Surveillance after resection of non-invasive intraductal papillary mucinous neoplasms (IPMN). A systematic review.

BACKGROUND: The ideal surveillance strategy after partial pancreatectomy for non-invasive IPMN remains undefined and existing guidelines provide conflicting recommendations. The present study was developed in anticipation of the joint meeting of the International Association of Pancreatology (IAP) and the Japan Pancreas Society (JPS) held in Kyoto in July 2022. METHODS: An international team of experts developed the four clinical questions (CQ) to operationalize issues pertaining to surveillance of patients in this context. A systematic review was designed following the PRISMA guidelines and registered in PROSPERO. The search strategy was executed in PubMed/Medline (Ovid), Embase, the Cochrane Library and Web of Science databases. Four investigators individually extracted data from the selected studies and drafted recommendations for each CQ. These were subsequently discussed and agreed upon that the IAP/JPS meeting. RESULTS: From a total of 1098 studies identified through the initial search, 41 studies were included in the review and informed the recommendations. No studies providing level one data were identified in this systematic review, all studies included were cohort or case-control studies. CONCLUSIONS: There is a lack of level 1 data addressing the issue of surveillance of patients following partial pancreatectomy for non-invasive IPMN. The definition of remnant pancreatic lesion in this setting is largely heterogeneous across all studies evaluated. Herein we propose an inclusive definition of remnant pancreatic lesions to guide future prospective efforts for reporting the natural history and long-term outcomes of these patients.

Vascular endothelial growth factor inhibitors promote antitumor responses via tumor microenvironment immunosuppression in advanced colorectal cancer.

PURPOSE: This study aims to investigate changes in the tumor immune environment of patients who underwent therapy with a vascular endothelial growth factor (VEGF) inhibitor for advanced colorectal cancer. METHODS: Patients (n = 135) with T3 or T4 colorectal cancer were included in this retrospective study. They were classified as follows: patients who had not received preoperative treatment (UPFRONT group, n = 54), who had received FOLFOX as preoperative chemotherapy (FOLFOX group, n = 55), and who had undergone resection after combination FOLFOX and bevacizumab as unresectable colorectal cancer (B-MAB group, n = 26). The number of cytotoxic T lymphocytes (CTLs), FOXP3+ lymphocytes (including regulatory T cells (Tregs)), CD163+ monocytes (including M2-type tumor-associated macrophages (TAM-M2 type)), and programmed cell death 1 (PD-1)+ lymphocytes was evaluated immunohistochemically in the cancer cell area (CC) and stromal cell area (ST) of surgical specimens, and compared among the three groups. RESULTS: The CTL population did not differ among the three groups in both areas. In the B-MAB group, the numbers of PD-1+ cells in the ST, FOXP3+ lymphocytes in both areas, and CD163+monocytes in the ST was lower than that in the other two groups, and a correlation with the histological therapeutic effect was observed. CONCLUSIONS: In advanced colorectal cancer, VEGF inhibitors may decrease the number of PD-1+ cells and inhibit the infiltration of FOXP3+ lymphocytes and CD163+monocytes into the tumor environment.

Molecular Pathogenesis of Colorectal Cancer: Impact of Oncogenic Targets Regulated by Tumor Suppressive miR-139-3p.

We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) was significantly reduced in CRC tissues. Transient transfection assays revealed that expression of miR-139-3p blocked cancer cell malignant transformation (e.g., cell proliferation, migration, and invasion). Notably, expression of miR-139-3p markedly blocked RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation in CRC cells. A combination of in silico database and gene expression analyses of miR-139-3p-transfected cells revealed 29 putative targets regulated by miR-139-3p in CRC cells. RNA immunoprecipitation analysis using an Argonaute2 (AGO2) antibody revealed that KRT80 was efficiently incorporated into the RNA-induced silencing complex. Aberrant expression of Keratin 80 (KRT80) was detected in CRC clinical specimens by immunostaining. A knockdown assay using small interfering RNA (siRNA) targeting KRT80 showed that reducing KRT80 expression suppressed the malignant transformation (cancer cell migration and invasion) of CRC cells. Importantly, inhibiting KRT80 expression reduced AKT phosphorylation in CRC cells. Moreover, hexokinase-2 (HK2) expression was reduced in cells transfected with the KRT80 siRNAs or miR-139-3p. The involvement of miRNA passenger strands (e.g., miR-139-3p) in CRC cells is a new concept in miRNA studies. Our tumor-suppressive miRNA-based approach helps elucidate the molecular pathogenesis of CRC.

