patients who should undergo repeat pancreatectomy, perioperative clinical parameters were analyzed by Cox proportional regression models. RESULTS: Of 28 patients, 12 patients experienced recurrence within 3 years after repeat pancreatectomy. Kaplan-Meier analysis showed that the median cancer-specific overall survival time of patients with invasive pancreatic neoplasms was 61 months, showing favorable outcomes. High preoperative LMR (LMR ≥ 3.3) (p = 0.022), no portal vein resection (p = 0.021), no arterial resection (p = 0.037), and pathological lymph node negative (p = 0.0057) were identified as favorable prognostic parameters on univariate analysis, and LMR ≥ 3.3 (p = 0.0005), and pathological lymph node negative (p = 0.018) on multivariate analysis. CONCLUSIONS: Preoperative LMR is potentially a good indicator for selecting suitable patients to undergo repeat pancreatectomy in patients with isolated local recurrence of invasive pancreatic neoplasms.

Needle tract seeding recurrence of pancreatic cancer in the gastric wall with paragastric lymph node metastasis after endoscopic ultrasound-guided fine needle aspiration followed by pancreatectomy: a case report and literature review.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has high accuracy and a low complication rate; therefore, it has been widely used as a useful tool for diagnosis of and to determine treatment strategies for pancreatic tumors. Recently, reports of the recurrence of needle tract seeding after EUS-FNA are emerging. CASE PRESENTATION: An 83-year-old woman was referred to our hospital to undergo further examination of her pancreatic tumor. Multidetector computed tomography (MDCT) revealed a 25-mm-diameter mass in the pancreatic body. She underwent EUS-FNA (transgastric, 22-G needle, 2 passes) and was subsequently diagnosed with adenocarcinoma. Distal pancreatosplenectomy followed by adjuvant chemotherapy with S-1 for 6 months was performed. The level of carbohydrate antigen 19-9 gradually increased 22 months after surgery, and MDCT, which was performed 3 months later, revealed a 23-mm low-density mass in the stomach and paragastric lymph node swelling. Gastroendoscopy revealed a submucosal tumor, and endoscopic ultrasound revealed a hypoechoic mass in the submucosa of the gastric wall. Partial gastrectomy with lymph node resection was performed. The pathological findings showed adenocarcinoma extending from the subserosa to the submucosa and lymph node metastasis, consistent with a tumor recurrence from the resected pancreatic tumor. She received adjuvant chemotherapy with S-1; recurrence was not observed for 5 months, at the time of this writing. CONCLUSION: It is important to pay careful attention to the development of needle tract seeding in patients with pancreatic cancer diagnosed by EUS-FNA. This is the first case of needle tract seeding with lymph node metastasis, highlighting the need for caution and providing novel insight in the postoperative follow-up of patients with pancreatic body/tail cancer.

Outcome of interventional radiology for delayed postoperative hemorrhage in hepatobiliary and pancreatic surgery.

BACKGROUND AND AIM: Postoperative hemorrhage is a rare but potentially lethal complication of hepatobiliary and pancreatic surgeries. This study aimed to retrospectively evaluate the clinical outcome of patients with delayed postoperative hemorrhage and compare the results according to the surgical procedure. METHODS: Overall, 4220 patients underwent surgery for hepatobiliary and pancreatic diseases. Delayed postoperative hemorrhage (observed more than 24 h postoperatively) occurred in 62 patients. Of these, 61 underwent interventional radiology to achieve hemostasis. Patients' clinical data were analyzed retrospectively. The chi-squared or Fisher's exact test was used in data analysis. RESULTS: A total of 62 patients (1.5%) developed delayed postoperative hemorrhage; 61 (1.4%) of them underwent interventional radiology to achieve hemostasis. Median duration from surgery to interventional radiology was 19 days (range: 5-252 days). Sentinel bleeding was detected in 31 patients; Clinical success was achieved in 54 patients (88.5%) by interventional radiology. Overall mortality rate was 26.2%. Causes of 16 in-hospital deaths were uncontrollable hemorrhage (n = 4) and worsening of general condition after hemostasis (n = 12). Mortality rates were 50.0% (11/22) and 12.8% (5/39) after hepatobiliary surgery and pancreatic resection, respectively. Mortality rate was significantly higher after hepatobiliary surgery than after pancreatic surgery (P = 0.002). CONCLUSIONS: Interventional radiology can be successfully performed to achieve hemostasis for delayed hemorrhage after hepatobiliary and pancreatic surgeries. Because successful interventional radiology does not necessarily lead to survival, particularly after hepatobiliary surgery, meticulous attention to prevent surgical complications and intensive treatments before and after interventional radiology are required to improve outcomes.

[A Case of Anaplastic Carcinoma with Osteoclastlike Giant Cells of the Pancreas Concomitant with Lung Recurrence of Solitary Fibrous Tumor].

