Clinical Significance of Increased Skeletal Muscle Mass During Nab-Paclitaxel Plus Gemcitabine Treatment in Patients With Advanced Pancreatic Cancer.

OBJECTIVES: The clinical significance of increased skeletal muscle mass during nab-paclitaxel plus gemcitabine (AG) treatment in patients with advanced pancreatic cancer (APC) remains unknown. Therefore, we retrospectively investigated the characteristics of patients after AG treatment to evaluate the clinical significance of increased skeletal muscle mass during treatment. METHODS: From January 2015 to August 2021, 67 patients with APC received AG as first-line chemotherapy at Higashiosaka City Medical Center. Of these patients, 39 received second-line (2L) chemotherapy after AG therapy, and 28 received best supportive care. Patients' characteristics at the end of AG treatment were compared retrospectively between these 2 groups, and the relevant factors at the end of first-line treatment for 2L chemotherapy induction were analyzed. RESULTS: A performance status of 0 to 1 and increased skeletal muscle mass during AG therapy were independently associated with 2L chemotherapy induction in multivariate analysis. A high relative dose intensity (≥50%) in the first 8 weeks of AG treatment was more frequently found in patients with increased skeletal muscle mass during treatment ( P = 0.037). CONCLUSIONS: Increased skeletal muscle mass during AG treatment might contribute to the higher prevalence of 2L chemotherapy induction in patients with APC.

[A Case of Laparoscopic Uterine and Vaginal Resection for Local Recurrence after Abdominoperineal Resection for Anal Canal Cancer].

The patient was an 80s woman. She visited our hospital with chief complaint of melena, and further evaluation revealed anal canal cancer. We performed robot-assisted abdominoperineal resection(D3 lymphadenectomy)and lateral lymph node dissection. The pathological diagnosis was anal canal cancer, muc>por1>tub2, T3N1bM0, pStage Ⅲb. One year after the surgery, she had a mass in the soft tissue of perineum on CT scan and PET-CT showed abnormal accumulation, which was diagnosed as local recurrence. At the same time, she also had a mass with abnormal accumulation in ascending colon, and it was diagnosed as ascending colon cancer. In both cases, we judged radical resection was possible, and the policy of surgery was decided. First, laparoscopic ileocecal resection was performed. The local recurrence lesion became a mass, invading the soft tissue of the perineum, the posterior wall of the vagina, and the cervix. So, we performed laparoscopic excision of local recurrent region together with the uterus and the posterior wall of the vagina. Based on the result of pathological examination, the patient was diagnosed with ascending colon cancer(tub1, pT1bN1aM0, pStage Ⅲa), and recurrence of anal canal cancer. The postoperative course is good and there are no signs of recurrence for 6 months after the operation.

Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer.

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.

Microsatellite instability in patients with hepato-biliary-pancreatic malignancies in clinical practice (KHBO 1903).

BACKGROUND: This study aimed to determine the prevalence of microsatellite instability (MSI)-high status in hepato-biliary-pancreatic malignancies in clinical practice and the clinical characteristics of and therapeutic results of pembrolizumab on patients with MSI-high cancers. METHODS: The subjects were 283 patients who had undergone MSI tests for unresectable, metastatic hepato-biliary-pancreatic malignancies at seven hospitals. The tests were polymerase chain reaction fragment analyses using the microsatellite markers consisting of BAT25, BAT26, NR21, NR24, and MONO27. Formalin-fixed, paraffin-embedded blocks, prepared according to the guidelines of the Japan Society of Pathology were used within 4 years after sampling. There were 13 patients with cancers high in MSI, including eight patients receiving pembrolizumab treatment. The clinical characteristics of these patients and therapeutic outcomes of their pembrolizumab treatment were investigated. RESULTS: MSI-high was detected in 13 (4.6%) of the 283 patients with hepato-biliary-pancreatic malignancies. None of these 13 patients had been diagnosed with Lynch syndrome. Of the Eight patients receiving pembrolizumab, a complete response was observed in three patients, a partial response in one patient, and stable disease in three patients. The objective response rate was 50% and the disease control rate was 87.5%. CONCLUSION: MSI-high was detected in 4.6% of patients with hepato-biliary-pancreatic malignancies. There was a 50% objective response rate to pembrolizumab treatment for MSI-high cancers. The evaluation of MSI status by the current method using appropriately prepared tissue samples was to be a reliable and accurate approach to both the determination of MSI status and estimation of the effectiveness of pembrolizumab.

Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer.

OBJECTIVE: Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS: Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS: Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS: Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.

[A Case of Robotic-Assisted Total Pelvic Exenteration for Locally Advanced Rectal Cancer Invading the Prostate].

The patient was a 60s man, whose chief complaint of melena and weight loss. He visited our hospital, and further evaluation revealed rectal cancer(Rb)invading the prostate with obturator lymph node metastasis. The clinical diagnosis was T4b (prostate)N3M0, Stage Ⅲc. He was administered 4 courses of CAPOX plus bevacizumab. After chemotherapy the primary tumor and lymph nodes showed PR, the diagnosis of ycT4bN1bM0, Stage Ⅲc. We performed robot-assisted total pelvic exenteration. He has been cancer-free for 5 months.

[A Case of Laparoscopic Total Pelvic Exenteration for Sigmoid Colon Cancer Using Infrared Illumination System (IRIS)].

The patient was 80s woman, whose chief complaint of fever and abdominal pain. She visited our hospital, and further evaluation revealed sigmoid colon cancer invading the uterus and abdominal wall. The pooling of pus in the uterus was formed and we diagnosed as pyometra. The clinical diagnosis was T4b(uterus, abdominal wall)N0M0, cStage Ⅱc. We performed laparoscopic sigmoidectomy, uterus and bilateral ovaries. We report a case in which the intraoperative infrared illumination system(IRIS)was used to support the identification of the ureter by near-infrared light and total pelvic exenteration could be safely performed.

[A Case of Early Appendiceal Adenocarcinoma Coexisting with High-Grade Appendiceal Mucinous Neoplasm].

We report a case of a female in her fifties with early appendiceal adenocarcinoma coexisting with high-grade appendiceal mucinous neoplasm(HAMN)with a review of the literature. The patient presented to our hospital because of an enlarged appendix noted by contrast-enhanced CT performed for hematuria. Contrast-enhanced CT showed that the appendix had swollen to 10 mm and mucus had accumulated inside, which had no evidence of obvious malignancy. She was followed up on CT once a year. Four years after her first visit, she underwent laparoscopic appendectomy for a definitive diagnosis. There were no adhesions or inflammation in her abdominal cavity, and the appendix root was dissected with an automatic anastomosis device. Her resected specimen macroscopically showed mild wall thickening, but no obvious neoplastic lesion. Pathological examination revealed that in many areas centered on the tip of the appendix, highly columnar atypical epithelium with enhanced mucus production was densely proliferated in the form of glandular tubular and papillary. The nuclei of the proliferating epithelium were large and the fission image was conspicuous, but they remained in the mucosa. Pathological examination diagnosed as HAMN according to the WHO classification. The atypical epithelium in a small area at the tip was particularly strong in nuclear atypia, and showed a strong positive diffusely in p53, which was an image of well-differentiated tubular adenocarcinoma. The pathological diagnosis was V, Type 0-Ⅱb, 2 mm, tub1 in HAMN, pTis, Ly0, V0, Pn0, pPM0, pDM0, pRM0, R0. Six months have passed since the operation, but no recurrence has been observed.

A case report of simple mucinous cyst of pancreas detected by rupture.

INTRODUCTION: Simple mucinous cyst (SMC) of pancreas is a disease defined by the Baltimore Consensus in 2014. Pancreatic mucus-producing neoplasms are considered to be premalignant tumors, but SMC is not considered to have a risk of malignancy or recurrence. PRESENTATION OF CASE: The case was a woman in her 50s with a chief complaint of abdominal pain. A blood exam showed an increase in the inflammatory response, and a slight increase of Amylase. CT showed a cystic lesion 80 mm in size at tail of the pancreas, and disproportionate fat stranding and ascites around it. We diagnosed peritonitis associated with the rupture of a cystic lesion accompanied by pancreatitis. Abdominal pain was improving, and we decided to proceed with the detailed examination. MRI showed a uniform hyper-intensity on T2WI, and a nodular-like hypo-intensity was observed inside, which was enhanced. During the follow-up, the lesion had gradually grown and re-ruptured. As we could not deny malignancy by image findings, distal pancreatectomy was performed. The intracystic fluid was browny and turbid, and Amylase, CEA and CA19-9 of the cystic fluid were elevated. We diagnosed it SMC by histopathological findings. Currently, she had no recurrence for 1 year. DISCUSSION: SMC is a type of true cysts, so rupture was rare. However, if the cyst wall becomes weak due to complications such as acute pancreatitis. It is probable that our case had pancreatitis and the cyst wall was weakened. CONCLUSION: SMC detected by rupture was very rare, so we report this case.