Molecular pathogenesis of breast cancer: impact of miR-99a-5p and miR-99a-3p regulation on oncogenic genes.

Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expression levels of two miRNAs derived from pre-miR-99a (miR-99a-5p and miR-99a-3p) were suppressed in cancerous tissues. The aim of this study was to identify oncogenic genes controlled by pre-miR-99a that are closely involved in the molecular pathogenesis of BrCa. A total of 113 genes were identified as targets of pre-miR-99a regulation (19 genes modulated by miR-99a-5p, and 95 genes regulated by miR-99a-3p) in BrCa cells. Notably, FAM64A was targeted by both of the miRNAs. Among these targets, high expression of 16 genes (C5orf22, YOD1, SLBP, F11R, C12orf49, SRPK1, ZNF250, ZNF695, CDK1, DNMT3B, TRIM25, MCM4, CDKN3, PRPS, FAM64A, and DESI2) significantly predicted reduced survival of BrCa patients based upon The Cancer Genome Atlas (TCGA) database. In this study, we focused on FAM64A and investigated the relationship between FAM64A expression and molecular pathogenesis of BrCa subtypes. The upregulation of FAM64A was confirmed in BrCa clinical specimens. Importantly, the expression of FAM64A significantly differed between patients with Luminal-A and Luminal-B subtypes. Our data strongly suggest that the aberrant expression of FAM64A is involved in the malignant transformation of BrCa. Our miRNA-based approaches (identification of tumor-suppressive miRNAs and their controlled targets) will provide novel information regarding the molecular pathogenesis of BrCa.

RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p.

To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.

Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis.

Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This study aimed to identify the oncogenes closely involved in PDAC molecular pathogenesis under the regulation of miR-30a-3p. Ectopic expression assays showed that miR-30a-3p expression inhibited the aggressiveness of the PDAC cells, suggesting that miR-30a-3p acts as a tumor-suppressive miRNA in PDAC cells. We further identified 102 putative targets of miR-30a-3p regulation in PDAC cells by combining in silico analysis with gene expression data. Of these, ten genes (EPS8, HMGA2, ENDOD1, SLC39A10, TGM2, MGLL, SERPINE1, ITGA2, DTL, and UACA) were independent prognostic factors in multivariate analysis of survival of patients with PDAC (p < 0.01). We also investigated the oncogenic function of the integrin ITGA2 in PDAC cell lines. The integrin family comprises cell adhesion molecules expressed as heterodimeric, transmembrane proteins on the surface of various cells. Overexpression of ITGA2/ITGB1 (an ITGA2 binding partner) was detected in the PDAC clinical specimens. The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.

[Curative Resection for Unresectable Locally Advanced Colorectal Cancer Following Intensive Chemotherapy plus Molecular Targeted Agent - Report of Three Cases].

Intensive chemotherapy plus molecular targeted agent improve overall survival for patients with unresectable colorectal cancer.We performed laparoscopic surgery following intensive chemotherapy of mFOLFOX6 or FOLFIRI plus molecular targeted agent for 3 patients with unresectable locally advanced colorectal cancer with abscess formation.A 60-year-old man was diagnosed as having unresectable rectal cancer with abscess formation and underwent curative resection after partial response following chemotherapy.A 42-year-old woman was diagnosed as having unresectable sigmoid colon cancer with abscess formation and underwent curative resection after partial response following chemotherapy.A 56-year-old woman was diagnosed as having unresectable sigmoid colon cancer with abscess formation and underwent curative resection after partial response following chemotherapy.They are alive after surgery for 69, 74 and 72 months, respectively.Intensive chemotherapy plus molecular targeted agent for unresectalbe locally advanced colorectal cancer with abscess formation will be one of useful strategies for minimum invasive surgery and effective local control.