A 32-year-old woman presented with epigastric pain and an abdominal mass. Abdominal CT showed a 130mm pancreatic tail mass with an enhanced rim, central necrosis, and small calcification. A 6mm lung tumor was also found via chest CT. Her medical history included surgical resection of cerebral solitary fibrous tumor when she was 24 years old. When she was 31 years old, it had recurred but was cured by gamma knife radiosurgery. We performed distal pancreatectomy and splenectomy with lymph node dissection. According to pathological and immunohistochemical findings, it was diagnosed as an anaplastic carcinoma with osteoclast-like giant cells. She underwent surgical resection of the lung tumor 2 months after pancreatic resection and was diagnosed with metastasis from the solitary fibrous tumor. Fourteen months since undergoing pancreatectomy, the patient experienced no recurrence from both diseases. We report a rare resected case of anaplastic carcinoma of pancreas concomitant with recurrent solitary fibrous tumor.

Is hepatic artery coil embolization useful in distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic cancer?

BACKGROUND: The exact contribution of preoperative coil embolization in distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for the prevention of ischemic liver complication is not fully elucidated. METHODS: From January 2004 to July 2015, 31 patients underwent DP-CAR for the pancreatic body-tail cancer. Twenty-three patients received preoperative coil embolization. The characteristics and operative outcomes were analyzed retrospectively. RESULTS: The median survival time and 1- and 3-year overall survival rates were 23.7 months and 74.2% and 34.4%, respectively. No 30-day mortality occurred in any of the patients. Postoperative liver infarction developed only in 8 patients (25.8%) even though 7 of 8 patients had undergone preoperative coil embolization. Tumor contact with the gastroduodenal artery (GDA)/proper hepatic artery (PHA) on preoperative multi-detector computed tomography (MDCT), tumor size, operative time, portal vein resection, and stenosis of the GDA/PHA after DP-CAR are related to liver infarction. Among them, postoperative stenosis of the GDA/PHA on MDCT, which was observed in all 8 patients with liver infarction, was the most closely related factor to postoperative liver infarction. Tumor contact with the GDA/PHA did not worsen the R0 resection rate or overall survival rate. CONCLUSION: Our data indicate that preoperative coil embolization of the common hepatic artery is not useful in DP-CAR as long as GDA is completely preserved during surgery.

[Anaplastic Carcinoma of the Pancreas of the Spindle Cell Type with Rapid Growth and Liver Metastases after Resection-A Case Report].

An 81-year-old man was referred to our department because of rapid progression of a cystic lesion in the pancreatic tail. Abdominal CT revealed a heterogeneously enhancing tumor, measuring 70mm in diameter, in the pancreatic tail, encompassing a low-density area with calcification and directly invading the spleen. We diagnosed the patient with malignant transformation of solid-pseudopapillary neoplasm and performed distal pancreatectomy with splenectomy, partial transverse colectomy, and partial resection of the diaphragm. Histopathological examination revealed anaplastic carcinoma of the pancreas of the spindle cell type, and R0 resection was achieved. Anastomotic leakage of the transverse colon occurred on postoperative day 4, and ileostomy was performed. Multiple liver metastases were observed on postoperative day 27, and the patient was orally administered with S-1. Although he was discharged on postoperative day 50, he died of cancer on postoperative day 61. Anaplastic carcinoma of the pancreas has a poor prognosis, and an early multidisciplinary treatment should be performed.

[A Case of Pancreatic Metastasis from Colon Cancer Successfully Treated with Capecitabine/Oxaliplatin plus Bevacizumab].

A 50-year-old man underwent low anterior resection for rectal cancer. The final diagnosis was rectal cancer of pT3N0M0, fStage Ⅱ. CT performed for examination of obstructive jaundice at 17 months after surgery revealed metastatic lesions of the pancreatic head and right lung. By core needle biopsies, the lesions were pathologically diagnosed as metachronous metastases of rectal cancer. Chemotherapy was carried out but was discontinued at 5 courses due to severe side effects. The pancreatic metastasis disappeared after 11 months. As the lung metastasis remained, a right upper lobectomy was performed 1 month later. The patient remains alive without recurrence 6 months after the partial lung resection.

Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer Patients Treated with Gemcitabine Plus Cisplatin Combination Therapy Followed by Radical Surgery.

BACKGOUND: We have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC. METHODS: The subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC. RESULTS: Reduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy. CONCLUSIONS: Preoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC.

[A case of main-duct IPMN with multicentric invasive carcinoma].

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas often contains multifocal lesions, and total pancreatectomy is sometimes needed for curative resection. We report here our experience with a case of IPMN with multiple invasive carcinoma foci that was successfully treated with total pancreatectomy. A 66-year-old man had jaundice, and a computed tomography (CT) scan revealed a hypovascular mass in the pancreas head in conjunction with calcification and dilation of the entire main pancreatic duct. He was diagnosed with pancreas head cancer and chronic pancreatitis, and a pancreaticoduodenectomy was planned. Intraoperative pathological examination revealed papillary growth of high grade dysplasia in the main and branch duct epithelium and perineural invasion of the atypical glands. After 2 additional resections, we performed a total pancreatectomy. Pathological findings showed that the pancreas head tumor was an invasive carcinoma derived from main-duct IPMN of the pancreas. It was a mucinous carcinoma with calcification. Moreover, we found other multiple, discontinuous invasive foci in the body and tail of the pancreas which were undetectable by preoperative imaging. This case was highly suggestive for preoperative diagnosis for pancreas tumor and developmental pattern of main-duct IPMN.