[A Case of Giant Intestinal GIST That Was Resected Just after TAE].

A 42-year-old woman visited our hospital complaining of fever and diarrhea. She had abdominal swelling and muscular defense. CT revealed a lobulated tumor occupying the lower abdomen. The tumor contained solid and cystic areas. The main artery vascularizing the tumor was the ileocecal artery, so we considered the tumor to be derived from the intestine or mesentery. We anticipated massive bleeding due to resection, and immediately after the embolization of the artery just before the operation. A vascular bundle from the terminal ileum and mesentery was found on the dorsal side of the tumor, and an outflow from the inferior mesenteric vein was also observed. We ligated each vessel and performed ileocecal resection. The operation lasted 4 hours and 18 minutes, with an estimated blood loss of 2,585 mL, requiring the transfusion of 6 units of concentrated red blood cells. According to histopathological findings, tumor cells with spindle-shaped to ellipsoidal nuclei proliferated in bundles and intricately, and immunostaining was positive for c-kit and DOG-1. We identified the tumor as high-risk GIST. The clinical course after the operation was uneventful. She continued to take imatinib for 3 years and is currently alive and without recurrence for 6 years after the operation.

The impact of peritoneal lavage cytology in biliary tract cancer (KHBO1701): Kansai Hepato-Biliary Oncology Group.

BACKGROUND: Only few studies in literature have analyzed the clinical effects of peritoneal lavage status in biliary tract cancers. AIM: We aimed to assess the effect of cytology-positive peritoneal lavage on survival for patients with biliary tract cancer who underwent curative resection. METHODS: The KHBO1701 study was a multi-institutional retrospective study that assessed the clinical effects of peritoneal lavage cytology in biliary tract cancers. Using clinicopathological data from 11 Japanese institutions, we compared long-term outcomes between patients with cytology-positive and cytology-negative peritoneal lavage. RESULTS: Of 169 patients who underwent curative resection, 164 were cytology-negative, and five were cytology-positive. The incidence of portal invasion and preoperative carbohydrate antigen 19-9 levels were higher in the cytology-positive group than in the cytology-negative group. The incidence of peritoneal metastatic recurrence was also higher, and overall survival tended to be worse in the cytology-positive group. In contrast, recurrence-free survival was similar between the cytology-negative and cytology-positive groups. CONCLUSIONS: The positive status of peritoneal lavage cytology could moderately affect the survival of patients with biliary tract cancers. Given that surgical resection is the only curative treatment option, it may be acceptable to resect biliary tract cancers without other non-curative factors, regardless of peritoneal lavage cytology status.

A case of multiple serous cystadenoma of pancreas.

INTRODUCTION: Typically, SCN is single and doesn't invade around tissue. In our case, tumors were multiple and had gradually grown and caused vein stenosis. This is extremely rare and unique resected multiple SCN case. In addition, I report that it was thought to be educational that even benign tumors could cause such changes. PRESENTATION OF CASE: A 60-year-old female was diagnosed with 3 multilocular cystic tumors in distal pancreas by contrast enhanced computed tomography (CT) at the preoperative staging for rectal neoplasm. The diameters of cystic tumors were 22/23/29 mm. The CT showed that the tumors had multiple internal septa enhanced in the arterial phase and the second tumor contained internal calcifications located centrally. The main pancreatic duct was not dilated. Although SCN often occurred single and multiple SCN was very rare, we diagnosed that the tumors were suspected microcystic type SCN because they had typical image findings. So, we planned to follow up every six months after resection for rectal neoplasm. 2 years and half later, they had gradually grown, and splenic vein stenosis appeared. The pancreatic parenchyma atrophy and dilatation of the main pancreatic duct had been gradually progressing. We performed distal pancreatectomy because of possibility of malignancy. The histopathological findings showed that 2 cystic tumors the side of pancreatic head had a connection and had typical findings of SCA of pancreas. The other tumor was independent from two tumors. They had no malignant findings. DISCUSSION: At first, we expected tumor invasion had caused the changes. But tumors had no malignant findings, so we considered that compression from the tumor had caused stenosis, and obstructive pancreatitis had induced the pancreatic parenchyma atrophy. CONCLUSION: We learned from this case that not only invasion but also compression caused vein stenosis and pancreatic duct dilation.

