Clinical Implications of the Degree of Pancreatic Invasion in Ampulla of Vater Carcinoma.

BACKGROUND: Ampulla of Vater carcinoma (AVC) stage T3 was subdivided according to the degree of pancreatic invasion into T3a (≤ 0.5 cm) and T3b (> 0.5 cm) by the 8th edition of the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) cancer staging system. However, the differences in clinicopathological features and survival outcomes between the two categories have not been well discussed. PATIENTS AND METHODS: We retrospectively analyzed 133 consecutive patients who underwent pancreatoduodenectomy for AVC at our institution between 2002 and 2020. Clinicopathological features and survival outcomes of patients with AVC were analyzed, with a focus on the depth of pancreatic invasion. In addition, the survival outcomes of patients with T3 AVC were compared with those of patients with resectable pancreatic head carcinoma (R-PhC) who underwent pancreatoduodenectomy during the same period. RESULTS: The overall survival (OS) in patients with T3b AVC (n = 12) was significantly worse than that in patients with T3a AVC (n = 39) [median survival time (MST) 9.2 vs. 74.5 months, p < 0.001). A multivariate analysis identified T3b tumor (hazard ratio 5.64, p = 0.009) as an independent prognostic factor. The OS of patients with T3a AVC was significantly better than that of patients with R-PhC who received adjuvant chemotherapy (n = 276, MST 35.0 months, p = 0.007). In contrast, the OS of patients with T3b AVC tended to be worse than that of patients with R-PhC managed without adjuvant chemotherapy, although this difference was not statistically significant (n = 163; MST, 17.5; p = 0.140). CONCLUSIONS: AVC with > 0.5 cm invasion into the pancreas was associated with poor survival and represented advanced tumor progression to systemic disease.

Subdivision of pT1N0 (American Joint Committee on Cancer 8th edition) distal cholangiocarcinoma for adjuvant chemotherapy consideration.

BACKGROUND: The adjuvant S-1 trial affirmed adjuvant chemotherapy for biliary tract cancer but excluded pT1N0 distal cholangiocarcinoma (DCC) according to the seventh edition of the American Joint Committee on Cancer (AJCC) classification. The introduction of tumor depth of invasion (DOI) for T-classification in the eighth edition complicates identifying DCC patients less likely to benefit from adjuvant chemotherapy. METHODS: Our cohort consisted of 185 patients with DCC who underwent pancreaticoduodenectomy between 2002 and 2019. We compared clinicopathological factors and survival outcomes between pT1N0 patients in the seventh edition and those in the eighth edition. New DOI cutoffs for subdividing pT1N0 (8th edition) patients were evaluated to identify patients less likely to benefit from adjuvant chemotherapy. RESULTS: Transitioning to the eighth edition increased in pT1N0 cases from eight to 46. The 5-year cumulative recurrence rates of them were 14.3% for the seventh edition and 28.3% for the eighth edition. We proposed a DOI cutoff of <2 mm, at which the 5-year cumulative recurrence rate was 11.5%. CONCLUSION: The eighth AJCC classification revealed that a significant proportion of pT1N0 DCC patients were at risk for recurrence. A DOI cutoff of <2 mm may be considered to potentially improve patient selection for adjuvant chemotherapy.

Positive impact of laparoscopic hepatectomy versus open hepatectomy on body size-corrected bleeding in obese patients.

PURPOSE: Laparoscopic hepatectomy (LH) is reported to cause less bleeding than open hepatectomy (OH) in obese patients; however, there are no reports addressing this issue in terms of body size-corrected bleeding. METHODS: The subjects of this study were 31 obese and 149 non-obese patients who underwent LH and 32 obese and 245 non-obese patients who underwent OH. Bleeding corrected for body surface area (C-BL) was compared between the obese and non-obese patients who underwent each procedure. A multivariate analysis for increased C-BL was performed using the median C-BL for each procedure. RESULTS: The median C-BL tended to be higher in the obese patients than in the non-obese patients who underwent LH, but there was no significant difference (72 vs. 42 mL/m2, P = 0.050). However, it was significantly higher in the obese patients than in the non-obese patients who underwent OH (542 vs. 333 mL/m2, P = 0.002). In a multivariate analysis, for OH, sectionectomy or more (OR 3.20, P < 0.001) and a high BMI (OR 2.76, P = 0.018) were found to be independent risk factors, whereas for LH, a high BMI was not (OR 1.58, P = 0.301). CONCLUSIONS: Obesity was identified as a risk factor for increased bleeding with body size correction for OH, but the risk was reduced for LH.

Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

BACKGROUND: The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. METHODS: We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. RESULTS: The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. CONCLUSIONS: The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.

Predictive score for identifying intrahepatic cholangiocarcinoma patients without lymph node metastasis: a basis for omitting lymph node dissection.

BACKGROUND: This study aimed to develop a predictive score for intrahepatic cholangiocarcinoma (ICC) in patients without lymph node metastasis (LNM) using preoperative factors. METHODS: A retrospective analysis of 113 ICC patients who underwent liver resection with systemic lymph node dissection between 2002 and 2021 was conducted. A multivariate logistic regression analysis was used as a predictive scoring system for node-negative patients based on the ß coefficients of preoperatively available factors. RESULTS: LNM was observed in 36 patients (31.9%). Four factors were associated with LNM: suspicion of LNM on MDCT (odds ratio [OR] 13.40, p < 0.001), low-vascularity tumor (OR 6.28, p = 0.005), CA19-9 ≥500 U/mL (OR 5.90, p = 0.010), and tumor location in the left lobe (OR 3.67, p = 0.057). The predictive scoring system was created using these factors (assigning 3 points for suspected LNM on MDCT, 2 points for CA19-9 ≥500 U/mL, 2 points for low vascularity tumor, and 1 point for tumor location in the left lobe). A score cutoff value of 4 resulted in 0.861 sensitivity and a negative predictive value of 0.922 for detecting LNM. Notably, no patients with peripheral tumors and a score of ≤3 had LNM. CONCLUSION: The developed scoring system may effectively help identify ICC patients without LNM.

New criteria of resectability for pancreatic cancer: A position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS).

The symposium "New criteria of resectability for pancreatic cancer" was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice.

Perioperative assessment of indocyanine green elimination rate accurately predicts postoperative liver failure in patients undergoing hepatectomy.

BACKGROUND: This study aimed to evaluate the usefulness of perioperative indocyanine green elimination rate (ICG-K) as a predictive factor of posthepatectomy liver failure (PHLF). METHODS: This study enrolled 193 patients who underwent hepatectomy between 2013 and 2019. We analyzed the relationship between estimated ICG-K (ICG-Krem) calculated by the preoperative ICG-K and the residual liver volume ratio, ICG-K at days 1 and 7 after hepatectomy (ICG-Kpod1, ICG-Kpod7), and grade B or C PHLF. RESULTS: Grade B and C PHLF were observed in eight and two patients, respectively. ICG-Krem and ICG-Kpod1 were highly correlated (correlation coefficient [CC] 0.715), and ICG-Krem and ICG-Kpod7 were moderately correlated (CC 0.653). Receiver-operating characteristic curve analyses indicated that ICG-Krem and ICG-Kpod1 had moderate diagnostic value, while ICG-Kpod7 had high diagnostic value (area under the curve 0.703, 0.845 and 0.937, respectively). Multivariate analysis demonstrated that ICG-Kpod7 (relative risk [RR] 26.04, P = .012) and postoperative bile leakage (PBL) (RR 226.0, P < .001) were independent predictive factors for PHLF. PBL induced PHLF in seven patients, respectively. CONCLUSIONS: ICG-Krem correlated well with postoperative ICG-K, having moderate accuracy as a predictor of PHLF. However, the clinical relevance of postoperatively measuring ICG-K is limited because PHLF is greatly affected by surgical and postoperative factors.

Biological and conditional factors should be included when defining criteria for resectability for patients with pancreatic cancer.

BACKGROUND: This study aimed to evaluate novel resectability criteria for pancreatic ductal adenocarcinoma (PDAC) proposed by the International Association of Pancreatology (IAP) by comparing them with the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: 369 patients who underwent upfront surgery for PDAC were retrospectively analyzed. Overall survival (OS) of each group as defined by either of the guidelines were compared and preoperative prognostic factors for OS were identified. RESULTS: Based on the IAP-criteria, 157 patients were classified as resectable (R), 192 as borderline resectable (BR) and 20 as unresectable (UR), with the median survival time (MST) of 40 months, 17 and 11, respectively. In contrast to the NCCN-criteria, BR demonstrated significantly better OS than UR (P = 0.023) under the IAP-criteria. Performance status ≥2 (hazard ratio [HR]: 2.47, P = 0.014) and lymph node metastasis suspected by imaging (HR: 1.55, P = 0.003) were identified as independent prognostic factors by the multivariate analysis along with portal or arterial invasion, while carbohydrate antigen 19-9 ≥ 500 U/ml was not (HR: 1.23, P = 0.190). CONCLUSION: The IAP-criteria, which includes biological and conditional factors, resulted in superior separation of survival curves stratified by the resectablity when compared with the NCCN-criteria.