Genetic assessment of IPMN for predicting concomitant pancreatic ductal adenocarcinoma.

OBJECTIVE: Krüppel-like transcription factor 4(KLF4) mutations are more frequently observed in low-grade lesions than in high-grade lesions of intraductal papillary mucinous neoplasms (IPMN) of the pancreas. However, the role of KLF4 mutations in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study clarified the rate and effect of KLF4 mutations in IPMN with concomitant PDAC. METHODS: DNA was extracted from 65 formalin-fixed and paraffin-embedded samples from 52 patients including 13 IPMN with concomitant PDAC and 39 IPMN alone. A comprehensive screening was performed using next-generation sequencing (NGS) for the 5 IPMNs with concomitant PDAC and 5 IPMNs alone, followed by targeted sequencing for KLF4, GNAS, and KRAS mutations. RESULTS: In NGS screening, KRAS mutations were observed in all samples except for one, GNAS mutation in two IPMNs with concomitant PDAC, and a KLF4 mutation in one IPMN with concomitant PDAC. Targeted sequence detected KLF4 mutations in 11 of the 52 IPMNs. Concomitant PDAC developed only in the non-intestinal, non-invasive, and branch duct IPMN cases, and KLF4 mutations were more frequent in this IPMN type than in the other type (36% vs. 10%, p = 0.04). For this IPMN type with KLF4 mutation, PDAC-prediction sensitivity, specificity, and accuracy were 63%, 82%, and 79%, respectively. CONCLUSION: For selected IPMNs with non-intestinal, non-invasive, and branch duct, genetic assessment might be a helpful tool for predicting the possible development of concomitant PDAC, although a prospective validation study using a larger study population is needed.

Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct expression patterns and potential markers of progression.

In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies. Significance: This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.

Metal-free laparoscopic distal pancreatectomy using transpancreatic mattress suture with polyglycolic acid sheet and fibrin glue: A case report.

Laparoscopic distal pancreatectomy (LDP) is the standard surgery for malignant and premalignant tumors of the pancreatic body and tail. A stapler is commonly used to close the pancreatic stump due to its simplicity; however, the use of a stapler is associated with the risk of metal allergy and postoperative pancreatic fistula, especially in thick pancreases. Here, we present a case of LDP without metal instruments, including staplers and clips, in a 54-year-old woman with a metal allergy and a thick pancreas. The pancreatic stump was closed using the transpancreatic mattress suture method with a polyglycolic acid sheet (PGA) and fibrin glue. The postoperative course was uneventful. Metal-free LDP is useful and can be adopted regardless of the patient's background, such as a metal allergy or pancreatic thickness.

Are intratumoral microbiota involved in the progression of intraductal papillary mucinous neoplasms of the pancreas?

BACKGROUND: Microbiota have been reported to influence the development of various gastrointestinal neoplasms through the mechanism of sustained inflammation; however, few data are available regarding their influence on intraductal papillary mucinous neoplasms. The aim of this study was to assess the association between specific microbiota and the clinicopathologic characteristics of intraductal papillary mucinous neoplasms of the pancreas. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded samples of 30 patients who underwent pancreatectomy for intraductal papillary mucinous neoplasm, and polymerase chain reaction was used to create sequence libraries using the primer set for the V3 and V4 region of 16S recombinant DNA. Filtered sequence reads were then processed into operational taxonomic units with a 97% identity threshold and the relative abundance of bacteria compared between the 2 groups using operational taxonomic units. RESULTS: There was a trend toward fewer Firmicutes and more Proteobacteria and Fusobacteria in the relative abundance of main duct operational taxonomic units than in branch duct operational taxonomic units. The relative abundances of Bacteroidetes (P < .01) and Fusobacteria (P = .04) were significantly higher in invasive intraductal papillary mucinous neoplasms than in noninvasive intraductal papillary mucinous neoplasms. The relative abundance of the intestinal type was significantly lower in Firmicutes than the relative abundance of the nonintestinal type (P = .04). Notably, main duct operational taxonomic units with the intestinal subtype were affected by increased proportions of Proteobacteria and Fusobacteria, and Fusobacteria were abundant in the intestinal type of invasive main duct operational taxonomic units. CONCLUSION: Intratumoral microbiota may be involved in the progression of operational taxonomic units.