Predictive implications of decreased CA19-9 at 8 weeks during nab-paclitaxel plus gemcitabine for the induction of second-line chemotherapy for patients with advanced pancreatic cancer.

BACKGROUND: Second-line (2L) chemotherapy after nab-paclitaxel plus gemcitabine (AG) is important for improving the survival of patients with advanced pancreatic cancer (APC). However, many patients fail to receive 2L chemotherapy because of rapid disease progression. Therefore, early recognition of any ineffectiveness during AG might lead to an increased induction rate of 2L chemotherapy. AIM: We investigated the significance of treatment response at 8 weeks as a predictive factor for the induction of 2L chemotherapy after AG. METHODS AND RESULTS: From January 2015 to January 2019, 41 patients with APC underwent AG as first-line chemotherapy at our institute. Thirty-three patients were evaluated at 8 weeks. Sixteen patients (48%) underwent 2L chemotherapy and 17 (52%) underwent no 2L chemotherapy. Clinical features and treatment response at 8 weeks were, retrospectively, compared among patients. Predictive factors for the induction of 2L chemotherapy were analyzed. Patients with an objective response by 8 weeks received 2L chemotherapy more frequently (P = .026). Decreased CA19-9 (<50%) at 8 weeks was identified as an independent negative predictive factor for the induction of 2L chemotherapy. CONCLUSIONS: Decreased CA19-9 (<50%) at 8 weeks may indicate the ineffectiveness of AG and signify that a move to 2L chemotherapy may be required without delay.

Bridge to surgery using a self-expandable metallic stent for stages II-III obstructive colorectal cancer.

BACKGROUND: Bridge to surgery (BTS) using a self-expandable metallic stent (SEMS) for the treatment of obstructive colorectal cancer improves the patient's quality of life. This study aimed to examine prognostic factors of obstructive colorectal cancer. METHODS: We analyzed stage II-III resectable colon cancer cases (Cur A) retrospectively registered between January 2005 and December 2017. Overall, 117 patients with Cur A obstructive colorectal cancer were evaluated: 67 of them underwent emergency surgery (ES Group) and 50 of them after BTS with SEMS placement (BTS group). We compared surgical results and prognoses between the two groups. RESULTS: A total of 50 patients underwent endoscopic SEMS placement, which technical success of 96% and morbidity rate of 18%. Primary anastomosis rates were 77.6% in ES and 95.7% in BTS (p <  0.001); postoperative complication, 46.3% in ES and 10.5% in BTS (p <  0.001); pathological findings of lymphatic invasion, 66.7% in ES and 100% in BTS (p <  0.001); venous invasion were 66.8% in ES and 92% in BTS (p = 0.04); and recurrence of 25.4% in ES and 39.1% in BTS. The 3-year overall survival was significantly different between two groups (ES, 86.8%:BTS, 58.8%), BTS is worse than ES (log-rank test; p <  0.001). Venous invasion independently predicted worsened recurrence-free and overall survival. CONCLUSIONS: The vascular invasiveness was correlated with tumor progression after SEMS placement, and the survival rate was lower in BTS. SEMS potentially worsens prognostic outcomes in stage II-III obstructive colorectal cancer.

Efficacy of S-1 in second-line chemotherapy after nab-paclitaxel plus gemcitabine for patients with advanced pancreatic cancer.