Impact of the Controlling Nutritional Status Score on the Prognosis After Curative Resection of Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: The controlling nutritional status (CONUT) score is a useful tool to evaluate immune-nutritional status. This study aimed to investigate the impact of the CONUT score on short- and long-term outcomes after curative resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: Consecutive 344 PDAC patients receiving pancreatectomy without neoadjuvant therapy were examined retrospectively. After the best predictive value of the CONUT score for survival was identified, association between the CONUT score and long-term outcomes was evaluated using log-rank tests and a Cox regression model. Then correlations between the CONUT score and postoperative complications were analyzed. RESULTS: The optimal cutoff value of the CONUT score was 4. The high CONUT score group showed significantly lower overall survival than the low CONUT score group (P = 0.002). In contrast, no significant difference in recurrence-free survival was found (P = 0.43). A multivariate analysis demonstrated that high CONUT score had an independent association with overall survival (hazard ratio, 1.64; P = 0.003). The CONUT score showed no association with postoperative pancreatic fistula, Clavien-Dindo grade, or postoperative hospital stay. CONCLUSION: The CONUT score had an independent association with survival in patients with PDAC after pancreatectomy and was not associated with recurrence or postoperative complications.

Combined resection of the transpancreatic common hepatic artery preserving the gastric arterial arcade without arterial reconstruction in hepatopancreatoduodenectomy: a case report.

BACKGROUND: Surgeons sometimes must plan pancreatoduodenectomy (PD) for patients with a variant common hepatic artery (CHA) branching from the superior mesenteric artery (SMA) penetrating the pancreatic parenchyma, known as a transpancreatic CHA (tp-CHA). CASE PRESENTATION: A 67-year-old man was admitted to our hospital because of liver dysfunction. A duodenal tumor was identified by gastrointestinal endoscopy, and a biopsy revealed a neuroendocrine tumor. Computed tomography showed multiple metastases in the left three sections of the liver. As an anatomical variant, the CHA branched from the SMA and passed through the parenchyma of the pancreatic head, and all hepatic arteries branched from the CHA. Furthermore, the arcade between the left and right gastric artery (RGA) was detected, and the RGA branched from the root of the left hepatic artery. PD and left trisectionectomy of the liver were performed. The tp-CHA was resected with the pancreatic head, and the gastric arterial arcade was preserved to maintain the right posterior hepatic arterial flow. Postoperatively, there were no signs of hepatic ischemia. CONCLUSIONS: When planning PD, including hepatopancreatoduodenectomy, for patients with a tp-CHA, surgeons should simulate various situations for maintaining the hepatic arterial flow. The preservation of the gastric arterial arcade is an option for maintaining the hepatic arterial flow to avoid arterial reconstruction.

Pancreaticoduodenectomy with hepatic arterial revascularization for pancreatic head cancer with stenosis of the celiac axis due to compression by the median arcuate ligament: a case report.

A 71-year-old woman presented to our hospital because pancreatic head cancer was suspected on a medical checkup. Computed tomography showed a 30 mm low-density lesion in the pancreatic head, and the stenosis of the celiac axis (CA) due to the median arcuate ligament (MAL) compression. We made a preoperative diagnosis of pancreatic head cancer and performed laparotomy. Transection of the MAL failed to restore adequate hepatic arterial flow, necessitating arterial revascularization, which was achieved by end-to-end anastomosis between the gastroduodenal artery and the middle colic artery. After reconstruction, Doppler ultrasonography showed improved hepatic arterial signal. The patient was discharged 16 days after surgery with no complications. When planning pancreaticoduodenectomy (PD) for such patients with CA stenosis due to MAL compression, surgeons should simulate a situation of insufficient hepatic arterial flow after division of the MAL, and prepare for reconstruction of the hepatic artery during PD.

Combined Antrectomy Reduces the Incidence of Delayed Gastric Emptying after Pancreatoduodenectomy.