Feasibility of Surveillance for Mucinous Cystic Neoplasm of the Pancreas: A Multi-Institutional Retrospective Study of 328 Patients by the Japanese Pancreatic Society.

OBJECTIVE: We aimed to elucidate the feasibility of surveillance of patients with mucinous cystic neoplasm (MCN). METHODS: We performed a retrospective, multi-institutional study of 328 patients who underwent surgery for MCN at 18 Japanese institutions. Patients with MCN were divided into an immediate surgery group and a surveillance group, which underwent surgery after surveillance. RESULTS: The median surveillance period until surgery in the surveillance group was 27 months (range, 7-165 months). Compared with the immediate surgery group, the surveillance group showed smaller tumor diameter (46 vs 50 mm, P = 0.01), more frequent laparoscopic approach (58% vs 37%, P < 0.01), and less frequent malignancy (7% vs 15%, P = 0.03). The new appearance of mural nodules and elevation of serum tumor markers were associated with malignancy in the surveillance group. Two patients in the surveillance group experienced postoperative recurrence, although there was no significant difference in recurrence or disease-free survival between the two groups. In the surveillance group, the 1-, 5-, and 10-year cumulative incidence rates of malignant MCN were 0.8%, 5.6%, and 36.5%, respectively. CONCLUSION: As the risk of progression to malignant MCNs increases over the long term, MCNs should be resected rather than subjected to unnecessary surveillance.

Surgical Stress Evaluation of Left Lateral Sectionectomy Based on Skeletal Muscle Catabolism.

BACKGROUND: By examining skeletal muscle catabolism, we aimed to investigate whether laparoscopic left lateral sectionectomy (LLS) is less invasive compared with the open approach. METHODS: The psoas muscle index (PMI) was measured using computed tomography images before and after surgery. We assessed the relationship between the perioperative PMI reduction rate and the estimation of physiologic ability and surgical stress (E-PASS) score and then compared the PMI reduction rates associated with different approaches. RESULTS: Of the 31 patients, 13 and 18 underwent the open and laparoscopic approaches, respectively. A strong correlation was observed between the PMI reduction rates and surgical stress scores (SSS) ( r =0.561, P <0.01). The laparoscopic approach was associated with a significantly lower PMI reduction rate ( P <0.01) and SSS ( P <0.01) than the open approach. CONCLUSION: Laparoscopic LLS should be less invasive than the open approach from the perspective of not only perioperative outcomes but also skeletal muscle catabolism.

Multidisciplinary treatment of advanced or recurrent solid pseudopapillary neoplasm of the pancreas: three case reports.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor that predominantly affects young females. Prognosis is excellent; however, 10-15% of patients show metastasis at the time of surgery or develop tumor recurrence after pancreatectomy. CASE PRESENTATION: We reviewed the clinical course of three patients with advanced or recurrent SPN and subsequently underwent multidisciplinary treatment at our institution between 2002 and 2019. The primary tumor was resected in all three patients, and metastases were also resected if indicated. Intensive combined therapy, including re-resection, chemotherapy, ablation, arterial chemoembolization, and radiation therapy, allowed all patients to survive for a long time. The literature review showed that resection seems to be more effective than other treatments for metastatic SPN. CONCLUSIONS: Multidisciplinary treatment, including resection, may improve the prognosis of patients with SPN with recurrence or metastasis.

Implications of PD-1, Tim-3, and TIGIT Expression for Cancer Immunity and Pancreatic Cancer Prognosis.