BACKGROUND: Second-line (2 L) chemotherapy is important for improved survival. However, the efficacy of S-1 after nab-paclitaxel plus gemcitabine (AG) for advanced pancreatic cancer (APC) remains unclear. AIM: We retrospectively investigated the clinical impact of S-1 after AG. METHODS AND RESULTS: From January 2015 to July 2018, 37 patients with APC underwent AG as first-line chemotherapy at our institute. Of these patients, 14 (38%) underwent S-1 as 2 L chemotherapy after AG (S-1 group), five (14%) received another agent after AG, and 18 (49%) underwent no 2 L chemotherapy (best supportive care [BSC] group). The clinical features were retrospectively compared between the S-1 and BSC groups. Prognostic factors for residual survival (RS) were analyzed using a Cox proportional hazards model. The induction rate of 2 L chemotherapy was 51%, and most patients received S-1 monotherapy (74%). The disease control rate and progression-free survival duration were 57.1% and 2.8 months, respectively. The median RS duration in the S-1 and BSC groups was 5.2 and 2.4 months, respectively; this difference was statistically significant (hazard ratio, 0.33; P = .005). The median overall survival duration in the S-1 and BSC groups was 12.3 and 5.0 months, respectively; this difference was also statistically significant (hazard ratio, 0.26; P = .001). The efficacy of S-1 in 2L chemotherapy for RS was identified in the multivariate analysis, as was age (<65 vs ≥65 y) and the presence of liver metastasis. CONCLUSION: The antitumor activity of S-1 was retained after AG, and the induction of S-1 after AG might improve the prognosis of patients with APC.

[Clinical Significance of Palliative Esophageal Stent Placement for Esophageal Cancer].

BACKGROUND: Since the introduction of the guideline for the diagnosis and treatment of esophageal carcinoma in 2007, the indication for placing an esophageal stent has changed, especially with respect to the treatment of esophageal stricture after chemoradiotherapy(CRT). For CRT cases, irradiation after stent placement and stent placement after CRT are not recommended due to the risk of perforation. METHODS: Thirty-eight patients who underwent esophageal stenting in our department between January 2007 and December 2018 and who were diagnosed with thoracic esophageal cancer were included in this study. We retrospectively examined the safety and treatment effect of esophageal stent placement. RESULTS: Prior cancer therapy was observed in 16 cases(8 cases of chemotherapy and 8 cases of CRT). In the no prior therapy group, 13 cases were treated with BSC and 9 cases with chemotherapy. Esophageal stent placement after CRT was performed in 8 cases. Esophageal stent was placed 9(6-14)months after CRT. The stent patency period was 5(1-11)months, and the survival period after stent placement was 6(1-12)months. There was no difference in the frequency of complications and treatment outcomes of the CRT group compared with the non-CRT group. CONCLUSION: Cases undergoing esophageal stent placement after CRT can expect therapeutic effects similar to those of other cases. However, complications such as perforation can be fatal; thus, careful consideration should be given to each individual case for esophageal stent placement after CRT.

[A Case of Brain, Lung, and Adrenal Metastasis from Colorectal Cancer Controlled by Loco-Regional Surgery].

A 64-year-old man presented with the chief complaint of weakness in the left half of his body. He fell down on the road while riding a bicycle and was transported to the emergency room. A contrast-enhanced brain MRI revealed a 28mm ringshaped mass in the right frontal lobe. A craniotomy was performed 14 days later. The histopathological diagnosis showed the tumor as a well-differentiated tubular adenocarcinoma. Postoperative examination revealed a rectal cancer and a left lung mass. A low-anterior resection was performed 1 month after the craniotomy, and a partial lung resection was performed 2 months after the rectal excision. Metachronous solitary metastasis of the left adrenal gland was noticed 10 months after the removal of the lung metastasis and we subsequently performed a left adrenalectomy. The patient is not undergoing any active treatment 13 months after the adrenalectomy, but has no signs of recurrence. The loco-regional surgery was enabled for local control of multi-relapsed lesions from rectal cancer.

[A Case of Early Rectal Cancer Accompanied by Multiple Liver Abscesses].

An 81-year-old female who suffered from headache and general fatigue was diagnosed multiple liver abscesses by abdominal computed tomography(CT). Antibiotics and percutaneous transhepatic abscess drainage(PTAD)were performed, liver abscesses were improved. During the treatment, followed abdominal CT indicated lower rectal tumor. An early rectal cancer accompanied by multiple liver abscesses was diagnosed and performed surgery. The histological diagnosis was Rb, type 1, tub2, pT1b(SM 8,000 µm), Ly0, V1a, pN0, pStage Ⅰ. After surgery, the patient remains free from liver abscess. We report early colorectal cancer with multiple liver abscesses in Japanese literature.