BACKGROUND: There are a few reports that compare the rate of postoperative complications between subtotal stomach-preserving pancreatoduodenectomy (SSPPD) and antrectomy-combined pancreatoduodenectomy (ACPD), especially with respect to delayed gastric emptying (DGE) after pancreatoduodenectomy (PD). METHODS: From 2002 to 2013, 628 patients who underwent SSPPD (n = 78) or ACPD (n = 550) were enrolled in this study. The rate of DGE and the nutritional status were compared between patients receiving ACPD and SSPPD. RESULTS: The overall morbidity rate (p = 0.830) was comparable between both groups; however, the incidence of DGE grade B or C was significantly higher in the SSPPD group than that in the ACPD group (16 vs. 7%, p = 0.007). A multivariate analysis identified SSPPD rather than ACPD (p = 0.007) and portal vein resection and reconstruction (p = 0.028) to be independent risk factors for DGE grade B or C. The changes in the body weight and nutritional parameters 3, 6, and 12 months after surgery were comparable between 2 groups. CONCLUSIONS: SSPPD and not ACPD was an independent risk factor for grade B or C DGE, but the postoperative nutritional status was comparable between the 2 groups based on the limited nutritional data. Combined resection of antrum will help reduce the risk of DGE after PD.

The Impact of Serosal Invasion on Prognosis after Curative Hepatectomy for Hepatocellular Carcinoma: Invasion to Adjacent Organs and Rupture of Tumor Were Crucial Tumor-Related Prognostic Factors Needed for Survival.

BACKGROUND/AIMS: Several tumor factors seem to be related to the hepatocellular carcinoma (HCC) prognosis, but they are not definitive, except for major vascular invasion. We analyzed the impact of serosal invasion, which is histologically classified into four groups according to the definition of the Liver Cancer Study Group of Japan - S0: no tumor invasion of serosa, S1: tumor invasion of serosa, S2: tumor invasion of adjacent organs, S3: tumor rupture with intraperitoneal bleeding. METHODS: This retrospective study included 421 consecutive patients who underwent hepatectomy as an initial treatment for HCC between September 2002 and December 2014. RESULTS: Kaplan-Meier analysis and log-rank tests revealed that both recurrence-free survival (RFS) and disease-specific survival (DSS) worsened as the serosal invasion status advanced. Multivariate analyses showed that S2/S3 was independently correlated with RFS (hazard ratio [HR] 3.52; p  < 0.001) and DSS (HR 2.58; p  = 0.039). Another multivariate analysis showed that serosal invasion (S1-S3) was independently correlated with RFS (HR 1.70; p = 0.015) but not with DSS (HR 1.38; p = 0.27). CONCLUSION: Invasion to adjacent organs and tumor rupture were crucial prognostic factors for both DSS and RFS. Serosal invasion was an independent prognostic factor only for RFS.

Vascularity and Tumor Size are Significant Predictors for Recurrence after Resection of a Pancreatic Neuroendocrine Tumor.

BACKGROUND: It is difficult to identify patients at high risk of recurrence after pancreatectomy for pancreatic neuroendocrine tumor (PNET) using only the grading classification, especially the G2 category, which includes both benign and low- and high-grade malignant tumors. METHODS: Forty-one patients with PNET who underwent pancreatectomy were enrolled in this study. We defined the computed tomography (CT) ratio as the CT value of the tumor divided by that of non-tumorous pancreatic parenchyma using the late arterial phase dynamic CT. The optimal cut-off values for CT ratio and tumor size were determined using p-values that were calculated using the log-rank test. RESULTS: The optimal cut-off values of CT ratio and tumor size for dividing patients into groups according to the greatest difference in disease-free survival (DFS) were 0.85 (p < 0.001) and 3.0 cm (p < 0.001), respectively. In analysis using Spearman's correlation coefficient, CT ratio (p = 0.007) and tumor size (p = 0.003) were individually associated with the Ki-67 proliferative index. Cox proportional hazard analysis identified that a CT ratio <0.85 (n = 10, p = 0.006) and tumor size ≥3.0 cm (n = 13, p = 0.023) were independent prognostic factors associated with DFS. All patients in the CT ratio ≥0.85 and tumor size <3.0 cm group (n = 23, including seven patients with G2 disease) did not develop recurrence after surgery. On the other hand, 5-year DFS in the CT ratio <0.85 and tumor size ≥3.0 cm group (n = 5, including three patients with G2 disease) was zero. CONCLUSIONS: PNETs with a CT ratio <0.85 and tumor size ≥3.0 cm should be considered as having a high risk of recurrence after pancreatectomy.