Controversies in the diagnosis and treatment of periampullary tumours

Most tumours in the head of the pancreas are adenocarcinomas of the exocrine pancreas. However, carcinomas located in the head of the pancreas may originate from the papilla of Vater, the distal part of the common bile duct, or the duodenum. Tumours of that region, within 2 cm of the greater duodenal papilla, have been usually described as periampullary neoplasms. Adenocarcinomas separated from the major duodenal papilla and located in the major pancreatic duct, common bile duct, or duodenum are identified as ductal pancreatic carcinomas, distal bile duct cholangiocarcinomas or duodenal carcinomas. Surgical treatment is the only chance for cure. Pancreatoduodenectomy is the procedure of choice. Regional lymphadenectomy and removal of at least 16 lymph nodes are necessary for optimal long-term outcomes. Indications for adjuvant chemotherapy remain controversial. This review evaluates the available data on the pathological assessment of periampullary tumours and discusses the controversies of therapeutic management, emphasising adjuvant treatment.     

CLINICAL ANALYSIS OF 150 PATIENTS WITH PERIAMPULLARY CARCINOMA

ＣＬＩＮＩＣＡＬＡＮＡＬＹＳＩＳＯＦ１５０ＰＡＴＩＥＮＴＳＷＩＴＨＰＥＲＩＡＭＰＵＬＬＡＲＹＣＡＲＣＩＮＯＭＡ￥ＷｕＸｉａｎｇｄｅ；吴祥德；ＳｏｎｇＺｈｅｎｃｈｕａｎ；宋振川；ＧｅｎｇＣｕｉｚｈｉ；耿翠芝；ＬｉＢｉｎｇｈｕｉ；李秉慧（Ｄｅｐａｒｔｍｅ...     

475例壶腹周围癌的外科治疗

目的比较不同年代壶腹周围癌患者外科治疗的特点和疗效．方法回顾性分析1958年至2003年外科治疗的壶腹周围癌患者475例。结果1958年至1976年的128例壶腹周围癌中,胰头癌、壶腹癌、胆管下端癌和十二指肠癌的手术切除率分别为26．6％(21／79)、86．2％(25／29)、38．5％(5／13)和57．1％(4／7);1977年至1987年的70例壶腹周围癌中,胰头癌、壶腹癌、胆管下端癌及十二指肠癌切除率分别为26．7％(16／60)、66．7％(4／6)、100％(1／1)和66．7％(2／3);1988年至1998年的147例壶腹周围癌中,胰头癌、壶腹癌、胆管下端癌及十二指肠癌切除率分别为20．2％(22／109)、75．0％(12／16)、50．0％(2／4)和66．7％(12／18);1999年至2003年的130例壶腹周围癌中．胰头癌、壶腹癌、胆管下端癌及十二指肠癌切除率分别为20．4％(20／98)、100(4／4)、75．0％(12／16)和83．3％(10／12)。1958年至2003年期间,胆管下端癌的发生率在壶腹周围癌中显著增高,术前总胆红素平均值呈下降趋势,术中输血量较前明显减少;手术切除的肿瘤直径平均值较前缩小。1999年至2003年间所有的胰十二指肠切除患者术前均未行减黄处理,并发症仍然显著降低,结论由于新的围手术期治疗和监护技术的进步,壶腹周围癌的手术死亡率和并发症发生率均有显著下降,但胰头癌的手术切除率和生存率仍然没有显著变化。     

THE EXPRESSION OF CYTOKERATINS IN HUMAN HEPATOCELLULAR AND CHOLANGIOCELLULAR CARCINOMAS

ＴＨＥＥＸＰＲＥＳＳＩＯＮＯＦＣＹＴＯＫＥＲＡＴＩＮＳＩＮＨＵＭＡＮＨＥＰＡＴＯＣＥＬＬＵＬＡＲＡＮＤＣＨＯＬＡＮＧＩＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＳ￥ＳｕＱｉｎ；苏勤；Ｌｉｕｙａｎｆａｎｇ；刘彦仿（ＤｅｐａｒｔｍｅｎｔｏｆＰａｔｈｏｌｏｇｙ，...     