BACKGROUND/AIM: The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment. MATERIALS AND METHODS: We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis. RESULTS: An increased number of CD8+ T cells in pancreatic cancer tissue was significantly associated with a better patient prognosis. Additionally, patients with a higher ratio of PD-1 expression to CD8+ T cells had a worse prognosis. We observed no correlation between the Tim-3/Galectin-9 and CD155/TIGIT pathways and patient prognosis. CONCLUSION: Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.

Curative resection after chemotherapy and chemoradiotherapy for postoperative recurrence of pancreatic tail cancer in the abdominal wall: a case report.

BACKGROUND: Locoregional recurrence and metastasis to the liver, peritoneum, and lung are the most common recurrent patterns of pancreatic ductal adenocarcinoma (PDAC) after radical resection. Recurrence in the abdominal wall is extremely rare. Herein, we report our experience with a patient who had recurrent PDAC in the abdominal wall with long-term survival by means of multidisciplinary therapy. CASE PRESENTATION: A 76-year-old Japanese woman was diagnosed with resectable pancreatic tail cancer. She underwent distal pancreatectomy with regional lymphadenectomy after two cycles of gemcitabine plus S-1 as neoadjuvant therapy. She also received eight cycles of S-1 as adjuvant chemotherapy. Approximately 14 months after the initial surgery, imaging examinations identified a mass suggesting recurrence in the abdominal wall at the middle wound that involved the transverse colon. After two cycles of gemcitabine plus nab-paclitaxel, chemoradiotherapy (S-1 plus 45 Gy) and seven cycles of modified FOLFIRINOX (5-fluorouracil/leucovorin, irinotecan, and oxaliplatin) were administered. The patient did not develop any new recurrent lesions during chemotherapy and chemoradiotherapy. Therefore, the recurrent lesion in the abdominal wall and the involved transverse colon were resected. We confirmed the lack of peritoneal dissemination during surgery. Pathological examination revealed that the resected lesion was metastasis of primary PDAC, and the surgical margin was 1 mm. However, re-recurrence localized in the abdominal wall was detected 9 months later. The re-recurrent lesion was diagnosed as local recurrence of the first recurrent lesion. We performed a second resection of the abdominal wall using a femoral myocutaneous flap to achieve sufficient surgical margin. The pathological findings of the resected specimen were the same as those of the previous specimens, and the resection margin was negative. The patient's postoperative course was uneventful. Seven years after the initial surgery and 3 years and 7 months after the third surgery, the patient is alive with no signs of recurrence. CONCLUSIONS: Long-term survival could be achieved by radical resection with sufficient surgical margins for recurrence of PDAC in the abdominal wall if new other recurrent lesions, including peritoneal dissemination, are prevented through chemotherapy.

Impact of Oncogenic Targets Controlled by Tumor-Suppressive miR-30a-5p in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease. MATERIALS AND METHODS: In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples. RESULTS: A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells. CONCLUSION: The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.

Useful Technique for Creating a Good Liver Parenchymal Visual Transection Plane During Laparoscopic Partial Hepatectomy.

BACKGROUND: Creating a good surgical visual field is one of the most important factors for performing a successful surgery. Here, we introduce a useful technique for creating a good liver parenchymal visual transection plane during laparoscopic partial hepatectomy and compare the perioperative outcomes of our current technique with those of conventional techniques. METHODS: We reviewed the data of patients who underwent laparoscopic partial hepatectomy between July 2016 and December 2020. The current technique for creating transection planes was first applied in our department in April 2019. The patients were divided into conventional (forceps) and current (silicone ring) technique groups, depending on the surgical technique. RESULTS: Twenty-eight and 12 patients underwent laparoscopic partial hepatectomy using the conventional and current techniques, respectively, when the difficulty level-as determined by IWATE criteria-was low. Although the tumor size was significantly larger (median: 22.5 vs. 15 mm, P=0.04) in the current technique group, the estimated intraoperative blood loss was significantly lower (median: 50 vs. 100 mL, P=0.01), and the median surgical margin was significantly longer (median: 7 vs. 3 mm, P=0.02). There were no significant between-group differences in surgical time (median: 344 vs. 240 min, P=0.14), postoperative hospital stay duration (median: 11 vs. 9.5 d, P=0.051), and the incidence of complications (P=0.63). CONCLUSION: We believe that the technique involving the use of a silicone ring can result in better surgical outcomes as it provides a good visual hepatic transection plane during laparoscopic partial hepatectomy.