[A case of huge advanced hepatocellular carcinoma resected after hepatic arterial infusion therapy of 5-FU/LV/CDDP].

A 58-year-old man was referred to our hospital for a huge tumor occupying the entire right lobe of the liver. An imaging method revealed a 15 cm-sized hepatocellular carcinoma in the right lobe which extended to the internal segment across the middle hepatic vein. The serum AFP level was 15.3 ng/mL, and the level of protein induced by vitamin K absence or antagonist II was 4,340 mAU/mL. We judged it unresectable, then arterial infusion chemotherapy using 5-fluorouracil, cisplatin, and Leucovorin was performed. After 4 courses, the tumor was markedly reduced to 56 mm. We performed an extended right lobectomy. In the operative finding, although the tumor partially reached the internal segment, the middle hepatic vein was preserved. Nine months after operation, no sign of recurrence was found. It is suggested that hepatic arterial infusion therapy is useful for pre-operative therapy of far-advanced hepatocellular carcinoma as a part of combined modality therapy.

Prediction of mismatch repair deficient biliary tract cancer: Role of morphological features and host immune response detected by routine hematoxylin-eosin staining.

BACKGROUND/PURPOSE: The objective of this study was to determine the frequency and predictors of biliary tract cancer (BTC) with deficient DNA mismatch repair (dMMR) in Japan. METHODS: Immunostaining and microsatellite instability analysis were performed for mismatch repair-related proteins in tissue specimens from 662 patients who underwent surgery for BTC between 2001 and 2017 to identify dMMR-BTC. We compared dMMR-BTC and proficient MMR (pMMR)-BTC based on patient demographics, pathological features, and host immune responses characterized by the percentage of stromal tumor infiltrating lymphocytes (sTIL percentage) and tertiary lymphoid structures (TLS). RESULTS: The incidence of dMMR-BTC was 2.3%. Significant predictors of dMMR-BTC were its primary lesion being intrahepatic cholangiocarcinoma (odds ratio [OR] 6.34, P = .004), presence of signet ring cell component (OR 35.62, P < .001), sTIL percentage ≥40% (OR 3.43, P = .038), and presence of TLS (OR 22.22, P < .001). The sensitivity, specificity, and negative likelihood ratio for any one or more of these four variables to be positive were 93.3%, 57.8%, and 0.12, respectively. CONCLUSION: Evaluation of histopathological findings and host immune response based on conventional histochemical staining is useful for efficient and inexpensive diagnostic screening of dMMR-BTC patients.

Successful treatment of a locally advanced unresectable pancreatic cancer patient with interstitial pneumonitis by conversion surgery following gemcitabine plus nab-paclitaxel chemotherapy: A case report.

Conversion surgery is an attractive strategy to improve the outcomes for locally advanced unresectable (UR-LA) pancreatic ductal adenocarcinoma (PDAC). The present case report, presents a case of successful conversion surgery following the treatment of a patient with UR-LA PDAC, suffering from interstitial pneumonitis (IP), using a combination of gemcitabine and nab-paclitaxel (GnP). A 67-year-old woman presented at the hospital with a high level of carbohydrate antigen 19-9 (CA19-9; 1,713 U/ml). Radiological examination revealed a pancreatic tumor in contact with the superior mesenteric artery, with invasion extending to the most proximal draining jejunal branch into the superior mesenteric vein. The patient was diagnosed with UR-LA PDAC. Following 6 courses of GnP therapy, the tumor size markedly decreased from 50 to 18 mm, and the level of CA19-9 also decreased from 1,713 to 60.1 U/ml. Due to the progression of IP, the patient was administered steroid medication along with a restart of tacrolimus for the treatment of dermatomyositis and IP. After recovery from her lung condition, an additional 3 courses of GnP therapy were administered, and then pancreatoduodenectomy was performed. The patient was still alive 14 months post-surgery with no recurrence. Between July 2009 and September 2017, conversion surgery was performed for 18 cases of UR-LA PDAC treated with gemcitabine plus S-1 (GS) therapy, and 11 cases with GnP therapy. The percentage of median CA19-9 and median tumor volume reductions were 73.7 and 51.6%, respectively, following GS therapy, and 86.7 and 68.8%, respectively, following GnP therapy. Tumor reduction following GnP therapy was significantly higher than that after GS therapy (P=0.02). GnP therapy is a suitable regimen to shrink the tumor mass in patients with UR-LA PDAC. Careful management of systemic conditions is required to treat patients with PDAC and IP when using GnP therapy. Conversion surgery should be considered for recognizing radiological responses (tumor shrinkage adjacent to major arteries) and reductions in CA19-9 levels.