Tumors of ampulla of Vater: A case series and review of chemotherapy options

Carcinomas of the Ampulla of Vater are rare tumors, accounting for 0.2% of gastrointestinal cancers. Compared with other biliary tract neoplasms, these tumors have a relatively favorable prognosis after surgical resection. Based on their epithelium of origin, two subtypes of ampullary carcinoma have been recently distinguished: intestinal and pancreatobiliary. This study evaluates histopathological features and outcomes of ampullary carcinoma and to compares the survival of these tumors to that of other biliary tract tumors. The chemotherapic options available for ampullary cancer are also reviewed. We analyzed data from 20 consecutive patients with ampullary carcinomas and 26 patients with other biliary tract carcinomas, observed in our Institution. Statistical analysis was performed by using either Fisher’s exact test or χ2 test for categorical variables. Median time of survival was calculated and compared using the Log-Rank test. Similar distribution of demographic characteristics and stage between ampullary and other biliary tract cancers was observed. Patients with ampullary cancer underwent surgery more frequently than other biliary cancers while chemotherapy and radiotherapy were used equally. In accordance with the literature, a longer median survival was observed in the group of ampullary carcinomas.     

Intracellular localization of CK2α as a prognostic factor in invasive breast carcinomas

Overexpression of the ubiquitous protein kinase, CK2α, has been reported in various human cancers. Here, we demonstrate that nuclear and nucleolar CK2α localization in invasive ductal carcinomas of the breast is a reliable predictor of poor prognosis. Cellular localization of CK2α in nuclei and nucleoli was analyzed immunohistochemically using surgical tissue blocks from 112 patients, who had undergone surgery without neoadjuvant chemotherapy. Clinical data collection and median follow‐up period were for more than 5 y. In total, 93.8% of patients demonstrated elevated CK2α expression in nuclei and 36.6% of them displayed elevated expression predominantly in nucleoli. Clinicopathological malignancy was strongly correlated with elevated nuclear and nucleolar CK2α expression. Recurrence‐free survival was significantly worse (P = .0002) in patients with positive nucleolar CK2α staining. The 5‐y survival rate decreased to a roughly 50% in nucleolar CK2α‐positive patients of triple‐negative (P = .0069) and p Stage 3 (P = .0073) groups. In contrast, no patients relapsed or died in the triple‐negative group who exhibited a lack of nucleolar CK2α staining. Evaluation of nucleolar CK2α staining showed a high secondary index with a hazard ratio of 6.629 (P = .001), following lymph node metastasis with a hazard ratio of 14.30 (P = .0008). Multivariate analysis demonstrated that nucleolar CK2α is an independent factor for recurrence‐free survival. Therefore, we propose that histochemical evaluation of nucleolar CK2α‐positive staining may be a new and robust prognostic indicator for patients who need further treatment. Functional consequences of nucleolar CK2 dysfunction may be a starting point to facilitate development of novel treatments for invasive breast carcinoma.     

Prognostic impact of syndecan-1 expression in invasive ductal breast carcinomas

Carcinoma cells lack syndecan-1 expression when they are transiting from an epithelial to a less-differentiated mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Furthermore, a shift of syndecan-1 expression from malignant epithelial cells to reactive stromal cells has also been observed during progression of many carcinomas. Finally, epithelial and/or stromal syndecan-1 expression is of prognostic value in many carcinomas. Because recent results are contradictory in breast carcinomas, we have re-evaluated the prognostic significance of syndecan-1 expression in a cohort of 80 patients with invasive ductal breast carcinomas. The tumours from 80 patients diagnosed with invasive ductal breast carcinomas were used to construct a tissue microarray, which was stained with syndecan-1 by immunohistochemistry. We correlated syndecan-1 expression with clinicopathologic parameters and relapse-free survival (RFS). Exclusive epithelial expression of syndecan-1 is observed in 61.25% of the patients, whereas exclusive stromal expression is observed in 30% of the patients. Only 8.75% of the patients had both stromal and epithelial expressions of syndecan-1. A significant correlation was found between the loss of syndecan-1 epithelial expression and the syndecan-1 stromal expression with high grade of malignancy (P=0.011). The loss of syndecan-1 epithelial expression is correlated with RFS (P=0.001). Using multivariate Cox analysis, loss of epithelial syndecan-1 expression was the only prognostic indicator (P<0.001). We concluded that the loss of syndecan-1 epithelial expression was of strong prognostic value in breast carcinomas.     

Association between posttreatment α-fetoprotein reduction and outcomes in real-world US patients with advanced hepatocellular carcinoma

Background

Clinical trials suggest α-fetoprotein (AFP) reduction may be prognostic among patients with advanced hepatocellular carcinoma. However, the association of AFP reduction with outcomes in real-world settings is unclear.