Clinical Benefits of Conversion Surgery for Unresectable Pancreatic Ductal Adenocarcinoma: A Single-Institution, Retrospective Analysis.

BACKGROUND: Unresectable pancreatic ductal adenocarcinoma (UR-PDAC) has a poor prognosis. Conversion surgery is considered a promising strategy for improving the prognosis of UR-PDAC. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PDAC. METHODS: We retrospectively evaluated patients with PDAC who were referred to our department for possible surgical resection between January 2006 and December 2019. Conversion surgery was performed only in patients with UR-PDAC who could expect R0 resection. We analyzed the prognostic factors for overall survival among patients who underwent conversion surgery. RESULTS: Overall, 638 patients with advanced pancreatic cancer were enrolled in this study. According to resectability, resectable cancer (R) was present in 180 patients, borderline resectable cancer (BR) was present in 60 patients, unresectable locally advanced cancer (UR-LA) was present in 252 patients, and unresectable cancer with distant metastasis (UR-M) was present in 146 patients. Conversion surgery was performed in 20 of the 398 UR cases (5.1%). The median period between the initial therapy and conversion surgery was 15.5 months. According to the Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, the treatment response was CR in one patient, PR in 13, SD in five, and PD in one. Downstaging was pathologically determined in all cases. According to the Evans grading system, grade I was observed in four patients (20%), grade IIb was observed in seven (35%), III was observed in seven (35%), and IV was observed in two (10%). We compared the overall survival period from initial treatment among patients undergoing conversion surgery; the median overall survival durations in the conversion surgery, R, BR, UR-LA, and UR-M groups were 73.7, 32.7, 22.7, 15.7, and 8.8 months, respectively. Multivariate analysis revealed that the presence or absence of chemoradiotherapy (CRT) and the RECIST partial response (PR)/complete response (CR) for the main tumor were statistically significant prognostic factors for overall survival among patients undergoing conversion surgery (p = 0.004 and 0.03, respectively). CONCLUSION: In UR-PDAC, it is important to perform multidisciplinary treatment, including CRT with conversion surgery.

Locally advanced cholangiolocellular carcinoma successfully treated with curative resection after downsizing chemotherapy: a case report.

BACKGROUND: Cholangiolocellular carcinoma (CoCC) is an extremely rare disease comprising less than 1% of all primary malignant liver tumors. No effective treatment other than resection has been established. Herein, we report a case of locally advanced CoCC diagnosed as unresectable, which was successfully treated with curative resection after downsizing chemotherapy. CASE PRESENTATION: A 59-year-old Japanese woman with chronic hepatitis B was diagnosed with locally advanced intrahepatic cholangiocellular carcinoma. As it was difficult to perform R0 resection in the local hospital, chemotherapy combined with gemcitabine plus cisplatin was administered every 3 weeks. After a total of 10 courses of chemotherapy over 10 months the tumor was shown to be reduced in size by computed tomography imaging, and she was referred to our department for surgical resection. The effect of chemotherapy was classified as a "partial response" in the response evaluation criteria of solid tumors. After adding one course of chemotherapy, an extended left hepatectomy with resection of the caudate lobe was performed. R0 resection was achieved. Based on the pathological findings, the final diagnosis of CoCC was determined and eight courses of S-1 adjuvant chemotherapy were administered. At 14 months after the operation, the patient was alive without tumor recurrence. CONCLUSIONS: Downsizing chemotherapy with gemcitabine and cisplatin may be an effective treatment strategy in locally advanced CoCC. Further evidence is required to establish an optimal strategy for the treatment of locally advanced CoCC.