Methods

Patients with advanced hepatocellular carcinoma between January 1, 2011, and June 30, 2021, first-line tyrosine kinase inhibitor, and baseline and posttreatment AFP values (closest to 8 ± 2 weeks after first-line initiation) were included. AFP reduction was defined as ≥20% decrease from baseline vs <20% or no decrease. Real-world overall survival and progression-free survival (rwPFS) were defined as time from posttreatment AFP measurement to death, and the first progression event or death, respectively. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models adjusted for potential confounders and baseline AFP. Effect modification by baseline AFP and hepatocellular carcinoma risk factors was assessed.

Results

Among 533 patients, median baseline AFP was higher in those with AFP reduction than those without (N = 166, 210 µg/L vs N = 367, 150 µg/L). There was a 35% decrease in hazard of death for patients with reduction vs without (aHR = 0.65; 95% CI, 0.52–0.81; median, 10.3 vs 5.9 months). Results were similar for rwPFS (aHR = 0.66; 95% CI, 0.54–0.81; median, 4.6 vs 2.6 months). AFP reduction was associated with better outcomes among patients with baseline AFP ≥400 µg/L or with history of hepatitis B virus, hepatitis C virus, or alcohol use. Only the interaction between baseline AFP and reduction in association with rwPFS was statistically significant.

Conclusions

For certain etiologies, posttreatment AFP change may be more important than baseline AFP for prognosis. Further work should characterize the prognostic implications of longitudinal AFP changes during treatment.

Plain Language Summary

• The prognostic value of the change in α-fetoprotein (AFP) concentration after treatment initiation is less established, particularly in real-world settings.
• Longitudinal data from a large nationwide cohort of patients with advanced hepatocellular carcinoma (HCC) treated with first-line tyrosine kinase inhibitor in routine practice revealed that ≥20% reduction in posttreatment AFP levels was associated with better real-world overall survival and progression-free survival after adjusting for baseline AFP levels and other factors.
• The results also suggested that the associations may be stronger among patients with a history of HCC risk factors (e.g., hepatitis C virus, alcohol) or with higher baseline AFP levels.

     

Ampullary carcinoma in patients under 50 years of age with a poor prognosis

Clinicopathologic features of 145 Japanese patients with ampullary carcinoma were compared among three age groups. The 145 patients were divided into three groups by the patient's age at the time of operation; there were 24 patients in group I (younger) aged less than or equal to 50 years, 99 in group II (ordinary) aged 51-69, and 22 in group III (elderly) aged greater than or equal to 70. The three groups showed no significant difference in sex, icterus, duration of icterus, size of the tumor, year of operation, macroscopic type, histopathologic type, tumor margin, lymphatic permeation, venous invasion, or pancreatic invasion. The survival curve of group I was worse than those of groups II and III. Multivariate regression analysis using 11 prognostic variables failed to reveal that the age of the patient at the time of operation was an independent factor. The younger patients aged less than or equal to 50 fared worse than the elderly patients aged greater than or equal to 70, because the group I tumors included a significantly greater number of advanced ampullary carcinoma with more frequent perineural invasion than did the group III tumors.     

Clinical outcomes and prognostic factors following the surgical resection of renal cell carcinoma spinal metastases

The efficacy of surgical resection in metastatic renal cell carcinoma is an active and important research field in the postcytokine era. Bone metastases, especially in the spine, compromise patient performance status. Metastasectomy is indicated, if feasible, because it helps to achieve the best clinical outcomes possible compared with other treatments. This study examined the postoperative survival and prognostic factors in patients who underwent metastasectomy of spinal lesions. The retrospective study included 65 consecutive patients with metastatic renal cell carcinomas who were operated on by spinal metastasectomy between 1995 and 2017 at our institution. The cancer-specific survival times from the first spinal metastasectomy to death or the last follow-up (≥3 years) were determined using Kaplan-Meier analysis. Potential factors influencing survival were analyzed using Cox proportional hazard models. Planned surgical resection of all the spine tumors was achieved in all patients. Of these, 38 had complete metastasectomy of all visible metastases, including extraspinal lesions. In all patients, the estimated median cancer-specific survival time was 100 months. The 3-, 5-, and 10-year cancer-specific survival rates were 77%, 62%, and 48%, respectively. The survival times after spinal metastasectomy were similar in both cytokine and postcytokine groups. In multivariate analyses, postoperative disability, the coexistence of liver metastases, multiple spinal metastases, and incomplete metastasectomy were significant risk factors associated with short-term survival. Complete metastasectomy, including extraspinal metastases, was associated with improved cancer-specific survival. Proper patient selection and complete metastasectomy provide a better prognosis in metastatic renal cell carcinoma patients.     

Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Fran?ais d'Immunothérapie.

Interleukin-2 (IL-2) or/and interferon (IFN) are routinely used for treating patients with metastatic renal cell cancer. However, results have been disappointing, with a majority of treatment failure. Over 6 years, the Groupe Fran?ais d'Immunothérapie enrolled 782 patients in successive multicenter trials using cytokine regimens. Univariate and multivariate analyses were performed on this large prospective database to identify prognostic factors for survival. The presence of biological signs of inflammation, short time interval from renal tumor to metastases (<1 year), elevated neutrophil counts, liver metastases, bone metastases, patient performance status (PS), the number of metastatic sites, alkaline phosphatases and hemoglobin levels were predictive of survival outcome. When compared with previous results, our study showed that PS, number of metastatic sites, disease-free interval, biological signs of inflammation and hemoglobin levels can be considered as validated prognostic factors. We also identified four independent factors predictive of rapid progression under cytokine treatment: presence of hepatic metastases, short interval from renal tumor to metastases (<1 year), more than one metastatic site and elevated neutrophil counts. Patients who combined at least three of these factors have >80% probability of rapid progression despite treatment. We think that these results must be taken into account when making the decision to treat with cytokine.     

甲状腺未分化癌疗效及预后因素分析(附23例报告)

目的　从影响甲状腺未分化癌疗效及预后的因素探讨早诊早治和合理的综合治疗。方法　甲状腺未分化癌 2 3例 ,男 11例 ,女 12例 ,最小年龄 40岁 ,最大年龄 82岁 ,平均 5 7.17岁。病史最长 37年 ,最短 15天。其中颈部肿物 19例 ,有浸润症状如声音嘶哑、呼吸困难、吞咽困难 10例。以单纯手术 ,手术加放疗 ,手术残留而放疗 ,姑息治疗四种方法进行。结果　 1、2、3、5、10年生存率分别为 6 0 .8%、39.1%、30 .4%、13%、8.6 %。结论　治疗预后与原发灶、转移淋巴结大小及治疗方法的选择有密切关系。所以 ,早诊早治和合理的综合治疗非常重要     

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

BACKGROUND:

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.

METHODS:

Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re‐reviewed by genitourinary pathologists according to strict criteria.

RESULTS:

Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high‐grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) ‐positive. Over a mean follow‐up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5‐year recurrence‐free and cancer‐specific survival probabilities (±SD) were 69% ± 1% and 73% ± 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P = .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P = .001), high tumor grade (HR: 1.7, P = .001), increasing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P = .002), and LVI (HR: 1.4, P = .02) were independently associated with cancer‐specific survival.

CONCLUSIONS:

Radical nephroureterectomy provided durable local control and cancer‐specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Cancer 2009. © 2009 American Cancer Society.     

Management and outcomes of mixed adenoneuroendocrine carcinoma of the ampulla of Vater: A systematic review and pooled analysis of 56 patients

BackgroundTumors of mixed neuroendocrine and nonneuroendocrine histology are classified as collision, combined, or amphicrine and can occur in most organs, including the hepato-pancreato-biliary tract. Given the rarity of mixed adenoneuroendocrine carcinoma (MANEC) of the ampulla of Vater, the patient characteristics, management, and outcomes remain unclear. We sought to systematically review the worldwide literature on ampullary MANECs.MethodsEligible studies were identified through a systematic search of the MEDLINE (via PubMed), Scopus, and Cochrane Library databases (end-of-search-date: January 5th, 2022), according to the PRISMA 2020 statement.ResultsA total of 39 studies reporting on 56 patients with ampullary MANEC were included. The median age was 63.0 (interquartile range [IQR]: 51.0–69.0) years and 55.6% were male (n = 25/45). Most had combined tumors (64.4%; n = 29/45), followed by collision (24.4%; n = 11/45), and amphicrine tumors (11.1%; n = 5/45). More than half had lymph node metastasis (56.8%; n = 25/44), yet only 7.9% had distant metastasis (n = 3/38). Tumor resection (i.e., mostly pancreaticoduodenectomy) was performed in 96.3% (n = 52/54), followed by adjuvant chemotherapy in 61.8% (n = 21/34). Nearly half experienced disease recurrence (47.2%; n = 17/36) over a median follow-up of 12.0 (IQR: 3.0–16.0) months, and 42.1% (n = 16/38) died over a median follow-up of 12.0 (IQR: 4.0–18.0) months. The most common cause of death was disease progression/recurrence in 81.3% (n = 13/16).ConclusionEarly diagnosis and management of ampullary MANEC is challenging yet crucial to improve outcomes since many patients are diagnosed at an advanced disease stage and have unfavorable outcomes. Multicenter granular data are warranted to further understand and improve outcomes in these patients.     

General features of gastric carcinomas and comparison of HSP70 and NK cell immunoreactivity with prognostic factors

During the period of 1996-1998 ninety-four gastrectomy specimens with gastric carcinoma referred to Erciyes University, Medical Faculty, Department of Pathology, were examined histopathologically, histochemically and immunohistochemically. General characteristics of gastric carcinomas and prognostic factors were studied. According the Lauren classification, of the 94 cases of gastric carcinomas, 56 were intestinal type, 21 were diffuse type and 17 were mixed type carcinoma. The association rates of Helicobacter pylori, chronic atrophic gastritis and intestinal metaplasia with gastric carcinomas were high. There was strong immunorectivity with HSP70 in 62,5% of the intestinal type carcinomas. This ratios were lower in diffuse and mixed type carcinomas (p<0.05). The more tumor size and invasion depth increased, the more HSP70 immunoreactivity was obtained (p<0.05). HSP70 immunorectivity was considerably higher in the patients having lymph node metastasis and vascular invasion (p<0.05). It was found that the NK cell number was low in the tumor but higher around the tumor in early gastric carcinomas, compared with advanced carcinomas (p>0.05). In the tumors larger than 10 cm with vascular invasion, NK cell number was lower around the tumor (p>0.05). Defining prognostic factors of gastric carcinomas is of importance to clinicians. It is thought that HSP70 immunoreactivity, besides invasion depth, lymph node metastasis, vascular invasion, tumor size and inflammatory reaction against the tumor, is important in prognosis and associated with advanced stage.     

Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal

PURPOSE: To evaluate our data concerning the prognostic factors for locoregional control, survival, late complications, and sphincter conservation in a series of epidermoid cancers of the anal canal without clinical evidence of metastasis. METHODS AND MATERIALS: Between June 1972 and January 1997, 305 patients were treated with curative-intent radiotherapy (RT). The T stage according to the 1987 International Union Against Cancer classification was T1 in 26, T2 in 141, T3 in 104, and T4 in 34. Forty-nine patients had nodal involvement at presentation. The pretreatment anal function score, according to our in-house system, was 0 for 22 patients, 1 for 182, 2 for 74, 3 for 7, and 4 for 11 patients; for 9 patients, scores were unavailable. The treatment started with external beam radiotherapy (EBRT) in 303 patients (median dose 45 Gy). After a rest period of 4-6 weeks, a boost of 20 Gy was delivered by EBRT in 279 patients and by interstitial (192)Ir brachytherapy in 17 patients. Seven patients received only one course of EBRT (mean dose 49.5 Gy), and 2 patients were treated with interstitial (192)Ir brachytherapy alone (55 Gy and 60 Gy). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 patients. The mean follow-up was 103 months (median 84). RESULTS: At the end of RT, the local tumor clinical complete response rate was 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Of the 61 locally progressive tumors, 27 (44%) were salvaged with abdominoperineal resection. The rate of local tumor relapse was 12%. Among 37 local tumor relapses, 20 (54%) were salvaged with abdominoperineal resection and one with interstitial (192)Ir brachytherapy. The overall local control rate (with or without salvage local therapy) was 84%. The local control rate with good anal function (score 0 or 1) was 56.5%. Of 181 available patients with their anus preserved, 94% had good anal function. For a subgroup of 15 patients with a tumor length of <2 cm and without nodal involvement, the clinical complete response rate after RT completion was 100%, the local control rate with or without local salvage treatment was 100%, and among 13 available patients with their anus preserved, the anal function score was good in 12 patients (92%). The 10-year disease-free survival rate was 74%. After multivariate analysis, three independent predictive factors significantly influenced disease-free survival: the interval between the two courses of RT (>38 days vs. < or =38 days, p = 0.0025), pretreatment anal function score (0 vs. 1 vs. 2 vs. 3 vs. 4, p = 4.4.10(-6)), and clinical complete response after RT completion (no complete response vs. complete response, p = 2.5.10(-14)). CONCLUSION: We confirm the excellent results with RT in T1 and T2 lesions. However, to improve survival without colostomy with good anal sphincter function, chemoradiotherapy should be preferred for tumors > or =2 cm in length and for locally advanced tumors.